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Histrelin

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Feb.02.2024

Histrelin

Indications/Dosage

Labeled

  • precocious puberty
  • prostate cancer

Off-Label

    † Off-label indication

    For the palliative treatment of advanced prostate cancer

    Subcutaneous depot implant dosage (Vantas ONLY)

    Adult males

    1 implant (50 mg of histrelin acetate to deliver 41 mg histrelin) inserted subcutaneously in the upper arm every 12 months; remove the implant after 12 months of therapy. At the time of implant removal, another implant may be inserted to continue therapy. In a multicenter, open-label, phase 3 clinical trial of patients with prostate cancer (n = 138), treatment with a single histrelin implant for at least 52 weeks decreased the mean serum testosterone concentration by approximately 1.4% at the end of week 1, by 76.3% at the end of week 2, by 96.1% at the end of week 4, and by 96.3% at week 52; mean serum testosterone levels were below the 50 ng/dL castrate threshold by the end of week 4. Serum testosterone was suppressed to below the castrate level in all evaluable patients on day 28 (n = 134); all patients who were missing values at day 28 were castrate by the time of their next visit at day 56. In a subset of 17 patients, mean serum testosterone concentrations increased by approximately 40.9% on day 2, and then decreased to below baseline by week 2, and to below the 50 ng/dL castrate threshold by week 4; serum testosterone concentrations remained below the castrate level in this subset for the entire treatment period. Serum prostate specific antigen (PSA), a secondary endpoint, decreased to within normal limits by week 24 in 93% of patients.[30369] A phase 2, dose-finding clinical trial found similar decreases in serum testosterone levels with the use of 1, 2, or 4 histrelin implants for the palliation of advanced prostate cancer; the insertion of more than 1 histrelin implant is not necessary.[30373]

    For the treatment of central precocious puberty

    NOTE: Histrelin has been designated an orphan drug by the FDA for this indication.

    Subcutaneous dosage (implant; Supprelin LA)

    Children 2 to 12 years

    50 mg subcutaneously every 12 months. The implant provides a continuous release of histrelin 65 mcg/day for 12 months of hormonal therapy. Monitor hormonal and clinical parameters at month 1, every 6 months thereafter, and further as clinically appropriate to ensure adequate suppression. Remove and replace the implant after 12 months to continue therapy; the implant has been designed to continue to release histrelin for a few additional weeks in order to allow flexibility for medical appointments.[33431]

    Therapeutic Drug Monitoring

    Maximum Dosage Limits

    • Adults

      No more than 1 Vantas subcutaneous implant insertion at any one time.

    • Geriatric

      No more than 1 Vantas subcutaneous implant insertion at any one time.

    • Adolescents

      No more than 1 Supprelin LA subcutaneous implant inserted at any one time, although most children with precocious puberty will discontinue histrelin therapy around adolescence.

    • Children

      Children 2 years and older: No more than 1 Supprelin LA subcutaneous implant inserted at any time.

      Children younger than 2 years: Safety and efficacy have not been established.

    • Infants

      Safety and efficacy have not been established.

    Patients with Hepatic Impairment Dosing

    Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.

    Patients with Renal Impairment Dosing

    CrCL 15 mL/min or higher: No dosage adjustments are needed.

    CrCL less than 15 mL/min: Specific guidelines are not available; no dosage adjustments are recommended.[30369]

    † Off-label indication
    Revision Date: 02/02/2024, 02:07:00 AM

    References

    30369 - Vantas (histrelin implant) package insert. Chadds Ford, PA: Endo Pharmaceuticals Solutions Inc.; 2022 Feb.30373 - Schlegel PN, Kuzma P, Frick J, et al. Effective long-term androgen suppression in men with prostate cancer using a hydrogel implant with the GnRH agonist histrelin. Urology 2001;58:578-82.33431 - Supprelin LA (histrelin implant) package insert. Chadds Ford, PA: Endo Pharmaceuticals Solutions Inc.; 2022 April.

    How Supplied

    Histrelin Acetate Implant

    Vantas 50mg Implant (55592-0500) (Endo Pharmaceuticals Inc) (off market)

    Histrelin Acetate Implant

    Vantas 50mg Implant (67979-0500) (Endo Pharmaceuticals Solutions Inc. formerly Indevus) (off market)

    Histrelin Acetate Implant [Precocious puberty]

    Supprelin LA 50mg Implant (67979-0002) (Endo Pharmaceuticals Solutions Inc. formerly Indevus) null

    Histrelin Acetate Solution for injection

    Supprelin 200mcg/ml Solution for Injection (53922-8015) (Schering Plough Products LLC) (off market)

    Histrelin Acetate Solution for injection

    Supprelin 500mcg/ml Solution for Injection (53922-8016) (Schering Plough Products LLC) (off market)

    Histrelin Acetate Solution for injection

    Supprelin 1000mcg/ml Solution for Injection (53922-8017) (Schering Plough Products LLC) (off market)

    Description/Classification

    Description

    Histrelin acetate is a synthetic nonapeptide analog of gonadotropin releasing hormone (GnRH); the implant is a sterile, non-biodegradable, diffusion-controlled hydrogel polymer reservoir. Histrelin functions as a GnRH agonist, and is a potent inhibitor of gonadotropin secretion when given continuously at therapeutic doses. It is FDA approved for the palliative treatment of advanced prostate cancer and for the treatment of central precocious puberty. Initial transient increases of estradiol and/or testosterone may cause a temporary worsening of symptoms. However, testosterone concentrations in men being treated for advanced prostate cancer are reduced to castration levels within 2 to 4 weeks of starting therapy. In pediatric patients, LH levels decrease to prepubertal levels within 1 month of treatment, with a resultant decrease in the serum concentrations of sex steroids (i.e., estrogen or testosterone). Implant insertion is a surgical procedure.[30369][33431]

    Classifications

    • Antineoplastic and Immunomodulating Agents
      • Cytostatic Hormone Therapy
        • Cytostatic Hormone Agonists
          • Cytostatic Gonadotropin-Releasing Hormone Agonists
    • Systemic Hormonal Agents (excluding Sex Hormones)
      • Pituitary and Hypothalamic Hormones
        • Hypothalamic Hormones
          • Gonadotropin-Releasing Hormone Agonists
    Revision Date: 02/02/2024, 02:07:00 AM

    References

    30369 - Vantas (histrelin implant) package insert. Chadds Ford, PA: Endo Pharmaceuticals Solutions Inc.; 2022 Feb.33431 - Supprelin LA (histrelin implant) package insert. Chadds Ford, PA: Endo Pharmaceuticals Solutions Inc.; 2022 April.

    Administration Information

    General Administration Information

    For storage information, see the specific product information within the How Supplied section.

    Hazardous Drugs Classification

    • NIOSH 2016 List: Group 1 [63664]
    • NIOSH (Draft) 2020 List: Table 2
    • Observe and exercise appropriate precautions for handling, preparation, administration, and disposal of hazardous drugs.
    • Use double chemotherapy gloves and a protective gown. Prepare in a biological safety cabinet or compounding aseptic containment isolator with a closed system drug transfer device. Eye/face and respiratory protection may be needed during preparation and administration.[63664]

    Route-Specific Administration

    Injectable Administration

    Subcutaneous Administration

    Insertion (Vantas and Supprelin LA):

    • Wear sterile gloves and use aseptic technique to minimize any chance of infection.
    • Open the implant vial just before the time of insertion by removing the metal band and carefully pouring the sterile contents (implant and sterile saline) onto the sterile field drape. The implant can be handled with sterile gloves or with the sterile mosquito clamp provided. Avoid bending or pinching the implant.
    • The patient should lay on his back, ideally with the arm least used positioned so that the physician has ready access to the inner aspect of the upper arm. The suggested optimum site for insertion is approximately half-way between the shoulder and elbow, in line with the crease between the biceps and triceps muscles.
    • Swab insertion area with topical antiseptic, then overlay with the fenestrated sterile field drape provided so that the opening is over the insertion site.
    • The method of anesthesia (i.e., local, conscious sedation, general) is at the provider's discretion. Local anesthetic is provided with the insertion kit, which may be injected into the subcutaneous tissue starting at the planned incision site, then infiltrating along the intended subcutaneous path, up to the length of the implant (slightly more than 1 inch).
    • Grasp the sterile insertion tool and confirm that the cannula is fully extended by inspecting the position of the green retraction button; the button should be locked in position all the way forward, towards the cannula, farthest from the handle.
    • Pick up the implant using sterile gloves or the mosquito clamp. The implant may be slightly curved and/or partially flattened after refrigerated storage; it may be rolled between the fingers and thumb a few times using a sterile glove to make it more symmetrical prior to loading into the tool.
    • Insert the implant into the insertion tool; do not force the implant into the cannula. If resistance is felt, remove the implant and manually manipulate or roll as needed prior to re-insertion into the cannula. The tip of the implant should be visible at the beveled end of the cannula.
    • With a sterile scalpel, make an incision transverse to the long axis of the arm, large enough to allow the bore of the cannula to be inserted into the subcutaneous tissue. Especially in pediatric patients, ensure that there is sufficient length of upper arm available to fit the implant easily within the intended insertion space.
    • Visibly raise the skin at all times during pocket-making and insertion ("tenting") to ensure correct placement of the implant just under the skin.
    • To ease insertion, a "pocket" for the implant may be created by blunt dissection through the incision, using the cannula of the loaded insertion tool, a sterile hemostatic clamp, or equivalent surgical tool; this tool should be inserted subcutaneously and should not enter the muscle, as this will cause difficulty with removal without improving efficacy. If using the cannula of the loaded insertion tool, insert the length of the cannula up to, but not farther than, the inscribed black ine on the cannula; DO NOT depress the green retraction button. Pull the tool back almost the beveled tip of the cannula.
    • Advance the insertion tool forward again, so that the cannula completely re-enters the pocket, no farther than the inscribed black line. Be sure the insertion path is immediately subcutaneous.
    • Hold the tool in place with the base against the patient's arm. Carefully depress the green retraction button to release the locking mechanism, then slide the button back toward the handle until it stops. Keep the body of the insertion tool in place and apply pressure to the skin over the implant to help ensure the implant remains in the subcutaneous pocket.
    • Retracting the button causes the cannula to withdraw from the incision, leaving the implant in the subcutaneous tissue. Do not further advance the cannula once the retraction process has started, and do not withdraw the insertion tool until the button is fully retracted to avoid pulling out the implant. Thee tool may be withdrawn when retraction is complete.
    • Confirm placement of the implant by palpation. The tip of the implant may not be visible through the incision.
    • Close the incision with absorbable sutures and/or sterile adhesive surgical strips. Adhesion of strips may be improved by the application of benzoin tincture antiseptic, which should be allowed to dry before applying the adhesive strips.
    • Cover the incision site with sterile gauze pads and secure the dressing with a bandage.
    • Advise patients to avoid wetting the arm for 24 hours after implant insertion, and to avoid heavy lifting or strenuous exertion of the inserted arm for 7 days after insertion.[30369][33431]

     

    Removal (Vantas and Supprelin LA):

    • Remove the histrelin implant after 12 months of therapy. Wear sterile gloves and use aseptic technique to minimize any chance of infection.
    • Most necessary supplies are provided in the implantation kit. Place the sterilized components needed for implant removal onto the non-fenestrated sterile field drape.
    • The patient should lay on his back, ideally with the arm least used positioned so that the physician has ready access to the inner aspect of the upper arm. The suggested optimum site for insertion is approximately half-way between the shoulder and elbow, in line with the crease between the biceps and triceps muscles.
    • Locate the implant to be removed by palpating the inner aspect of the upper arm, near the incision from the prior year. Ultrasound may be used if the implant is difficult to palpate; if ultrasound fails, other imaging techniques (e.g., CT or MRI) may be used to locate it. Plain films are not recommended as the implant is not radiopaque.
    • Swab area above and around the previous implant with topical antiseptic, then overlay with the fenestrated sterile field drape provided so that the opening is over the previous insertion site.
    • The method of anesthesia (i.e., local, conscious sedation, general) is at the provider's discretion. Local anesthetic is provided with the histrelin implantation kit, which may be injected into the subcutaneous tissue around the planned incision site (the site of the previous implant).
    • Using a sterile scalpel, make an incision of adequate size to allow implant removal and, if a new implant will be inserted, large enough for the bore of the cannula of the insertion tool. The tip of the implant should be visible through the incision, possibly covered by a pseudocapsule of tissue. It may be necessary to palpate the head of the implant through the incision, especially if it is not visible; additionally, the distal end of the implant may need to be massaged forward toward the incision.
    • Carefully nick the pseudocapsule to reveal the polymer tip of the implant. Widening the opening by inserting the mosquito clamp into the hold and opening the clamp may ease extraction.
    • Gently but securely grasp the implant with the sterile mosquito clamp and extract the implant.
    • If inserting a new implant, see instructions above. The new implant may be inserted into the same pocket as the removed implant, or at a new site.
    • Close the incision with absorbable sutures and/or sterile adhesive surgical strips. Adhesion of strips may be improved by the application of benzoin tincture antiseptic, which should be allowed to dry before applying the adhesive strips.

    Clinical Pharmaceutics Information

    From Trissel's 2‚Ñ¢ Clinical Pharmaceutics Database
      Revision Date: 02/02/2024, 02:07:00 AM

      References

      30369 - Vantas (histrelin implant) package insert. Chadds Ford, PA: Endo Pharmaceuticals Solutions Inc.; 2022 Feb.33431 - Supprelin LA (histrelin implant) package insert. Chadds Ford, PA: Endo Pharmaceuticals Solutions Inc.; 2022 April.63664 - CDC National Institute for Occupational Safety and Health (NIOSH). NIOSH List of Antineoplastic and Other Hazardous Drugs in Healthcare Settings 2016. DHHS (NIOSH) Publication Number 2016-161, September 2016. Available on the World Wide Web at https://www.cdc.gov/niosh/docs/2016-161/pdfs/2016-161.pdf?id=10.26616/NIOSHPUB2016161

      Adverse Reactions

      Moderate

      • amblyopia
      • anemia
      • bone pain
      • constipation
      • depression
      • diabetes mellitus
      • dyspnea
      • dysuria
      • edema
      • elevated hepatic enzymes
      • erythema
      • hematoma
      • hematuria
      • hot flashes
      • hypercalcemia
      • hypercholesterolemia
      • hyperglycemia
      • impotence (erectile dysfunction)
      • migraine
      • neuropathic pain
      • osteopenia
      • osteoporosis
      • palpitations
      • pseudotumor cerebri
      • QT prolongation
      • testicular atrophy
      • tumor flare
      • urinary retention
      • vaginal bleeding

      Mild

      • abdominal pain
      • appetite stimulation
      • arthralgia
      • back pain
      • breast enlargement
      • diaphoresis
      • dizziness
      • dysmenorrhea
      • ecchymosis
      • emotional lability
      • epistaxis
      • fatigue
      • flushing
      • gynecomastia
      • headache
      • hypertrichosis
      • increased urinary frequency
      • infection
      • influenza
      • injection site reaction
      • insomnia
      • irritability
      • lethargy
      • libido decrease
      • malaise
      • menorrhagia
      • myalgia
      • nausea
      • night sweats
      • pruritus
      • tremor
      • vomiting
      • weakness
      • weight gain
      • weight loss

      Severe

      • anaphylactoid reactions
      • hot flashes
      • myocardial infarction
      • pituitary apoplexy
      • renal failure (unspecified)
      • seizures
      • spinal cord compression
      • stroke
      • suicidal ideation
      • visual impairment

      The most common adverse reaction associated with histrelin therapy in men undergoing treatment for prostate cancer is hot flashes (65.5%). Of those men experiencing hot flashes while receiving histrelin therapy, 2.3% reported severe hot flashes, 25.4% reported moderate hot flashes, and 37.7% reported mild hot flashes. As a result of decreased testosterone, approximately 5.3% of men experience testicular atrophy during histrelin therapy; additional consequences of testosterone suppression reported in patients with advanced prostate cancer included impotence (erectile dysfunction) (3.5%), libido decrease (2.3%), and gynecomastia (4.1%). Flushing, diaphoresis, night sweats, breast pain, breast tenderness, and sexual dysfunction were also each reported in fewer than 2% of patients treated with histrelin (Vantas) in clinical trials.[30369] Gynecomastia and breast tenderness were each reported in one pediatric patient treated with histrelin (Supprelin LA) for central precocious puberty in 2 single-arm clinical trials. Histrelin, like other GnRH agonists, causes a transient increase in serum concentrations of the gonadotropins and the sex steroids (e.g., testosterone in males and females and estrogen in females) during the first few weeks of treatment. Patients may experience worsening of symptoms such as breast enlargement in girls with precocious puberty during this period. In children with central precocious puberty, suppression of gonadal steroids and manifestations of puberty decrease within 4 weeks of histrelin implant insertion.[33431]

      Transient increases in serum testosterone causing worsening symptoms or new symptoms, known as tumor flare symptoms, may occur in patients receiving histrelin for the treatment of advanced prostate cancer during the first week of therapy. Symptoms may include bone pain, neuropathy (neuropathic pain), hematuria, or ureteral/bladder obstruction. Cases of spinal cord compression, which may result in paralysis, and ureteral obstruction, which may cause renal impairment, have been reported with GnRH agonists. Mild renal impairment (CrCL 30 to 59 mL/min) occurred in 2.9% of patients with advanced prostate cancer who received histrelin in 2 clinical trials (n = 171), which returned to a normal range by the next visit; 1.8% of patients developed moderate to severe renal impairment. In clinical trials of patients with advanced prostate cancer, decreased creatinine clearance, bone pain, back pain, aggravated back pain, aggravated hematuria, aggravated renal failure (unspecified), increased urinary frequency, urinary retention, and dysuria each were reported in less than 2% of patients who received histrelin.[30369] Transient increases in serum concentrations of estradiol in females and testosterone in both sexes may also occur during the first week of therapy for pediatric patients receiving histrelin for the treatment of central precocious puberty, during which new symptoms or worsening of symptoms may occur; however, within 4 weeks of initiation of therapy, suppression of gonadal steroids occurs and manifestations of puberty decrease.[33431]

      Among 47 children with central precocious puberty who received histrelin, 1 patient reported menorrhagia and 1 reported dysmenorrhea; metrorrhagia was reported as possibly related in 2 patients. Histrelin, like other GnRH agonists, causes a transient increase in serum concentrations of the gonadotropins and the sex steroids (e.g., testosterone in males and females and estrogen in females) during the first few weeks of treatment. Patients may experience worsening of symptoms such as light vaginal bleeding in girls with precocious puberty during this period; suppression of gonadal steroids and manifestations of puberty decrease within 4 weeks of histrelin implant insertion.[33431]

      Cases of pituitary apoplexy, a syndrome due to a sudden infarction or hemorrhage in the pituitary gland, have been reported after the administration of gonadotropin-releasing hormone (GnRH) agonists, most commonly in elderly males receiving GnRH agonists in the treatment of advanced prostate cancer, although it has been reported when used for other indications as well. In a majority of these cases, a pituitary adenoma was diagnosed with a majority of pituitary apoplexy cases occurring within 2 weeks of the final dose, and some within the first hour. In these cases, pituitary apoplexy has presented as a sudden and severe headache, nausea, vomiting, visual changes including reduction in visual field (visual impairment) and ocular paresis, altered mental status, and sometimes cardiovascular collapse. Immediate medical management may be required.[31507] [31508] [30369] One pediatric patient treated with histrelin for central precocious puberty developed a benign pituitary tumor.[33431]

      Injection site reaction involving the implant site (e.g., ecchymosis, erythema, pain, implant area protrusion, itching, soreness, swelling, and tingling) was the most commonly reported adverse reaction (51.1%) in 2 single-arm clinical trials of pediatric patients with central precocious puberty treated with histrelin (n = 47). In these trials, the following additional implant site reactions were reported separately: keloid scar (6.4%), scar (6.4%), suture-related complication (6.4%), application site pain (4.3%), and post-procedural pain (4.3%); wound infection, erythema, and pruritus were each reported in 1 patient.[33431] In a detailed evaluation for implant site reactions (n = 138), 13.8% of men with advanced prostate cancer experienced mild local or insertion site reactions including bruising (7.2%), pain/soreness/tenderness (3.6%), erythema (2.8%), and swelling (0.7%), mostly associated with initial insertion or removal and insertion of a new implant. The majority of these reactions began and resolved within the first 2 weeks following implant insertion, but persisted in 2.8% of patients; an additional 2.8% of patients developed application-site reactions after the first 2 weeks. Two patients had local infections/inflammations; one resolved after treatment with antibiotics and the other resolved without treatment. The incidence of local reactions after insertion of subsequent implants was comparable to those seen after initial insertion. In 2 clinical trials of patients with advanced prostate cancer (n = 171), implant site reaction occurred in 5.8%, while generalized pruritus, male genital pruritus, contusion, hypertrichosis, and hematoma were each reported in less than 2% of patients. In all clinical trials combined, an implant was not recovered in 8 patients. For 2 of these patients with advanced prostate cancer, serum testosterone rose above castrate level and the implant was neither palpable nor visualized with ultrasound; they were believed to have been extruded without the patient being aware. In the other 6 patients, serum testosterone remained below castrate level, but the implant was not palpable and no further diagnostic tests were conducted; one patient underwent an in-clinic surgical exploration that did not locate the implant.[30369] Rare events of spontaneous extrusion have also been observed in pediatric patients, and implant breakage was reported in postmarketing experience with pediatric patients. If the implant is not retrieved completely, the remaining pieces should be removed following the manufacturer's instructions.[33431]

      Anaphylactoid reactions to synthetic GnRH or GnRH agonist analogs have been reported in the literature and are theoretically possible with the use of histrelin regardless of indication.[30370] [30371]

      Long periods of medical castration in men will have effects on bone density such as osteoporosis. Decreased bone density has been reported in the medical literature in men who have had orchiectomy or who have been treated with a GnRH agonist analog such as histrelin.[30369] GnRH analog therapy can reduce bone mineral density in men as well as women. Reduced bone mineral density and osteopenia are also a concern if GnRH or LH-RH analogs are used in adolescent children. LH-RH analogs (aka GnRH analogs) have been used alone or added to growth hormone (rh-GH) therapy to moderately increase adult height in adolescents with normally timed puberty and idiopathic short status; the LH-RH analogs delay puberty and thus prolong the period of bone growth via delay of sex hormone-induced growth-plate senescence. In one study, the use of LH-RH agonist for 4 years, the typical duration needed to see an increase in adult height, was found to decrease bone mineral density in the lumbosacral region to more than 1 standard deviation below the population mean in 82% of adolescent patients receiving the LH-RH agonist. The authors concluded that LH-RH agonist therapy cannot be routinely recommended to augment height in short adolescents with normally timed puberty; for most adolescents the potential benefit of treatment would not outweigh the risks.[27524]

      Emotional lability (e.g., crying, irritability, impatience, anger, and aggression) has been observed in postmarketing experience with patients treated with GnRH agonists, including histrelin. Depression, including rare reports of suicidal ideation and attempt, have also been reported with GnRH agonists, including histrelin, in children treated for central precocious puberty. Mood swings were also reported in 1 pediatric patient treated with histrelin for central precocious puberty. Many, but not all, of these patients had a history of psychiatric illness or other comorbidities with an increased risk of depression.[33431] [30369] In patients with advanced prostate cancer, insomnia occurred in 2.9% of patients in 2 clinical trials, while depression and irritability were each reported in less than 2%. Monitor for the development or worsening of psychiatric symptoms during treatment with histrelin.[30369]

      In men, an increased risk of myocardial infarction, sudden cardiac death, and stroke has been reported in association with the use of GnRH analogs, although the risk appears low based on the reported odds ratios. Carefully evaluate cardiovascular risk factors and weigh the known benefits and risks of GnRH agonists such as histrelin when determining appropriate treatment for prostate cancer. Androgen deprivation therapy may also cause QT prolongation. In clinical trials, hypercholesterolemia, palpitations, ventricular extrasystoles, stent occlusion, exertional dyspnea, and peripheral edema/fluid retention were noted in less than 2% of patients treated with histrelin.[30369] The FDA evaluated data from published studies comparing outcomes in patients undergoing androgen deprivation therapy to treat prostate cancer versus patients not undergoing this treatment; most of the studies reported small, but statistically significant, increased risks of cardiovascular events in men receiving GnRH agonists. At this time, there are no known comparable studies evaluating the risk of cardiovascular disease in women or children taking GnRH agonists for other indications.[40127] [42122]

      In clinical trials of men with advanced prostate cancer treated with histrelin, less than 2% of patients had a hepatic disorder or elevated hepatic enzymes (e.g., increased aspartate aminotransferase). During the postmarketing period, severe liver injury was reported in association with histrelin; the toxicity was reversible with the removal of the histrelin implant.[30369]

      In men, hyperglycemia and an increased risk of developing diabetes mellitus have been reported in association with the use of GnRH analogs such as histrelin. In clinical trials of patients with advanced prostate cancer treated with histrelin, increased blood glucose was noted in less than 2% of patients.[30369] The FDA evaluated data from published studies comparing outcomes in patients undergoing androgen deprivation therapy to treat prostate cancer versus patients not undergoing this treatment; most of the studies reported small, but statistically significant, increased risks of diabetes in men receiving GnRH agonists. At this time, there are no known comparable studies evaluating the risk of diabetes in women or children taking GnRH agonists for other indications.[40127] [42122] Periodically monitor patients' blood glucose concentration and/or glycosylated hemoglobin; hyperglycemia may represent diabetes mellitus development or worsening of glycemic control in patients with the condition.[30369]

      In 2 clinical trials of patients with advanced prostate cancer treated with histrelin, the following gastrointestinal adverse reactions were reported: constipation (3.5%), weight gain (2.3%), weight loss (less than 2%), abdominal pain (less than 2%), nausea (less than 2%), appetite stimulation (less than 2%), and food craving (less than 2%).[30369] Weight gain occurred in 1 pediatric patient treated with histrelin for central precocious puberty (n = 47).[33431]

      One pediatric patient with Stargardt's Disease who received histrelin for the treatment of central precocious puberty experienced amblyopia.[33431]

      Seizures have been reported in postmarketing experience with histrelin in patients with a history of epilepsy, cerebrovascular disorders, CNS anomalies or tumors, and in patients on concomitant mediations that have been associated with seizures; seizures have also been reported in patients without any risk factors.[33431] [30369] Pseudotumor cerebri (idiopathic intracranial hypertension) has been reported in pediatric patients during postmarketing experience.[33431] Dizziness, muscle twitching, and tremor were each reported in less than 2% of patients with advanced prostate cancer treated with histrelin in 2 clinical trials (n = 171).[30369]

      An influenza-like illness possibly related to histrelin therapy was reported in one pediatric patient being treated for central precocious puberty in 2 single-arm clinical trials (n = 47).[33431]

      Fatigue (9.9%) and headache (2.9%) were reported in 2 clinical trials of patients with advanced prostate cancer treated with histrelin (n = 171); additionally, arthralgia, feeling cold, lethargy, limb pain, malaise, myalgia, neck pain, generalized pain, renal calculus, and weakness were each reported in less than 2% of patients in these trials.[30369] In 2 single-arm trials of pediatric patients receiving histrelin for central precocious puberty (n = 47), headache, migraine, and feeling cold were each reported by 1 patient.[33431]

      Epistaxis that was possibly related to histrelin therapy was reported in 1 pediatric patient being treated for central precocious puberty in 2 single-arm clinical trials (n = 47).[33431]

      Anemia, hypercalcemia, increased blood lactate dehydrogenase, increased blood testosterone, and increased prostatic acid phosphatase were each reported in less than 2% of patients treated with histrelin in 2 clinical trials of patients with advanced prostate cancer (n = 171).[30369]

      Revision Date: 02/02/2024, 02:07:00 AM

      References

      27524 - Yanovski JA, Rose SR, Municchi G, et al. Treatment with a luteinizing hormone-releasing hormone agonist in adolescents with short stature. N Engl J Med 2003;348:908-17.30369 - Vantas (histrelin implant) package insert. Chadds Ford, PA: Endo Pharmaceuticals Solutions Inc.; 2022 Feb.30370 - Potashnik G, Lunenfeld E, Spitz E, et al. Anaphylactic reaction to gonadotropin-releasing hormone. N Engl J Med 1993;328:815.30371 - Letterie GS, Stevenson D, Shah A. Recurrent anaphylaxis to a depot form of GnRH analogue. Obstet Gynecol 1991;78(5 pt 2):943.31507 - Randeva HS, Schoebel J, Byrne J, et al. Classical pituitary apoplexy: clinical features, management, and outcome. Clin Endocrinol 1999;51:181-8.31508 - Faustini-Fustini M. Pituitary apoplexy after leuprolide administration for carcinoma of the prostate: what's new? Clin Endocrinol 1997;46:378.33431 - Supprelin LA (histrelin implant) package insert. Chadds Ford, PA: Endo Pharmaceuticals Solutions Inc.; 2022 April.40127 - Food and Drug Administration (US FDA) News Release. Ongoing Safety Review of GnRH Agonists and possible increased risk of diabetes and certain cardiovascular diseases. . Retrieved May 3, 2010. Available on the World Wide Web at: http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm210576.htm.42122 - Food and Drug Administration (US FDA) Drug Safety Communication. Updated to ongoing safety review of GnRH Agonists and notification to manufacturers of GnRH Agonists to add new safety information to labeling regarding increased risk of diabetes and certain cardiovascular diseases. Retrieved October 20, 2010. Available on the World Wide Web at: http://www.fda.gov/Drugs/DrugSafety/ucm229986.htm.

      Contraindications/Precautions

      Absolute contraindications are italicized.

      • Gonadotropin-Releasing Hormone (GnRH) analogs hypersensitivity
      • apheresis
      • AV block
      • bladder obstruction
      • bradycardia
      • breast-feeding
      • cardiac disease
      • cardiomyopathy
      • celiac disease
      • children
      • depression
      • diabetes mellitus
      • electrolyte imbalance
      • females
      • fever
      • geriatric
      • heart failure
      • human immunodeficiency virus (HIV) infection
      • hyperglycemia
      • hyperparathyroidism
      • hypocalcemia
      • hypokalemia
      • hypomagnesemia
      • hypothermia
      • hypothyroidism
      • infants
      • infertility
      • laboratory test interference
      • long QT syndrome
      • myocardial infarction
      • neonates
      • osteoporosis
      • pheochromocytoma
      • pituitary insufficiency
      • pregnancy
      • pseudotumor cerebri
      • QT prolongation
      • renal impairment
      • rheumatoid arthritis
      • seizure disorder
      • sickle cell disease
      • sleep deprivation
      • spinal cord compression
      • stroke
      • suicidal ideation
      • systemic lupus erythematosus (SLE)
      • urinary tract obstruction

      Histrelin is contraindicated in patients with hypersensitivity to histrelin, Gonadotropin-Releasing Hormone (GnRH), or with Gonadotropin-Releasing Hormone (GnRH) analogs hypersensitivity.[30370] [30371] [33431] [30369]

      Due to transient increases in testosterone levels, histrelin (Vantas) may cause a sudden onset or worsening of prostate cancer (flare), such as bone pain, neuropathy, hematuria, or urinary tract obstruction or bladder obstruction. Patients with prostate cancer and urinary tract obstruction or metastatic vertebral lesions should be monitored carefully for signs of renal impairment or spinal cord compression, respectively, during initial histrelin treatment.[30369]

      Therapy with histrelin results in suppression of the pituitary-gonadal system. Results of diagnostic tests for pituitary insufficiency and gonadotropic and gonadal functions conducted during and after histrelin therapy may be affected.

      The safety and efficacy of the Vantas implant dosage form of histrelin has not been established in infants and children. Supprelin LA is FDA-approved for use in children 2 years of age and older with central precocious puberty; it is not recommended for use in neonates, infants, and children younger than 2 years of age, as safety and efficacy have not been established.[30369] [33431]

      Histrelin should be used with caution in patients with pre-existing osteoporosis. GnRH analog therapy can reduce bone mineral density.[30369] Reduced bone mineral density and osteopenia are also a concern if GnRH or LH-RH analogs are used in adolescent children.[27524]

      The use of GnRH analogs in men has been reported in association with hyperglycemia and an increased risk of developing diabetes mellitus. Carefully weigh the known benefits and risks of GnRH agonists such as histrelin when determining appropriate treatment for prostate cancer. Periodically monitor patients' blood glucose concentration and/or glycosylated hemoglobin; hyperglycemia may represent diabetes mellitus development or worsening of glycemic control in patients with the condition. Manage patients according to current clinical practice. There are no known comparable studies evaluating the risk of diabetes in women, children, or adolescents taking GnRH agonists for other indications.[30369] [40127] [42122]

      Use histrelin with caution in patients with depression and emotional instability; monitor patients for worsening of psychiatric symptoms during treatment with histrelin. During postmarketing experience, emotional lability, such as crying, irritability, impatience, anger, and aggression were reported. Depression, including rare reports of suicidal ideation and attempt, were reported in children treated for central precocious puberty. Many, but not all, of these patients had a history of psychiatric illness or other comorbidities with an increased risk of depression.[33431]

      Use histrelin with caution in patients with a preexisting seizure disorder. Seizures have been reported during postmarketing surveillance in patients with a history of epilepsy, cerebrovascular disorders, central nervous system anomalies or tumors, and patients on concomitant medications that have been associated with seizures. Seizures have also been reported in patients without any risk factors.[33431]

      The use of GnRH analogs in men has been reported in association with an increased risk of myocardial infarction, sudden cardiac death, and stroke although the risk appears to be low based on the reported odds ratios. Additionally, myocardial infarction and stroke may increase the risk of histrelin prolonging the QT interval. Carefully evaluate risk factors for cardiac disease and weigh the known benefits and risks of GnRH agonists such as histrelin when determining appropriate treatment for prostate cancer. Monitor patients for signs and symptoms suggestive of the development of cardiovascular disease and manage according to current clinical practice. There are no known comparable studies evaluating the risk of cardiovascular disease in women, children, or adolescents taking GnRH agonists for other indications.[28432] [28457] [30369] [40127] [42122] [56592] [65180]

      Androgen deprivation therapy may prolong the QT/QTc interval. Use histrelin with caution in patients with conditions that may increase the risk of QT prolongation including congenital long QT syndrome, bradycardia, AV block, heart failure, stress-related cardiomyopathy, myocardial infarction, stroke, hypomagnesemia, hypokalemia, hypocalcemia, or in patients receiving medications known to prolong the QT interval or cause electrolyte imbalance. Females, geriatric patients, patients with sleep deprivation, pheochromocytoma, sickle cell disease, hypothyroidism, hyperparathyroidism, hypothermia, systemic inflammation (e.g., human immunodeficiency virus (HIV) infection, fever, and some autoimmune diseases including rheumatoid arthritis, systemic lupus erythematosus (SLE), and celiac disease) and patients undergoing apheresis procedures (e.g., plasmapheresis [plasma exchange], cytapheresis) may also be at increased risk for QT prolongation.[28432] [28457] [56592] [30369] [65180]

      Therapy with histrelin results in suppression of the pituitary-gonadal system. Laboratory test interference may occur during and after histrelin therapy; specifically diagnostic tests of pituitary gonadotropic and gonadal functions.[30369]

      Based on findings in animals and its mechanism of action, histrelin may cause infertility in males of reproductive potential.[30369]

      While Supprelin LA (histrelin) may be used in female children, the safety and efficacy of Vantas (histrelin) have not been established in females. Although there are no adequately controlled studies in pregnant women, histrelin can cause fetal harm or death when administered during pregnancy based on its mechanism of action and animal studies. Expected hormonal changes that occur with histrelin treatment increase the risk for pregnancy loss. Advise pregnant patients and females and females of reproductive potential of the risk to the fetus. Increased fetal mortality and post-implantation loss occurred when histrelin was administered to pregnant rats during organogenesis at exposures amounting to 0.2 to 3 times the human exposure based on body surface area. These doses also reduced maternal weight gain, stimulated ovarian follicular development, increased placental weight, and caused abnormal morphology and an increase in fetal size. In pregnant rabbits, administration of histrelin during organogenesis resulted in increased fetal mortality and abortion/early termination at the 2 highest doses and caused total litter loss at all doses (exposures of approximately 8 to 31 times human exposure at the recommended dose based on body surface area). Females may also be at increased risk for histrelin prolonging the QT interval.[28432] [28457] [30369] [33431] [56592] [65180]

      Due to the potential for serious adverse reactions in nursing infants from histrelin, advise women to discontinue breast-feeding during treatment. It is not known whether histrelin is present in human milk, although many drugs are excreted in human milk.[30369]

      Gonadotropin releasing hormone (GnRH) agonists, such as histrelin, have been associated with cases of pseudotumor cerebri (idiopathic intracranial hypertension) in pediatric patients. Monitor patients for signs and symptoms including headache, papilledema, blurred vision, diplopia, loss of vision, pain behind the eye or pain with eye movement, tinnitus, dizziness, and nausea.[33431]

      Revision Date: 02/02/2024, 02:07:00 AM

      References

      27524 - Yanovski JA, Rose SR, Municchi G, et al. Treatment with a luteinizing hormone-releasing hormone agonist in adolescents with short stature. N Engl J Med 2003;348:908-17.28432 - Roden, DM. Drug-induced prolongation of the QT interval. New Engl J Med 2004;350:1013-22.28457 - Crouch MA, Limon L, Cassano AT. Clinical relevance and management of drug-related QT interval prolongation. Pharmacotherapy 2003;23:881-908.30369 - Vantas (histrelin implant) package insert. Chadds Ford, PA: Endo Pharmaceuticals Solutions Inc.; 2022 Feb.30370 - Potashnik G, Lunenfeld E, Spitz E, et al. Anaphylactic reaction to gonadotropin-releasing hormone. N Engl J Med 1993;328:815.30371 - Letterie GS, Stevenson D, Shah A. Recurrent anaphylaxis to a depot form of GnRH analogue. Obstet Gynecol 1991;78(5 pt 2):943.33431 - Supprelin LA (histrelin implant) package insert. Chadds Ford, PA: Endo Pharmaceuticals Solutions Inc.; 2022 April.40127 - Food and Drug Administration (US FDA) News Release. Ongoing Safety Review of GnRH Agonists and possible increased risk of diabetes and certain cardiovascular diseases. . Retrieved May 3, 2010. Available on the World Wide Web at: http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm210576.htm.42122 - Food and Drug Administration (US FDA) Drug Safety Communication. Updated to ongoing safety review of GnRH Agonists and notification to manufacturers of GnRH Agonists to add new safety information to labeling regarding increased risk of diabetes and certain cardiovascular diseases. Retrieved October 20, 2010. Available on the World Wide Web at: http://www.fda.gov/Drugs/DrugSafety/ucm229986.htm.56592 - van Noord C, Eijgelsheim M, Stricker BH. Drug- and non-drug-associated QT interval prolongation. Br J Clin Pharmacol 2010;70(1):16-23.65180 - Woosley RL, Heise CW, Gallo T, et al. QTFactors List. Oro Valley, AZ: AZCERT, Inc.; Accessed March 31, 2020. Available on the World Wide Web at: https://crediblemeds.org/ndfa-list/

      Mechanism of Action

      Histrelin acetate is a gonadotropin releasing hormone (GnRH) agonist that is a potent inhibitor of gonadotropin secretion when given continuously in therapeutic doses. Following an initial stimulatory phase, the chronic, subcutaneous administration of histrelin acetate desensitizes responsiveness of the pituitary gonadotropin, which causes a reduction in testicular steroidogenesis. In humans, there is an initial increase in circulating levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH), which in turn transiently increases the production of gonadal steroids (e.g., estradiol and estrone in premenopausal females, and testosterone and dihydrotestosterone in males). However, with sustained administration, histrelin causes a reversible down-regulation of the GnRH receptors in the pituitary gland and desensitization of the pituitary gonadotropins, resulting in decreased levels of LH and FSH.[30369][33431]

       

      Central Precocious Puberty: Long-term treatment with histrelin suppresses the LH response to GnRH, causing LH levels to decease to prepubertal levels within 1 month of treatment. As a result, serum concentrations of sex steroids (i.e., estrogen or testosterone) also decrease, ceasing progression of secondary sexual development in most patients. Additionally, linear growth velocity is slowed, which improves the chance of attaining predicted adult height.[33431]

       

      Advanced Prostate Cancer: Testosterone is reduced to castration levels within 2 to 4 weeks after initiation of treatment.[30369]

      Revision Date: 02/02/2024, 02:07:00 AM

      References

      30369 - Vantas (histrelin implant) package insert. Chadds Ford, PA: Endo Pharmaceuticals Solutions Inc.; 2022 Feb.33431 - Supprelin LA (histrelin implant) package insert. Chadds Ford, PA: Endo Pharmaceuticals Solutions Inc.; 2022 April.

      Pharmacokinetics

      Histrelin is administered by a subcutaneous insertion of an implant containing histrelin acetate. The apparent volume of distribution (Vd) of histrelin following a subcutaneous bolus dose (500 mg) in healthy volunteers was 58.3 +/- 7.86 liters. In vitro, the mean fraction of unbound drug in plasma was 29.5% +/- 8.9%. Histrelin was metabolized by C-terminal dealkylation, resulting in one metabolite, in an in vitro drug metabolism study using human hepatocytes; peptide fragments resulting from hydrolysis are also likely metabolites. Following a subcutaneous bolus dose in healthy volunteers, the mean apparent clearance was 179 +/- 37.8 mL/min, and the mean terminal half-life was 3.92 +/- 1.01 hours. The mean apparent clearance following a 50 mg histrelin acetate implant in patients with prostate cancer (n = 17) was 174 +/- 56.5 mL/min. Drug excretion studies were not conducted with histrelin implants.[30369]

       

      Affected cytochrome P450 isoenzymes: None

      No pharmacokinetic-based drug interaction studies were conducted with histrelin implants.[30369][33431]

      Route-Specific Pharmacokinetics

      Oral Route

      Histrelin acetate is not active when given orally.[30369]

      Subcutaneous Route

      Mean peak serum concentrations of histrelin were 1.1 +/- 0.375 ng/mL following subcutaneous insertion of one histrelin 50 mg implant in patients with advanced prostate cancer (n = 17), occurring at a median of 12 hours. Continuous subcutaneous release was evident, as serum levels were sustained throughout the 52-week dosing period; the mean serum histrelin concentration at the end of 52 weeks was 0.13 +/- 0.065 ng/mL. Observed serum concentrations over 8 weeks following insertion of a second implant after 52 weeks were comparable to the same period following the first implant. The average rate of subcutaneous drug release from 41 implants assayed for residual drug content was 56.7 +/- 7.71 mcg/day. The relative bioavailability for the histrelin implant in prostate cancer patients with normal renal and hepatic function compared to a subcutaneous bolus dose in healthy male volunteers was 92%. Serum histrelin concentrations in prostate cancer patients were proportional to dose after insertion of 1, 2, 3, or 4 histrelin implants (n = 42).[30369]

      Special Populations

      Hepatic Impairment

      The influence of hepatic insufficiency on histrelin pharmacokinetics and dosing has not been adequately studied.[30369]

      Renal Impairment

      Serum histrelin concentrations were approximately 50% higher in prostate cancer patients with mild to severe renal impairment (n = 42; CrCL, 15 to 60 mL/min) compared to patients with no renal impairment (n = 92) (0.392 ng/mL vs. 0.264 ng/mL); these changes in exposure are not considered clinically relevant.[30369]

      Pediatrics

      The median maximum histrelin serum concentration was 0.43 ng/mL in a pharmacokinetic evaluation of pediatric patients receiving histrelin therapy for the treatment of central precocious puberty (n = 47); this concentration is expected to maintain gonadotropins at prepubertal levels. Median serum histrelin concentrations remained above the limit of quantification for the treatment period; histrelin acetate levels were sustained throughout the study period for most subjects. There was no apparent difference between subjects naive to a LHRH agonist treatment and subjects previously treated with a LHRH agonist.[33431]

      Ethnic Differences

      Average serum histrelin concentrations were similar when compared for hispanic (n = 7), black (n = 30), and caucasian (n = 77) patients.[30369]

      Revision Date: 02/02/2024, 02:07:00 AM

      References

      30369 - Vantas (histrelin implant) package insert. Chadds Ford, PA: Endo Pharmaceuticals Solutions Inc.; 2022 Feb.33431 - Supprelin LA (histrelin implant) package insert. Chadds Ford, PA: Endo Pharmaceuticals Solutions Inc.; 2022 April.

      Pregnancy/Breast-feeding

      females, pregnancy

      While Supprelin LA (histrelin) may be used in female children, the safety and efficacy of Vantas (histrelin) have not been established in females. Although there are no adequately controlled studies in pregnant women, histrelin can cause fetal harm or death when administered during pregnancy based on its mechanism of action and animal studies. Expected hormonal changes that occur with histrelin treatment increase the risk for pregnancy loss. Advise pregnant patients and females and females of reproductive potential of the risk to the fetus. Increased fetal mortality and post-implantation loss occurred when histrelin was administered to pregnant rats during organogenesis at exposures amounting to 0.2 to 3 times the human exposure based on body surface area. These doses also reduced maternal weight gain, stimulated ovarian follicular development, increased placental weight, and caused abnormal morphology and an increase in fetal size. In pregnant rabbits, administration of histrelin during organogenesis resulted in increased fetal mortality and abortion/early termination at the 2 highest doses and caused total litter loss at all doses (exposures of approximately 8 to 31 times human exposure at the recommended dose based on body surface area). Females may also be at increased risk for histrelin prolonging the QT interval.[28432] [28457] [30369] [33431] [56592] [65180]

      breast-feeding

      Due to the potential for serious adverse reactions in nursing infants from histrelin, advise women to discontinue breast-feeding during treatment. It is not known whether histrelin is present in human milk, although many drugs are excreted in human milk.[30369]

      Revision Date: 02/02/2024, 02:07:00 AM

      References

      28432 - Roden, DM. Drug-induced prolongation of the QT interval. New Engl J Med 2004;350:1013-22.28457 - Crouch MA, Limon L, Cassano AT. Clinical relevance and management of drug-related QT interval prolongation. Pharmacotherapy 2003;23:881-908.30369 - Vantas (histrelin implant) package insert. Chadds Ford, PA: Endo Pharmaceuticals Solutions Inc.; 2022 Feb.33431 - Supprelin LA (histrelin implant) package insert. Chadds Ford, PA: Endo Pharmaceuticals Solutions Inc.; 2022 April.56592 - van Noord C, Eijgelsheim M, Stricker BH. Drug- and non-drug-associated QT interval prolongation. Br J Clin Pharmacol 2010;70(1):16-23.65180 - Woosley RL, Heise CW, Gallo T, et al. QTFactors List. Oro Valley, AZ: AZCERT, Inc.; Accessed March 31, 2020. Available on the World Wide Web at: https://crediblemeds.org/ndfa-list/

      Interactions

      Level 1 (Severe)

      • Cisapride
      • Dronedarone
      • Ketoconazole
      • Levoketoconazole
      • Pimozide
      • Thioridazine

      Level 2 (Major)

      • Adagrasib
      • Amiodarone
      • Amisulpride
      • Amoxapine
      • Amoxicillin; Clarithromycin; Omeprazole
      • Anagrelide
      • Androgens
      • Arsenic Trioxide
      • Artemether; Lumefantrine
      • Asenapine
      • Azithromycin
      • Bedaquiline
      • Brexpiprazole
      • Buprenorphine
      • Buprenorphine; Naloxone
      • Cariprazine
      • Ceritinib
      • Chloroquine
      • Chlorpromazine
      • Citalopram
      • Clarithromycin
      • Codeine; Phenylephrine; Promethazine
      • Codeine; Promethazine
      • Crizotinib
      • Danazol
      • Desflurane
      • Deutetrabenazine
      • Dextromethorphan; Quinidine
      • Disopyramide
      • Dofetilide
      • Donepezil
      • Donepezil; Memantine
      • Droperidol
      • Eliglustat
      • Encorafenib
      • Entrectinib
      • Eribulin
      • Erythromycin
      • Esterified Estrogens; Methyltestosterone
      • Fexinidazole
      • Flecainide
      • Fluphenazine
      • Foscarnet
      • Glasdegib
      • Halogenated Anesthetics
      • Haloperidol
      • Hydroxychloroquine
      • Ibutilide
      • Iloperidone
      • Inotuzumab Ozogamicin
      • Isoflurane
      • Ivosidenib
      • Lansoprazole; Amoxicillin; Clarithromycin
      • Lefamulin
      • Lenvatinib
      • Lopinavir; Ritonavir
      • Lorcaserin
      • Loxapine
      • Macimorelin
      • Maprotiline
      • Methadone
      • Methyldopa
      • Methyltestosterone
      • Metoclopramide
      • Midostaurin
      • Mobocertinib
      • Molindone
      • Moxifloxacin
      • Nilotinib
      • Olanzapine
      • Olanzapine; Fluoxetine
      • Olanzapine; Samidorphan
      • Ondansetron
      • Osimertinib
      • Oxaliplatin
      • Oxandrolone
      • Oxymetholone
      • Ozanimod
      • Pacritinib
      • Paliperidone
      • Panobinostat
      • Pazopanib
      • Pentamidine
      • Perphenazine
      • Perphenazine; Amitriptyline
      • Pimavanserin
      • Pitolisant
      • Ponesimod
      • Prasterone, Dehydroepiandrosterone, DHEA (Dietary Supplements)
      • Prasterone, Dehydroepiandrosterone, DHEA (FDA-approved)
      • Procainamide
      • Promethazine
      • Promethazine; Dextromethorphan
      • Promethazine; Phenylephrine
      • Propafenone
      • Quetiapine
      • Quinidine
      • Quinine
      • Quizartinib
      • Ramelteon
      • Ribociclib
      • Ribociclib; Letrozole
      • Risperidone
      • Saquinavir
      • Selpercatinib
      • Sevoflurane
      • Siponimod
      • Sorafenib
      • Sotalol
      • Testosterone
      • Tetrabenazine
      • Thiothixene
      • Toremifene
      • Trandolapril; Verapamil
      • Trazodone
      • Trifluoperazine
      • Valbenazine
      • Vandetanib
      • Vemurafenib
      • Verapamil
      • Vonoprazan; Amoxicillin; Clarithromycin
      • Ziprasidone

      Level 3 (Moderate)

      • Alfuzosin
      • Apomorphine
      • Aripiprazole
      • Atomoxetine
      • Bismuth Subcitrate Potassium; Metronidazole; Tetracycline
      • Bismuth Subsalicylate; Metronidazole; Tetracycline
      • Cabotegravir; Rilpivirine
      • Ciprofloxacin
      • Clofazimine
      • Clozapine
      • Dasatinib
      • Dexmedetomidine
      • Dolasetron
      • Dolutegravir; Rilpivirine
      • Efavirenz
      • Efavirenz; Emtricitabine; Tenofovir Disoproxil Fumarate
      • Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate
      • Emtricitabine; Rilpivirine; Tenofovir alafenamide
      • Emtricitabine; Rilpivirine; Tenofovir Disoproxil Fumarate
      • Escitalopram
      • Etrasimod
      • Fingolimod
      • Fluconazole
      • Fluoxetine
      • Fluvoxamine
      • Fostemsavir
      • Gemifloxacin
      • Gemtuzumab Ozogamicin
      • Gilteritinib
      • Granisetron
      • Hydroxyzine
      • Itraconazole
      • Lapatinib
      • Levofloxacin
      • Lithium
      • Lofexidine
      • Loperamide
      • Loperamide; Simethicone
      • Mefloquine
      • Metronidazole
      • Mifepristone
      • Mirtazapine
      • Ofloxacin
      • Osilodrostat
      • Pasireotide
      • Posaconazole
      • Primaquine
      • Prochlorperazine
      • Ranolazine
      • Rilpivirine
      • Romidepsin
      • Sertraline
      • Sodium Stibogluconate
      • Solifenacin
      • Sunitinib
      • Tacrolimus
      • Tamoxifen
      • Telavancin
      • Tolterodine
      • Triclabendazole
      • Vardenafil
      • Venlafaxine
      • Voclosporin
      • Voriconazole
      • Vorinostat
      Adagrasib: (Major) Concomitant use of adagrasib and androgen deprivation therapy (i.e., histrelin) increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. [30369] [68325] Alfuzosin: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., histrelin) outweigh the potential risks of QT prolongation in patients receiving alfuzosin. Androgen deprivation therapy may prolong the QT/QTc interval. Based on electrophysiology studies performed by the manufacturer, alfuzosin may also prolong the QT interval in a dose-dependent manner. [28261] [30369] Amiodarone: (Major) Concomitant use of amiodarone and androgen deprivation therapy (i.e., histrelin) increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. Due to the extremely long half-life of amiodarone, a drug interaction is possible for days to weeks after drug discontinuation. [28224] [28432] [28457] [30369] Amisulpride: (Major) Monitor ECGs for QT prolongation when amisulpride is administered with histrelin. Amisulpride causes dose- and concentration- dependent QT prolongation. Androgen deprivation therapy (i.e., histrelin) may also prolong the QT/QTc interval. [30369] [65068] Amoxapine: (Major) Avoid coadministration of histrelin with amoxapine due to the risk of reduced efficacy of histrelin. Amoxapine can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; histrelin is a GnRH analog. [28558] [45411] Amoxicillin; Clarithromycin; Omeprazole: (Major) Consider whether the benefits of androgen deprivation therapy (i.e., histrelin) outweigh the potential risks of QT prolongation in patients receiving clarithromycin. Clarithromycin is associated with an established risk for QT prolongation and torsade de pointes (TdP). Androgen deprivation therapy may also prolong the QT/QTc interval. [28225] [28238] [30369] Anagrelide: (Major) Do not use anagrelide with other drugs that prolong the QT interval such as histrelin. Torsade de pointes (TdP) and ventricular tachycardia have been reported with anagrelide; in addition, dose-related increases in mean QTc and heart rate were observed in healthy subjects. Androgen deprivation therapy (e.g., histrelin) also prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. [30163] [30369] Androgens: (Major) Avoid concurrent use of androgens with gonadotropin releasing hormone (GnRH) agonists such as histrelin. Histrelin inhibits steroidogenesis; concomitant use with androgens may counteract this therapeutic effect. [30369] [33431] Apomorphine: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., histrelin) outweigh the potential risks of QT prolongation in patients receiving apomorphine since concurrent use may increase the risk of QT prolongation. Androgen deprivation therapy may prolong the QT/QTc interval. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure. [28661] [30369] Aripiprazole: (Moderate) Concomitant use of aripiprazole and androgen deprivation therapy (i.e., histrelin) may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. [30369] [42845] Arsenic Trioxide: (Major) Avoid concomitant use of arsenic trioxide with histrelin; discontinue or select an alternative drug that does not prolong the QT interval prior to starting arsenic trioxide therapy. If concomitant drug use is unavoidable, frequently monitor electrocardiograms. Torsade de pointes (TdP), QT interval prolongation, and complete atrioventricular block have been reported with arsenic trioxide use. Androgen deprivation therapy (i.e., histrelin) may also prolong the QT/QTc interval. [30369] [59438] Artemether; Lumefantrine: (Major) Avoid coadministration of artemether with histrelin if possible due to the risk of QT prolongation. Consider ECG monitoring if histrelin must be used with or after artemether; lumefantrine treatment. Artemether; lumefantrine is associated with prolongation of the QT interval. Androgen deprivation therapy (i.e., histrelin) may prolong the QT/QTc interval. [30369] [35401] (Major) Avoid coadministration of lumefantrine with histrelin if possible due to the risk of QT prolongation. Consider ECG monitoring if histrelin must be used with or after artemether; lumefantrine treatment. Artemether; lumefantrine is associated with prolongation of the QT interval. Androgen deprivation therapy (i.e., histrelin) may prolong the QT/QTc interval. [30369] [35401] Asenapine: (Major) Avoid coadministration of histrelin with asenapine due to the risk of reduced efficacy of histrelin as well as the risk of QT prolongation. Asenapine can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; histrelin is a GnRH analog. Additionally, asenapine has been associated with QT prolongation. Androgen deprivation therapy (i.e., histrelin) may also prolong the QT/QTc interval. [30369] [36343] [45411] Atomoxetine: (Moderate) Concomitant use of atomoxetine and androgen deprivation therapy (i.e., histrelin) may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. [28405] [30369] Azithromycin: (Major) Avoid coadministration of azithromycin with histrelin due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Androgen deprivation therapy may prolong the QT/QTc interval. [28855] [30369] [43974] [65157] [65170] Bedaquiline: (Major) Frequently monitor ECGs for QT prolongation if coadministration of bedaquiline with histrelin is necessary. Bedaquiline has been reported to prolong the QT interval; coadministration with other QT prolonging drugs may result in additive or synergistic prolongation of the QT interval. Androgen deprivation therapy may also prolong the QT/QTc interval. [30369] [52746] Bismuth Subcitrate Potassium; Metronidazole; Tetracycline: (Moderate) Concomitant use of metronidazole and androgen deprivation therapy (i.e., histrelin) may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. [30369] [36894] Bismuth Subsalicylate; Metronidazole; Tetracycline: (Moderate) Concomitant use of metronidazole and androgen deprivation therapy (i.e., histrelin) may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. [30369] [36894] Brexpiprazole: (Major) Avoid coadministration of histrelin with brexpiprazole due to the risk of reduced efficacy of histrelin. Brexpiprazole can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; histrelin is a GnRH analog. [45411] [59949] Buprenorphine: (Major) Consider whether the benefits of androgen deprivation therapy (i.e., histrelin) outweigh the potential risks of QT prolongation in patients receiving buprenorphine. Buprenorphine has been associated with QT prolongation and has a possible risk of torsade de pointes (TdP). FDA-approved labeling for some buprenorphine products recommend avoiding use with Class 1A and Class III antiarrhythmic medications while other labels recommend avoiding use with any drug that has the potential to prolong the QT interval. Androgen deprivation therapy may also prolong the QT/QTc interval. [30369] [41235] [60270] Buprenorphine; Naloxone: (Major) Consider whether the benefits of androgen deprivation therapy (i.e., histrelin) outweigh the potential risks of QT prolongation in patients receiving buprenorphine. Buprenorphine has been associated with QT prolongation and has a possible risk of torsade de pointes (TdP). FDA-approved labeling for some buprenorphine products recommend avoiding use with Class 1A and Class III antiarrhythmic medications while other labels recommend avoiding use with any drug that has the potential to prolong the QT interval. Androgen deprivation therapy may also prolong the QT/QTc interval. [30369] [41235] [60270] Cabotegravir; Rilpivirine: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., histrelin) outweigh the potential risks of QT prolongation in patients receiving rilpivirine as concurrent use may increase the risk of QT prolongation. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation. Androgen deprivation therapy may also prolong the QT/QTc interval. [30369] [44376] Cariprazine: (Major) Avoid coadministration of histrelin with cariprazine due to the risk of reduced efficacy of histrelin. Cariprazine can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; histrelin is a GnRH analog. [45411] [60164] Ceritinib: (Major) Avoid coadministration of ceritinib with histrelin if possible due to the risk of QT prolongation. If concomitant use is unavoidable, periodically monitor ECGs and electrolytes; an interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if QT prolongation occurs. Ceritinib causes concentration-dependent QT prolongation. Androgen deprivation therapy (i.e., histrelin) may prolong the QT/QTc interval. [30369] [57094] Chloroquine: (Major) Avoid coadministration of chloroquine with histrelin due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Chloroquine is associated with an increased risk of QT prolongation and torsade de pointes (TdP); the risk of QT prolongation is increased with higher chloroquine doses. Androgen deprivation therapy (i.e., histrelin) may prolong the QT/QTc interval. [28229] [28230] [28231] [29758] [30369] [65157] [65170] Chlorpromazine: (Major) Avoid coadministration of histrelin with chlorpromazine due to the risk of reduced efficacy of histrelin; QT prolongation may also occur. Chlorpromazine can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; histrelin is a GnRH analog. Additionally, chlorpromazine, a phenothiazine, is associated with an established risk of QT prolongation and torsade de pointes (TdP). Androgen deprivation therapy (i.e., histrelin) may also prolong the QT/QTc interval. [28415] [30369] [43065] [45411] Ciprofloxacin: (Moderate) Concomitant use of ciprofloxacin and androgen deprivation therapy (i.e., histrelin) may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. [28432] [28457] [29833] [30369] [33145] [43411] [48869] [48871] Cisapride: (Contraindicated) Because of the potential for QT prolongation and torsade de pointes (TdP), the use of histrelin with cisapride is contraindicated. Prolongation of the QT interval and ventricular arrhythmias, including TdP and death, have been reported with cisapride. Androgen deprivation therapy (e.g., histrelin) also prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. [28978] [30369] [47221] Citalopram: (Major) Concomitant use of citalopram and histrelin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. [28269] [30369] Clarithromycin: (Major) Consider whether the benefits of androgen deprivation therapy (i.e., histrelin) outweigh the potential risks of QT prolongation in patients receiving clarithromycin. Clarithromycin is associated with an established risk for QT prolongation and torsade de pointes (TdP). Androgen deprivation therapy may also prolong the QT/QTc interval. [28225] [28238] [30369] Clofazimine: (Moderate) Concomitant use of clofazimine and androgen deprivation therapy (i.e., histrelin) may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. [30369] [63936] Clozapine: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., histrelin) outweigh the potential risks of QT prolongation in patients receiving clozapine as concurrent use may increase the risk of QT prolongation. Androgen deprivation therapy may prolong the QT/QTc interval. Treatment with clozapine has been associated with QT prolongation, torsade de pointes (TdP), cardiac arrest, and sudden death. [28262] [30369] Codeine; Phenylephrine; Promethazine: (Major) Avoid coadministration of histrelin with promethazine due to the risk of reduced efficacy of histrelin; QT prolongation may also occur. Promethazine can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; leuprolide is a GnRH analog. Promethazine, a phenothiazine, is associated with a possible risk for QT prolongation. Androgen deprivation therapy (i.e., histrelin) may also prolong the QT/QTc interval. [28225] [30369] [45411] [55578] Codeine; Promethazine: (Major) Avoid coadministration of histrelin with promethazine due to the risk of reduced efficacy of histrelin; QT prolongation may also occur. Promethazine can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; leuprolide is a GnRH analog. Promethazine, a phenothiazine, is associated with a possible risk for QT prolongation. Androgen deprivation therapy (i.e., histrelin) may also prolong the QT/QTc interval. [28225] [30369] [45411] [55578] Crizotinib: (Major) Avoid coadministration of crizotinib with histrelin due to the risk of QT prolongation. If concomitant use is unavoidable, monitor ECGs for QT prolongation and monitor electrolytes. An interruption of therapy, dose reduction, or discontinuation of therapy may be necessary for crizotinib if QT prolongation occurs. Crizotinib has been associated with concentration-dependent QT prolongation. Androgen deprivation therapy (e.g., histrelin) also prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. [30369] [45458] Danazol: (Major) Avoid concurrent use of androgens with gonadotropin releasing hormone (GnRH) agonists such as histrelin. Histrelin inhibits steroidogenesis; concomitant use with androgens may counteract this therapeutic effect. [30369] [33431] Dasatinib: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., histrelin) outweigh the potential risks of QT prolongation in patients receiving dasatinib as concurrent use may increase the risk of QT prolongation. Androgen deprivation therapy may prolong the QT/QTc interval. In vitro studies have shown that dasatinib also has the potential to prolong the QT interval. [30369] [32387] Desflurane: (Major) Consider whether the benefits of androgen deprivation therapy (i.e., histrelin) outweigh the potential risks of QT prolongation in patients receiving halogenated anesthetics. Androgen deprivation therapy may prolong the QT/QTc interval. Halogenated anesthetics can also prolong the QT interval. [28457] [28458] [28754] [28755] [28756] [30369] Deutetrabenazine: (Major) Avoid coadministration of histrelin with deutetrabenazine due to the risk of reduced efficacy of histrelin. Deutetrabenazine can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin-releasing hormone (GnRH) receptors; histrelin is a GnRH analog. Androgen deprivation therapy (i.e., histrelin) may also prolong the QT/QTc interval. Deutetrabenazine may prolong the QT interval, but the degree of QT prolongation is not clinically significant when deutetrabenazine is administered within the recommended dosage range. [30369] [45411] [61845] Dexmedetomidine: (Moderate) Concomitant use of dexmedetomidine and androgen deprivation therapy (i.e., histrelin) may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. [30369] [67509] Dextromethorphan; Quinidine: (Major) Consider whether the benefits of androgen deprivation therapy (i.e., histrelin) outweigh the potential risks of QT prolongation in patients receiving quinidine. Quinidine administration is associated with QT prolongation and torsade de pointes (TdP). Androgen deprivation therapy may also prolong the QT/QTc interval. [30369] [42280] [47357] Disopyramide: (Major) Consider whether the benefits of androgen deprivation therapy (i.e., histrelin) outweigh the potential risks of QT prolongation in patients receiving disopyramide. Androgen deprivation therapy may prolong the QT/QTc interval. Disopyramide administration is also associated with QT prolongation and torsade de pointes (TdP). [28228] [30369] Dofetilide: (Major) Coadministration of dofetilide and histrelin is not recommended as concurrent use may increase the risk of QT prolongation. Dofetilide, a Class III antiarrhythmic agent, is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Androgen deprivation therapy (i.e., histrelin) may prolong the QT/QTc interval. [28221] [28432] [28457] [30369] Dolasetron: (Moderate) Consider whether the benefits of androgen deprivation therapy outweigh the potential risks in patients receiving dolasetron as concurrent use may increase the risk of QT prolongation. Androgen deprivation therapy (i.e., histrelin) may prolong the QT/QTc interval. Dolasetron has been associated with a dose-dependent prolongation in the QT, PR, and QRS intervals on an electrocardiogram. [28308] [30369] [50275] Dolutegravir; Rilpivirine: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., histrelin) outweigh the potential risks of QT prolongation in patients receiving rilpivirine as concurrent use may increase the risk of QT prolongation. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation. Androgen deprivation therapy may also prolong the QT/QTc interval. [30369] [44376] Donepezil: (Major) Consider whether the benefits of androgen deprivation therapy (i.e., histrelin) outweigh the potential risks of QT prolongation in patients receiving donepezil as concurrent use may increase the risk of QT prolongation. Androgen deprivation therapy may prolong the QT/QTc interval. Case reports indicate that QT prolongation and torsade de pointes (TdP) can occur during donepezil therapy. [30369] [59321] [59322] Donepezil; Memantine: (Major) Consider whether the benefits of androgen deprivation therapy (i.e., histrelin) outweigh the potential risks of QT prolongation in patients receiving donepezil as concurrent use may increase the risk of QT prolongation. Androgen deprivation therapy may prolong the QT/QTc interval. Case reports indicate that QT prolongation and torsade de pointes (TdP) can occur during donepezil therapy. [30369] [59321] [59322] Dronedarone: (Contraindicated) Because of the potential for torsade de pointes (TdP), use of histrelin with dronedarone is contraindicated. Dronedarone administration is associated with a dose-related increase in the QTc interval. The increase in QTc is approximately 10 milliseconds at doses of 400 mg twice daily (the FDA-approved dose) and up to 25 milliseconds at doses of 1,600 mg twice daily. Although there are no studies examining the effects of dronedarone in patients receiving other QT prolonging drugs, coadministration of such drugs may result in additive QT prolongation. Androgen deprivation therapy (e.g., histrelin) is known to prolong the QT interval. [30369] [36101] Droperidol: (Major) Droperidol should not be used in combination with any drug known to have potential to prolong the QT interval, such as histrelin. If coadministration is unavoidable, use extreme caution; initiate droperidol at a low dose and increase the dose as needed to achieve the desired effect. Droperidol administration is associated with an established risk for QT prolongation and torsade de pointes (TdP). Some cases have occurred in patients with no known risk factors for QT prolongation and some cases have been fatal. Androgen deprivation therapy (i.e., histrelin) may prolong the QT/QTc interval. [28235] [28236] [28237] [30369] [51289] Efavirenz: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., histrelin) outweigh the potential risks of QT prolongation in patients receiving efavirenz as concurrent use may increase the risk of QT prolongation. Androgen deprivation therapy may prolong the QT/QTc interval. Prolongation of the QTc interval has also been observed with the use of efavirenz. [28442] [30369] Efavirenz; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., histrelin) outweigh the potential risks of QT prolongation in patients receiving efavirenz as concurrent use may increase the risk of QT prolongation. Androgen deprivation therapy may prolong the QT/QTc interval. Prolongation of the QTc interval has also been observed with the use of efavirenz. [28442] [30369] Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., histrelin) outweigh the potential risks of QT prolongation in patients receiving efavirenz as concurrent use may increase the risk of QT prolongation. Androgen deprivation therapy may prolong the QT/QTc interval. Prolongation of the QTc interval has also been observed with the use of efavirenz. [28442] [30369] Eliglustat: (Major) Consider whether the benefits of androgen deprivation therapy (i.e., histrelin) outweigh the potential risks of QT prolongation in patients receiving eliglustat. Androgen deprivation therapy may prolong the QT/QTc interval. Eliglustat is also predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations. [30369] [57803] Emtricitabine; Rilpivirine; Tenofovir alafenamide: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., histrelin) outweigh the potential risks of QT prolongation in patients receiving rilpivirine as concurrent use may increase the risk of QT prolongation. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation. Androgen deprivation therapy may also prolong the QT/QTc interval. [30369] [44376] Emtricitabine; Rilpivirine; Tenofovir Disoproxil Fumarate: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., histrelin) outweigh the potential risks of QT prolongation in patients receiving rilpivirine as concurrent use may increase the risk of QT prolongation. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation. Androgen deprivation therapy may also prolong the QT/QTc interval. [30369] [44376] Encorafenib: (Major) Avoid coadministration of encorafenib and histrelin due to the risk of QT prolongation. If concurrent use cannot be avoided, monitor ECGs for QT prolongation and monitor electrolytes; correct hypokalemia and hypomagnesemia prior to treatment. Encorafenib has been associated with dose-dependent QT prolongation. Androgen deprivation therapy (i.e., histrelin) may also prolong the QT/QTc interval. [30369] [63317] Entrectinib: (Major) Avoid coadministration of entrectinib with histrelin due to the risk of QT prolongation. Entrectinib has been associated with QT prolongation. Androgen deprivation therapy (i.e., histrelin) may prolong the QT/QTc interval. [30369] [64567] Eribulin: (Major) Closely monitor ECGs for QT prolongation if coadministration of eribulin with histrelin is necessary. Eribulin has been associated with QT prolongation. Androgen deprivation therapy (i.e., histrelin) may also prolong the QT/QTc interval. [30369] [42449] Erythromycin: (Major) Concomitant use of histrelin and erythromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. [30369] [43258] Escitalopram: (Moderate) Concomitant use of escitalopram and androgen deprivation therapy (i.e., histrelin) may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. [28270] [30369] Esterified Estrogens; Methyltestosterone: (Major) Avoid concurrent use of androgens with gonadotropin releasing hormone (GnRH) agonists such as histrelin. Histrelin inhibits steroidogenesis; concomitant use with androgens may counteract this therapeutic effect. [30369] [33431] Etrasimod: (Moderate) Concomitant use of etrasimod and androgen deprivation therapy (i.e., histrelin) may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. Etrasimod has a limited effect on the QT/QTc interval at therapeutic doses but may cause bradycardia and atrioventricular conduction delays which may increase the risk for TdP in patients with a prolonged QT/QTc interval. [30369] [69114] Fexinidazole: (Major) Concomitant use of fexinidazole and androgen deprivation therapy (i.e., histrelin) increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. [30369] [66812] Fingolimod: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., histrelin) outweigh the potential risks of QT prolongation in patients receiving fingolimod as concurrent use may increase the risk of QT prolongation. Androgen deprivation therapy may prolong the QT/QTc interval. Fingolimod initiation results in decreased heart rate and may prolong the QT interval. Fingolimod has not been studied in patients treated with drugs that prolong the QT interval, but drugs that prolong the QT interval have been associated with cases of TdP in patients with bradycardia. [30369] [41823] Flecainide: (Major) Consider whether the benefits of androgen deprivation therapy (i.e., histrelin) outweigh the potential risks of QT prolongation in patients receiving flecainide. Flecainide is a Class IC antiarrhythmic associated with a possible risk for QT prolongation and/or torsade de pointes (TdP); flecainide increases the QT interval, but largely due to prolongation of the QRS interval. Androgen deprivation therapy may also prolong the QT/QTc interval. Although causality for TdP has not been established for flecainide, patients receiving concurrent drugs that have the potential for QT prolongation may have an increased risk of developing proarrhythmias. [23774] [28752] [30369] Fluconazole: (Moderate) Concomitant use of fluconazole and androgen deprivation therapy (i.e., histrelin) may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. [28674] [30369] Fluoxetine: (Moderate) Concomitant use of fluoxetine and androgen deprivation therapy (i.e., histrelin) may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. [30369] [32127] [44058] Fluphenazine: (Major) Avoid coadministration of histrelin with fluphenazine due to the risk of reduced efficacy of histrelin; QT prolongation may also occur. Fluphenazine can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; histrelin is a GnRH analog. Additionally, androgen deprivation therapy (i.e., histrelin) may prolong the QT/QTc interval. Fluphenazine is also associated with a possible risk for QT prolongation. Theoretically, fluphenazine may increase the risk of QT prolongation if coadministered with other drugs that have a risk of QT prolongation. [28415] [30369] [45411] Fluvoxamine: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., histrelin) outweigh the potential risks of QT prolongation in patients receiving fluvoxamine. Androgen deprivation therapy may prolong the QT/QTc interval. Prolongation of the QT interval and torsade de pointes (TdP) has also been reported during fluvoxamine post-marketing use. [30369] [50507] Foscarnet: (Major) Avoid coadministration of foscarnet with histrelin due to the risk of QT prolongation. Androgen deprivation therapy (i.e., histrelin) may prolong the QT/QTc interval. Both QT prolongation and torsade de pointes (TdP) have been reported during postmarketing use of foscarnet. [28377] [30369] Fostemsavir: (Moderate) Consider whether the benefits of androgen deprivation therapy outweigh the potential risks in patients receiving other QT prolonging agents. Androgen deprivation therapy (i.e., histrelin) may prolong the QT/QTc interval. Supratherapeutic doses of fostemsavir (2,400 mg twice daily, four times the recommended daily dose) have been shown to cause QT prolongation. Fostemsavir causes dose-dependent QT prolongation. [30369] [65666] Gemifloxacin: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., histrelin) outweigh the potential risks of QT prolongation in patients receiving gemifloxacin as concurrent use may increase the risk of QT prolongation. Androgen deprivation therapy may prolong the QT/QTc interval. Gemifloxacin may also prolong the QT interval in some patients. The maximal change in the QTc interval occurs approximately 5 to 10 hours following oral administration of gemifloxacin. The likelihood of QTc prolongation may increase with increasing dose of the drug; therefore, the recommended dose should not be exceeded especially in patients with renal or hepatic impairment where the Cmax and AUC are slightly higher. Androgen deprivation therapy may also prolong the QT/QTc interval. [28424] [28432] [28457] [29833] [30369] [33144] [33145] [33146] [48869] [48871] Gemtuzumab Ozogamicin: (Moderate) Obtain an ECG and serum electrolytes prior to initiation of concomitant use of gemtuzumab ozogamicin and histrelin due to the potential for additive QT prolongation and the risk of torsade de pointes (TdP); monitor ECGs and electrolytes as needed during treatment. Androgen deprivation therapy (i.e., histrelin) may prolong the QT/QTc interval. Although QT interval prolongation has not been reported with gemtuzumab, it has been reported with other drugs that contain calicheamicin. [30369] [62292] Gilteritinib: (Moderate) Use caution and monitor for additive QT prolongation if concurrent use of gilteritinib and histrelin is necessary. Consider whether the benefits of androgen deprivation therapy outweigh the potential risks in patients receiving other QT prolonging agents. Androgen deprivation therapy (i.e., histrelin) may prolong the QT/QTc interval. Gilteritinib has also been associated with QT prolongation. [30369] [63787] Glasdegib: (Major) Avoid coadministration of glasdegib with histrelin due to the potential for additive QT prolongation. If coadministration cannot be avoided, monitor patients for increased risk of QT prolongation with increased frequency of ECG monitoring. Glasdegib therapy may result in QT prolongation and ventricular arrhythmias including ventricular fibrillation and ventricular tachycardia. Androgen deprivation therapy (i.e., histrelin) may also prolong the QT/QTc interval. [30369] [63777] Granisetron: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., histrelin) outweigh the potential risks of QT prolongation in patients receiving granisetron as concurrent use may increase the risk of QT prolongation. Androgen deprivation therapy may prolong the QT/QTc interval. Granisetron has also been associated with QT prolongation. [30369] [31723] Halogenated Anesthetics: (Major) Consider whether the benefits of androgen deprivation therapy (i.e., histrelin) outweigh the potential risks of QT prolongation in patients receiving halogenated anesthetics. Androgen deprivation therapy may prolong the QT/QTc interval. Halogenated anesthetics can also prolong the QT interval. [28457] [28458] [28754] [28755] [28756] [30369] Haloperidol: (Major) Avoid coadministration of histrelin with haloperidol due to the risk of reduced efficacy of histrelin; QT prolongation may also occur. Haloperidol can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; histrelin is a GnRH analog. Additionally, QT prolongation and torsade de pointes (TdP) have been observed during haloperidol treatment; excessive doses (particularly in the overdose setting) or IV administration may be associated with a higher risk. Androgen deprivation therapy (i.e., histrelin) may prolong the QT/QTc interval. [23500] [23779] [28307] [28415] [30369] [45411] Hydroxychloroquine: (Major) Concomitant use of hydroxychloroquine and histrelin acetate increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. [30369] [41806] [65157] [65170] Hydroxyzine: (Moderate) Concomitant use of hydroxyzine and androgen deprivation therapy (i.e., histrelin) may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. [30369] [47129] Ibutilide: (Major) Consider whether the benefits of androgen deprivation therapy (i.e., histrelin) outweigh the potential risks of QT prolongation in patients receiving ibutilide. Ibutilide administration can cause QT prolongation and torsade de pointes (TdP); proarrhythmic events should be anticipated. The potential for proarrhythmic events with ibutilide increases with the coadministration of other drugs that prolong the QT interval. Androgen deprivation therapy may also prolong the QT/QTc interval. [30369] [41830] Iloperidone: (Major) Avoid coadministration of histrelin with iloperidone due to the risk of reduced efficacy of histrelin; QT prolongation may also occur. Iloperidone can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; histrelin is a GnRH analog. Iloperidone has been associated with QT prolongation. Androgen deprivation therapy (i.e., histrelin) may prolong the QT/QTc interval. [30369] [36146] [45411] Inotuzumab Ozogamicin: (Major) Avoid coadministration of inotuzumab with histrelin due to the potential for additive QT prolongation and torsade de pointes (TdP). If coadministration is unavoidable, obtain ECGs prior to the start of treatment and periodically during treatment. Inotuzumab has been associated with QT interval prolongation. Androgen deprivation therapy (i.e., histrelin) may prolong the QT/QTc interval. [30369] [62245] Isoflurane: (Major) Consider whether the benefits of androgen deprivation therapy (i.e., histrelin) outweigh the potential risks of QT prolongation in patients receiving halogenated anesthetics. Androgen deprivation therapy may prolong the QT/QTc interval. Halogenated anesthetics can also prolong the QT interval. [28457] [28458] [28754] [28755] [28756] [30369] Itraconazole: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., histrelin) outweigh the potential risks of QT prolongation in patients receiving itraconazole as concurrent use may increase the risk of QT prolongation. Itraconazole has been associated with prolongation of the QT interval. Androgen deprivation therapy may also prolong the QT/QTc interval. [30369] [40233] [57441] Ivosidenib: (Major) Avoid coadministration of ivosidenib with histrelin if possible due to an increased risk of QT prolongation. If concomitant use is unavoidable, monitor ECGs for QTc prolongation and monitor electrolytes; correct any electrolyte abnormalities as clinically appropriate. An interruption of therapy and dose reduction of ivosidenib may be necessary if QT prolongation occurs. Prolongation of the QTc interval and ventricular arrhythmias have been reported in patients treated with ivosidenib. Androgen deprivation therapy (i.e., histrelin) also may prolong the QT/QTc interval. [30369] [63368] Ketoconazole: (Contraindicated) Avoid concomitant use of ketoconazole and androgen deprivation therapy (i.e., histrelin) due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation. [27982] [30369] [67231] Lansoprazole; Amoxicillin; Clarithromycin: (Major) Consider whether the benefits of androgen deprivation therapy (i.e., histrelin) outweigh the potential risks of QT prolongation in patients receiving clarithromycin. Clarithromycin is associated with an established risk for QT prolongation and torsade de pointes (TdP). Androgen deprivation therapy may also prolong the QT/QTc interval. [28225] [28238] [30369] Lapatinib: (Moderate) Consider whether the benefits of androgen deprivation therapy outweigh the potential risks in patients receiving lapatinib as concurrent use may increase the risk of QT prolongation. Androgen deprivation therapy (i.e., histrelin) may prolong the QT/QTc interval. Lapatinib has been associated with concentration-dependent QT prolongation; ventricular arrhythmias and torsade de pointes (TdP) have been reported in postmarketing experience with lapatinib. [30369] [33192] Lefamulin: (Major) Avoid coadministration of lefamulin with histrelin as concurrent use may increase the risk of QT prolongation. If coadministration cannot be avoided, monitor ECG during treatment. Lefamulin has a concentration dependent QTc prolongation effect. The pharmacodynamic interaction potential to prolong the QT interval of the electrocardiogram between lefamulin and other drugs that effect cardiac conduction is unknown. Androgen deprivation therapy (i.e., histrelin) may prolong the QT/QTc interval. [30369] [64576] Lenvatinib: (Major) Avoid coadministration of lenvatinib with histrelin due to the risk of QT prolongation. Prolongation of the QT interval has been reported with lenvatinib therapy. Androgen deprivation therapy (i.e., histrelin) may prolong the QT/QTc interval. [30369] [58782] Levofloxacin: (Moderate) Concomitant use of levofloxacin and androgen deprivation therapy (i.e., histrelin) may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. [28421] [28432] [28457] [29833] [30369] [33144] [33145] [33146] [48869] [48871] Levoketoconazole: (Contraindicated) Avoid concomitant use of ketoconazole and androgen deprivation therapy (i.e., histrelin) due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation. [27982] [30369] [67231] Lithium: (Moderate) Concomitant use of lithium and androgen deprivation therapy (i.e., histrelin) may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. [30369] [59809] [59810] [59811] Lofexidine: (Moderate) Monitor ECGs for QT prolongation if coadministration of lofexidine with histrelin is necessary. Lofexidine prolongs the QT interval. Androgen deprivation therapy (i.e., histrelin) may also prolong the QT/QTc interval. [30369] [63161] Loperamide: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., histrelin) outweigh the potential risks of QT prolongation in patients receiving loperamide. At high doses, loperamide has been associated with serious cardiac toxicities, including syncope, ventricular tachycardia, QT prolongation, torsade de pointes (TdP), and cardiac arrest. Androgen deprivation therapy may also prolong the QT/QTc interval. [30106] [30369] [60864] Loperamide; Simethicone: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., histrelin) outweigh the potential risks of QT prolongation in patients receiving loperamide. At high doses, loperamide has been associated with serious cardiac toxicities, including syncope, ventricular tachycardia, QT prolongation, torsade de pointes (TdP), and cardiac arrest. Androgen deprivation therapy may also prolong the QT/QTc interval. [30106] [30369] [60864] Lopinavir; Ritonavir: (Major) Avoid coadministration of lopinavir with histrelin due to the potential for additive QT prolongation. If use together is necessary, obtain a baseline ECG to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Lopinavir is associated with QT prolongation. Androgen deprivation therapy (i.e., histrelin) may prolong the QT/QTc interval. [28341] [30369] [65157] [65170] Lorcaserin: (Major) Avoid coadministration of histrelin with lorcaserin due to the risk of reduced efficacy of histrelin. Lorcaserin can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; histrelin is a GnRH analog. [45411] [51065] Loxapine: (Major) Avoid coadministration of histrelin with loxapine due to the risk of reduced efficacy of histrelin. Loxapine can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; histrelin is a GnRH analog. [43462] [45411] Macimorelin: (Major) Avoid concurrent administration of macimorelin with drugs that prolong the QT interval, such as histrelin. Use of these drugs together may increase the risk of developing torsade de pointes-type ventricular tachycardia. Sufficient washout time of drugs that are known to prolong the QT interval prior to administration of macimorelin is recommended. Treatment with macimorelin has been associated with an increase in the corrected QT (QTc) interval. Androgen deprivation therapy (i.e., histrelin) may also prolong the QT/QTc interval. [30369] [62723] Maprotiline: (Major) Consider whether the benefits of androgen deprivation therapy (i.e., histrelin) outweigh the potential risks of QT prolongation in patients receiving maprotiline. Maprotiline has been reported to prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Cases of long QT syndrome and torsade de pointes (TdP) tachycardia have been described with maprotiline use, but rarely occur when the drug is used alone in normal prescribed doses and in the absence of other known risk factors for QT prolongation. Androgen deprivation therapy may also prolong the QT/QTc interval. Limited data are available regarding the safety of maprotiline in combination with other QT-prolonging drugs. [28225] [28759] [30369] Mefloquine: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., histrelin) outweigh the potential risks of QT prolongation in patients receiving mefloquine as concurrent use may increase the risk of QT prolongation. Androgen deprivation therapy may prolong the QT/QTc interval. There is evidence that the use of halofantrine after mefloquine causes a significant lengthening of the QTc interval. Mefloquine alone has not been reported to cause QT prolongation. [28301] [30369] Methadone: (Major) Coadministration of methadone with histrelin should be undertaken with extreme caution and a careful assessment of the benefits of therapy versus the risks of QT prolongation. Methadone is associated with an increased risk for QT prolongation and torsade de pointes (TdP), especially at higher doses (greater than 200 mg/day but averaging approximately 400 mg/day in adult patients). Most cases involve patients being treated for pain with large, multiple daily doses of methadone, although cases have been reported in patients receiving doses commonly used for maintenance treatment of opioid addiction. Androgen deprivation therapy may prolong the QT/QTc interval. [28319] [28320] [28321] [28322] [30369] [33136] Methyldopa: (Major) Avoid coadministration of histrelin with methyldopa due to the risk of reduced efficacy of histrelin. Methyldopa can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; histrelin is a GnRH analog. [29252] [45411] Methyltestosterone: (Major) Avoid concurrent use of androgens with gonadotropin releasing hormone (GnRH) agonists such as histrelin. Histrelin inhibits steroidogenesis; concomitant use with androgens may counteract this therapeutic effect. [30369] [33431] Metoclopramide: (Major) Avoid coadministration of histrelin with metoclopramide due to the risk of reduced efficacy of histrelin. Metoclopramide can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; histrelin is a GnRH analog. [28953] [45411] Metronidazole: (Moderate) Concomitant use of metronidazole and androgen deprivation therapy (i.e., histrelin) may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. [30369] [36894] Midostaurin: (Major) Consider periodic monitoring of EGCs for QT prolongation if coadministration of histrelin and midostaurin is necessary. Prolongation of the QT interval was reported in patients who received midostaurin in clinical trials. Androgen deprivation therapy (i.e., histrelin) may also prolong the QT/QTc interval. [30369] [61906] Mifepristone: (Moderate) Concomitant use of mifepristone and androgen deprivation therapy (i.e., histrelin) may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. [30369] [48697] Mirtazapine: (Moderate) Concomitant use of mirtazapine and androgen deprivation therapy (i.e., histrelin) may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. [30369] [40942] Mobocertinib: (Major) Concomitant use of mobocertinib and androgen deprivation therapy (i.e., histrelin) increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. [30369] [66990] Molindone: (Major) Avoid coadministration of histrelin with molindone due to the risk of reduced efficacy of histrelin. Molindone can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; histrelin is a GnRH analog. [28820] [45411] Moxifloxacin: (Major) Consider whether the benefits of androgen deprivation therapy (i.e., histrelin) outweigh the potential risks of QT prolongation in patients receiving moxifloxacin. Quinolones have been associated with a risk of QT prolongation. Although extremely rare, torsade de pointes (TdP) has been reported during postmarketing surveillance of moxifloxacin; these reports generally involved patients with concurrent medical conditions or concomitant medications that may have been contributory. Androgen deprivation therapy may also prolong the QT/QTc interval. [28423] [28432] [28457] [29833] [30369] [33144] [33145] [33146] [48869] [48871] Nilotinib: (Major) Avoid administration of nilotinib with histrelin due to the risk of QT interval prolongation. Sudden death and QT prolongation have occurred in patients who received nilotinib therapy. Androgen deprivation therapy (i.e., histrelin) may also prolong the QT/QTc interval. [30369] [58766] Ofloxacin: (Moderate) Concomitant use of ofloxacin and androgen deprivation therapy (i.e., histrelin) may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. [28432] [28457] [29833] [30369] [30738] [33144] [33145] [33146] [48869] [48871] Olanzapine: (Major) Avoid coadministration of histrelin with olanzapine due to the risk of reduced efficacy of histrelin; QT prolongation may also occur. Olanzapine can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; histrelin is a GnRH analog. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval. Androgen deprivation therapy (i.e., histrelin) may also prolong the QT/QTc interval. [28785] [30369] [32732] [32734] [32745] [32746] [45411] Olanzapine; Fluoxetine: (Major) Avoid coadministration of histrelin with olanzapine due to the risk of reduced efficacy of histrelin; QT prolongation may also occur. Olanzapine can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; histrelin is a GnRH analog. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval. Androgen deprivation therapy (i.e., histrelin) may also prolong the QT/QTc interval. [28785] [30369] [32732] [32734] [32745] [32746] [45411] (Moderate) Concomitant use of fluoxetine and androgen deprivation therapy (i.e., histrelin) may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. [30369] [32127] [44058] Olanzapine; Samidorphan: (Major) Avoid coadministration of histrelin with olanzapine due to the risk of reduced efficacy of histrelin; QT prolongation may also occur. Olanzapine can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; histrelin is a GnRH analog. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval. Androgen deprivation therapy (i.e., histrelin) may also prolong the QT/QTc interval. [28785] [30369] [32732] [32734] [32745] [32746] [45411] Ondansetron: (Major) Concomitant use of ondansetron and histrelin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. Do not exceed 16 mg of IV ondansetron in a single dose; the degree of QT prolongation associated with ondansetron significantly increases above this dose. [30369] [31266] Osilodrostat: (Moderate) Monitor ECGs in patients receiving osilodrostat with histrelin. Osilodrostat is associated with dose-dependent QT prolongation. Androgen deprivation therapy (i.e., histrelin) may also prolong the QT/QTc interval. [30369] [65098] Osimertinib: (Major) Avoid coadministration of histrelin with osimertinib if possible due to the risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, periodically monitor ECGs for QT prolongation and monitor electrolytes; an interruption of osimertinib therapy with dose reduction or discontinuation may be necessary if QT prolongation occurs. Concentration-dependent QTc prolongation occurred during clinical trials of osimertinib. Androgen deprivation therapy (i.e., histrelin) may also prolong the QT/QTc interval. [30369] [60297] Oxaliplatin: (Major) Monitor ECGs for QT prolongation and monitor electrolytes in patients receiving oxaliplatin concomitantly with histrelin; correct electrolyte abnormalities prior to administration of oxaliplatin. Prolongation of the QT interval and ventricular arrhythmias including fatal torsade de pointes (TdP) have been reported with oxaliplatin use in postmarketing experience. Androgen deprivation therapy (i.e., histrelin) may also prolong the QT/QTc interval. [30369] [41958] Oxandrolone: (Major) Avoid concurrent use of androgens with gonadotropin releasing hormone (GnRH) agonists such as histrelin. Histrelin inhibits steroidogenesis; concomitant use with androgens may counteract this therapeutic effect. [30369] [33431] Oxymetholone: (Major) Avoid concurrent use of androgens with gonadotropin releasing hormone (GnRH) agonists such as histrelin. Histrelin inhibits steroidogenesis; concomitant use with androgens may counteract this therapeutic effect. [30369] [33431] Ozanimod: (Major) In general, do not initiate ozanimod in patients taking histrelin due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). If treatment initiation is considered, seek advice from a cardiologist. Ozanimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. Androgen deprivation therapy (i.e., histrelin) may prolong the QT/QTc interval. [30369] [65169] Pacritinib: (Major) Concomitant use of pacritinib and androgen deprivation therapy (i.e., histrelin) increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. [30369] [67427] Paliperidone: (Major) Avoid coadministration of histrelin with paliperidone due to the risk of reduced efficacy of histrelin and the risk of QT prolongation. Paliperidone can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; histrelin is a GnRH analog. Paliperidone has been associated with QT prolongation; torsade de pointes (TdP) and ventricular fibrillation have been reported in the setting of overdose. Androgen deprivation therapy (i.e., histrelin) may also prolong the QT/QTc interval. [30369] [40936] [45411] Panobinostat: (Major) Coadministration of panobinostat with histrelin is not recommended due to the risk of QT prolongation. Prolongation of the QT interval has been reported with panobinostat treatment. Androgen deprivation therapy (i.e., histrelin) may also prolong the QT/QTc interval. [30369] [58821] Pasireotide: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., histrelin) outweigh the potential risks of QT prolongation in patients receiving pasireotide as concurrent use may increase the risk of QT prolongation. Prolongation of the QT interval has occurred with pasireotide at therapeutic and supra-therapeutic doses. Androgen deprivation therapy may also prolong the QT/QTc interval. [30369] [52611] Pazopanib: (Major) Coadministration of pazopanib and histrelin is not advised due to the risk of QT prolongation. If concomitant use is unavoidable, closely monitor ECGs for QT interval prolongation. Pazopanib has been reported to prolong the QT interval. Androgen deprivation therapy (i.e., histrelin) may also prolong the QT/QTc interval. [30369] [37098] Pentamidine: (Major) Consider whether the benefits of androgen deprivation therapy (i.e., histrelin) outweigh the potential risks of QT prolongation in patients receiving pentamidine. Systemic pentamidine has been associated with QT prolongation. Androgen deprivation therapy may prolong the QT/QTc interval. [23620] [23778] [28419] [28879] [30369] Perphenazine: (Major) Avoid coadministration of histrelin with perphenazine due to the risk of reduced efficacy of histrelin; QT prolongation may also occur. Perphenazine can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; histrelin is a GnRH analog. Perphenazine is associated with a possible risk for QT prolongation. Theoretically, perphenazine may increase the risk of QT prolongation if coadministered with other drugs that have a risk of QT prolongation. Androgen deprivation therapy (i.e., histrelin) may also prolong the QT/QTc interval. [28415] [30369] [45411] Perphenazine; Amitriptyline: (Major) Avoid coadministration of histrelin with perphenazine due to the risk of reduced efficacy of histrelin; QT prolongation may also occur. Perphenazine can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; histrelin is a GnRH analog. Perphenazine is associated with a possible risk for QT prolongation. Theoretically, perphenazine may increase the risk of QT prolongation if coadministered with other drugs that have a risk of QT prolongation. Androgen deprivation therapy (i.e., histrelin) may also prolong the QT/QTc interval. [28415] [30369] [45411] Pimavanserin: (Major) Coadministration of pimavanserin with histrelin should generally be avoided due to the risk of QT prolongation. Pimavanserin may cause QT prolongation. Androgen deprivation therapy (i.e., histrelin) may also prolong the QT/QTc interval. [30369] [60748] Pimozide: (Contraindicated) Because of the potential for torsade de pointes (TdP), use of histrelin with pimozide is contraindicated; the efficacy of histrelin may also be reduced. Pimozide is associated with a well-established risk of QT prolongation and TdP. Androgen deprivation therapy (i.e., histrelin) may also prolong the QT/QTc interval. Pimozide can also cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; histrelin is a GnRH analog. [28225] [30369] [43463] [45411] Pitolisant: (Major) Avoid coadministration of pitolisant with histrelin as concurrent use may increase the risk of QT prolongation. Pitolisant prolongs the QT interval. Androgen deprivation therapy (i.e., histrelin) may prolong the QT/QTc interval. [30369] [64562] Ponesimod: (Major) In general, do not initiate ponesimod in patients taking histrelin due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). If treatment initiation is considered, seek advice from a cardiologist. Ponesimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ponesimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. Androgen deprivation therapy (i.e., histrelin) may prolong the QT/QTc interval. [30369] [66527] Posaconazole: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., histrelin) outweigh the potential risks of QT prolongation in patients receiving posaconazole as concurrent use may increase the risk of QT prolongation. Posaconazole has been associated with prolongation of the QT interval as well as rare cases of torsade de pointes (TdP). Androgen deprivation therapy may also prolong the QT/QTc interval. [30369] [32723] Prasterone, Dehydroepiandrosterone, DHEA (Dietary Supplements): (Major) Avoid concurrent use of androgens with gonadotropin releasing hormone (GnRH) agonists such as histrelin. Histrelin inhibits steroidogenesis; concomitant use with androgens may counteract this therapeutic effect. [30369] [33431] Prasterone, Dehydroepiandrosterone, DHEA (FDA-approved): (Major) Avoid concurrent use of androgens with gonadotropin releasing hormone (GnRH) agonists such as histrelin. Histrelin inhibits steroidogenesis; concomitant use with androgens may counteract this therapeutic effect. [30369] [33431] Primaquine: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., histrelin) outweigh the potential risks of QT prolongation in patients receiving primaquine as concurrent use may increase the risk of QT prolongation. Primaquine has the potential to cause QT prolongation. Androgen deprivation therapy may also prolong the QT/QTc interval. [30369] [41984] Procainamide: (Major) Consider whether the benefits of androgen deprivation therapy (i.e., histrelin) outweigh the potential risks of QT prolongation in patients receiving procainamide. Procainamide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Androgen deprivation therapy may also prolong the QT/QTc interval. [28250] [30369] Prochlorperazine: (Moderate) Monitor for reduced efficacy of gonadotropin releasing hormone (GnRH) analogues, such as histrelin, during intermittent prochlorperazine use; avoid chronic concomitant use. Hyperprolactinemia reduces the number of pituitary GnRH receptors which may reduce histrelin efficacy. Prolactin elevations have been observed with prochlorperazine use and typically resolve rapidly following discontinuation. [30369] [45411] [69332] Promethazine: (Major) Avoid coadministration of histrelin with promethazine due to the risk of reduced efficacy of histrelin; QT prolongation may also occur. Promethazine can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; leuprolide is a GnRH analog. Promethazine, a phenothiazine, is associated with a possible risk for QT prolongation. Androgen deprivation therapy (i.e., histrelin) may also prolong the QT/QTc interval. [28225] [30369] [45411] [55578] Promethazine; Dextromethorphan: (Major) Avoid coadministration of histrelin with promethazine due to the risk of reduced efficacy of histrelin; QT prolongation may also occur. Promethazine can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; leuprolide is a GnRH analog. Promethazine, a phenothiazine, is associated with a possible risk for QT prolongation. Androgen deprivation therapy (i.e., histrelin) may also prolong the QT/QTc interval. [28225] [30369] [45411] [55578] Promethazine; Phenylephrine: (Major) Avoid coadministration of histrelin with promethazine due to the risk of reduced efficacy of histrelin; QT prolongation may also occur. Promethazine can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; leuprolide is a GnRH analog. Promethazine, a phenothiazine, is associated with a possible risk for QT prolongation. Androgen deprivation therapy (i.e., histrelin) may also prolong the QT/QTc interval. [28225] [30369] [45411] [55578] Propafenone: (Major) Concomitant use of propafenone and histrelin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. [28287] [30369] Quetiapine: (Major) Concomitant use of quetiapine and histrelin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. [29118] [30369] [33068] [33072] [33074] Quinidine: (Major) Consider whether the benefits of androgen deprivation therapy (i.e., histrelin) outweigh the potential risks of QT prolongation in patients receiving quinidine. Quinidine administration is associated with QT prolongation and torsade de pointes (TdP). Androgen deprivation therapy may also prolong the QT/QTc interval. [30369] [42280] [47357] Quinine: (Major) Avoid coadministration of quinine with histrelin due to the risk of QT prolongation and torsade de pointes (TdP). Quinine has been associated with QT prolongation and rare cases of TdP. Androgen deprivation therapy (i.e., histrelin) may also prolong the QT/QTc interval. [30369] [31403] Quizartinib: (Major) Concomitant use of quizartinib and androgen deprivation therapy (i.e., histrelin) increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. [30369] [69220] Ramelteon: (Major) Avoid coadministration of histrelin with ramelteon due to the risk of reduced efficacy of histrelin. Ramelteon can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; histrelin is a GnRH analog. [31359] [45411] Ranolazine: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., histrelin) outweigh the potential risks of QT prolongation in patients receiving ranolazine as concurrent use may increase the risk of QT prolongation. Androgen deprivation therapy may prolong the QT/QTc interval. Ranolazine is associated with dose- and plasma concentration-related increases in the QTc interval. Although there are no studies examining the effects of ranolazine in patients receiving other QT prolonging drugs, coadministration of such drugs may result in additive QT prolongation. [30369] [31938] Ribociclib: (Major) Avoid coadministration of ribociclib with histrelin due to the risk of QT prolongation. Ribociclib has been shown to prolong the QT interval in a concentration-dependent manner. Ribociclib-related ECG changes typically occurred within the first four weeks of treatment and were reversible with dose interruption. Androgen deprivation therapy (i.e., histrelin) may also prolong the QT/QTc interval. [30369] [61816] Ribociclib; Letrozole: (Major) Avoid coadministration of ribociclib with histrelin due to the risk of QT prolongation. Ribociclib has been shown to prolong the QT interval in a concentration-dependent manner. Ribociclib-related ECG changes typically occurred within the first four weeks of treatment and were reversible with dose interruption. Androgen deprivation therapy (i.e., histrelin) may also prolong the QT/QTc interval. [30369] [61816] Rilpivirine: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., histrelin) outweigh the potential risks of QT prolongation in patients receiving rilpivirine as concurrent use may increase the risk of QT prolongation. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation. Androgen deprivation therapy may also prolong the QT/QTc interval. [30369] [44376] Risperidone: (Major) Avoid coadministration of histrelin with risperidone due to the risk of reduced efficacy of histrelin; QT prolongation may also occur. Risperidone can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; histrelin is a GnRH analog. Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. Androgen deprivation therapy (i.e., histrelin) may also prolong the QT/QTc interval. [28225] [28414] [30369] Romidepsin: (Moderate) Monitor ECGs for QT prolongation and monitor electrolytes at baseline and periodically during treatment if coadministration of romidepsin with histrelin is necessary. Romidepsin has been reported to prolong the QT interval. Androgen deprivation therapy (i.e., histrelin) may also prolong the QT/QTc interval. [30369] [37292] Saquinavir: (Major) Concomitant use of saquinavir and androgen deprivation therapy (i.e., histrelin) increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. [28995] [30369] Selpercatinib: (Major) Monitor ECGs more frequently for QT prolongation if coadministration of selpercatinib with histrelin is necessary due to the risk of additive QT prolongation. Concentration-dependent QT prolongation has been observed with selpercatinib therapy. Androgen deprivation therapy (i.e., histrelin) may prolong the QT/QTc interval. [30369] [65387] Sertraline: (Moderate) Concomitant use of sertraline and androgen deprivation therapy (i.e., histrelin) may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. The degree of QT prolongation associated with sertraline is not clinically significant when administered within the recommended dosage range; QT prolongation has been described at 2 times the maximum recommended dose. [28343] [30369] [64391] [64392] [64394] [64395] [64396] Sevoflurane: (Major) Consider whether the benefits of androgen deprivation therapy (i.e., histrelin) outweigh the potential risks of QT prolongation in patients receiving halogenated anesthetics. Androgen deprivation therapy may prolong the QT/QTc interval. Halogenated anesthetics can also prolong the QT interval. [28457] [28458] [28754] [28755] [28756] [30369] Siponimod: (Major) In general, do not initiate treatment with siponimod in patients receiving histrelin due to the potential for QT prolongation. Consult a cardiologist regarding appropriate monitoring if siponimod use is required. Siponimod therapy prolonged the QT interval at recommended doses in a clinical study. Androgen deprivation therapy (i.e., histrelin) may prolong the QT/QTc interval. [30369] [64031] Sodium Stibogluconate: (Moderate) Concomitant use of sodium stibogluconate and androgen deprivation therapy (i.e., histrelin) may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. [30369] [64608] Solifenacin: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., histrelin) outweigh the potential risks of QT prolongation in patients receiving solifenacin. Solifenacin has been associated with dose-dependent prolongation of the QT interval; torsade de pointes (TdP) has been reported with postmarketing use, although causality was not determined. Androgen deprivation therapy may also prolong the QT/QTc interval. [30369] [30515] Sorafenib: (Major) Avoid coadministration of sorafenib with histrelin due to the risk of additive QT prolongation. If concomitant use is unavoidable, monitor electrocardiograms and correct electrolyte abnormalities. An interruption or discontinuation of sorafenib therapy may be necessary if QT prolongation occurs. Sorafenib is associated with QTc prolongation. Androgen deprivation therapy (i.e., histrelin) may also prolong the QT/QTc interval. [30369] [31832] Sotalol: (Major) Concomitant use of sotalol and histrelin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. [28234] [30369] Sunitinib: (Moderate) Consider whether the benefits of androgen deprivation therapy outweigh the potential risks in patients receiving sunitinib as concurrent use may increase the risk of QT prolongation. Androgen deprivation therapy (i.e., histrelin) may prolong the QT/QTc interval. Sunitinib can prolong the QT interval. [30369] [31970] Tacrolimus: (Moderate) Consider the benefits of androgen deprivation therapy and monitor ECG and electrolytes periodically during treatment if tacrolimus is administered with histrelin as concurrent use may increase the risk of QT prolongation. Tacrolimus may prolong the QT interval and cause torsade de pointes (TdP). Androgen deprivation therapy (i.e., histrelin) may prolong the QT/QTc interval. [28611] [30369] [55401] [60497] Tamoxifen: (Moderate) Concomitant use of tamoxifen and androgen deprivation therapy (i.e., histrelin) may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. [30369] [61870] [61871] [61872] Telavancin: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., histrelin) outweigh the potential risks of QT prolongation in patients receiving telavancin as concurrent use may increase the risk of QT prolongation. Androgen deprivation therapy may prolong the QT/QTc interval and telavancin has been associated with QT prolongation. [30369] [36615] Testosterone: (Major) Avoid concurrent use of androgens with gonadotropin releasing hormone (GnRH) agonists such as histrelin. Histrelin inhibits steroidogenesis; concomitant use with androgens may counteract this therapeutic effect. [30369] [33431] Tetrabenazine: (Major) Avoid coadministration of histrelin with tetrabenazine due to the risk of reduced efficacy of histrelin; QT prolongation may also occur. Tetrabenazine can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; histrelin is a GnRH analog. Tetrabenazine also causes a small increase in the corrected QT interval (QTc). Androgen deprivation therapy (i.e., histrelin) may also prolong the QT/QTc interval. [30369] [34389] [45411] Thioridazine: (Contraindicated) Because of the potential for torsade de pointes (TdP), use of histrelin with thioridazine is contraindicated; the efficacy of histrelin may also be reduced. Thioridazine is associated with a well-established risk of QT prolongation and TdP and is considered contraindicated for use along with agents that may prolong the QT interval and increase the risk of TdP, and/or cause orthostatic hypotension. Androgen deprivation therapy (i.e., histrelin) may also prolong the QT/QTc interval. Thioridazine can also cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; histrelin is a GnRH analog. [28225] [28293] [30369] [45411] Thiothixene: (Major) Avoid coadministration of histrelin with thiothixene due to the risk of reduced efficacy of histrelin. Thiothixene can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; histrelin is a GnRH analog. [45411] [46957] Tolterodine: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., histrelin) outweigh the potential risks of QT prolongation in patients receiving tolterodine. Tolterodine has been associated with dose-dependent prolongation of the QT interval, especially in poor CYP2D6 metabolizers. Androgen deprivation therapy may also prolong the QT/QTc interval. [30369] [31112] Toremifene: (Major) Avoid coadministration of histrelin with toremifene due to the risk of additive QT prolongation. If concomitant use is unavoidable, closely monitor ECGs for QT prolongation and monitor electrolytes. Toremifene has been shown to prolong the QTc interval in a dose- and concentration-related manner. Androgen deprivation therapy (i.e., histrelin) may also prolong the QT/QTc interval. [28822] [30369] Trandolapril; Verapamil: (Major) Avoid coadministration of histrelin with verapamil due to the risk of reduced efficacy of histrelin. Verapamil can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; histrelin is a GnRH analog. [28273] [45411] Trazodone: (Major) Concomitant use of trazodone and histrelin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. [30369] [38831] Triclabendazole: (Moderate) Concomitant use of triclabendazole and androgen deprivation therapy (i.e., histrelin) may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. [30369] [63962] Trifluoperazine: (Major) Avoid coadministration of histrelin with trifluoperazine due to the risk of reduced efficacy of histrelin; QT prolongation may also occur. Trifluoperazine can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; histrelin is a GnRH analog. Trifluoperazine is also associated with a possible risk for QT prolongation. Theoretically, trifluoperazine may increase the risk of QT prolongation if coadministered with other drugs that have a risk of QT prolongation. Androgen deprivation therapy (i.e., histrelin) may also prolong the QT/QTc interval. [28415] [30369] [45411] Valbenazine: (Major) Avoid concurrent use of histrelin with valbenazine due to the risk of reduced efficacy of histrelin. Valbenazine can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; histrelin is a GnRH analog. [45411] [61873] Vandetanib: (Major) Avoid coadministration of vandetanib with histrelin due to an increased risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, monitor ECGs for QT prolongation and monitor electrolytes; correct hypocalcemia, hypomagnesemia, and/or hypomagnesemia prior to vandetanib administration. An interruption of vandetanib therapy or dose reduction may be necessary for QT prolongation. Vandetanib can prolong the QT interval in a concentration-dependent manner; TdP and sudden death have been reported in patients receiving vandetanib. Androgen deprivation therapy (i.e., histrelin) may also prolong the QT/QTc interval. [30369] [43901] Vardenafil: (Moderate) Concomitant use of vardenafil and androgen deprivation therapy (i.e., histrelin) may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. [28216] [30369] Vemurafenib: (Major) Closely monitor ECGs for QT prolongation if coadministration of vemurafenib with histrelin is necessary. Vemurafenib has been associated with QT prolongation. Androgen deprivation therapy (i.e., histrelin) may prolong the QT/QTc interval. [30369] [45335] Venlafaxine: (Moderate) Concomitant use of venlafaxine and androgen deprivation therapy (i.e., histrelin) may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. [30369] [33715] Verapamil: (Major) Avoid coadministration of histrelin with verapamil due to the risk of reduced efficacy of histrelin. Verapamil can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; histrelin is a GnRH analog. [28273] [45411] Voclosporin: (Moderate) Concomitant use of voclosporin and histrelin may increase the risk of QT prolongation. Consider interventions to minimize the risk of progression to torsades de pointes (TdP), such as ECG monitoring and correcting electrolyte abnormalities, particularly in patients with additional risk factors for TdP. Voclosporin has been associated with QT prolongation at supratherapeutic doses. Androgen deprivation therapy (i.e., histrelin) may prolong the QT/QTc interval. [30369] [66336] Vonoprazan; Amoxicillin; Clarithromycin: (Major) Consider whether the benefits of androgen deprivation therapy (i.e., histrelin) outweigh the potential risks of QT prolongation in patients receiving clarithromycin. Clarithromycin is associated with an established risk for QT prolongation and torsade de pointes (TdP). Androgen deprivation therapy may also prolong the QT/QTc interval. [28225] [28238] [30369] Voriconazole: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., histrelin) outweigh the potential risks of QT prolongation in patients receiving voriconazole as concurrent use may increase the risk of QT prolongation. Voriconazole has been associated with QT prolongation and rare cases of torsade de pointes. Androgen deprivation therapy may also prolong the QT/QTc interval. [28158] [30369] Vorinostat: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., histrelin) outweigh the potential risks of QT prolongation in patients receiving vorinostat. Vorinostat therapy is associated with a risk of QT prolongation. Androgen deprivation therapy may also prolong the QT/QTc interval. [30369] [32789] Ziprasidone: (Major) Concomitant use of ziprasidone and histrelin should be avoided due to a potential for additive QT prolongation. Clinical trial data indicate that ziprasidone causes QT prolongation; there are postmarketing reports of torsade de pointes (TdP) in patients with multiple confounding factors. Androgen deprivation therapy (i.e., histrelin) may prolong the QT/QTc interval. [28233] [30369]
      Revision Date: 02/02/2024, 02:07:00 AM

      References

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Br J Clin Pharmacol. 1991 Dec;32(6):677-84.

      Monitoring Parameters

      • blood glucose
      • ECG
      • glycosylated hemoglobin A1c (HbA1c)
      • prostate-specific antigen (PSA)
      • serum electrolytes
      • serum estradiol concentrations
      • serum gonadotropin concentrations
      • serum testosterone concentrations

      US Drug Names

      • Supprelin
      • Supprelin LA
      • Vantas
      ;