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    Cidofovir

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    Oct.20.2024

    Cidofovir

    Indications/Dosage

    Labeled

    • cytomegalovirus (CMV) infection
    • cytomegalovirus (CMV) retinitis
    • cytomegalovirus (CMV) retinitis prophylaxis

    General Dosing Information

    • NOTE: To minimize the potential for renal toxicity, patients must receive oral probenecid and hydration with normal saline concurrently with cidofovir.[28388]
      • Probenecid
        • Adults: 2 g PO given 3 hours prior to each cidofovir infusion, followed by 1 g PO at 2 and 8 hours following the completion of the cidofovir infusion.[28388][67327]
        • Pediatrics: 25 to 40 mg/kg/dose (Max: 2 g/dose) PO given 3 hours prior to each cidofovir infusion, followed by 10 to 20 mg/kg/dose (Max: 1 g/dose) PO at 2 and 8 hours following the completion of the cidofovir infusion.[67325][67326][70821]
      • Hydration
        • Adults: Infuse 1 L of 0.9% Sodium Chloride Injection over 1 to 2 hours immediately prior to cidofovir infusion. Patients who can tolerate the fluid load should receive a second liter over 1 to 3 hours starting with or after the completion of the cidofovir infusion.[28388]
        • Pediatrics: Infuse 20 mL/kg/hour (Max: 1 L) of 0.9% Sodium Chloride Injection over 1 to 2 hours immediately prior to cidofovir infusion and post infusion.[67325][67329] IV hydration may also be given at 3 times the maintenance rate initiated 1 hour before and continued until 1 hour after the completion of cidofovir infusion, followed by hydration at 2 times the maintenance rate for an additional 2 hours.[26495][67330][67333]

    Off-Label

    • adenovirus infection
    • adenovirus infection prophylaxis
    • condylomata acuminata
    • cytomegalovirus (CMV) disease prophylaxis
    • cytomegalovirus (CMV) pneumonitis
    • cytomegalovirus (CMV)-associated gastrointestinal disease
    • eczema vaccinatum
    • generalized vaccinia
    • herpes genitalis
    • herpes labialis
    • herpes simplex virus infection
    • human papillomavirus (HPV) infection
    • molluscum contagiosum
    • monkeypox virus (mpox) infection
    • vaccinia necrosum (progressive vaccinia)
    † Off-label indication

    For the treatment of cytomegalovirus (CMV) infection, including cytomegalovirus (CMV) retinitis, cytomegalovirus (CMV)-associated gastrointestinal disease† (i.e., esophagitis† or colitis†), and cytomegalovirus (CMV) pneumonitis†

    for the treatment of CMV retinitis in persons living with HIV

    Intravenous dosage

    Adults

    5 mg/kg/dose IV once weekly for 2 weeks. For immediate sight-threatening lesions (i.e., within 1,500 microns of the fovea), give in combination with intravitreal injections of ganciclovir or foscarnet. Follow induction therapy with chronic maintenance therapy (secondary prophylaxis). Guidelines suggest cidofovir as second-line therapy.[28388] [34362]

    Adolescents†

    5 mg/kg/dose IV once weekly for 2 weeks. For immediate sight-threatening lesions (i.e., within 1,500 microns of the fovea), give in combination with intravitreal injections of ganciclovir or foscarnet. Follow induction therapy with chronic maintenance therapy (secondary prophylaxis). Guidelines suggest cidofovir as second-line therapy.[34362]

    for the treatment of CMV retinitis in persons with cancer† or solid organ transplant recipients†

    Intravenous dosage

    Adults

    5 mg/kg/dose IV once weekly for 2 weeks, then 5 mg/kg/dose IV every 2 weeks until clinical resolution of disease and virologic clearance. For immediate sight-threatening lesions (i.e., within 1,500 microns of the fovea), give in combination with intravitreal injections of ganciclovir or foscarnet. Guidelines suggest cidofovir as second- or third-line therapy.[34362] [69330] [69334] [69356] [70680] [70682] [70690] [70694] [70698]

    Adolescents

    5 mg/kg/dose IV once weekly for 2 weeks, then 5 mg/kg/dose IV every 2 weeks until clinical resolution of disease and virologic clearance. For immediate sight-threatening lesions (i.e., within 1,500 microns of the fovea), give in combination with intravitreal injections of ganciclovir or foscarnet. Guidelines suggest cidofovir as second- or third-line therapy.[34362] [69330] [69334] [69356] [70682] [70690] [70694] [70698] [70699] [70700] [70704]

    Infants and Children

    5 mg/kg/dose IV once weekly for 2 weeks, then 5 mg/kg/dose IV every 2 weeks until clinical resolution of disease and virologic clearance. Guidelines suggest cidofovir as second- or third-line therapy.[69330] [69334] [69356] [70682] [70694] [70699] [70700] [70704]

    for the treatment of CMV-associated gastrointestinal disease† (i.e., esophagitis† or colitis†) in persons with cancer or solid organ transplant recipients

    Intravenous dosage

    Adults

    5 mg/kg/dose IV once weekly for 2 weeks, then 5 mg/kg/dose IV every 2 weeks until clinical resolution of disease and virologic clearance. Guidelines suggest cidofovir as second- or third-line therapy.[69330] [69334] [69356] [70680] [70682] [70694]

    Infants, Children, and Adolescents

    5 mg/kg/dose IV once weekly for 2 weeks, then 5 mg/kg/dose IV every 2 weeks until clinical resolution of disease and virologic clearance. Guidelines suggest cidofovir as second- or third-line therapy.[69330] [69334] [69356] [70682] [70694] [70699] [70700] [70704]

    for the treatment of CMV pneumonitis† in persons with cancer or solid organ transplant recipients

    Intravenous dosage

    Adults

    5 mg/kg/dose IV once weekly for 2 weeks, then 5 mg/kg/dose IV every 2 weeks until clinical resolution of disease and virologic clearance. Guidelines suggest cidofovir as second- or third-line therapy.[69330] [69334] [69356] [70680] [70682] [70694] Consider the addition of intravenous immune globulin.[69330] [69334] [69356] [70682]

    Infants, Children, and Adolescents

    5 mg/kg/dose IV once weekly for 2 weeks, then 5 mg/kg/dose IV every 2 weeks until clinical resolution of disease and virologic clearance. Guidelines suggest cidofovir as second- or third-line therapy.[69330] [69334] [69356] [70682] [70694] [70699] [70700] [70704] Consider the addition of intravenous immune globulin.[69330] [69334] [69356] [70682] [70700]

    For cytomegalovirus (CMV) disease prophylaxis† and cytomegalovirus (CMV) retinitis prophylaxis, including use as preemptive therapy and secondary prophylaxis (i.e., long-term suppressive therapy)

    for preemptive therapy to prevent CMV infection in allogeneic hematopoietic cell transplant (HCT) recipients†

    Intravenous dosage

    Adults

    5 mg/kg/dose IV once weekly for at least 2 weeks and until CMV detection methods are negative or vial load has declined to below a predefined threshold. Alternatively, if viral load is decreasing after 1 to 2 weeks, may change to maintenance dosing of 5 mg/kg/dose IV every 2 weeks until CMV detection methods are negative.[70694]

    Infants, Children, and Adolescents

    5 mg/kg/dose IV once weekly for at least 2 weeks and until CMV detection methods are negative or vial load has declined to below a predefined threshold. Alternatively, if viral load is decreasing after 1 to 2 weeks, may change to maintenance dosing of 5 mg/kg/dose IV every 2 weeks until CMV detection methods are negative.[70694] [70699] [70704]

    for secondary cytomegalovirus (CMV) disease prophylaxis (i.e., long-term suppressive therapy), including cytomegalovirus (CMV) retinitis prophylaxis, in persons living with HIV

    Intravenous dosage

    Adults

    5 mg/kg/dose IV every 2 weeks as an alternative maintenance therapy after treatment of acute infection. For patients who experience progression of CMV retinitis while receiving maintenance therapy, re-induction treatment with the same drug used for maintenance followed by reinstitution of maintenance therapy is recommended.[28388] [34362] Discontinuation of secondary prophylaxis may be considered after consultation with an ophthalmologist in persons who have had a sustained immune response to highly active antiretroviral therapy (i.e., CD4 counts greater than 100 cells/mm3 for 3 to 6 months), have been on CMV treatment for at least 3 to 6 months, and have no active lesions. Restart maintenance therapy if subsequent CD4 counts drop to less than 100 cells/mm3, as relapse occurs most frequently in those patients whose counts decrease to less than 50 cells/mm3 after stopping treatment. However, because relapses may occur at any CD4 count, all patients who have had maintenance CMV therapy discontinued should continue to undergo regular ophthalmologic monitoring (every 3 months) for early detection of CMV relapse (as well as for immune reconstitution uveitis).[34362]

    Adolescents†

    5 mg/kg/dose IV every 2 weeks as an alternative maintenance therapy after treatment of acute infection. For patients who experience progression of CMV retinitis while receiving maintenance therapy, re-induction treatment with the same drug used for maintenance followed by reinstitution of maintenance therapy is recommended.[28388] [34362] Discontinuation of secondary prophylaxis may be considered after consultation with an ophthalmologist in persons who have had a sustained immune response to highly active antiretroviral therapy (i.e., CD4 counts greater than 100 cells/mm3 for 3 to 6 months), have been on CMV treatment for at least 3 to 6 months, and have no active lesions. Restart maintenance therapy if subsequent CD4 counts drop to less than 100 cells/mm3, as relapse occurs most frequently in those patients whose counts decrease to less than 50 cells/mm3 after stopping treatment. However, because relapses may occur at any CD4 count, all patients who have had maintenance CMV therapy discontinued should continue to undergo regular ophthalmologic monitoring (every 3 months) for early detection of CMV relapse (as well as for immune reconstitution uveitis).[34362]

    Infants† and Children†

    5 mg/kg/dose IV every 2 weeks as an alternative maintenance therapy after treatment of acute infection. For patients who experience progression of CMV retinitis while receiving maintenance therapy, re-induction treatment with the same drug used for maintenance followed by reinstitution of maintenance therapy is recommended. Discontinuation of secondary prophylaxis may be considered in pediatric patients who have received at least 6 months of highly active antiretroviral therapy with a sustained increase (more than 6 months) in CD4 percentage of at least 15% (pediatric patients younger than 5 years) or CD4 count more than 100 cells/mm3 (children 6 years and older). For retinitis, the decision to discontinue secondary prophylaxis should be made in consultation with an ophthalmologist. Routine follow-up (every 3 to 6 months) with an ophthalmologist is recommended. Restart maintenance therapy if CD4 percentage is less than 15% in pediatric patients younger than 5 years or if CD4 count is less than 100 cells/mm3 in children 6 years and older.[34361]

    For the treatment of adenovirus infection† in hematopoietic stem cell transplant (HCT) and solid organ transplant recipients

    Intravenous dosage

    Adults

    Optimal dosing has not been established and various regimens have been reported based on transplant center-specific protocols. An induction dose of 5 mg/kg/dose IV once weekly for 2 to 3 weeks, followed by maintenance dose of 5 mg/kg/dose IV every 2 weeks until resolution or viral clearance is commonly used.[67328] [67384] Other protocols use 5 mg/kg/dose IV once weekly or 1 mg/kg/dose IV 3 times weekly until resolution or viral clearance.[67323] [67324] [67327] [67328] Although the 1 mg/kg 3 times weekly dose may cause less renal toxicity, it may be associated with breakthrough CMV and HSV infections and the emergence of antiviral resistance.[51812] [67328] [67333]

    Infants, Children, and Adolescents

    Optimal dosing has not been established and various regimens have been reported based on transplant center-specific protocols. An induction dose of 5 mg/kg/dose IV once weekly for 2 to 3 weeks, followed by a maintenance dose of 5 mg/kg/dose IV every 2 weeks until resolution or viral clearance is commonly used.[67323] [67325] [67328] [67331] [67334] [67384] Other dosing protocols use 5 mg/kg/dose IV once weekly or 1 mg/kg/dose IV 3 times weekly until resolution or viral clearance.[67323] [67324] [67329] [67330] [67333] Although the 1 mg/kg 3 times weekly dose may cause less renal toxicity, it may be associated with breakthrough CMV and HSV infections and the emergence of antiviral resistance.[51812] [67328] [67333]

    For the treatment of external genital and perianal warts (condylomata acuminata†) or recurrent respiratory papillomatosis† (laryngeal papillomatosis) due to human papillomavirus (HPV) infection†

    for the treatment of condylomata acuminata† (genital and perianal warts)

    Topical dosage†

    Adults

    Apply topically to wart(s) once daily for 5 days per week for 8 weeks is recommended by guidelines as a treatment option.[34362] [66938] In a placebo-controlled trial, 30 patients were treated with cidofovir 1% gel once daily or placebo. Overall 16 of 19 patients had a complete or partial response to cidofovir (9 complete responses) versus only 2 patients in the placebo group after a median of 43 days of treatment.[26749]

    Adolescents

    Apply topically to wart(s) once daily for 5 days per week for 8 weeks is recommended by guidelines as a treatment option.[34362]

    Intralesional dosage†

    Adults

    15 mg/mL solution injected directly into the wart; maximum of 1 mL per treatment session. May repeat injections every 4 weeks for a total of 3 to 4 treatments.[34362]

    Adolescents

    15 mg/mL solution injected directly into the wart; maximum of 1 mL per treatment session. May repeat injections every 4 weeks for a total of 3 to 4 treatments.[34362]

    for the treatment of recurrent respiratory papillomatosis† (laryngeal papillomatosis)

    Intralesional dosage†

    Adults

    A review of 20 published reports involving 185 patients with adult onset recurrent respiratory papillomatosis (AORRP) and 85 patients under the age of 12 with juvenile onset recurrent respiratory papillomatosis (JORRP) found intralesional cidofovir to be an effective adjuvant therapy. Cidofovir was administered via intralesional injection at a concentration ranging from 2.5 to 15 mg/mL (mean 7.5 mg/mL). The mean number of injections administered per person was 6 (range 2 to 13 doses). The injection frequency ranged from 2 to 8 weeks, with a mean interval between injections of 26 days. The overall efficacy for AORRP was 74% complete response, 23.8% partial response, 0.6% no response, and 1.6% discontinued therapy. For JORRP, the overall efficacy was 56.5% complete response, 31.8% partial response, and 11.7% no response.[66302]

    Children and Adolescents

    A review of 20 published reports involving 185 patients with adult onset recurrent respiratory papillomatosis (AORRP) and 85 patients under the age of 12 with juvenile onset recurrent respiratory papillomatosis (JORRP) found intralesional cidofovir to be an effective adjuvant therapy. Cidofovir was administered via intralesional injection at a concentration ranging from 2.5 to 15 mg/mL (mean 7.5 mg/mL). The mean number of injections administered per person was 6 (range 2 to 13 doses). The injection frequency ranged from 2 to 8 weeks, with a mean interval between injections of 26 days. The overall efficacy for AORRP was 74% complete response, 23.8% partial response, 0.6% no response, and 1.6% discontinued therapy. For JORRP, the overall efficacy was 56.5% complete response, 31.8% partial response, and 11.7% no response.[66302]

    For the treatment of molluscum contagiosum†

    Topical dosage†

    Adults

    In case reports, cidofovir gel 1% to 3% used 1 to 2 times per day has led to successful resolution of this condition. In addition, patients treated with cidofovir for CMV retinitis have reported resolution of molluscum contagiosum.[26751]

    For the treatment of acyclovir-resistant mucocutaneous herpes simplex virus infection†, including herpes genitalis† and herpes labialis†, in persons living with HIV

    Intravenous dosage

    Adults

    5 mg/kg/dose IV once weekly for at least 21 to 28 days as an alternative.[34362] [66938]

    Adolescents

    5 mg/kg/dose IV once weekly for at least 21 to 28 days as an alternative.[34362] [66938]

    Topical dosage†

    Adults

    1% topical gel applied to lesions once daily for at least 21 to 28 days as an alternative.[34362] Alternatively, 1% topical gel applied to lesions 2 to 4 times daily for genital infections.[66938]

    Adolescents

    1% topical gel applied to lesions once daily for at least 21 to 28 days as an alternative.[34362] Alternatively, 1% topical gel applied to lesions 2 to 4 times daily for genital infections.[66938]

    NOTE: Vaccinia immune globulin, VIG is the preferred treatment. Cidofovir is only available via the CDC under an investigational new drug (IND) protocol and by special request to the CDC Drug and Immunobiologics Service (404-639-3670). Cidofovir efficacy for this indication is not proven. Cidofovir is only used in vaccinia cases that fail to respond to VIG, as additional therapy in a patient severely ill (near death), or in the case that VIG supplies are exhausted.[31173]

    Intravenous dosage

    Adults

    Contact the CDC for IND protocol enrollment and product availability. 5 mg/kg IV as a one time dose infused over 60 minutes. A second dose 1 week later may be considered if clinically indicated.[31173]

    Children

    Pediatric dosage is not known.

    For preemptive therapy to prevent adenovirus infection (adenovirus infection prophylaxis†) in high-risk seropositive hematopoietic cell transplant (HCT) recipients

    Intravenous dosage

    Adults

    5 mg/kg/dose IV once weekly or 1 mg/kg/dose IV 3 times weekly for 2 to 4 weeks or until viral clearance and/or immune recovery.[51812] [67323] [67324] 5 mg/kg/dose IV once weekly for 2 to 3 weeks, followed by 5 mg/kg/dose IV every other week until viral clearance and/or immune recovery has also been reported.[67323] [67324] [67384] Although the 1 mg/kg 3 times weekly dose may cause less renal toxicity, it is insufficient to treat concomitant CMV infection; if concomitant CMV infection is present, the 5 mg/kg once weekly dose is recommended.[51812]

    Infants, Children, and Adolescents

    5 mg/kg/dose IV once weekly or 1 mg/kg/dose IV 3 times weekly for 2 to 4 weeks or until viral clearance and/or immune recovery.[51812] [67323] [67324] 5 mg/kg/dose IV once weekly for 2 to 3 weeks, followed by 5 mg/kg/dose IV every other week until viral clearance and/or immune recovery has also been reported.[67323] [67324] [67384] Although the 1 mg/kg 3 times weekly dose may cause less renal toxicity, it is insufficient to treat concomitant CMV infection; if concomitant CMV infection is present, the 5 mg/kg once weekly dose is recommended.[51812]

    For the treatment of monkeypox virus (mpox) infection†

    NOTE: There is no FDA-approved treatment for monkeypox virus (mpox) infections; however, the CDC suggests potential use of cidofovir.[67654]

    NOTE: Many cases of monkeypox virus (mpox) infection are mild and self-limiting in the absence of specific therapy; however, the prognosis depends on multiple factors such as previous vaccination status, initial health status, concurrent illnesses, and comorbidities. Persons for whom treatment may be considered (after consultation with the CDC) include: [67654] [67802] [68061]

    • Persons with severe disease or other complications
    • Involvement of anatomic areas which might result in serious sequelae that include scarring or strictures
    • Persons who may be a high risk for disease:
      • Persons with severe immunocompromise
      • Persons with a condition affecting skin integrity
      • Pregnant or breast-feeding persons

    Intravenous dosage

    Adults

    5 mg/kg/dose IV once weekly for 2 doses as adjunctive therapy with tecovirimat; based on individual patient risk-benefit assessment and disease progression, treatment may be extended beyond 14 days, or shortened due to lack of virologic or clinical response or due to adverse events. For people with HIV or severe immunocompromise and severe disease, consider early intervention with combination therapy at the time of the first medical encounter, in consultation with CDC or an expert in mpox treatment. Additionally, people with HIV not currently taking antiretroviral therapy (ART) should initiate a treatment regimen as soon as possible.[34362] [67654] [70312]

    Therapeutic Drug Monitoring

    Maximum Dosage Limits

    • Adults

      5 mg/kg/week IV.

    • Geriatric

      5 mg/kg/week IV.

    • Adolescents

      Safety and efficacy have not been established; however, doses up to 5 mg/kg/week IV have been used off-label.

    • Children

      Safety and efficacy have not been established; however, doses up to 5 mg/kg/week IV have been used off-label.

    • Infants

      Safety and efficacy have not been established; however, doses up to 5 mg/kg/week IV have been used off-label.

    • Neonates

      Safety and efficacy have not been established.

    Patients with Hepatic Impairment Dosing

    No dosage adjustment required.

    Patients with Renal Impairment Dosing

    Adult patients (FDA-approved labeling)

    CrCl more than 55 mL/minute: No dosage adjustments necessary unless SCr increases from 0.3 to 0.4 above baseline.

    CrCl 55 mL/minute or less: Systemic cidofovir therapy is contraindicated; also contraindicated in patients with a SCr more than 1.5 mg/dL or a urine protein of 100 mg/dL or more (equivalent to 2+ proteinuria)

    Dosage adjustments based on changes in serum creatinine (SCr):

    For increases in SCr of 0.3 to 0.4 mg/dL above baseline: Decrease cidofovir dose to 3 mg/kg/dose IV.

    For increases in SCr of 0.5 mg/dL or more above baseline or the development of 3+ proteinuria: Discontinue IV cidofovir.[28388]

     

    Adult patients (alternative)†

    The following dose adjustment has been used in patients receiving an initial dose of 1 mg/kg/dose IV 3 times weekly for adenovirus infection prophylaxis and treatment:

    For increases in SCr of 0.3 to 0.4 mg/dL above baseline: Decrease cidofovir dose to 0.5 mg/kg/dose IV 3 times weekly.[67327]

     

    Pediatric patients†

    1 mg/kg/dose IV 3 times weekly for 2 weeks, followed by the same dose every other week has been used for adenovirus infection prophylaxis and treatment in patients with renal dysfunction (serum creatinine more than 1.5 mg/dL, creatinine clearance less than 90 mL/minute/1.73 m2, and 2+ proteinuria).[51812][67328][67331]

     

    Intermittent hemodialysis or Peritoneal dialysis†

    Avoid use.[32569]

     

    Continuous renal replacement therapy (CRRT)†

    Avoid use; if needed, 2 mg/kg/dose IV once weekly.[32569]

    † Off-label indication
    Revision Date: 10/20/2024, 07:31:23 PM

    References

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Expanded Access IND Protocol: Use of tecovirimat (TPOXX) for treatment of human non-variola orthopoxvirus infections in adults and children version 6.3. Updated December 19, 2023. Retrieved February 7, 2024. Available at on the World Wide Web at: https://www.cdc.gov/poxvirus/mpox/clinicians/obtaining-tecovirimat.html.69330 - Kotton CN, Kumar D, Caliendo AM, et al. The Third International Consensus Guidelines on the Management of Cytomegalovirus in Solid-organ Transplantation. Transplantation 2018;102:900-931.69334 - National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology. Prevention and Treatment of Cancer-Related Infections. Version 3.2022; Oct 28, 2022.69356 - Ljungman P, de la Camara R, Robin C, et al. Guidelines for the management of cytomegalovirus infection in patients with haematological malignancies and after stem cell transplantation from the 2017 European Conference on Infections in Leukaemia (ECIL 7). Lancet Infect Dis 2019;19:e260-e272.70312 - Rao AK, Schrodt CA, Minhaj FS, et al. Interim clinical treatment considerations for severe manifestations of Mpox - United States, February 2023. MMWR 2023;72:232-43.70680 - Bonatti H, Sifri CD, Larcher C, et al. Use of cidofovir for cytomegalovirus disease refractory to ganciclovir in solid organ recipients. Surg Infect (Larchmt) 2017;18:128-136.70682 - Razonable RR, Humar A. Cytomegalovirus in solid organ transplant recipients-Guidelines of the American Society of Transplantation Infectious Diseases Community of Practice. Clin Transplant 2019;33:e13512.70690 - Munro M, Yadavalli T, Fonteh C, et al. Cytomegalovirus Retinitis in HIV and Non-HIV Individuals. Microorganisms 2019;8:55.70694 - Hakki M, Aitken SL, Danziger-Isakov L, et al. American Society for Transplantation and Cellular Therapy Series: #3-Prevention of Cytomegalovirus Infection and Disease After Hematopoietic Cell Transplantation. Transplant Cell Ther 2021;27:707-719.70698 - Fan JJ, Tao Y, Hwang DK. Comparison of intravitreal ganciclovir monotherapy and combination with foscarnet as initial therapy for cytomegalovirus retinitis. Int J Ophthalmol 2018;11:1638-1642.70699 - Hiskey L, Madigan T, Ristagno EH, et al. Prevention and management of human cytomegalovirus in pediatric HSCT recipients: A review. Front Pediatr 2022;10:1039938.70700 - Wattles BA, Kim AJ, Cheerva AC, et al. Cytomegalovirus Treatment in Pediatric Hematopoietic Stem Cell Transplant Patients. J Pediatr Hematol Oncol 2017;39:241-248.70704 - Valencia Deray KG, Danziger-Isakov LA, Downes KJ. Current and emerging antiviral agents in the prevention and treatment of cytomegalovirus in pediatric transplant recipients. J Pediatric Infect Dis Soc 2024;13:S14-S21.70821 - American Academy of Pediatrics. Red Book: 2024-2027 Report of the Committee on Infectious Diseases. 33rd ed. Elk Grove Village, IL: American Academy of Pediatrics; 2024.

    How Supplied

    Cidofovir Solution for injection

    Cidofovir 375mg/5mL Solution for Injection (67457-0210) (Mylan Institutional LLC ) null

    Cidofovir Solution for injection

    Cidofovir 75mg/mL Solution for Injection (23155-0216) (Avet Pharmaceuticals Inc.) nullCidofovir 75mg/mL Solution for Injection package photo

    Cidofovir Solution for injection

    Vistide 75mg/ml Solution for Injection (61958-0101) (Gilead Sciences Inc) (off market)

    Description/Classification

    Description

    Cidofovir is an acyclic phosphonate nucleotide analog antiviral agent used for the treatment of cytomegalovirus (CMV), herpes virus infections, and adenovirus infections.[28388][51812][67328] Nucleotides differ chemically and pharmacologically from nucleosides (e.g., zidovudine). Nucleotides are combinations of purine or pyrimidine bases along with an attached sugar and phosphate moiety that is highly stable to serum esterase cleavage, and are the individual units that make up RNA and DNA. Unlike nucleoside analogs, cidofovir is not dependent upon intracellular activation for its antiviral activity. Other advantages of cidofovir include once-weekly dosing and activity against certain ganciclovir-, foscarnet-, and acyclovir-resistant CMV strains.[28388] Cidofovir exhibits other antiviral activity in vitro, including activity against poxviruses. Cidofovir is also available off-label via a treatment IND from the US CDC for the treatment of severe reactions to the vaccinia (smallpox) vaccine in selected circumstances.[27215] Systemic cidofovir can cause serious adverse reactions, including renal toxicity; close attention to administration protocols (concurrent probenecid and IV saline hydration) and clinical monitoring are recommended.[28388]

    Classifications

    • General Anti-infectives Systemic
      • Antivirals For Systemic Use
        • Herpes Virus, incl. Cytomegalovirus (CMV), Antivirals
          • Nucleoside and Nucleotide DNA Polymerase Inhibitor Antivirals
    Revision Date: 10/20/2024, 07:31:23 PM

    References

    27215 - Centers for Disease Control and Prevention (CDC). Smallpox home page. Accessed February 15, 2022. Available on the World Wide Web at: www.cdc.gov/smallpox/28388 - Cidofovir injection solution package insert. Morgantown, WV: Mylan Institutional LLC; 2021 Apr.51812 - Tomblyn M, Chiller T, Einsele H, et al. Guidelines for preventing infectious complications among hematopoietic cell transplantation recipients: A global perspective. Biol Blood Marrow Transplant 2009;15:1143-1238.67328 - Florescu DF, Schaenman JM, AST Infectious Diseases Community of Practice. Adenovirus in solid organ transplant recipients: Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice. Clin Transplant 2019;33:e13527.

    Administration Information

    General Administration Information

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

    • NOTE: To minimize the potential for renal toxicity, patients must receive oral probenecid and hydration with normal saline concurrently with cidofovir.[28388]
      • Probenecid
        • Adults: 2 g PO given 3 hours prior to each cidofovir infusion, followed by 1 g PO at 2 and 8 hours following the completion of the cidofovir infusion.[28388][67327]
        • Pediatrics: 25 to 40 mg/kg/dose (Max: 2 g/dose) PO given 3 hours prior to each cidofovir infusion, followed by 10 to 20 mg/kg/dose (Max: 1 g/dose) PO at 2 and 8 hours following the completion of the cidofovir infusion.[67325][67326][70821]
      • Hydration
        • Adults: Infuse 1 L of 0.9% Sodium Chloride Injection over 1 to 2 hours immediately prior to cidofovir infusion. Patients who can tolerate the fluid load should receive a second liter over 1 to 3 hours starting with or after the completion of the cidofovir infusion.[28388]
        • Pediatrics: Infuse 20 mL/kg/hour (Max: 1 L) of 0.9% Sodium Chloride Injection over 1 to 2 hours immediately prior to cidofovir infusion and post infusion.[67325][67329] IV hydration may also be given at 3 times the maintenance rate initiated 1 hour before and continued until 1 hour after the completion of cidofovir infusion, followed by hydration at 2 times the maintenance rate for an additional 2 hours.[26495][67330][67333]

    Hazardous Drugs Classification

    • NIOSH 2016 List: Group 2 [63664]
    • NIOSH (Draft) 2020 List: Table 1
    • Observe and exercise appropriate precautions for handling, preparation, administration, and disposal of hazardous drugs.
    • Preparation and administration of cidofovir solutions should follow guidelines established for other potentially mutagenic agents, such as chemotherapy agents, including preparation in a Class II laminar flow biological safety cabinet. Personnel preparing and administering this agent should wear protective surgical gloves and closed front surgical-type gowns with knit cuffs.[28388]
    • Eye/face and respiratory protection may be needed during preparation and administration.[63664][67506][67507]

    Route-Specific Administration

    Injectable Administration

    • Cidofovir is administered via intravenous infusion. Do not administer intraocularly.
    • Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.

    Intravenous Administration

    Dilution

    • Dilute each dose in 100 mL 0.9% Sodium Chloride for injection.
    • Use diluted solutions of cidofovir within 24 hours of preparation. These solutions may be stored at room temperature or under refrigeration.[28388]

     

    Intravenous infusion

    • Infuse over 1 hour.[28388]

    Clinical Pharmaceutics Information

    From Trissel's 2‚Ñ¢ Clinical Pharmaceutics Database

    Cidofovir

    pH Range
    Adjusted to pH 7.4.
    ReferencesAnon. Manufacturer's information and labeling. (Package insert).
    Osmolality/Osmolarity
    Cidofovir concentrated injection is hypertonic and must be diluted for administration. In dextrose 5%, cidofovir 0.21 mg/mL and 8.12 mg/mL have osmolalities of 241 and 286 mOsm/kg, respectively. In sodium chloride 0.9%, cidofovir 0.21 mg/mL and 8.12 mg/mL have osmolalities of 275 and 315 mOsm/kg, respectively. In dextrose 5% in sodium chloride 0.45%, cidofovir 0.085 mg/mL and 3.51 mg/mL have osmolalities of 382 and 392 mOsm/kg, respectively.
    ReferencesYuan LC, Samuels GJ, Visor GC. Stability of cidofovir in 0.9% sodium chloride injection and in 5% dextrose injection. Am J Health-Syst Pharm. 1996; 53
    Stability
    Cidofovir in intact containers stored as directed by the manufacturer is stable until the labeled expiration date. Infusion solutions: The manufacturer indicates that cidofovir diluted in 100 mL of sodium chloride 0.9% is stable for 24 hours. The manufacturer indicates that if the admixture is not used immediately, it should be stored under refrigeration but still limited to use within 24 hours of preparation. However, longer stability has been reported in stability studies. Cidofovir is compatible and stable for at least 24 hours in dextrose 5%, and dextrose 5% in sodium chloride 0.45%. However, stability and compatibility in Ringer's and lactated Ringer's has not been established. Longer stability periods have also been reported. Bing reported that cidofovir 6 mg/mL in sodium chloride 0.9% was stable for at least 30 days at room temperature. Hennere et al. reported that cidofovir 6.25 mg/mL in sodium chloride 0.9% was stable for 150 days at room and refrigeration temperatures. See Packaged in Syringes below. Packaged in Syringes: Hennere et al. evaluated the stability of cidofovir 6.25 mg/mL in sodium chloride 0.9% packaged in polypropylene syringes. No visible particulate matter or color changes occurred. Stability-indicating HPLC analysis found little or no loss of cidofovir in 150 days in samples stored refrigerated at 4 to 8 degree C, at room temperature of 25 degree C exposed to or protected from light, and at an elevated temperature of 32 degree C.
    ReferencesAnon. Manufacturer's information and labeling. (Package insert).
    ReferencesBing CM, Chamallas SN, Filibeck DJ, et al. Extended stability for Parenteral Drugs, 4th ed., Bethesda, MD: American Society of Health-System Pharmacists. 2009;
    ReferencesHennere G, Havard L, Bonan B, et al. Stability of cidofovir in extemporaneously prepared syringes. Am J Health-Syst Pharm. 2005; 62
    ReferencesYuan LC, Samuels GJ, Visor GC. Stability of cidofovir in 0.9% sodium chloride injection and in 5% dextrose injection. Am J Health-Syst Pharm. 1996; 53
    Light Exposure
    No unacceptable adverse effect on drug concentration due to normal fluorescent light exposure was observed in a stability study of cidofovir in infusion solutions.
    ReferencesYuan LC, Samuels GJ, Visor GC. Stability of cidofovir in 0.9% sodium chloride injection and in 5% dextrose injection. Am J Health-Syst Pharm. 1996; 53
    Freezing
    The manufacturer indicates that freezing should not be used to extend the stability of cidofovir admixtures in sodium chloride 0.9% beyond the recommended 24 hours. However, Ennis and Dahl reported that cidofovir 0.2 and 8.2 mg/mL in sodium chloride 0.9% in polyvinyl chloride (PVC) and in polyethylene/polypropylene (polyolefin) containers was physically and chemically stable for 5 days frozen at -20 degree C. Stiles et al. evaluated in vitro the antiviral activity of cidofovir 0.5% in sodium chloride 0.9% packaged in glass and plastic vials for use as a veterinary ophthalmic solution. Samples were stored at 4, -20, and -80degree C for 180 days. The antiviral activity against feline herpes virus (FHV-1) was tested after storage for 30, 60, 120, and 180 days. The antiviral activity was found to be unchanged at any point during the 6-month test period.
    ReferencesAnon. Manufacturer's information and labeling. (Package insert).
    ReferencesEnnis RD, Dahl TC. Stability of cidofovir in 0.9% sodium chloride injection for five days. Am J Health-Syst Pharm. 1997; 54
    ReferencesStiles J, Gwin W, Pogranichniy R. Stability of 0.5% cidofovir stored under various conditions for up to 6 months. Vet Ophthalmol. 2010; 13
    Sorption Leaching
    The manufacturer indicates that cidofovir is compatible with glass, polyvinyl chloride (PVC), and ethylene/propylene copolymer (polyolefin) containers. Yuan et al. and Ennis and Dahl reported no loss of cidofovir due to sorption to PVC containers and administration sets and ethylene/propylene copolymer (polyolefin) containers.
    ReferencesAnon. Manufacturer's information and labeling. (Package insert).
    ReferencesEnnis RD, Dahl TC. Stability of cidofovir in 0.9% sodium chloride injection for five days. Am J Health-Syst Pharm. 1997; 54
    ReferencesYuan LC, Samuels GJ, Visor GC. Stability of cidofovir in 0.9% sodium chloride injection and in 5% dextrose injection. Am J Health-Syst Pharm. 1996; 53
    Other Information
    Cidofovir is cited by NIOSH as a drug that should be handled as hazardous.
    ReferencesAnon. Preventing occupational exposure to antineoplastic and other hazardous drugs in health care settings. NIOSH Publication No. 2004-165. 2004; 165
    Stability Max
    Maximum reported stability periods: In D5W- 24 hours at room temperature and refrigerated. In NS- 150 days at room temperature and refrigerated.
    ReferencesAnon. Manufacturer's information and labeling. (Package insert).
    ReferencesHennere G, Havard L, Bonan B, et al. Stability of cidofovir in extemporaneously prepared syringes. Am J Health-Syst Pharm. 2005; 62
      Revision Date: 10/20/2024, 07:31:23 PMCopyright 2004-2024 by Lawrence A. Trissel. All Rights Reserved.

      References

      26495 - Hoffman JA, Shah AJ, Ross LA, et al. Adenoviral infections and a prospective trial of cidofovir in pediatric hematopoietic stem cell transplantation. Biol Blood Marrow Transplant 2001;7:388-394.28388 - Cidofovir injection solution package insert. Morgantown, WV: Mylan Institutional LLC; 2021 Apr.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/NIOSHPUB201616167325 - Bhadri VA, Lee-Horn L, Shaw PJ, et al. Safety and tolerability of cidofovir in high-risk pediatric patients. Transpl Infect Dis 2009;11:373-379.67326 - Cesaro S, Zhou X, Manzardo C, et al. Cidofovir for cytomegalovirus reactivation in pediatric patients after hematopoietic stem cell transplantation. J Clin Virol 2005;34:129-132.67327 - Permpalung N, Mahoney MV, Alonso CD. Adjunctive use of cidofovir and intravenous immunoglobulin to treat invasive adenoviral disease in solid organ transplant recipients. Pharmacotherapy 2018;38:1260-1266.67329 - Williams KM, Agwu AL, Dabb AA, et al. A clinical algorithm identifies high risk pediatric oncology and bone marrow transplant patients likely to benefit from treatment of adenoviral infection. J Pediatr Hematol Oncol 2009;31:825-831.67330 - Doan ML, Mallory GB, Kaplan SL, et al. Treatment of adenovirus pneumonia with cidofovir in pediatric lung transplant recipients. J Heart Lung Transplant 2007;26:883-889.67333 - Anderson EJ, Guzman-Cottrill JA, Kletzel M, et al. High-risk adenovirus-infected pediatric allogeneic hematopoietic progenitor cell transplant recipients and preemptive cidofovir therapy. Pediatr Transplant 2008;12:219-227.67506 - American Society of Health-System Pharmacists. ASHP guidelines on handling hazardous drugs. Am J Health-Syst Pharm. 2018; 75:1996-2031.67507 - NIOSH [2016]. NIOSH Alert: Preventing Occupational Exposures to Antineoplastics and Other Hazardous Drugs in Health Care Settings. U.S. Department of Health and Human Services, Public Health Service, Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health, DHHS (NIOSH) Publication No. 2016-161.70821 - American Academy of Pediatrics. Red Book: 2024-2027 Report of the Committee on Infectious Diseases. 33rd ed. Elk Grove Village, IL: American Academy of Pediatrics; 2024.

      Adverse Reactions

      Mild

      • abdominal pain
      • acne vulgaris
      • agitation
      • alopecia
      • anorexia
      • anxiety
      • arthralgia
      • asthenia
      • back pain
      • chills
      • cough
      • dental caries
      • diarrhea
      • diplopia
      • dizziness
      • drowsiness
      • dysgeusia
      • dyspepsia
      • epistaxis
      • fever
      • flatulence
      • gingivitis
      • headache
      • hiccups
      • hyperventilation
      • hypothermia
      • infection
      • injection site reaction
      • insomnia
      • leukocytosis
      • libido increase
      • malaise
      • miosis
      • muscle cramps
      • myalgia
      • nausea
      • nocturia
      • ocular hypotonia
      • ocular pain
      • otalgia
      • pallor
      • paresthesias
      • pharyngitis
      • photosensitivity
      • polyuria
      • pruritus
      • rash
      • rhinitis
      • seborrhea
      • sinusitis
      • skin discoloration
      • syncope
      • tinnitus
      • tongue discoloration
      • tremor
      • urticaria
      • vertigo
      • vomiting
      • weight gain
      • weight loss
      • xerophthalmia
      • xerostomia

      Moderate

      • amblyopia
      • amnesia
      • anemia
      • ataxia
      • bone pain
      • candidiasis
      • cataracts
      • chest pain (unspecified)
      • cholangitis
      • colitis
      • confusion
      • conjunctivitis
      • constipation
      • dehydration
      • delirium
      • depression
      • dysphagia
      • dyspnea
      • dysuria
      • edema
      • elevated hepatic enzymes
      • encephalopathy
      • esophagitis
      • fecal incontinence
      • furunculosis
      • gastritis
      • glycosuria
      • hallucinations
      • hematuria
      • hemoptysis
      • hepatitis
      • hepatomegaly
      • hyperacusis
      • hypercalcemia
      • hyperesthesia
      • hyperglycemia
      • hyperlipidemia
      • hypertension
      • hypertonia
      • hypocalcemia
      • hypoglycemia
      • hypokalemia
      • hypomagnesemia
      • hyponatremia
      • hypophosphatemia
      • hypotension
      • hypotonia
      • hypoxia
      • infertility
      • iritis
      • jaundice
      • leukopenia
      • lymphadenopathy
      • melena
      • metabolic acidosis
      • migraine
      • myasthenia
      • myoclonia
      • nephrolithiasis
      • neutropenia
      • oral ulceration
      • orthostatic hypotension
      • peripheral edema
      • peripheral neuropathy
      • peripheral vasodilation
      • phlebitis
      • phosphaturia
      • proctitis
      • sinus tachycardia
      • skin ulcer
      • splenomegaly
      • stomatitis
      • thrombocytopenia
      • urinary incontinence
      • urinary retention

      Severe

      • angioedema
      • bone fractures
      • cardiomyopathy
      • corneal opacification
      • exfoliative dermatitis
      • Fanconi syndrome
      • GI bleeding
      • hearing loss
      • heart failure
      • hepatic necrosis
      • hyperkalemia
      • keratitis
      • laryngeal edema
      • nephrotoxicity
      • new primary malignancy
      • ocular hypotonia
      • osteonecrosis
      • pancreatitis
      • pancytopenia
      • pneumothorax
      • proteinuria
      • renal failure (unspecified)
      • renal tubular necrosis
      • retinal detachment
      • seizures
      • teratogenesis
      • thrombotic thrombocytopenic purpura
      • uveitis
      • visual impairment

      The dose-limiting adverse reaction of intravenous cidofovir is dose-dependent nephrotoxicity (i.e., renal tubular necrosis or proximal tubule cell injury). Acute renal failure (unspecified) resulting in dialysis or contributing to death has occurred with as few as 1 or 2 doses. Renal toxicity developed in 59% of patients receiving 5 mg/kg IV every other week and presented as more than 1+ proteinuria, serum creatinine (Scr) elevations 0.4 mg/dL or more, and decreased creatinine clearance to less than 55 mL/min. Maintenance dose reductions from 5 mg/kg to 3 mg/kg were required in 26 to 29% of patients. Renal tubular damage resulting in renal wasting syndrome and decreased serum bicarbonate leading to metabolic acidosis and Fanconi syndrome have also been noted. During clinical trials, decreases in serum bicarbonate to 16 mEq/L or less were observed in 16% of patients. Fanconi syndrome, reported in 1% of recipients, can present as glycosuria, bicarbonaturia, phosphaturia, hypophosphatemia, hypouricemia, elevated Scr, and acute renal failure. Fatal cases of metabolic acidosis in association with liver dysfunction and pancreatitis have also been reported. Other urogenital adverse events occurring in cidofovir-treated patients during clinical trials included proteinuria (50% to 88%), elevated Scr (12% to 24%), dysuria, glycosuria, hematuria, nephrolithiasis or kidney stones, nocturia, polyuria, prostatic disorders, toxic nephropathy, urethritis, urinary incontinence, and urinary retention. In an effort to reduce the potential for nephrotoxicity, intravenous prehydration with normal saline and concurrent administration of probenecid are recommended with each cidofovir infusion. Additionally, healthcare providers are advised to monitor serum creatinine and urine protein concentrations within 48 hours of each dose. Dose adjustment may need to be made based on changes in the patients renal function. Do not administer cidofovir with other nephrotoxic medications.[28388]

      Neutropenia defined as 500 cells/mm3 or less and less than 750 cells/mm3 occurred in 24% and 43%, respectively, of patients receiving cidofovir infusions during clinical trials. Additionally, granulocyte colony stimulating factors (G-CSF) were used in 39% of cidofovir treated patients. Healthcare providers are advised to monitor neutrophil counts in patients during therapy. Other hematologic and lymphatic adverse events observed during clinical trials include anemia (24%), hypochromic anemia, leukocytosis, leukopenia, lymphadenopathy, lymphoma-like reactions, pancytopenia, splenomegaly, thrombocytopenia, and thrombotic thrombocytopenic purpura (TTP).[28388]

      Ocular hypotonia, or a 50% or greater decrease from baseline in intraocular pressure, was reported in 24% of 70 patients studied during cidofovir clinical trials. Additionally, 3 patients (4%) experienced severe hypotony, defined as an intraocular pressure of 0 to 1 mm Hg. The risk of ocular hypotony may be increased in patients with preexisting diabetes mellitus. Iritis and uveitis were reported in 15 of 135 (11%) patients during clinical trials and during the postmarketing period. Patients who experienced iritis were more likely to have been previously treated for CMV retinitis, to be diabetic, or to be receiving protease inhibitors. The onset of iritis occurred after an average of 4.9 +/- 1.8 days after the first dose.[24859] Many patients who developed anterior uveitis were able to continue therapy while receiving concomitant topical corticosteroids with or without cycloplegic therapy. Healthcare providers are advised to monitor intraocular pressure and for signs and symptoms of uveitis and iritis during treatment. Other ocular adverse events observed during clinical trials include visual impairment, amblyopia, blindness, cataracts, conjunctivitis, corneal lesion, corneal opacification, diplopia, xerophthalmia, ocular pain, keratitis, miosis, refraction disorder, retinal detachment, visual field defect, and decreased visual acuity.[28388]

      During clinical trials, a variety of gastrointestinal (GI) adverse events were experienced by recipients of cidofovir, including nausea (7% to 69%), vomiting (7% to 69%), diarrhea (26%), anorexia (23%), cachexia, abdominal pain, colitis, constipation, esophagitis, dyspepsia, dysphagia, dysgeusia, fecal incontinence, flatulence, gastritis, GI bleeding, gingivitis, melena, proctitis, stomatitis, tongue discoloration, oral ulceration, dental caries, dehydration, thirst, weight gain, weight loss, and xerostomia.[28388]

      Cases of infection were reported by 12% to 28% of cidofovir recipients during clinical trials. Specific infection sites or types included bronchitis, pharyngitis, pneumonia (9%), rhinitis, sinusitis, otitis media, otitis externa, oral candidiasis or moniliasis (18%), cholangitis, cellulitis, mastitis, urinary tract infection, herpes simplex, cryptococcosis, flu-like symptoms, and sepsis. Adverse events potentially associated with infection and reported by cidofovir-treated patients included fever (14% to 58%), chills (22%), increased cough (19%), increased sputum, dyspnea (8% to 23%), and urinary casts.[28388]

      The 2 most commonly reported cidofovir-associated dermatologic adverse reactions during clinical trials were rash (30%) and alopecia (27%). Other dermatologic adverse events included injection site reaction, photosensitivity, acne vulgaris, cyst, eczema, exfoliative dermatitis, furunculosis, nail disorder, pruritus, seborrhea, skin discoloration, skin hypertrophy, skin ulcer, sweating, urticaria, and xeroderma.[28388]

      Cidofovir therapy has been associated with hearing loss, with or without tinnitus, otalgia, and hyperacusis.[28388]

      Patients receiving cidofovir treatment during clinical trials experienced neurologic adverse events. The most commonly reported neurologic adverse events included asthenia (43%) and headache (30%). Other reported adverse reactions include malaise, migraine, abnormal dreams, acute brain syndrome, agitation, amnesia, anxiety, nervousness, confusion, cerebrovascular disorder, seizures and tremor, myoclonia, twitching, ataxia or abnormal gait, incoordination, facial paralysis, hemiplegia, delirium, dementia, depression, dizziness, drug dependence, encephalopathy, hallucinations, libido increase, insomnia, peripheral neuropathy, paresthesias, hyperesthesia, drowsiness, speech disorder, personality disorder, and vertigo.[28388]

      Musculoskeletal adverse events reported by cidofovir recipients during clinical trials include back pain, neck pain, arthralgia, arthrosis, osteonecrosis, bone fractures, bone pain, leg muscle cramps, myalgia, myasthenia, hypertonia, and hypotonia.[28388]

      Patients treated with cidofovir during clinical trials experienced cardiovascular adverse events including chest pain (unspecified), cardiomyopathy, heart failure, hypertension, hypotension, orthostatic hypotension with syncope, pallor, phlebitis, cardiogenic shock, sinus tachycardia, edema, facial edema, peripheral edema, and peripheral vasodilation.[28388]

      Cases of hepatitis, hepatomegaly, hepatic necrosis, jaundice, and elevated hepatic enzymes have been observed in patients receiving cidofovir during clinical trials.[28388]

      Metabolic adverse events that have occurred in patients receiving treatment with cidofovir during clinical trials include hypercalcemia, hypocalcemia, hyperglycemia, hypoglycemia, hyperkalemia, hypokalemia, hyperlipidemia, hypomagnesemia, hyponatremia, hypoproteinemia, increased alkaline phosphatase, and increased lactic dehydrogenase.[28388]

      Respiratory adverse events occurring in recipients of cidofovir during clinical trials include respiratory alkalosis, asthma, epistaxis, hemoptysis, hiccups, hyperventilation, hypoxia, laryngeal edema, and pneumothorax.[28388]

      Cidofovir has been associated with teratogenesis in animal studies involving rats and rabbits; therefore, women of childbearing age should use effective contraception during and for 1 month following treatment. Men should be advised to practice barrier contraception during and for 3 months after treatment. Men should also be informed that cidofovir has caused reduced testes weight and hypospermia in animal. This finding may correlate to human male infertility.[28388]

      Adverse events not discussed elsewhere in this monograph and observed in cidofovir recipients during clinical trials include allergic reactions, angioedema, hypothermia, adrenal cortex insufficiency, and accidental injury.[28388]

      Cidofovir has the potential to be a carcinogen in humans and may cause a new primary malignancy. In animal studies, mammary adenocarcinomas in rates were noted.[28388]

      Revision Date: 10/20/2024, 07:31:23 PM

      References

      24859 - Davis JL, et al. Iritis and hypotony after treatment with intravenous cidofovir for cytomegalovirus retinitis. Arch Ophthal 1997;115:733-7.28388 - Cidofovir injection solution package insert. Morgantown, WV: Mylan Institutional LLC; 2021 Apr.

      Contraindications/Precautions

      Absolute contraindications are italicized.

      • ocular exposure
      • probenecid hypersensitivity
      • proteinuria
      • renal disease
      • renal failure
      • renal impairment
      • sulfonamide hypersensitivity
      • accidental exposure
      • breast-feeding
      • children
      • contraception requirements
      • dehydration
      • diabetes mellitus
      • diarrhea
      • females
      • foscarnet therapy
      • geriatric
      • infertility
      • male-mediated teratogenicity
      • nephrotoxicity
      • neutropenia
      • new primary malignancy
      • pregnancy
      • reproductive risk

      Cidofovir is only indicated for treatment of cytomegalovirus (CMV) retinitis in patients with acquired immunodeficiency syndrome (AIDS). The safe and effective use of cidofovir for treatment of other CMV infections (e.g., gastroenteritis or pneumonitis), congenital or neonatal CMV disease, or CMV disease in non-HIV-infected persons has not been established.

      According to the manufacturer, cidofovir is contraindicated in patients with a known, severe probenecid hypersensitivity, sulfonamide hypersensitivity, or hypersensitivity to other sulfa-containing medications.[28388] Probenecid contains a sulfonamide side chain but does not contain the N4 aromatic amine or the N1-substituent present in sulfonamide antibiotics and thought to be responsible for hypersensitivity-type adverse reactions. The risk of cross-sensitivity in patients taking a nonantibiotic sulfonamide that have a history of sulfonamide hypersensitivity is low and has been confirmed by recent observational studies.[32380] [32382] [32912] In general, patients with a history of hypersensitivity to any drug are predisposed to subsequent hypersensitivity reactions to other drugs.[32382] Because of this, patients with a history of sulfonamide hypersensitivity should be monitored for hypersensitivity reactions to other drugs, including cidofovir; however, treatment with a nonantibiotic sulfonamide may not need to be withheld in patients with a sulfonamide allergy as long as patients are monitored appropriately, especially if alternative therapies are not available.[32381]

      Cidofovir therapy is contraindicated in patients with baseline renal disease, renal impairment, or renal failure defined as a serum creatinine concentration greater than 1.5 mg/dL or calculated creatinine clearance 55 mL/min or less and in those who have at least 2+ proteinuria (urine protein 100 mg/dL or greater). Due to dose-dependent nephrotoxicity, renal function, including serum creatinine and urine protein, must be monitored within 48 hours of each dose of cidofovir and the dose of cidofovir modified for changes in renal function as appropriate. Proteinuria may be an early indication of nephrotoxicity. Intravenous normal saline and probenecid therapy must be given concurrently with cidofovir. In clinical trials, very high concentrations of cidofovir were found in the kidneys, and the transport into proximal tubular cells was faster than efflux into the urine, suggesting active tubular secretion. A high concentration of cidofovir in the kidney is believed to be directly related to renal toxicity, but the actual mechanism is unknown. Probenecid is used to antagonize the active tubular secretion of cidofovir in the proximal tubules. Prior foscarnet therapy has been associated with an increased risk of nephrotoxicity; these patients should be closely monitored. Cidofovir use is contraindicated in patients who are receiving agents with nephrotoxic potential. At least 7 days should pass following the administration of agents with nephrotoxic potential prior to the initiation of therapy with cidofovir. These nephrotoxic drugs include amphotericin B, foscarnet, IV pentamidine, IV aminoglycosides, vancomycin, and NSAIDs.[28388]

      Cidofovir therapy has been associated with neutropenia. Therefore, neutrophil counts should be monitored during cidofovir therapy.[28388]

      Dehydration should be avoided prior to and during cidofovir therapy. Adequate hydration is necessary in patients receiving cidofovir in order to prevent potential nephrotoxicity. Intravenous prehydration with at least 1 liter of normal saline should be administered prior to each infusion of cidofovir, with additional IV normal saline administered during or after each infusion when tolerated. Special attention should be given to repletion of fluids in patients with chronic diarrhea or AIDS-related wasting because they may have intravascular volume depletion.[28388]

      Direct ocular exposure of cidofovir should be avoided and intraocular administration is contraindicated. Direct injection has been associated with iritis, ocular hypotony and permanent vision impairment. Iritis is more likely to occur in patients previously treated for CMV retinitis, those having diabetes mellitus, or receiving protease inhibitors. Patients should be monitored for the development of iritis and uveitis during cidofovir therapy.[24859] In addition, intraocular pressures should be monitored during cidofovir therapy as decreases in intraocular pressure associated with decreases in visual acuity have been reported.

      Although there are no adequate and well-controlled studies in pregnant women, cidofovir was embryotoxic and teratogenic in animal studies. Cidofovir was embryotoxic (reduced fetal body weights) in rats at 1.5 mg/kg/day and in rabbits at 1 mg/kg/day, doses which were also maternally toxic, following daily intravenous dosing during the period of organogenesis. The no-observable-effect levels for embryotoxicity in rats (0.5 mg/kg/day) and in rabbits (0.25 mg/kg/day) were approximately 0.04 and 0.05 times the clinical dose (5 mg/kg every other week) based on AUC, respectively. An increased incidence of fetal external, soft tissue, and skeletal anomalies (meningocele, short snout, and short maxillary bones) occurred in rabbits at the high dose (1 mg/kg/day) which was also maternally toxic. Cidofovir should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.[28388]

      The manufacturer warns of potential male-mediated teratogenicity as cidofovir causes reduced testes weight and hypospermia in animals. These effects may also occur in humans. Men should also be warned about the potential for infertility. Men should practice barrier contraceptive methods during and for 3 months after treatment with cidofovir.[28388]

      It is not known if cidofovir is excreted in human milk; however, use during breast-feeding is not recommended because of its potential for carcinogenic and other adverse effects in the infant. Additionally, cidofovir may be used to treat infections in patients with HIV and the Centers for Disease Control and Prevention (CDC) recommends that in the US, HIV-infected mothers not breast-feed their infants to avoid the risk of postnatal transmission of HIV. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a drug administered to the mother, health care providers are encouraged to report the adverse effect to the FDA.[28388] [46675]

      The manufacturer considers cidofovir to be a potential carcinogen in humans and may cause a new primary malignancy. In animal studies, mammary adenocarcinomas in rats was noted. Women should be warned about the carcinogenic potential of cidofovir and of the limited study of cidofovir in females. Women of childbearing potential should use effective contraception during and for 1 month after treatment with cidofovir. Cidofovir should be used cautiously in children in light of the risk of long-term carcinogenesis and reproductive toxicity.[28388]

      The safety and efficacy of cidofovir in patients older than 60 years has not been studied. Since geriatric patients commonly have reduced glomerular filtration, attention should be paid to renal function before and during therapy.[28388]

      Due to the mutagenic properties of cidofovir, healthcare personnel should take precautions to avoid accidental exposure to cidofovir. The National Institutes of Health (NIH) recommends cidofovir be prepared in a Class II laminar flow biologic safety cabinet and that personnel preparing the drug wear protective gloves and gowns. If cutaneous exposure occurs, wash and flush thoroughly with water. Excess cidofovir solution and all other materials used in the preparation and administration of this agent should be placed in a leak-proof, puncture-proof container.[28388]

      Based on data from animals, cidofovir may be associated with reproductive risk. Discuss contraception requirements with the patient. Advise females of reproductive potential to use effective contraception during treatment and for at least 1 month after the last dose. Men are advised to use condoms during treatment and for at least 3 months after the last dose.[28388]

      Revision Date: 10/20/2024, 07:31:23 PM

      References

      24859 - Davis JL, et al. Iritis and hypotony after treatment with intravenous cidofovir for cytomegalovirus retinitis. Arch Ophthal 1997;115:733-7.28388 - Cidofovir injection solution package insert. Morgantown, WV: Mylan Institutional LLC; 2021 Apr.32380 - Verdel BM, Souverein PC, Egberts AC, et al. Difference in risks of allergic reaction to sulfonamide drugs based on chemical structure. Ann Pharmacother 2006;40:1040-6.32381 - Johnson KK, Green DL, Rife JP, et al. Sulfonamide cross-reactivity: fact or fiction? Ann Pharmacother 2005;39:290-301.32382 - Strom BL, Schinnar R, Apter AJ, et al. Absence of cross-reactivity between sulfonamide antibiotics and sulfonamide nonantibiotics. New Engl J Med 2003;349:1628-35.32912 - Hemstreet BA, Page RL. Sulfonamide allergies and outcomes related to use of potentially cross-reactive drugs in hospitalized patients. Pharmacotherapy 2006;26:551-7.46675 - Centers for Disease Control and Prevention: Breastfeeding recommendation for human immunodeficiency virus (HIV), and acquired immunodeficiency virus (AIDS). Retrieved November 9, 2011. Available on the World Wide Web at: http://www.cdc.gov/breastfeeding/disease/hiv.htm.

      Mechanism of Action

      Cidofovir has antiviral activity against a wide variety of DNA viruses, including cytomegalovirus (CMV) and herpesviruses. In infected cells, cidofovir inhibits viral DNA polymerase, which is responsible for replication of new viral RNA and DNA. Cidofovir is taken up intracellularly via active transport or fluid-phase endocytosis to exert its antiviral effects. Intracellularly, cidofovir is metabolized to its active diphosphate form. Cidofovir competes with deoxycytosinetriphospate (dCTP) for incorporation into viral DNA. Cidofovir is much more selective for viral DNA polymerase versus human DNA polymerase. Once two consecutive molecules of cidofovir are incorporated into the viral DNA chain, DNA production is halted. Incorporation of one cidofovir molecule slows DNA production by 31%. Viral DNA polymerase is unable to remove cidofovir diphosphate once it has been incorporated into viral DNA. The prolonged activity of cidofovir may be due to its ability to stop DNA production and the fact that viral DNA polymerase is unable to remove cidofovir diphosphate once incorporated. The mechanism of action of cidofovir in human papillomavirus (HPV) differs from CMV, since HPV utilizes host cell DNA polymerase versus viral polymerase. HPV-infected cells treated with cidofovir show cell cycle arrest in the S-phase indicating decreased DNA production. Cidofovir has also been shown to induce DNA fragmentation and Caspase-3 protease activity, which is important in the induction of apoptosis in HVP-positive cells. Cidofovir also has activity against cervical cancer cells infected with HPV. Cidofovir also inhibits ribonucleotide reductase; although, the clinical significance of this is not known.

       

      It has also been postulated that cidofovir can accumulate in healthy cells, establishing a reservoir of drug. If the cell is invaded by a susceptible virus, cidofovir can inhibit the infection by reducing the production of new viral DNA. There are insufficient data at this time to assess the frequency and significance of resistance to cidofovir therapy following treatment in humans. Resistance to cidofovir, and cross-resistance between cidofovir, ganciclovir, and foscarnet has been observed in vitro.

      Revision Date: 10/20/2024, 07:31:23 PM

      References

      Pharmacokinetics

      Cidofovir is administered as an intravenous injection.

       

      Intracellularly, cidofovir is metabolized via pyrimidine nucleoside monophosphate kinase to cidofovir monophosphate and is then metabolized to the diphosphate analog. The diphosphate analog is further metabolized to cidofovir monophosphate-choline. The mean elimination half-lives of the monophosphate, diphosphate, and choline metabolites are 6, 17, and > 48 hours, respectively. The choline metabolite may serve as an intracellular reservoir of cidofovir diphosphate, the active form. Cellular protection from infection with herpes simplex virus and CMV has been documented in vitro for up to 7 days following treatment with cidofovir.

       

      Renal clearance is significantly higher than baseline creatinine clearance, suggesting that tubular secretion plays a large role in the clearance of cidofovir. At therapeutic doses of cidofovir, probenecid reduces tubular secretion so that the clearance of cidofovir is closer in magnitude to creatinine clearance. However, there is no significant change in cidofovir half-life. The administration of probenecid also results in an increase in cidofovir maximum concentration as compared to cidofovir alone.[25906]

      Route-Specific Pharmacokinetics

      Oral Route

      Due to low bioavailability (5—22%), cidofovir is not administered orally.

      Intravenous Route

      Following intravenous administration, cidofovir distributes in total body water. Serum concentrations are proportional to dose and decline biexponentially. The plasma elimination half-life is 2.6 hours (+/- 1.2 hours).

      Special Populations

      Renal Impairment

      Cidofovir clearance decreases proportionally with creatinine clearance; cidofovir is poorly eliminated in patients with a creatinine clearance <= 55 mL/min. High flux hemodialysis has been shown to reduce the serum levels of cidofovir by approximately 75%.

      Revision Date: 10/20/2024, 07:31:23 PM

      References

      25906 - Cundy KC, Petty BG, Flaherty J, et al. Clinical pharmacokinetics of cidofovir in human immunodeficiency virus-infected patients. Antimicrob Agents Chemother 1995;39;1247-1252.

      Pregnancy/Breast-feeding

      pregnancy

      Although there are no adequate and well-controlled studies in pregnant women, cidofovir was embryotoxic and teratogenic in animal studies. Cidofovir was embryotoxic (reduced fetal body weights) in rats at 1.5 mg/kg/day and in rabbits at 1 mg/kg/day, doses which were also maternally toxic, following daily intravenous dosing during the period of organogenesis. The no-observable-effect levels for embryotoxicity in rats (0.5 mg/kg/day) and in rabbits (0.25 mg/kg/day) were approximately 0.04 and 0.05 times the clinical dose (5 mg/kg every other week) based on AUC, respectively. An increased incidence of fetal external, soft tissue, and skeletal anomalies (meningocele, short snout, and short maxillary bones) occurred in rabbits at the high dose (1 mg/kg/day) which was also maternally toxic. Cidofovir should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.[28388]

      breast-feeding

      It is not known if cidofovir is excreted in human milk; however, use during breast-feeding is not recommended because of its potential for carcinogenic and other adverse effects in the infant. Additionally, cidofovir may be used to treat infections in patients with HIV and the Centers for Disease Control and Prevention (CDC) recommends that in the US, HIV-infected mothers not breast-feed their infants to avoid the risk of postnatal transmission of HIV. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a drug administered to the mother, health care providers are encouraged to report the adverse effect to the FDA.[28388] [46675]

      Revision Date: 10/20/2024, 07:31:23 PM

      References

      28388 - Cidofovir injection solution package insert. Morgantown, WV: Mylan Institutional LLC; 2021 Apr.46675 - Centers for Disease Control and Prevention: Breastfeeding recommendation for human immunodeficiency virus (HIV), and acquired immunodeficiency virus (AIDS). Retrieved November 9, 2011. Available on the World Wide Web at: http://www.cdc.gov/breastfeeding/disease/hiv.htm.

      Interactions

      Level 1 (Severe)

      • Acetaminophen; Aspirin
      • Acetaminophen; Aspirin, ASA; Caffeine
      • Acetaminophen; Aspirin; Diphenhydramine
      • Acetaminophen; Ibuprofen
      • Acyclovir
      • Adefovir
      • Aldesleukin, IL-2
      • Aliskiren; Hydrochlorothiazide, HCTZ
      • Amikacin
      • Amiloride
      • Amiloride; Hydrochlorothiazide, HCTZ
      • Aminoglycosides
      • Amlodipine; Celecoxib
      • Amlodipine; Valsartan; Hydrochlorothiazide, HCTZ
      • Amphotericin B
      • Amphotericin B lipid complex (ABLC)
      • Amphotericin B liposomal (LAmB)
      • Aspirin, ASA
      • Aspirin, ASA; Butalbital; Caffeine
      • Aspirin, ASA; Caffeine
      • Aspirin, ASA; Caffeine; Orphenadrine
      • Aspirin, ASA; Carisoprodol; Codeine
      • Aspirin, ASA; Citric Acid; Sodium Bicarbonate
      • Aspirin, ASA; Dipyridamole
      • Aspirin, ASA; Omeprazole
      • Aspirin, ASA; Oxycodone
      • Atenolol; Chlorthalidone
      • Azilsartan; Chlorthalidone
      • Bacitracin
      • Benazepril; Hydrochlorothiazide, HCTZ
      • Bisoprolol; Hydrochlorothiazide, HCTZ
      • Brincidofovir
      • Bumetanide
      • Bupivacaine; Meloxicam
      • Butalbital; Aspirin; Caffeine; Codeine
      • Candesartan; Hydrochlorothiazide, HCTZ
      • Captopril; Hydrochlorothiazide, HCTZ
      • Celecoxib
      • Celecoxib; Tramadol
      • Chlorothiazide
      • Chlorpheniramine; Ibuprofen; Pseudoephedrine
      • Chlorthalidone
      • Clindamycin
      • Clofarabine
      • Cyclosporine
      • Diclofenac
      • Diclofenac; Misoprostol
      • Diflunisal
      • Diphenhydramine; Ibuprofen
      • Diphenhydramine; Naproxen
      • Diuretics
      • Enalapril; Hydrochlorothiazide, HCTZ
      • Eprosartan; Hydrochlorothiazide, HCTZ
      • Ethacrynic Acid
      • Etodolac
      • Fenoprofen
      • Flurbiprofen
      • Foscarnet
      • Fosinopril; Hydrochlorothiazide, HCTZ
      • Furosemide
      • Ganciclovir
      • Gentamicin
      • Hydrochlorothiazide, HCTZ
      • Hydrochlorothiazide, HCTZ; Moexipril
      • Hydrocodone; Ibuprofen
      • Ibuprofen
      • Ibuprofen; Famotidine
      • Ibuprofen; Oxycodone
      • Ibuprofen; Pseudoephedrine
      • Indapamide
      • Indomethacin
      • Irbesartan; Hydrochlorothiazide, HCTZ
      • Ketoprofen
      • Ketorolac
      • Lisinopril; Hydrochlorothiazide, HCTZ
      • Losartan; Hydrochlorothiazide, HCTZ
      • Meclofenamate Sodium
      • Mefenamic Acid
      • Meloxicam
      • Methenamine; Sodium Salicylate
      • Metolazone
      • Metoprolol; Hydrochlorothiazide, HCTZ
      • Nabumetone
      • Naproxen
      • Naproxen; Esomeprazole
      • Naproxen; Pseudoephedrine
      • Nonsteroidal antiinflammatory drugs
      • Olmesartan; Amlodipine; Hydrochlorothiazide, HCTZ
      • Olmesartan; Hydrochlorothiazide, HCTZ
      • Oxaprozin
      • Pamidronate
      • Paromomycin
      • Pentamidine
      • Piroxicam
      • Plazomicin
      • Quinapril; Hydrochlorothiazide, HCTZ
      • Salsalate
      • Spironolactone
      • Spironolactone; Hydrochlorothiazide, HCTZ
      • Streptomycin
      • Sulindac
      • Sumatriptan; Naproxen
      • Tacrolimus
      • Telavancin
      • Telmisartan; Hydrochlorothiazide, HCTZ
      • Tobramycin
      • Tolmetin
      • Torsemide
      • Triamterene
      • Triamterene; Hydrochlorothiazide, HCTZ
      • Valacyclovir
      • Valsartan; Hydrochlorothiazide, HCTZ
      • Vancomycin
      • Voclosporin
      • Zoledronic Acid

      Level 2 (Major)

      • Abacavir; Lamivudine, 3TC; Zidovudine, ZDV
      • Bismuth Subsalicylate
      • Bismuth Subsalicylate; Metronidazole; Tetracycline
      • Capreomycin
      • Choline Salicylate; Magnesium Salicylate
      • Cisplatin
      • Colistimethate, Colistin, Polymyxin E
      • Colistin
      • Dichlorphenamide
      • Lamivudine, 3TC; Zidovudine, ZDV
      • Magnesium Salicylate
      • Mannitol
      • Methotrexate
      • Oxaliplatin
      • Talimogene Laherparepvec
      • Zidovudine, ZDV

      Level 3 (Moderate)

      • Aprotinin
      • Atazanavir
      • Atazanavir; Cobicistat
      • Bictegravir; Emtricitabine; Tenofovir Alafenamide
      • Darunavir
      • Darunavir; Cobicistat
      • Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide
      • Doravirine; Lamivudine; Tenofovir disoproxil fumarate
      • Efavirenz; Emtricitabine; Tenofovir Disoproxil Fumarate
      • Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate
      • Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide
      • Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate
      • Emtricitabine
      • Emtricitabine; Rilpivirine; Tenofovir alafenamide
      • Emtricitabine; Rilpivirine; Tenofovir Disoproxil Fumarate
      • Emtricitabine; Tenofovir alafenamide
      • Emtricitabine; Tenofovir Disoproxil Fumarate
      • Entecavir
      • Fosamprenavir
      • Hyaluronidase, Recombinant; Immune Globulin
      • Immune Globulin IV, IVIG, IGIV
      • Indinavir
      • Inotersen
      • Lamivudine; Tenofovir Disoproxil Fumarate
      • Lopinavir; Ritonavir
      • Maraviroc
      • Nelfinavir
      • Nirmatrelvir; Ritonavir
      • Nitisinone
      • Protease inhibitors
      • Ritonavir
      • Saquinavir
      • Tenofovir Alafenamide
      • Tenofovir Alafenamide
      • Tenofovir Disoproxil Fumarate
      • Tipranavir

      Level 4 (Minor)

      • Cabozantinib
      • Probenecid
      • Probenecid; Colchicine
      Abacavir; lamiVUDine, 3TC; Zidovudine, ZDV: (Major) Concomitant use of probenecid with zidovudine may produce substantially higher serum concentrations of zidovudine. Because cidofovir must be given concomitantly with probenecid, the manufacturer of cidofovir recommends that on the days of concomitant cidofovir and probenecid therapy, zidovudine should either be discontinued temporarily or the zidovudine dosage should be reduced by 50%. Limited data suggest that probenecid may inhibit glucuronidation and/or reduce renal excretion of zidovudine. [28388] Acetaminophen; Aspirin, ASA; Caffeine: (Contraindicated) The concomitant administration of cidofovir and NSAIDs, such as aspirin, is contraindicated due to the potential for increased nephrotoxicity. Aspirin should be discontinued 7 days prior to beginning cidofovir. [28388] Acetaminophen; Aspirin, ASA; Caffeine: (Contraindicated) The concomitant administration of cidofovir and NSAIDs, such as aspirin, is contraindicated due to the potential for increased nephrotoxicity. Aspirin should be discontinued 7 days prior to beginning cidofovir. [28388] Acetaminophen; Aspirin: (Contraindicated) The concomitant administration of cidofovir and NSAIDs, such as aspirin, is contraindicated due to the potential for increased nephrotoxicity. Aspirin should be discontinued 7 days prior to beginning cidofovir. [28388] Acetaminophen; Aspirin; diphenhydrAMINE: (Contraindicated) The concomitant administration of cidofovir and NSAIDs, such as aspirin, is contraindicated due to the potential for increased nephrotoxicity. Aspirin should be discontinued 7 days prior to beginning cidofovir. [28388] Acetaminophen; Ibuprofen: (Contraindicated) The concomitant administration of cidofovir and nonsteroidal antiinflammatory drugs (NSAIDs) is contraindicated due to the potential for increased nephrotoxicity. NSAIDs should be discontinued 7 days prior to beginning cidofovir. [28388] Acyclovir: (Contraindicated) The administration of cidofovir with another potentially nephrotoxic agent, such as acyclovir, is contraindicated. Acyclovir should be discontinued at least 7 days prior to beginning cidofovir. [28388] Adefovir: (Contraindicated) The administration of cidofovir with another potentially nephrotoxic agent, such as adefovir, is contraindicated. Adefovir should be discontinued at least 7 days prior to beginning cidofovir. [28388] [28784] Aldesleukin, IL-2: (Contraindicated) Concomitant use of cidofovir and aldesleukin is contraindicated due to the increased risk of nephrotoxicity. [28388] [41853] Aliskiren; hydroCHLOROthiazide, HCTZ: (Contraindicated) The administration of cidofovir with another potentially nephrotoxic agent, such as diuretics, is contraindicated. Diuretics should be discontinued at least 7 days prior to beginning cidofovir. [28388] Amikacin: (Contraindicated) The administration of cidofovir with other potentially nephrotoxic agents, such as aminoglycosides, is contraindicated. These agents should be discontinued at least 7 days prior to beginning cidofovir. [5118] aMILoride: (Contraindicated) The administration of cidofovir with another potentially nephrotoxic agent, such as diuretics, is contraindicated. Diuretics should be discontinued at least 7 days prior to beginning cidofovir. [28388] aMILoride; hydroCHLOROthiazide, HCTZ: (Contraindicated) The administration of cidofovir with another potentially nephrotoxic agent, such as diuretics, is contraindicated. Diuretics should be discontinued at least 7 days prior to beginning cidofovir. [28388] Aminoglycosides: (Contraindicated) The administration of cidofovir with other potentially nephrotoxic agents, such as aminoglycosides, is contraindicated. These agents should be discontinued at least 7 days prior to beginning cidofovir. [5118] amLODIPine; Celecoxib: (Contraindicated) The concomitant administration of cidofovir and nonsteroidal antiinflammatory drugs (NSAIDs) is contraindicated due to the potential for increased nephrotoxicity. NSAIDs should be discontinued 7 days prior to beginning cidofovir. [28388] amLODIPine; Valsartan; hydroCHLOROthiazide, HCTZ: (Contraindicated) The administration of cidofovir with another potentially nephrotoxic agent, such as diuretics, is contraindicated. Diuretics should be discontinued at least 7 days prior to beginning cidofovir. [28388] Amphotericin B lipid complex (ABLC): (Contraindicated) The administration of cidofovir and other potentially nephrotoxic agents, such amphotericin B is contraindicated. Amphotericin B should be discontinued at least 7 days prior to beginning cidofovir. [35434] [5118] Amphotericin B liposomal (LAmB): (Contraindicated) The administration of cidofovir and other potentially nephrotoxic agents, such amphotericin B is contraindicated. Amphotericin B should be discontinued at least 7 days prior to beginning cidofovir. [35434] [5118] Amphotericin B: (Contraindicated) The administration of cidofovir and other potentially nephrotoxic agents, such amphotericin B is contraindicated. Amphotericin B should be discontinued at least 7 days prior to beginning cidofovir. [35434] [5118] Aprotinin: (Moderate) The manufacturer recommends using aprotinin cautiously in patients that are receiving drugs that can affect renal function, such as cidofovir, as the risk of renal impairment may be increased. [5118] [5204] Aspirin, ASA: (Contraindicated) The concomitant administration of cidofovir and NSAIDs, such as aspirin, is contraindicated due to the potential for increased nephrotoxicity. Aspirin should be discontinued 7 days prior to beginning cidofovir. [28388] Aspirin, ASA; Butalbital; Caffeine: (Contraindicated) The concomitant administration of cidofovir and NSAIDs, such as aspirin, is contraindicated due to the potential for increased nephrotoxicity. Aspirin should be discontinued 7 days prior to beginning cidofovir. [28388] Aspirin, ASA; Caffeine: (Contraindicated) The concomitant administration of cidofovir and NSAIDs, such as aspirin, is contraindicated due to the potential for increased nephrotoxicity. Aspirin should be discontinued 7 days prior to beginning cidofovir. [28388] Aspirin, ASA; Caffeine; Orphenadrine: (Contraindicated) The concomitant administration of cidofovir and NSAIDs, such as aspirin, is contraindicated due to the potential for increased nephrotoxicity. Aspirin should be discontinued 7 days prior to beginning cidofovir. [28388] Aspirin, ASA; Carisoprodol; Codeine: (Contraindicated) The concomitant administration of cidofovir and NSAIDs, such as aspirin, is contraindicated due to the potential for increased nephrotoxicity. Aspirin should be discontinued 7 days prior to beginning cidofovir. [28388] Aspirin, ASA; Citric Acid; Sodium Bicarbonate: (Contraindicated) The concomitant administration of cidofovir and NSAIDs, such as aspirin, is contraindicated due to the potential for increased nephrotoxicity. Aspirin should be discontinued 7 days prior to beginning cidofovir. [28388] Aspirin, ASA; Dipyridamole: (Contraindicated) The concomitant administration of cidofovir and NSAIDs, such as aspirin, is contraindicated due to the potential for increased nephrotoxicity. Aspirin should be discontinued 7 days prior to beginning cidofovir. [28388] Aspirin, ASA; Omeprazole: (Contraindicated) The concomitant administration of cidofovir and NSAIDs, such as aspirin, is contraindicated due to the potential for increased nephrotoxicity. Aspirin should be discontinued 7 days prior to beginning cidofovir. [28388] Aspirin, ASA; oxyCODONE: (Contraindicated) The concomitant administration of cidofovir and NSAIDs, such as aspirin, is contraindicated due to the potential for increased nephrotoxicity. Aspirin should be discontinued 7 days prior to beginning cidofovir. [28388] Atazanavir: (Moderate) Additive adverse effects may be seen when cidofovir is given with other agents that cause neutropenia. Patients receiving anti-retroviral protease inhibitors in combination with cidofovir may have an increased risk of iritis or uveitis. [24859] Atazanavir; Cobicistat: (Moderate) Additive adverse effects may be seen when cidofovir is given with other agents that cause neutropenia. Patients receiving anti-retroviral protease inhibitors in combination with cidofovir may have an increased risk of iritis or uveitis. [24859] Atenolol; Chlorthalidone: (Contraindicated) The administration of cidofovir with another potentially nephrotoxic agent, such as diuretics, is contraindicated. Diuretics should be discontinued at least 7 days prior to beginning cidofovir. [28388] Azilsartan; Chlorthalidone: (Contraindicated) The administration of cidofovir with another potentially nephrotoxic agent, such as diuretics, is contraindicated. Diuretics should be discontinued at least 7 days prior to beginning cidofovir. [28388] Bacitracin: (Contraindicated) The administration of cidofovir with another potentially nephrotoxic agent, such as bacitracin, is contraindicated. Bacitracin should be discontinued at least 7 days prior to beginning cidofovir. [28388] Benazepril; hydroCHLOROthiazide, HCTZ: (Contraindicated) The administration of cidofovir with another potentially nephrotoxic agent, such as diuretics, is contraindicated. Diuretics should be discontinued at least 7 days prior to beginning cidofovir. [28388] Bictegravir; Emtricitabine; Tenofovir Alafenamide: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with a nephrotoxic agent, such as cidofovir. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs; thus, increasing the risk of developing renal-related adverse reactions. [60269] [60688] (Moderate) Monitor for changes in serum creatinine and adverse reactions, such as lactic acidosis or hepatotoxicity if emtricitabine is administered in combination with nephrotoxic agents, such as cidofovir. Consider the potential for drug interaction prior to and during concurrent use of these medications. Both emtricitabine and cidofovir are excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. While no drug interactions due to competition for renal excretion have been observed, coadministration of these medications may increase concentrations of both drugs. [25906] [51664] Bismuth Subsalicylate: (Major) Due to the inhibition of renal prostaglandins by salicylates, concurrent use of salicylates and other nephrotoxic agents may lead to additive nephrotoxicity. Salicylates should be given with caution to patients taking cidofovir. [28388] Bismuth Subsalicylate; metroNIDAZOLE; Tetracycline: (Major) Due to the inhibition of renal prostaglandins by salicylates, concurrent use of salicylates and other nephrotoxic agents may lead to additive nephrotoxicity. Salicylates should be given with caution to patients taking cidofovir. [28388] Bisoprolol; hydroCHLOROthiazide, HCTZ: (Contraindicated) The administration of cidofovir with another potentially nephrotoxic agent, such as diuretics, is contraindicated. Diuretics should be discontinued at least 7 days prior to beginning cidofovir. [28388] Brincidofovir: (Contraindicated) Do not administer brincidofovir with intravenous cidofovir as use of these drugs together is considered duplicate therapy. Brincidofovir is a lipid-linked derivative of cidofovir that is intracellularly converted to cidofovir. [66710] Bumetanide: (Contraindicated) The administration of cidofovir with another potentially nephrotoxic agent, such as diuretics, is contraindicated. Diuretics should be discontinued at least 7 days prior to beginning cidofovir. [28388] BUPivacaine; Meloxicam: (Contraindicated) The concomitant administration of cidofovir and nonsteroidal antiinflammatory drugs (NSAIDs) is contraindicated due to the potential for increased nephrotoxicity. NSAIDs should be discontinued 7 days prior to beginning cidofovir. [28388] Butalbital; Aspirin; Caffeine; Codeine: (Contraindicated) The concomitant administration of cidofovir and NSAIDs, such as aspirin, is contraindicated due to the potential for increased nephrotoxicity. Aspirin should be discontinued 7 days prior to beginning cidofovir. [28388] Cabozantinib: (Minor) Monitor for an increase in cabozantinib-related adverse reactions if coadministration with cidofovir is necessary. Cabozantinib is a Multidrug Resistance Protein 2 (MRP2) substrate and cidofovir is an MRP2 inhibitor. MRP2 inhibitors have the potential to increase plasma concentrations of cabozantinib; however, the clinical relevance of this interaction is unknown. [52506] [60738] [60844] Candesartan; hydroCHLOROthiazide, HCTZ: (Contraindicated) The administration of cidofovir with another potentially nephrotoxic agent, such as diuretics, is contraindicated. Diuretics should be discontinued at least 7 days prior to beginning cidofovir. [28388] Capreomycin: (Major) Since capreomycin is eliminated by the kidney, coadministration with other potentially nephrotoxic drugs, including cidofovir, may increase serum concentrations of either drug. Theoretically, the chronic coadministration of these drugs may increase the risk of developing nephrotoxicity, even in patients who have normal renal function. Monitor patients for changes in renal function if these drugs are coadministered. [44155] [5118] Captopril; hydroCHLOROthiazide, HCTZ: (Contraindicated) The administration of cidofovir with another potentially nephrotoxic agent, such as diuretics, is contraindicated. Diuretics should be discontinued at least 7 days prior to beginning cidofovir. [28388] Celecoxib: (Contraindicated) The concomitant administration of cidofovir and nonsteroidal antiinflammatory drugs (NSAIDs) is contraindicated due to the potential for increased nephrotoxicity. NSAIDs should be discontinued 7 days prior to beginning cidofovir. [28388] Celecoxib; Tramadol: (Contraindicated) The concomitant administration of cidofovir and nonsteroidal antiinflammatory drugs (NSAIDs) is contraindicated due to the potential for increased nephrotoxicity. NSAIDs should be discontinued 7 days prior to beginning cidofovir. [28388] Chlorothiazide: (Contraindicated) The administration of cidofovir with another potentially nephrotoxic agent, such as diuretics, is contraindicated. Diuretics should be discontinued at least 7 days prior to beginning cidofovir. [28388] Chlorpheniramine; Ibuprofen; Pseudoephedrine: (Contraindicated) The concomitant administration of cidofovir and nonsteroidal antiinflammatory drugs (NSAIDs) is contraindicated due to the potential for increased nephrotoxicity. NSAIDs should be discontinued 7 days prior to beginning cidofovir. [28388] Chlorthalidone: (Contraindicated) The administration of cidofovir with another potentially nephrotoxic agent, such as diuretics, is contraindicated. Diuretics should be discontinued at least 7 days prior to beginning cidofovir. [28388] Choline Salicylate; Magnesium Salicylate: (Major) Since salicylates cause nephrotoxicity via a similar mechanism as NSAIDs, concurrent use of salicylates and cidofovir should be done with caution. [5118] (Major) Since salicylates cause nephrotoxicity, concurrent use of salicylates and cidofovir should be done with caution. [5118] CISplatin: (Major) Discontinue cisplatin at least 7 days prior to beginning cidofovir. Closely monitor renal function if concomitant use with cisplatin and cidofovir is necessary. Both drugs can cause nephrotoxicity, which may be exacerbated with the use of additional nephrotoxins. [28388] [28393] Clindamycin: (Contraindicated) Concomitant use of cidofovir and clindamycin is contraindicated due to the increased risk of nephrotoxicity. Clindamycin must be discontinued at least 7 days prior to starting therapy with cidofovir. [28388] [29120] Clofarabine: (Contraindicated) The concomitant use of cidofovir and clofarabine is contraindicated due to the potential for additive nephrotoxicity. Discontinue clofarabine 7 days prior to starting cidofovir. [28388] [54578] Colistimethate, Colistin, Polymyxin E: (Major) Theoretically, the chronic coadministration of these drugs may increase the risk of developing nephrotoxicity, even in patients who have normal renal function. Monitor patients for changes in renal function if these drugs are coadministered. Since colistimethate sodium is eliminated by the kidney, coadministration with other potentially nephrotoxic drugs, including cidofovir, may increase serum concentrations of either drug. [28388] [33636] Colistin: (Major) Theoretically, the chronic coadministration of these drugs may increase the risk of developing nephrotoxicity, even in patients who have normal renal function. Monitor patients for changes in renal function if these drugs are coadministered. Since colistimethate sodium is eliminated by the kidney, coadministration with other potentially nephrotoxic drugs, including cidofovir, may increase serum concentrations of either drug. [28388] [33636] cycloSPORINE: (Contraindicated) The administration of cidofovir with other potentially nephrotoxic agents, such as cyclosporine is contraindicated. Cyclosporine should be discontinued at least 7 days prior to beginning cidofovir. Monitor renal function and fluid status carefully during cyclosporine usage. [5118] Darunavir: (Moderate) Additive adverse effects may be seen when cidofovir is given with other agents that cause neutropenia. Patients receiving anti-retroviral protease inhibitors in combination with cidofovir may have an increased risk of iritis or uveitis. [24859] Darunavir; Cobicistat: (Moderate) Additive adverse effects may be seen when cidofovir is given with other agents that cause neutropenia. Patients receiving anti-retroviral protease inhibitors in combination with cidofovir may have an increased risk of iritis or uveitis. [24859] Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Moderate) Additive adverse effects may be seen when cidofovir is given with other agents that cause neutropenia. Patients receiving anti-retroviral protease inhibitors in combination with cidofovir may have an increased risk of iritis or uveitis. [24859] (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with a nephrotoxic agent, such as cidofovir. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs; thus, increasing the risk of developing renal-related adverse reactions. [60269] [60688] (Moderate) Monitor for changes in serum creatinine and adverse reactions, such as lactic acidosis or hepatotoxicity if emtricitabine is administered in combination with nephrotoxic agents, such as cidofovir. Consider the potential for drug interaction prior to and during concurrent use of these medications. Both emtricitabine and cidofovir are excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. While no drug interactions due to competition for renal excretion have been observed, coadministration of these medications may increase concentrations of both drugs. [25906] [51664] Dichlorphenamide: (Major) Use of dichlorphenamide and adefovir is not recommended because of increased cidofovir exposure and related adverse effects. Monitor closely for signs of drug toxicity if coadministration cannot be avoided. For example, it is important to monitor renal function and for neutropenia for all patients during treatment with cidofovir. Increased cidofovir exposure is possible. Cidofovir is a sensitive OAT1 substrate. Dichlorphenamide inhibits OAT1. Concurrent use may also increase the severity of metabolic acidosis, as both drugs may cause this side effect. Measure sodium bicarbonate concentrations at baseline and periodically during dichlorphenamide treatment. If metabolic acidosis occurs or persists, consider reducing the dose or discontinuing dichlorphenamide therapy. [28388] [56579] [60122] Diclofenac: (Contraindicated) The concomitant administration of cidofovir and nonsteroidal antiinflammatory drugs (NSAIDs) is contraindicated due to the potential for increased nephrotoxicity. NSAIDs should be discontinued 7 days prior to beginning cidofovir. [28388] Diclofenac; miSOPROStol: (Contraindicated) The concomitant administration of cidofovir and nonsteroidal antiinflammatory drugs (NSAIDs) is contraindicated due to the potential for increased nephrotoxicity. NSAIDs should be discontinued 7 days prior to beginning cidofovir. [28388] Diflunisal: (Contraindicated) The concomitant administration of cidofovir and nonsteroidal antiinflammatory drugs (NSAIDs) is contraindicated due to the potential for increased nephrotoxicity. NSAIDs should be discontinued 7 days prior to beginning cidofovir. [28388] diphenhydrAMINE; Ibuprofen: (Contraindicated) The concomitant administration of cidofovir and nonsteroidal antiinflammatory drugs (NSAIDs) is contraindicated due to the potential for increased nephrotoxicity. NSAIDs should be discontinued 7 days prior to beginning cidofovir. [28388] diphenhydrAMINE; Naproxen: (Contraindicated) The concomitant administration of cidofovir and nonsteroidal antiinflammatory drugs (NSAIDs) is contraindicated due to the potential for increased nephrotoxicity. NSAIDs should be discontinued 7 days prior to beginning cidofovir. [28388] Diuretics: (Contraindicated) The administration of cidofovir with another potentially nephrotoxic agent, such as diuretics, is contraindicated. Diuretics should be discontinued at least 7 days prior to beginning cidofovir. [28388] Doravirine; lamiVUDine; Tenofovir disoproxil fumarate: (Moderate) Tenofovir disoproxil fumarate should be avoided with concurrent or recent use of a nephrotoxic agent, such as cidofovir. If concurrent use is necessary, closely monitor for changes in renal function. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Concurrent administration with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs; thus, increasing the risk of developing renal-related adverse events. Renal impairment, which may include acute renal failure and hypophosphatemia, has been reported with the use of tenofovir disoproxil fumarate. [28193] [46638] Efavirenz; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Monitor for changes in serum creatinine and adverse reactions, such as lactic acidosis or hepatotoxicity if emtricitabine is administered in combination with nephrotoxic agents, such as cidofovir. Consider the potential for drug interaction prior to and during concurrent use of these medications. Both emtricitabine and cidofovir are excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. While no drug interactions due to competition for renal excretion have been observed, coadministration of these medications may increase concentrations of both drugs. [25906] [51664] (Moderate) Tenofovir disoproxil fumarate should be avoided with concurrent or recent use of a nephrotoxic agent, such as cidofovir. If concurrent use is necessary, closely monitor for changes in renal function. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Concurrent administration with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs; thus, increasing the risk of developing renal-related adverse events. Renal impairment, which may include acute renal failure and hypophosphatemia, has been reported with the use of tenofovir disoproxil fumarate. [28193] [46638] Efavirenz; lamiVUDine; Tenofovir Disoproxil Fumarate: (Moderate) Tenofovir disoproxil fumarate should be avoided with concurrent or recent use of a nephrotoxic agent, such as cidofovir. If concurrent use is necessary, closely monitor for changes in renal function. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Concurrent administration with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs; thus, increasing the risk of developing renal-related adverse events. Renal impairment, which may include acute renal failure and hypophosphatemia, has been reported with the use of tenofovir disoproxil fumarate. [28193] [46638] Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with a nephrotoxic agent, such as cidofovir. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs; thus, increasing the risk of developing renal-related adverse reactions. [60269] [60688] (Moderate) Monitor for changes in serum creatinine and adverse reactions, such as lactic acidosis or hepatotoxicity if emtricitabine is administered in combination with nephrotoxic agents, such as cidofovir. Consider the potential for drug interaction prior to and during concurrent use of these medications. Both emtricitabine and cidofovir are excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. While no drug interactions due to competition for renal excretion have been observed, coadministration of these medications may increase concentrations of both drugs. [25906] [51664] Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Monitor for changes in serum creatinine and adverse reactions, such as lactic acidosis or hepatotoxicity if emtricitabine is administered in combination with nephrotoxic agents, such as cidofovir. Consider the potential for drug interaction prior to and during concurrent use of these medications. Both emtricitabine and cidofovir are excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. While no drug interactions due to competition for renal excretion have been observed, coadministration of these medications may increase concentrations of both drugs. [25906] [51664] (Moderate) Tenofovir disoproxil fumarate should be avoided with concurrent or recent use of a nephrotoxic agent, such as cidofovir. If concurrent use is necessary, closely monitor for changes in renal function. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Concurrent administration with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs; thus, increasing the risk of developing renal-related adverse events. Renal impairment, which may include acute renal failure and hypophosphatemia, has been reported with the use of tenofovir disoproxil fumarate. [28193] [46638] Emtricitabine: (Moderate) Monitor for changes in serum creatinine and adverse reactions, such as lactic acidosis or hepatotoxicity if emtricitabine is administered in combination with nephrotoxic agents, such as cidofovir. Consider the potential for drug interaction prior to and during concurrent use of these medications. Both emtricitabine and cidofovir are excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. While no drug interactions due to competition for renal excretion have been observed, coadministration of these medications may increase concentrations of both drugs. [25906] [51664] Emtricitabine; Rilpivirine; Tenofovir alafenamide: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with a nephrotoxic agent, such as cidofovir. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs; thus, increasing the risk of developing renal-related adverse reactions. [60269] [60688] (Moderate) Monitor for changes in serum creatinine and adverse reactions, such as lactic acidosis or hepatotoxicity if emtricitabine is administered in combination with nephrotoxic agents, such as cidofovir. Consider the potential for drug interaction prior to and during concurrent use of these medications. Both emtricitabine and cidofovir are excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. While no drug interactions due to competition for renal excretion have been observed, coadministration of these medications may increase concentrations of both drugs. [25906] [51664] Emtricitabine; Rilpivirine; Tenofovir Disoproxil Fumarate: (Moderate) Monitor for changes in serum creatinine and adverse reactions, such as lactic acidosis or hepatotoxicity if emtricitabine is administered in combination with nephrotoxic agents, such as cidofovir. Consider the potential for drug interaction prior to and during concurrent use of these medications. Both emtricitabine and cidofovir are excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. While no drug interactions due to competition for renal excretion have been observed, coadministration of these medications may increase concentrations of both drugs. [25906] [51664] (Moderate) Tenofovir disoproxil fumarate should be avoided with concurrent or recent use of a nephrotoxic agent, such as cidofovir. If concurrent use is necessary, closely monitor for changes in renal function. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Concurrent administration with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs; thus, increasing the risk of developing renal-related adverse events. Renal impairment, which may include acute renal failure and hypophosphatemia, has been reported with the use of tenofovir disoproxil fumarate. [28193] [46638] Emtricitabine; Tenofovir alafenamide: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with a nephrotoxic agent, such as cidofovir. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs; thus, increasing the risk of developing renal-related adverse reactions. [60269] [60688] (Moderate) Monitor for changes in serum creatinine and adverse reactions, such as lactic acidosis or hepatotoxicity if emtricitabine is administered in combination with nephrotoxic agents, such as cidofovir. Consider the potential for drug interaction prior to and during concurrent use of these medications. Both emtricitabine and cidofovir are excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. While no drug interactions due to competition for renal excretion have been observed, coadministration of these medications may increase concentrations of both drugs. [25906] [51664] Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Monitor for changes in serum creatinine and adverse reactions, such as lactic acidosis or hepatotoxicity if emtricitabine is administered in combination with nephrotoxic agents, such as cidofovir. Consider the potential for drug interaction prior to and during concurrent use of these medications. Both emtricitabine and cidofovir are excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. While no drug interactions due to competition for renal excretion have been observed, coadministration of these medications may increase concentrations of both drugs. [25906] [51664] (Moderate) Tenofovir disoproxil fumarate should be avoided with concurrent or recent use of a nephrotoxic agent, such as cidofovir. If concurrent use is necessary, closely monitor for changes in renal function. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Concurrent administration with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs; thus, increasing the risk of developing renal-related adverse events. Renal impairment, which may include acute renal failure and hypophosphatemia, has been reported with the use of tenofovir disoproxil fumarate. [28193] [46638] Enalapril; hydroCHLOROthiazide, HCTZ: (Contraindicated) The administration of cidofovir with another potentially nephrotoxic agent, such as diuretics, is contraindicated. Diuretics should be discontinued at least 7 days prior to beginning cidofovir. [28388] Entecavir: (Moderate) Entecavir may affect renal function and should be used cautiously in combination with other drugs that may also affect renal function, including cidofovir. [5118] [8007] Eprosartan; hydroCHLOROthiazide, HCTZ: (Contraindicated) The administration of cidofovir with another potentially nephrotoxic agent, such as diuretics, is contraindicated. Diuretics should be discontinued at least 7 days prior to beginning cidofovir. [28388] Ethacrynic Acid: (Contraindicated) The administration of cidofovir with another potentially nephrotoxic agent, such as diuretics, is contraindicated. Diuretics should be discontinued at least 7 days prior to beginning cidofovir. [28388] Etodolac: (Contraindicated) The concomitant administration of cidofovir and nonsteroidal antiinflammatory drugs (NSAIDs) is contraindicated due to the potential for increased nephrotoxicity. NSAIDs should be discontinued 7 days prior to beginning cidofovir. [28388] Fenoprofen: (Contraindicated) The concomitant administration of cidofovir and nonsteroidal antiinflammatory drugs (NSAIDs) is contraindicated due to the potential for increased nephrotoxicity. NSAIDs should be discontinued 7 days prior to beginning cidofovir. [28388] Flurbiprofen: (Contraindicated) The concomitant administration of cidofovir and nonsteroidal antiinflammatory drugs (NSAIDs) is contraindicated due to the potential for increased nephrotoxicity. NSAIDs should be discontinued 7 days prior to beginning cidofovir. [28388] Fosamprenavir: (Moderate) Additive adverse effects may be seen when cidofovir is given with other agents that cause neutropenia. Patients receiving anti-retroviral protease inhibitors in combination with cidofovir may have an increased risk of iritis or uveitis. [24859] Foscarnet: (Contraindicated) The administration of cidofovir with another potentially nephrotoxic agent, such as foscarnet, is contraindicated. Foscarnet should be discontinued at least 7 days prior to beginning cidofovir. [28377] [28388] Fosinopril; hydroCHLOROthiazide, HCTZ: (Contraindicated) The administration of cidofovir with another potentially nephrotoxic agent, such as diuretics, is contraindicated. Diuretics should be discontinued at least 7 days prior to beginning cidofovir. [28388] Furosemide: (Contraindicated) The administration of cidofovir with another potentially nephrotoxic agent, such as diuretics, is contraindicated. Diuretics should be discontinued at least 7 days prior to beginning cidofovir. [28388] Ganciclovir: (Contraindicated) The administration of cidofovir with another potentially nephrotoxic agent, such as ganciclovir, is contraindicated. Ganciclovir should be discontinued at least 7 days prior to beginning cidofovir. [28388] [32676] Gentamicin: (Contraindicated) The administration of cidofovir with other potentially nephrotoxic agents, such as aminoglycosides, is contraindicated. These agents should be discontinued at least 7 days prior to beginning cidofovir. [5118] Hyaluronidase, Recombinant; Immune Globulin: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like cidofovir. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function. [5118] hydroCHLOROthiazide, HCTZ: (Contraindicated) The administration of cidofovir with another potentially nephrotoxic agent, such as diuretics, is contraindicated. Diuretics should be discontinued at least 7 days prior to beginning cidofovir. [28388] hydroCHLOROthiazide, HCTZ; Moexipril: (Contraindicated) The administration of cidofovir with another potentially nephrotoxic agent, such as diuretics, is contraindicated. Diuretics should be discontinued at least 7 days prior to beginning cidofovir. [28388] HYDROcodone; Ibuprofen: (Contraindicated) The concomitant administration of cidofovir and nonsteroidal antiinflammatory drugs (NSAIDs) is contraindicated due to the potential for increased nephrotoxicity. NSAIDs should be discontinued 7 days prior to beginning cidofovir. [28388] Ibuprofen: (Contraindicated) The concomitant administration of cidofovir and nonsteroidal antiinflammatory drugs (NSAIDs) is contraindicated due to the potential for increased nephrotoxicity. NSAIDs should be discontinued 7 days prior to beginning cidofovir. [28388] Ibuprofen; Famotidine: (Contraindicated) The concomitant administration of cidofovir and nonsteroidal antiinflammatory drugs (NSAIDs) is contraindicated due to the potential for increased nephrotoxicity. NSAIDs should be discontinued 7 days prior to beginning cidofovir. [28388] Ibuprofen; oxyCODONE: (Contraindicated) The concomitant administration of cidofovir and nonsteroidal antiinflammatory drugs (NSAIDs) is contraindicated due to the potential for increased nephrotoxicity. NSAIDs should be discontinued 7 days prior to beginning cidofovir. [28388] Ibuprofen; Pseudoephedrine: (Contraindicated) The concomitant administration of cidofovir and nonsteroidal antiinflammatory drugs (NSAIDs) is contraindicated due to the potential for increased nephrotoxicity. NSAIDs should be discontinued 7 days prior to beginning cidofovir. [28388] Immune Globulin IV, IVIG, IGIV: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like cidofovir. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function. [5118] Indapamide: (Contraindicated) The administration of cidofovir with another potentially nephrotoxic agent, such as diuretics, is contraindicated. Diuretics should be discontinued at least 7 days prior to beginning cidofovir. [28388] Indinavir: (Moderate) Additive adverse effects may be seen when cidofovir is given with other agents that cause neutropenia. Patients receiving anti-retroviral protease inhibitors in combination with cidofovir may have an increased risk of iritis or uveitis. [24859] Indomethacin: (Contraindicated) The concomitant administration of cidofovir and nonsteroidal antiinflammatory drugs (NSAIDs) is contraindicated due to the potential for increased nephrotoxicity. NSAIDs should be discontinued 7 days prior to beginning cidofovir. [28388] Inotersen: (Moderate) Use caution with concomitant use of inotersen and cidofovir due to the risk of glomerulonephritis and nephrotoxicity. [63624] Irbesartan; hydroCHLOROthiazide, HCTZ: (Contraindicated) The administration of cidofovir with another potentially nephrotoxic agent, such as diuretics, is contraindicated. Diuretics should be discontinued at least 7 days prior to beginning cidofovir. [28388] Ketoprofen: (Contraindicated) The concomitant administration of cidofovir and nonsteroidal antiinflammatory drugs (NSAIDs) is contraindicated due to the potential for increased nephrotoxicity. NSAIDs should be discontinued 7 days prior to beginning cidofovir. [28388] Ketorolac: (Contraindicated) The concomitant administration of cidofovir and nonsteroidal antiinflammatory drugs (NSAIDs) is contraindicated due to the potential for increased nephrotoxicity. NSAIDs should be discontinued 7 days prior to beginning cidofovir. [28388] lamiVUDine, 3TC; Zidovudine, ZDV: (Major) Concomitant use of probenecid with zidovudine may produce substantially higher serum concentrations of zidovudine. Because cidofovir must be given concomitantly with probenecid, the manufacturer of cidofovir recommends that on the days of concomitant cidofovir and probenecid therapy, zidovudine should either be discontinued temporarily or the zidovudine dosage should be reduced by 50%. Limited data suggest that probenecid may inhibit glucuronidation and/or reduce renal excretion of zidovudine. [28388] lamiVUDine; Tenofovir Disoproxil Fumarate: (Moderate) Tenofovir disoproxil fumarate should be avoided with concurrent or recent use of a nephrotoxic agent, such as cidofovir. If concurrent use is necessary, closely monitor for changes in renal function. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Concurrent administration with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs; thus, increasing the risk of developing renal-related adverse events. Renal impairment, which may include acute renal failure and hypophosphatemia, has been reported with the use of tenofovir disoproxil fumarate. [28193] [46638] Lisinopril; hydroCHLOROthiazide, HCTZ: (Contraindicated) The administration of cidofovir with another potentially nephrotoxic agent, such as diuretics, is contraindicated. Diuretics should be discontinued at least 7 days prior to beginning cidofovir. [28388] Lopinavir; Ritonavir: (Moderate) Additive adverse effects may be seen when cidofovir is given with other agents that cause neutropenia. Patients receiving anti-retroviral protease inhibitors in combination with cidofovir may have an increased risk of iritis or uveitis. [24859] Losartan; hydroCHLOROthiazide, HCTZ: (Contraindicated) The administration of cidofovir with another potentially nephrotoxic agent, such as diuretics, is contraindicated. Diuretics should be discontinued at least 7 days prior to beginning cidofovir. [28388] Magnesium Salicylate: (Major) Since salicylates cause nephrotoxicity, concurrent use of salicylates and cidofovir should be done with caution. [5118] Mannitol: (Major) Avoid use of mannitol and cidofovir, if possible. Concomitant administration of nephrotoxic drugs, such as cidofovir, increases the risk of renal failure after administration of mannitol. [33007] Maraviroc: (Moderate) Use caution and closely monitor for increased adverse effects during concurrent administration of maraviroc and cidofovir as increased maraviroc concentrations may occur. Maraviroc is a substrate of multidrug resistance-associated protein (MRP2); cidofovir is an inhibitor of MRP2. The effects of this transporter on the concentrations of maraviroc are unknown, although an increase in concentrations and thus, toxicity, are possible. [33473] [60844] Meclofenamate Sodium: (Contraindicated) The concomitant administration of cidofovir and nonsteroidal antiinflammatory drugs (NSAIDs) is contraindicated due to the potential for increased nephrotoxicity. NSAIDs should be discontinued 7 days prior to beginning cidofovir. [28388] Mefenamic Acid: (Contraindicated) The concomitant administration of cidofovir and nonsteroidal antiinflammatory drugs (NSAIDs) is contraindicated due to the potential for increased nephrotoxicity. NSAIDs should be discontinued 7 days prior to beginning cidofovir. [28388] Meloxicam: (Contraindicated) The concomitant administration of cidofovir and nonsteroidal antiinflammatory drugs (NSAIDs) is contraindicated due to the potential for increased nephrotoxicity. NSAIDs should be discontinued 7 days prior to beginning cidofovir. [28388] Methenamine; Sodium Salicylate: (Contraindicated) The concomitant administration of cidofovir and nonsteroidal antiinflammatory drugs (NSAIDs) is contraindicated due to the potential for increased nephrotoxicity. NSAIDs should be discontinued 7 days prior to beginning cidofovir. [28388] Methotrexate: (Major) Avoid concomitant use of methotrexate with cidofovir due to the risk of additive nephrotoxicity as well as an increased risk of severe methotrexate-related adverse reactions. If concomitant use is unavoidable, closely monitor for adverse reactions. Cidofovir and methotrexate are both nephrotoxic drugs; methotrexate is also renally eliminated. Coadministration of methotrexate with cidofovir may result in decreased renal function as well as increased methotrexate plasma concentrations. [28388] [60517] [66594] metOLazone: (Contraindicated) The administration of cidofovir with another potentially nephrotoxic agent, such as diuretics, is contraindicated. Diuretics should be discontinued at least 7 days prior to beginning cidofovir. [28388] Metoprolol; hydroCHLOROthiazide, HCTZ: (Contraindicated) The administration of cidofovir with another potentially nephrotoxic agent, such as diuretics, is contraindicated. Diuretics should be discontinued at least 7 days prior to beginning cidofovir. [28388] Nabumetone: (Contraindicated) The concomitant administration of cidofovir and nonsteroidal antiinflammatory drugs (NSAIDs) is contraindicated due to the potential for increased nephrotoxicity. NSAIDs should be discontinued 7 days prior to beginning cidofovir. [28388] Naproxen: (Contraindicated) The concomitant administration of cidofovir and nonsteroidal antiinflammatory drugs (NSAIDs) is contraindicated due to the potential for increased nephrotoxicity. NSAIDs should be discontinued 7 days prior to beginning cidofovir. [28388] Naproxen; Esomeprazole: (Contraindicated) The concomitant administration of cidofovir and nonsteroidal antiinflammatory drugs (NSAIDs) is contraindicated due to the potential for increased nephrotoxicity. NSAIDs should be discontinued 7 days prior to beginning cidofovir. [28388] Naproxen; Pseudoephedrine: (Contraindicated) The concomitant administration of cidofovir and nonsteroidal antiinflammatory drugs (NSAIDs) is contraindicated due to the potential for increased nephrotoxicity. NSAIDs should be discontinued 7 days prior to beginning cidofovir. [28388] Nelfinavir: (Moderate) Additive adverse effects may be seen when cidofovir is given with other agents that cause neutropenia. Patients receiving anti-retroviral protease inhibitors in combination with cidofovir may have an increased risk of iritis or uveitis. [24859] Nirmatrelvir; Ritonavir: (Moderate) Additive adverse effects may be seen when cidofovir is given with other agents that cause neutropenia. Patients receiving anti-retroviral protease inhibitors in combination with cidofovir may have an increased risk of iritis or uveitis. [24859] Nitisinone: (Moderate) Monitor for increased cidofovir-related adverse effects if coadministered with nitisinone. Increased cidofovir exposure is possible. Nitisinone inhibits OAT1. Cidofovir is an OAT1 substrate. [56579] [62200] Nonsteroidal antiinflammatory drugs: (Contraindicated) The concomitant administration of cidofovir and nonsteroidal antiinflammatory drugs (NSAIDs) is contraindicated due to the potential for increased nephrotoxicity. NSAIDs should be discontinued 7 days prior to beginning cidofovir. [28388] Olmesartan; amLODIPine; hydroCHLOROthiazide, HCTZ: (Contraindicated) The administration of cidofovir with another potentially nephrotoxic agent, such as diuretics, is contraindicated. Diuretics should be discontinued at least 7 days prior to beginning cidofovir. [28388] Olmesartan; hydroCHLOROthiazide, HCTZ: (Contraindicated) The administration of cidofovir with another potentially nephrotoxic agent, such as diuretics, is contraindicated. Diuretics should be discontinued at least 7 days prior to beginning cidofovir. [28388] Oxaliplatin: (Major) Avoid coadministration of oxaliplatin with cidofovir due to the risk of increased oxaliplatin-related adverse reactions. Cidofovir is known to be potentially nephrotoxic; because platinum-containing drugs like oxaliplatin are eliminated primarily through the kidney, oxaliplatin clearance may be decreased by coadministration with nephrotoxic agents. [28388] [41958] Oxaprozin: (Contraindicated) The concomitant administration of cidofovir and nonsteroidal antiinflammatory drugs (NSAIDs) is contraindicated due to the potential for increased nephrotoxicity. NSAIDs should be discontinued 7 days prior to beginning cidofovir. [28388] Pamidronate: (Contraindicated) The administration of cidofovir with another potentially nephrotoxic agent, such as pamidronate, is contraindicated. Pamidronate should be discontinued at least 7 days prior to beginning cidofovir. [28388] [31027] Paromomycin: (Contraindicated) The administration of cidofovir with other potentially nephrotoxic agents, such as aminoglycosides, is contraindicated. These agents should be discontinued at least 7 days prior to beginning cidofovir. [5118] Pentamidine: (Contraindicated) Additive nephrotoxicity may be seen with the combination of pentamidine and other agents that cause nephrotoxicity, including cidofovir. The combination use of IV pentamidine and cidofovir is contraindicated. Pentamidine should be discontinued at least 7 days prior to beginning cidofovir. [28879] [5118] Piroxicam: (Contraindicated) The concomitant administration of cidofovir and nonsteroidal antiinflammatory drugs (NSAIDs) is contraindicated due to the potential for increased nephrotoxicity. NSAIDs should be discontinued 7 days prior to beginning cidofovir. [28388] Plazomicin: (Contraindicated) The administration of cidofovir with other potentially nephrotoxic agents, such as aminoglycosides, is contraindicated. These agents should be discontinued at least 7 days prior to beginning cidofovir. [5118] Probenecid: (Minor) Probenecid impairs the tubular secretion of cidofovir. While cidofovir serum concentrations are higher as a result of the effects of probenecid, probenecid is recommended for use in combination with cidofovir to offset cidofovir-induced nephrotoxicity. [2565] Probenecid; Colchicine: (Minor) Probenecid impairs the tubular secretion of cidofovir. While cidofovir serum concentrations are higher as a result of the effects of probenecid, probenecid is recommended for use in combination with cidofovir to offset cidofovir-induced nephrotoxicity. [2565] Protease inhibitors: (Moderate) Additive adverse effects may be seen when cidofovir is given with other agents that cause neutropenia. Patients receiving anti-retroviral protease inhibitors in combination with cidofovir may have an increased risk of iritis or uveitis. [24859] Quinapril; hydroCHLOROthiazide, HCTZ: (Contraindicated) The administration of cidofovir with another potentially nephrotoxic agent, such as diuretics, is contraindicated. Diuretics should be discontinued at least 7 days prior to beginning cidofovir. [28388] Ritonavir: (Moderate) Additive adverse effects may be seen when cidofovir is given with other agents that cause neutropenia. Patients receiving anti-retroviral protease inhibitors in combination with cidofovir may have an increased risk of iritis or uveitis. [24859] Salsalate: (Contraindicated) The concomitant administration of cidofovir and nonsteroidal antiinflammatory drugs (NSAIDs), such as salsalate, is contraindicated due to the potential for increased nephrotoxicity. NSAIDs should be discontinued 7 days prior to beginning cidofovir. [28388] Saquinavir: (Moderate) Additive adverse effects may be seen when cidofovir is given with other agents that cause neutropenia. Patients receiving anti-retroviral protease inhibitors in combination with cidofovir may have an increased risk of iritis or uveitis. [24859] Spironolactone: (Contraindicated) The administration of cidofovir with another potentially nephrotoxic agent, such as diuretics, is contraindicated. Diuretics should be discontinued at least 7 days prior to beginning cidofovir. [28388] Spironolactone; hydroCHLOROthiazide, HCTZ: (Contraindicated) The administration of cidofovir with another potentially nephrotoxic agent, such as diuretics, is contraindicated. Diuretics should be discontinued at least 7 days prior to beginning cidofovir. [28388] Streptomycin: (Contraindicated) The administration of cidofovir with other potentially nephrotoxic agents, such as aminoglycosides, is contraindicated. These agents should be discontinued at least 7 days prior to beginning cidofovir. [5118] Sulindac: (Contraindicated) The concomitant administration of cidofovir and nonsteroidal antiinflammatory drugs (NSAIDs) is contraindicated due to the potential for increased nephrotoxicity. NSAIDs should be discontinued 7 days prior to beginning cidofovir. [28388] SUMAtriptan; Naproxen: (Contraindicated) The concomitant administration of cidofovir and nonsteroidal antiinflammatory drugs (NSAIDs) is contraindicated due to the potential for increased nephrotoxicity. NSAIDs should be discontinued 7 days prior to beginning cidofovir. [28388] Tacrolimus: (Contraindicated) The administration of cidofovir with another potentially nephrotoxic agent, such as tacrolimus is contraindicated. Tacrolimus should be discontinued at least 7 days prior to beginning cidofovir. [5118] Talimogene Laherparepvec: (Major) Consider the risks and benefits of treatment with talimogene laherparepvec before administering acyclovir or other antivirals to prevent or manage herpetic infection. Talimogene laherparepvec is a live, attenuated herpes simplex virus that is sensitive to acyclovir; coadministration with antiviral agents may cause a decrease in efficacy. [60260] Telavancin: (Contraindicated) The administration of cidofovir with other potentially nephrotoxic drugs such as telavancin is contraindicated. Discontinue telavancin at least 7 days prior to beginning cidofovir. [36615] [5118] Telmisartan; hydroCHLOROthiazide, HCTZ: (Contraindicated) The administration of cidofovir with another potentially nephrotoxic agent, such as diuretics, is contraindicated. Diuretics should be discontinued at least 7 days prior to beginning cidofovir. [28388] Tenofovir Alafenamide: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with a nephrotoxic agent, such as cidofovir. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs; thus, increasing the risk of developing renal-related adverse reactions. [60269] [60688] Tenofovir Alafenamide: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with a nephrotoxic agent, such as cidofovir. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs; thus, increasing the risk of developing renal-related adverse reactions. [60269] [60688] Tenofovir Disoproxil Fumarate: (Moderate) Tenofovir disoproxil fumarate should be avoided with concurrent or recent use of a nephrotoxic agent, such as cidofovir. If concurrent use is necessary, closely monitor for changes in renal function. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Concurrent administration with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs; thus, increasing the risk of developing renal-related adverse events. Renal impairment, which may include acute renal failure and hypophosphatemia, has been reported with the use of tenofovir disoproxil fumarate. [28193] [46638] Tipranavir: (Moderate) Additive adverse effects may be seen when cidofovir is given with other agents that cause neutropenia. Patients receiving anti-retroviral protease inhibitors in combination with cidofovir may have an increased risk of iritis or uveitis. [24859] Tobramycin: (Contraindicated) The administration of cidofovir with other potentially nephrotoxic agents, such as aminoglycosides, is contraindicated. These agents should be discontinued at least 7 days prior to beginning cidofovir. [5118] Tolmetin: (Contraindicated) The concomitant administration of cidofovir and nonsteroidal antiinflammatory drugs (NSAIDs) is contraindicated due to the potential for increased nephrotoxicity. NSAIDs should be discontinued 7 days prior to beginning cidofovir. [28388] Torsemide: (Contraindicated) The administration of cidofovir with another potentially nephrotoxic agent, such as diuretics, is contraindicated. Diuretics should be discontinued at least 7 days prior to beginning cidofovir. [28388] Triamterene: (Contraindicated) The administration of cidofovir with another potentially nephrotoxic agent, such as diuretics, is contraindicated. Diuretics should be discontinued at least 7 days prior to beginning cidofovir. [28388] Triamterene; hydroCHLOROthiazide, HCTZ: (Contraindicated) The administration of cidofovir with another potentially nephrotoxic agent, such as diuretics, is contraindicated. Diuretics should be discontinued at least 7 days prior to beginning cidofovir. [28388] valACYclovir: (Contraindicated) The administration of cidofovir with another potentially nephrotoxic agent, such as valacyclovir, is contraindicated. Valacyclovir should be discontinued at least 7 days prior to beginning cidofovir. [28388] [29970] Valsartan; hydroCHLOROthiazide, HCTZ: (Contraindicated) The administration of cidofovir with another potentially nephrotoxic agent, such as diuretics, is contraindicated. Diuretics should be discontinued at least 7 days prior to beginning cidofovir. [28388] Vancomycin: (Contraindicated) The administration of cidofovir other potentially nephrotoxic agents, such as IV vancomycin, is contraindicated. These agents should be discontinued at least 7 days prior to beginning cidofovir. [5118] Voclosporin: (Contraindicated) Concomitant use of cidofovir and voclosporin is contraindicated due to the increased risk of nephrotoxicity. Voclosporin must be discontinued at least 7 days prior to starting therapy with cidofovir. [28388] [66336] Zidovudine, ZDV: (Major) Concomitant use of probenecid with zidovudine may produce substantially higher serum concentrations of zidovudine. Because cidofovir must be given concomitantly with probenecid, the manufacturer of cidofovir recommends that on the days of concomitant cidofovir and probenecid therapy, zidovudine should either be discontinued temporarily or the zidovudine dosage should be reduced by 50%. Limited data suggest that probenecid may inhibit glucuronidation and/or reduce renal excretion of zidovudine. [28388] Zoledronic Acid: (Contraindicated) The administration of cidofovir with another potentially nephrotoxic agent, such as zoledronic acid, is contraindicated. Zoledronic acid should be discontinued at least 7 days prior to beginning cidofovir. [28388] [43421]
      Revision Date: 10/20/2024, 07:31:23 PM

      References

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Lake Forest, IL: Hospira, Inc.; 2020 Oct.28388 - Cidofovir injection solution package insert. Morgantown, WV: Mylan Institutional LLC; 2021 Apr.28393 - Platinol (cisplatin) for injection package insert. Paramus, NJ: WG Critical Care, LLC; 2022 March.28784 - Hepsera (adefovir dipivoxil) package insert. Foster City, CA: Gilead Sciences, Inc.; 2018 Dec.28879 - Pentamidine isethionate injection package insert. East Brunswick, NJ: Avet Pharmaceuticals Inc.; 2021 Jan.29120 - Cleocin (clindamycin injection) package insert. New York, NY: Pharmacia and Upjohn Company; 2022 May.29970 - Valtrex (valacyclovir) package insert. Research Triangle Park, NC: GlaxoSmithKline; 2022 Nov.31027 - Pamidronate disodium injection package insert. Lake Forest, IL: Hospira, Inc.; 2021 Apr.32676 - Cytovene IV (ganciclovir for injection) package insert. Montgomery, AL: H2-Pharma, LLC.; 2020 Jun.33007 - Osmitrol (mannitol) injection package insert. Deerfield, IL: Baxter Healthcare Corporation; 2019 Aug.33473 - Selzentry (maraviroc) package insert. Research Triangle Park, NC: ViiV Healthcare; 2020 Oct.33636 - Coly-Mycin M Parenteral (colistimethate sodium) package insert. Chestnut Ridge, NY: Par Pharmaceutical Companies, Inc.; 2015 Jul.35434 - AmBisome (amphotericin B liposome for injection) package insert. Northbrook, IL: Astellas Pharma US, Inc; 2020 May.36615 - Vibativ (telavancin) package insert. Nashville, TN: Cumberland Pharmaceuticals Inc.; 2020 July.41853 - Proleukin (aldesleukin) package insert. Malvern, PA: Clinigen, Inc.; 2023 Sept.41958 - Eloxatin (oxaliplatin) package insert. Bridgewater, NJ: Sanofi-aventis U.S. LLC; 2023 June.43421 - Reclast (zoledronic acid) injection package insert. East Hanover, NJ: Novartis Pharmaceuticals Corporation; 2020 Apr.44155 - Capastat (capreomycin sulfate injection) package insert. Lake Forest, IL: Akorn, Inc.; 2023 Jan.46638 - Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in adults and adolescents with HIV. Department of Health and Human Services. Available at https://clinicalinfo.hiv.gov/en/guidelines/hiv-clinical-guidelines-adult-and-adolescent-arv/whats-new-guidelines. Accessed Sept 12, 2024.51664 - Stribild (elvitegravir; cobicistat; emtricitabine; tenofovir disoproxil fumarate) package insert. Foster City, CA: Gilead Sciences, Inc; 2021 Sept.52506 - Cometriq (Cabozantinib) capsules package insert. South San Francisco, CA:Exelixis, Inc.; 2023 Aug54578 - Clolar (clofarabine) injection package insert. Cambridge, MA: Genzyme Corporation; 2022 July.56579 - U.S. Food and Drug Administration (FDA). For Healthcare Professionals: FDA's Examples of Drugs that Interact with CYP Enzymes and Transporter Systems. Retrieved Aug 2024. Available at: https://www.fda.gov/drugs/drug-interactions-labeling/healthcare-professionals-fdas-examples-drugs-interact-cyp-enzymes-and-transporter-systems60122 - Keveyis (dichlorphenamide) tablets package insert. Trevose, PA: Strongbridge US Inc.; 2019 Nov.60260 - Imlygic (talimogene laherparepvec) injection package insert. Thousand Oaks, CA: BioVex, Inc., a subsidiary of Amgen, Inc.; 2023 Feb60269 - Genvoya (elvitegravir; cobicistat; emtricitabine; tenofovir alafenamide) package insert. Foster City, CA: Gilead Sciences, Inc; 2022 Jan.60517 - Methotrexate sodium injection package insert. Lake Forrest, IL: Hospira Inc; 2021 June.60688 - Descovy (emtricitabine; tenofovir alafenamide) package insert. Foster City, CA: Gilead Sciences, Inc.; 2022 Jan.60738 - Cabometyx (Cabozantinib) tablets package insert. Alameda, CA: Exelixis, Inc.; 2023 Sept.60844 - Miller DS. Nucleoside phosphonate interactions with multiple organic anion transporters in renal proximal tubule. 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      Monitoring Parameters

      • CBC with differential
      • ophthalmologic exam
      • serum creatinine
      • urinalysis

      US Drug Names

      • Vistide
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