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Ganciclovir
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5 mg/kg/dose IV every 12 hours is recommended by the Infectious Diseases Society of America (IDSA). Although no duration is given for ganciclovir, 10 to 15 days duration of therapy is recommended for acyclovir.[34213]
5 mg/kg/dose IV every 12 hours. The American Academy of Pediatrics (AAP) recommends ganciclovir as the first line alternative when IV acyclovir is unavailable for patients with herpes simplex/varicella zoster infections in immunocompromised hosts and patients unable to tolerate oral acyclovir or valacyclovir.[52560]
6 mg/kg/dose IV every 12 hours. The American Academy of Pediatrics (AAP) recommends ganciclovir as the first line alternative when IV acyclovir is unavailable for patients with suspected or proven neonatal herpes simplex disease and herpes simplex/varicella zoster infections in immunocompromised hosts and patients unable to tolerate oral acyclovir or valacyclovir.[52560]
5 mg/kg/dose IV every 12 hours plus IV foscarnet (to stabilize the disease and maximize response); optimal duration has not been established. Routine maintenance therapy is not recommended unless there is concurrent retinitis, there have already been recurrent infections, or severe disease was present initially.[34213] [34362]
5 mg/kg/dose IV every 12 hours plus IV foscarnet (to stabilize the disease and maximize response). Continue treatment until there is symptomatic improvement, then follow with secondary prophylaxis (chronic maintenance therapy). Acutely, single drug therapy with ganciclovir is not recommended due to therapeutic failures.[34213] [34361]
6 mg/kg/dose IV every 12 hours for 6 weeks. If during the 6 weeks of therapy an infant is identified as HIV-infected, some experts recommend extending the course of therapy beyond 6 weeks.[34361]
5 mg/kg/dose IV every 12 hours for a minimum of 14 days or until all CNS symptoms have resolved is recommended by the IDSA.[34213]
5 mg/kg/dose IV every 12 hours for 14 to 21 days as an initial therapy. Systemic therapy may be combined with intravitreal ganciclovir or foscarnet for immediate sight-threatening lesions (i.e., within 1,500 microns of the fovea). Follow with chronic maintenance therapy.[32676] [34362]
5 mg/kg/dose IV every 12 hours for 14 to 21 days as an initial therapy. Systemic therapy may be combined with intravitreal ganciclovir or foscarnet for immediate sight-threatening lesions (i.e., within 1,500 microns of the fovea). Follow with chronic maintenance therapy.[32676] [34362]
5 mg/kg/dose IV every 12 hours for 14 to 21 days; may increase dose to 7.5 mg/kg/dose IV every 12 hours if needed. Consider adding IV foscarnet for sight-threatening disease. Follow with chronic maintenance therapy.[34361]
2 mg intravitreally once weekly until lesion inactivity is achieved for patients with immediate sight-threatening lesions (i.e., within 1,500 microns of the fovea). Intravitreal injections are given to achieve rapid high intraocular drug concentrations and should be administered in combination with systemic induction therapy.[34362]
2 mg intravitreally once weekly until lesion inactivity is achieved for patients with immediate sight-threatening lesions (i.e., within 1,500 microns of the fovea). Intravitreal injections are given to achieve rapid high intraocular drug concentrations and should be administered in combination with systemic induction therapy.[34362]
5 mg/kg/dose IV every 12 hours is recommended by the HIV guidelines for 21 to 42 days or until resolution of signs and symptoms; when patient can tolerate PO, switch to oral valganciclovir to complete therapy. Maintenance therapy is usually not necessary, but should be considered after relapse.[34362]
5 mg/kg/dose IV every 12 hours is recommended in the HIV guidelines. Therapy may be switched to oral valganciclovir once the patient can tolerate PO therapy. The total duration of therapy should be 21 to 42 days or until resolution of signs and symptoms.[34362]
5 mg/kg/dose IV every 12 hours for 14 to 21 days is recommended in the HIV guidelines for patients with disseminated disease; the dosage may be increased to 7.5 mg/kg/dose IV every 12 hours if needed.[34361]
In a small randomized, placebo-controlled trial, BMT patients with biopsy-documented CMV infection of the GI tract were treated with ganciclovir 2.5 mg/kg/dose IV every 8 hours for 14 days and did not demonstrate a superior clinical response or endoscopic appearance compared to the placebo group. Cultures were negative more often, however, in the ganciclovir group.[24288]
Experience is limited in HIV-infected patients. 5 mg/kg/dose IV every 12 hours is suggested by the HIV guidelines; however, optimal duration has not been established.[34362] In an open trial in BMT patients, ganciclovir 2.5 mg/kg/dose IV every 8 hours for 14 days, in combination with intravenous CMV-IVIG (on days 1, 2, 7, and 14) was studied. In patients who were still symptomatic, a maintenance dose of 5 mg/kg/dose IV once daily was given for an additional 14 days with CMV-IVIG on day 21. Twelve of 25 patients died a median of 12 days after treatment.[24033] In another trial in BMT patients, ganciclovir 2.5 mg/kg/dose IV every 8 hours for 20 days, then 5 mg/kg/dose IV once daily 3 to 5 times per week for 20 additional doses in combination with IV immune globulin was evaluated. Combination therapy was successful in 7 of 10 patients.[24376]
5 mg/kg/dose IV every 12 hours. For HIV-infected patients, treatment should be considered in patients with well-documented, histologic evidence of CMV pneumonitis. Data for treating CMV pneumonitis in HIV-infected patients is limited and the optimal duration of therapy has not been established.[34362] In 3 pediatric patients who developed CMV pneumonitis after allogenic stem cell transplant, 5 mg/kg/dose IV every 12 hours for 14 days, then 5 mg/kg/dose IV once daily for 5 to 7 days each week for 3 weeks was used. Intravenous immunoglobulin was given in addition to ganciclovir in all patients for part of the study period. Two of the 3 patients that developed CMV pneumonitis died; 1 of multiorgan failure and 1 of acute graft versus host disease.[52568]
5 mg/kg/dose IV every 12 hours for 14 to 21 days. For HIV-infected patients with disseminated disease, the dose may be increased to 7.5 mg/kg/dose IV every 12 hours if needed.[34361] 5 mg/kg/dose IV every 12 hours for 14 days, then 5 mg/kg/dose IV once daily for 5 to 7 days each week for 3 weeks was used in 3 pediatric patients who developed CMV pneumonitis after allogenic stem cell transplant. Intravenous immunoglobulin was given in addition to ganciclovir in all patients with CMV infection for part of the study period, and then only in patients with subnormal IgG. Two of the 3 patients that developed CMV pneumonitis died; 1 of multiorgan failure and 1 of acute graft versus host disease.[52568]
6 mg/kg/dose IV every 12 hours for 6 weeks. Dosage adjustments for the development of neutropenia may be required.[32656] [45501] This regimen is also recommended by the CDC for HIV-infected neonates; if a neonate is confirmed as being HIV-positive during the 6-week treatment course, some experts recommend extending the treatment course beyond 6 weeks.[34361] Clinical practice guidelines recommend antiviral treatment only for symptomatic neonates (first 30 days of life) with severe symptomatic focal organ disease or CNS disease.[34361] [57601]
5 mg/kg/dose IV every 12 hours for 7 to 14 days, followed by maintenance therapy of 5 mg/kg/dose IV daily for 7 days per week or 6 mg/kg/dose IV daily for 5 days per week through day 100 to 120 post-transplant.[32676] [51812] Other studies have examined similar doses starting 5 to 7 days prior to transplantation.[24258] [24290] Regimens are transplant center and recipient specific; high dose acyclovir or other co-therapies may be utilized.[24289] [24377] [23964]
5 mg/kg/dose IV twice daily for 5 to 7 days starting at engraftment, followed by 5 mg/kg/dose IV once daily through day 100 post-transplant. Monitor ANC at least twice weekly during ganciclovir therapy.[51812] Regimens are transplant center and recipient specific; consult local protocols.
5 mg/kg/dose IV twice daily for 7 to 14 days for allogeneic transplant recipients or for 7 days for autologous transplant recipients, then 5 mg/kg/dose IV once daily for maintenance. Continue maintenance therapy until CMV detection methods are negative. The minimum length of therapy is 2 weeks for autologous HCT; for allogenic HCT, the minimum is 2 weeks when 14-day induction is used or 3 weeks when a 7-day induction is used. Preemptive therapy is recommended for all allogeneic transplant recipients with evidence of CMV infection in blood by antigenemia, PCR for CMV DNA, or detection of CMV mRNA and for CMV seropositive autologous transplant recipients at high risk when CMV antigenemia is at least 5 cells/slide (or any level for recipients of CD34+ selected grafts).[51812] Regimens are transplant center and recipient specific; consult local protocols.
5 mg/kg/dose IV twice daily for 7 to 14 days for allogeneic transplant recipients or for 7 days for autologous transplant recipients, then 5 mg/kg/dose IV once daily for maintenance. Continue maintenance therapy until CMV detection methods are negative. The minimum length of therapy is 2 weeks for autologous HCT; for allogenic HCT, the minimum is 2 weeks when 14-day induction is used or 3 weeks when a 7-day induction is used. Preemptive therapy is recommended for all allogeneic transplant recipients with evidence of CMV infection in blood by antigenemia, PCR for CMV DNA, or detection of CMV mRNA and for CMV seropositive autologous transplant recipients at high risk when CMV antigenemia is at least 5 cells/slide (or any level for recipients of CD34+ selected grafts).[51812] Regimens are transplant center and recipient specific; consult local protocols.
5 mg/kg/dose IV twice daily for 7 to 14 days, then 5 mg/kg/dose IV once daily for 1 to 2 weeks or until the indicator test is negative. The minimum length of therapy is 2 weeks. Preemptive therapy is recommended when allogeneic transplant recipients, patients receiving steroids for GVHD, or patients who received CMV therapy less than 100 days after HCT have an antigenemia at least 5 cells/slide or at least 2 consecutive positive viremia or PCR tests.[51812] Regimens are transplant center and recipient specific; consult local protocols.
5 mg/kg/dose IV twice daily for 7 to 14 days, then 5 mg/kg/dose IV once daily for 1 to 2 weeks or until the indicator test is negative. The minimum length of therapy is 2 weeks. Preemptive therapy is recommended when allogeneic transplant recipients, patients receiving steroids for GVHD, or patients who received CMV therapy less than 100 days after HCT have an antigenemia at least 5 cells/slide or at least 2 consecutive positive viremia or PCR tests.[51812] Regimens are transplant center and recipient specific; consult local protocols.
5 mg/kg/dose IV twice daily for 7 to 14 days, followed by 5 mg/kg/dose IV once daily 7 days per week or 6 mg/kg/dose IV once daily 5 days per week is the FDA-approved dosage.[32676] 5 mg/kg/dose IV once daily starting within 10 days post-transplant and continuing for 3 months has been recommended. Studies have been conducted in recipients of kidney, kidney-pancreas, heart, heart-lung, liver, lung, and pancreas transplants.[24375] [24419]
5 mg/kg/dose IV once daily starting within 10 days post-transplant and continuing for up to 3 months has been recommended. Some protocols may extend therapy up to 6 months in highest risk patients. Regimens vary by transplant center, type of transplant, and recipient characteristics; consult local protocols. CMV hyperimmune globulin may be added to the ganciclovir regimen and/or the duration of IV therapy may vary.[32677]
5 mg/kg/day IV for the length of ATG therapy, followed by oral ganciclovir for 3 to 4 months, significantly reduced the incidence of CMV disease in patients who also were treated with ATG.[25495]
5 mg/kg/dose IV every 12 hours plus ganciclovir intravitreal injection and/or foscarnet intravitreal injection. The optimal duration has not been defined; duration should be determined clinically in consultation with an ophthalmologist.[34362]
5 mg/kg/dose IV every 12 hours plus ganciclovir intravitreal injection and/or foscarnet intravitreal injection. The optimal duration has not been defined; duration should be determined clinically in consultation with an ophthalmologist.[34362]
5 mg/kg/dose IV every 12 hours plus IV foscarnet plus ganciclovir intravitreal injection and/or foscarnet intravitreal injection. The optimal duration has not been defined; duration should be determined clinically in consultation with an ophthalmologist.[34361]
2 mg/0.05 mL intravitreal injection twice weekly, with or without foscarnet intravitreal injection, in combination with systemic therapy (i.e., ganciclovir or acyclovir). The optimal duration has not been defined; duration should be determined clinically in consultation with an ophthalmologist.[34362]
2 mg/0.05 mL intravitreal injection twice weekly, with or without foscarnet intravitreal injection, in combination with systemic therapy (i.e., ganciclovir or acyclovir). The optimal duration has not been defined; duration should be determined clinically in consultation with an ophthalmologist.[34362]
2 mg/0.05 mL intravitreal injection twice weekly, with or without foscarnet intravitreal injection, in combination with systemic therapy (i.e., acyclovir or ganciclovir plus foscarnet). The optimal duration has not been defined; duration should be determined clinically in consultation with an ophthalmologist.[34361]
5 mg/kg/dose IV every 12 hours for 3 weeks is recommended by the HIV guidelines.[34361] [34362]
5 mg/kg/dose IV every 12 hours may be useful as an adjunct to chemotherapy and antiretroviral therapy.[34361] [34362]
NOTE: Ganciclovir ophthalmic gel is an FDA-designated orphan drug for this indication.
1 drop in the affected eye(s) 5 times daily, approximately every 3 hours while awake, until corneal ulcer heals, then 1 drop in the affected eye(s) 3 times daily for 7 days.[36875]
1 drop in the affected eye(s) 5 times daily, approximately every 3 hours while awake, until corneal ulcer heals, then 1 drop in the affected eye(s) 3 times daily for 7 days.[36875]
2 mg/0.05 mL intravitreal injections given twice weekly until evidence of treatment response. Administer in combination with 10 to 14 days of IV acyclovir, then at least 14 weeks of oral valacyclovir is recommended by the HIV guidelines. Involvement of an experienced ophthalmologist is recommended.[34362]
2 mg/0.05 mL intravitreal injections given twice weekly until evidence of treatment response. Administer in combination with 10 to 14 days of IV acyclovir, then at least 14 weeks of oral valacyclovir is recommended by the HIV guidelines. Involvement of an experienced ophthalmologist is recommended.[34362]
NOTE: For CNS disease, see encephalitis.
5 mg/kg/dose IV every 12 hours. The American Academy of Pediatrics (AAP) recommends ganciclovir as the first line alternative when IV acyclovir is unavailable for herpes simplex/varicella zoster infections in immunocompromised hosts and patients unable to tolerate oral acyclovir or valacyclovir.[52560]
6 mg/kg/dose IV every 12 hours. The American Academy of Pediatrics (AAP) recommends ganciclovir as the first line alternative when IV acyclovir is unavailable in suspected or proven neonatal herpes simplex disease or herpes simplex/varicella zoster infections in immunocompromised hosts.[52560]
6 mg/kg/dose IV every 12 hours. The American Academy of Pediatrics (AAP) recommends ganciclovir as the first line alternative when IV acyclovir is unavailable in cases of suspected or proven neonatal herpes simplex disease.[52560]
5 mg/kg/dose IV every 12 hours for 1 to 3 weeks, followed by a maintenance dose of 5 mg/kg/dose IV once daily to 5 times weekly has been effective in small studies and case reports of immunocompromised adult patients with HHV-6 encephalitis.[57254] [57255] [57297] Ganciclovir alone or in combination with foscarnet is suggested as reasonable by the IDSA due to the lack of other therapeutic options.[34213]
5 mg/kg/dose IV every 12 hours for 1 to 3 weeks, followed by a maintenance dose of 5 mg/kg/dose IV once daily to 5 times weekly, has been effective in small studies and case reports of pediatric and adult patients with HHV-6 encephalitis.[52562] [57253] [57254] [57255] Higher doses of ganciclovir (18 to 24 mg/kg/day) have also been used in children, without side effects.[57253] [57296] Ganciclovir alone or in combination with foscarnet is suggested as reasonable by the IDSA due to the lack of other therapeutic options.[34213]
NOTE: Ganciclovir intravenous injection has been designated an orphan drug by the FDA for CMV retinitis.
NOTE: The HIV guidelines generally do not recommend ganciclovir for chronic suppressive therapy following acute CMV disease other than retinitis in adults and adolescents.[34362] In infants and children, chronic suppressive therapy is recommended after disseminated disease, neurologic disease, retinitis, or gastrointestinal disease with relapse.[34361]
NOTE: 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.[34361] [34362]
Following induction therapy for CMV retinitis, give chronic maintenance therapy of 5 mg/kg/dose IV daily for 7 days per week or 6 mg/kg/dose IV daily for 5 days per week; may switch to oral valganciclovir when the patient is clinically improving and there are no concerns about absorption. The duration of maintenance therapy depends on the immune status of the patient. For patients with HIV 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, secondary CMV retinitis prophylaxis may be discontinued after consultation with an ophthalmologist. Maintenance therapy should be restarted 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).[32676] [34362]
Following induction therapy for CMV retinitis, give chronic maintenance therapy of 5 mg/kg/dose IV daily; may switch to oral valganciclovir when the patient is clinically improving and there are no concerns about absorption. The duration of maintenance therapy depends on the immune status of the patient. For patients with HIV 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, secondary CMV retinitis prophylaxis may be discontinued after consultation with an ophthalmologist. Maintenance therapy should be restarted 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]
5 mg/kg/dose IV once daily is recommended as the preferred regimen in the HIV guidelines after induction therapy. Treatment duration depends on the immune status of the patient. Discontinuation of secondary prophylaxis may be considered in children 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]
2 mg intravitreally twice weekly for 3 weeks then weekly thereafter; alternately, 5 mg intravitreal injection once weekly has been studied.[32667] [32668]
10 mg/kg/day IV; 5 drops/day ophthalmic gel in each affected eye.
10 mg/kg/day IV; 5 drops/day ophthalmic gel in each affected eye.
Safety and efficacy have not been established for IV dosing; however, 10 mg/kg/day IV has been used off-label for the treatment of CMV infection. 5 drops/day ophthalmic gel in each affected eye.
2 to 12 years: Safety and efficacy have not been established for IV dosing; however, doses up to 15 mg/kg/day IV have been used off-label for the treatment of CMV infection. 5 drops/day ophthalmic gel in each affected eye.
1 year: Safety and efficacy have not been established; however, doses up to 15 mg/kg/day IV have been used off-label for the treatment of CMV infection.
Safety and efficacy have not been established; however, doses up to 15 mg/kg/day IV have been used off-label for the treatment of CMV infection.
Safety and efficacy have not been established; however, doses of 12 mg/kg/day IV have been used off-label for the treatment of congenital CMV disease.
No dosage adjustment necessary.
Modify dosage for intravenous induction therapy and maintenance therapy based on creatinine clearance (CrCl).
Adults:
Intravenous dosage adjustments (induction)
CrCl 70 mL/minute or more: no dosage adjustment needed.
CrCl 50 to 69 mL/minute: 2.5 mg/kg/dose IV every 12 hours.
CrCl 25 to 49 mL/minute: 2.5 mg/kg/dose IV every 24 hours.
CrCl 10 to 24 mL/minute: 1.25 mg/kg/dose IV every 24 hours.
CrCl less than 10 mL/minute: 1.25 mg/kg/dose IV 3 times a week after hemodialysis.
Intravenous dosage adjustments (maintenance)
CrCl 70 mL/minute or more: no dosage adjustment needed.
CrCl 50 to 69 mL/minute: 2.5 mg/kg/dose IV every 24 hours.
CrCl 25 to 49 mL/minute: 1.25 mg/kg/dose IV every 24 hours.
CrCl 10 to 24 mL/minute: 0.625 mg/kg/dose IV every 24 hours.
CrCl less than 10 mL/minute: 0.625 mg/kg/dose IV 3 times a week after hemodialysis.
Intermittent hemodialysis or Peritoneal dialysis
1.25 mg/kg/dose IV 3 times per week. Give all doses after dialysis sessions.[32569]
Continuous renal replacement therapy
Intravenous dosage adjustments (induction): 2.5 mg/kg/dose IV every 24 hours.
Intravenous dosage adjustments (maintenance): 1.25 mg/kg/dose IV every 24 hours.[32569]
Pediatrics:
Intravenous dosage adjustments (induction)
GFR 30 to 50 mL/minute/1.73 m2: 2.5 mg/kg/dose IV every 24 hours.
GFR 10 to 29 mL/minute/1.73 m2: 1.25 mg/kg/dose IV every 24 hours.
GFR less than 10 mL/minute/1.73 m2: 1.25 mg/kg/dose IV 3 times a week.[32569]
Intravenous dosage adjustments (maintenance)
GFR 30 to 50 mL/minute/1.73 m2: 1.25 mg/kg/dose IV every 24 hours.
GFR 10 to 29 mL/minute/1.73 m2: 0.625 mg/kg/dose IV every 24 hours.
GFR less than 10 mL/minute/1.73 m2: 0.625 mg/kg/dose IV 3 times a week.[32569]
Intermittent hemodialysis or Peritoneal dialysis
Give all doses after dialysis sessions.
Intravenous dosage adjustments (induction): 1.25 mg/kg/dose IV 3 times per week.
Intravenous dosage adjustments (maintenance): 0.625 mg/kg/dose IV 3 times per week.[32569]
Continuous renal replacement therapy
Intravenous dosage adjustments (induction): 2.5 mg/kg/dose IV every 24 hours.
Intravenous dosage adjustments (maintenance): 1.25 mg/kg/dose IV every 24 hours.[32569]
† Off-label indication
Ganciclovir is a synthetic, purine nucleoside analog used for the treatment and prevention of cytomegalovirus (CMV) infections. An ophthalmic gel is used for the treatment of herpetic keratitis.[32676] In addition, ganciclovir has been shown to be active against other viruses, including herpes simplex, varicella zoster, and human herpesvirus 6 and 8.[34362] Hematologic toxicity is common with systemic ganciclovir administration; dosage adjustments for neutropenia or thrombocytopenia may be required. The FDA originally approved intravenous ganciclovir in June 1989. Ganciclovir ophthalmic gel (Virgan) was given an orphan drug designation for acute herpetic keratitis in April 2007 and was granted full approval (Zirgan) in September of 2009.[36875][32676] Ganciclovir oral capsules and intraocular implant were withdrawn from the US market in 2013.
For storage information, see the specific product information within the How Supplied section.
Hazardous Drugs Classification
Reconstitution
Dilution
Premixed IV solution
Intermittent IV Infusion
Intravitreal injection†
NOTE: Ganciclovir is not approved by the FDA for administration via intravitreal injection.
Ganciclovir can cause significant bone marrow suppression. Anemia (2% to 26%), neutropenia (3% to 29%), pancytopenia, leukopenia (29% to 41%), thrombocytopenia (3% to 57%), and bone marrow failure all can occur. In addition, hemolytic anemia, agranulocytosis, and granulocytopenia have been noted during postmarketing reports.[32676] Related symptoms can include unusual bleeding or bruising. Both granulocytopenia and thrombocytopenia are usually reversible and respond to a dose reduction. Use of the drug is not recommended in patients with neutropenia defined as an absolute neutrophil count (ANC) less than 500 cells/mm3, anemia with hemoglobin less than 8 g/dL, or thrombocytopenia with a platelet count less than 25,000 cells/mm3. In neonates, ganciclovir therapy has been resumed when ANC is 750 cells/mm3 or more; then after treatment re-initiation, the dose reduced to one-half if subsequent ANC is less than 500/mm3, and therapy discontinued if neutropenia persisted while on the reduced dose.[32656] The incidence of hematologic reactions may be higher in bone marrow transplant patients and less in other transplant patients. The hematologic toxicity usually develops within the early weeks of therapy and is generally dose-related and reversible, but occasionally it can be prolonged or irreversible. Blood counts usually begin to recover within 3 to 7 days of discontinuing the drug. Colony-stimulating factors have been shown to increase neutrophil counts in patients receiving ganciclovir.[32676]
The most common gastrointestinal adverse effects of systemic ganciclovir include abdominal pain, anorexia (14% to 15%), diarrhea (41% to 44%), nausea, vomiting (13%), dysgeusia, and flatulence. Other GI-related adverse events include aphthous stomatitis, constipation, dyspepsia, eructation, GI perforation, pancreatitis, weight loss, and xerostomia (dry mouth). Intestinal ulceration was noted during postmarketing surveillance.[32676]
Adverse CNS effects are fairly common during systemic ganciclovir therapy and include abnormal dreams, anxiety, confusion, depression, dizziness, headache, insomnia, drowsiness and fatigue, dysphagia, hypoesthesia, abnormal thinking, paresthesias, peripheral neuropathy (8% to 9%), tremor, or more serious reactions such as seizures.[32676] Very few cases of ganciclovir-induced seizures have been reported.[23647] Other adverse events noted during postmarketing surveillance include dysesthesia, dysphasia, aphasia, encephalopathy, extrapyramidal reaction, facial palsies or cranial nerve palsies, hallucinations, increased intracranial pressure, irritability, loss of memory and memory impairment, oculomotor nerve paralysis, and stroke.[32676] Some CNS adverse effects have been caused by opportunistic infection rather than by the drug.
Systemic ganciclovir is moderately nephrotoxic. Mild to moderate increases in serum creatinine have been reported during therapy. In general, this adverse reaction occurs during the first week of therapy and is reversible. If renal function worsens during therapy, the ganciclovir dosage should be reduced since ganciclovir is extensively eliminated unchanged via glomerular filtration. Patients receiving ganciclovir following transplantation seem to have a higher incidence of nephrotoxicity as compared to patients treated for CMV retinitis. Between 12% to 58% of patients may experience serum creatinine concentrations of 1.5 to 2.4 mg/dL; serum creatinine concentrations of 2.5 mg/dL or more may be seen in up to 20% of patients. Renal failure (unspecified), decreased creatinine clearance, abnormal renal function, hematuria, increased urinary frequency, and urinary retention have also been reported with ganciclovir therapy. Hemolytic-uremic syndrome and renal tubular disorder were noted in postmarketing reports.[32676]
Dermatologic and allergic adverse effects reported during ganciclovir therapy include alopecia, hyperhidrosis (11% to 12%), pruritus (5% to 6%), dermatitis, rash (unspecified), urticaria, and xerosis (dry skin). Phlebitis or injection site reaction (e.g., local inflammation, pain) can occur with IV ganciclovir. Rash, pruritus, or urticaria may indicate hypersensitivity to ganciclovir. Allergic reaction, anaphylactoid reactions, exfoliative dermatitis, and Stevens-Johnson syndrome have been noted in postmarketing reports.[32676]
Ganciclovir is considered a potential carcinogen in humans and may cause a new primary malignancy. Ganciclovir has been associated with clastogenesis during in vitro testing at doses 2.8- to 10-times the normal human dose but not at doses comparable to human exposure. Tumors have developed in mice treated with approximately one-tenth to 1.4 times the human dose. Most tumors were of epithelial or vascular origin, although histiocytic sarcoma of the liver was reported. Tumors appeared in some tissues for which there is no human counterpart.[32676]
Animal and limited human data indicate that ganciclovir may cause temporary or permanent spermatogenesis inhibition and subsequent infertility in males and suppression of fertility in females. Effects on spermatogenesis were reversible at lower doses and irreversible at higher doses. In addition, ganciclovir causes teratogenesis in animals and should not be used during pregnancy. Advise women of childbearing potential about the necessity of using effective contraception during treatment. Females should use effective contraception during and for at least 30 days after treatment with ganciclovir. Males must practice barrier contraception during and for at least 90 days after treatment with ganciclovir.[28463] [32676]
Infection (9% to 13%), sepsis (4% to 15%), catheter-related infection (4% to 9%), and catheter-related sepsis (1% to 8%) were reported during ganciclovir clinical trials. Other, less frequently reported infections included cellulitis, influenza, upper respiratory tract infections, urinary tract infections, and candida infections including oral candidiasis.[32676]
General adverse events associated with the use of systemic ganciclovir include fever (38% to 48%), chills (7% to 10%), enlarged abdomen, asthenia, chest pain (unspecified), congenital anomaly, edema, malaise, unspecified pain, testicular hypotrophy/testicular atrophy, and potentially fatal multiple organ failure.[32676]
Elevated hepatic enzymes were reported with the use of systemic ganciclovir. Hepatic failure, cholelithiasis, cholestasis, and hepatitis were noted during postmarketing reports.[32676]
Tinnitus, otalgia, and hearing loss (deafness) were reported with the use of systemic ganciclovir. Loss of the sense of smell (anosmia) was noted during postmarketing reports.[32676]
Increased cough and dyspnea were reported with systemic ganciclovir. Bronchospasm and pulmonary fibrosis were noted during postmarketing reports.[32676]
Arthralgia, muscle cramps, muscle spasms, back pain, myalgia, and myasthenia have been reported with the use of systemic ganciclovir. Other adverse events noted during postmarketing surveillance include arthritis, myelopathy, and rhabdomyolysis.[32676]
Hypertension, hypotension, arrhythmia exacerbation, and peripheral vasodilation were reported with the use of systemic ganciclovir. Other cardiovascular adverse events reported during postmarketing surveillance include cardiac arrest, cardiac conduction abnormalities, peripheral ischemia, torsade de pointes, vasculitis, and ventricular tachycardia.[32676]
Retinal detachment may occur with systemic (8% to 11% of adults) administration of ganciclovir; however, the precise relationship to the drug is not clear. Retinal detachment has occurred in patients with CMV retinitis both before and after initiation of ganciclovir therapy.[32676] Adverse reactions associated with administration of ganciclovir ophthalmic gel include blurred vision (60%), ocular irritation (20%), punctate keratitis (5%), and conjunctival hyperemia (5%).[36875] Other ocular reactions noted with systemic ganciclovir include abnormal vision or visual impairment, ocular pain, conjunctivitis, macular edema, and vitreous disorder. Xerophthalmia and cataracts were noted in postmarketing reports with systemic ganciclovir.[32676]
Metabolic adverse events noted during postmarketing surveillance with ganciclovir include metabolic acidosis, hypertriglyceridemia, hypercalcemia, hyponatremia, and syndrome of inappropriate antidiuretic hormone secretion (SIADH).[32676]
Ganciclovir is contraindicated in patients with a significant ganciclovir hypersensitivity, valganciclovir hypersensitivity, or acyclovir hypersensitivity.[32676] [61771] Although not specifically contraindicated by the manufacturer, ganciclovir ophthalmic gel should be used with extreme caution in these patients as well. Because of similar chemical structures and possible cross-sensitivity, ganciclovir should not be used in patients with famciclovir hypersensitivity, penciclovir hypersensitivity, or valacyclovir hypersensitivity. Alternative agents such as foscarnet or cidofovir may be suitable since they are not structurally related to these antivirals.
Use systemic ganciclovir with caution in patients with bone marrow suppression or to those who are receiving other myelosuppressive chemotherapy or radiation therapy. Severe anemia, leukopenia, neutropenia, pancytopenia, and thrombocytopenia have been reported during ganciclovir therapy. The frequency and severity of these events vary widely in different patient populations. Patients with neutropenia (absolute neutrophil count (ANC) less than 500 cells/mm3), anemia (hemoglobin less than 8 g/dL), or thrombocytopenia (platelet count less than 25,000 cells/mm3) should not receive the drug. Complete blood counts with differential and platelet counts should be performed frequently, especially in patients who have experienced previous drug-induced leukopenia or in patients with a baseline ANC less than 1,000 cells/mm3. The manufacturer notes that ganciclovir should only be used as indicated within the prescribing information; avoid unnecessary use.[32676] [61771]
Ganciclovir toxicity may be increased with rapid administration which results in excessive plasma levels. Do not administer ganciclovir by rapid or bolus IV, instead administer by slow IV infusion at a constant rate over 1 hour. Do not give ganciclovir by subcutaneous administration or intramuscular administration.[32676] [61771]
Adjust systemic ganciclovir dosage in patients with renal impairment because it is primarily eliminated unchanged via renal mechanisms. Avoid dehydration in patients on ganciclovir therapy; maintain renal elimination with adequate hydration and fluid intake. The risk of toxic reactions to ganciclovir is greater in patients with renal impairment, especially renal failure. Although clinical studies did not include sufficient numbers of geriatric patients, dose selection for these patients should be cautious, reflecting the greater frequency of decreased cardiac, hepatic, or renal function, and of concomitant disease or drug therapy.[32676]
Take care to avoid accidental exposure to ganciclovir during preparation, handling or administration, due to the potential mutagenicity and alkaline pH of intravenous ganciclovir. Although human data are not available, the development of neoplastic disease is a potential risk to consider during ganciclovir therapy based on animal carcinogenicity data. The use of protective gowns, gloves and goggles is recommended. Avoid direct contact of ganciclovir solution with skin or mucous membranes. If skin contact occurs, wash thoroughly with soap and water. Following ocular exposure, rinse eyes thoroughly with plain water. Consider handling and disposing of ganciclovir according to guidelines issued for antineoplastic agents. There is no agreement that all the procedures recommended in the guidelines are necessary or appropriate for ganciclovir. The manufacturer notes that ganciclovir should only be used as indicated within the prescribing information; avoid unnecessary use.[32676]
Because of the potential for long-term carcinogenicity and reproductive toxicity, carefully consider the risks and benefits of using systemic ganciclovir therapy in neonates, infants, children, and adolescents. Carcinogenicity and impaired fertility have occurred in animal models at doses similar to those used in humans; the precise risk in human patients is not known. Although specific human data are not available, it is considered probable in humans that ganciclovir at recommended doses may cause temporary or permanent inhibition of spermatogenesis.[32676]
Ganciclovir is associated with reproductive risk. The drug can be teratogenic if taken by the father near the time of conception (male-mediated teratogenicity) or by the mother during pregnancy. Discuss contraception requirements with the patient. Females should use effective contraception during and for at least 30 days after treatment with ganciclovir. Males must use a condom during and for at least 90 days after treatment. Females of reproductive potential should undergo pregnancy testing prior to initiation of ganciclovir. In addition, based on animal and limited human data, ganciclovir may cause temporary or permanent inhibition of spermatogenesis and subsequent infertility. Animal studies also indicate that suppression of fertility in females may occur.[32676]
Antimicrobial resistance to ganciclovir may develop following prolonged treatment and has been reported in ganciclovir naive individuals. The possibility of viral resistance should be considered in patients who show poor clinical response or who experience persistent viral excretion during therapy.[32676]
There are no adequate and well-controlled human studies evaluating use of ganciclovir during pregnancy; however, based on data from animal studies, ganciclovir may be teratogenic or embryotoxic at doses recommended for human use. If considering use of ganciclovir in a pregnant female, consider that most maternal CMV infections are subclinical or may be associated with mononucleosis-like syndrome. However, in immunocompromised patients, CMV infections are often symptomatic and associated with significant morbidity and mortality. Also consider that the risk and severity of congenital CMV infection appear to be higher in infants born to mother with primary CMV infection than in those born to mothers with reactivation of the disease. Of the newborns who are infected with CMV, only 10% are symptomatic at birth and the mortality rate among symptomatic infants is about 10%; however, approximately 50% to 90% of the surviving infants may experience significant problems, including sensorineural hearing loss, mental retardation, and other neurologic defects. It is not known if topically administered ophthalmic ganciclovir could result in significant systemic absorption; therefore, the manufacturer recommends the administration of ophthalmic ganciclovir to pregnant women only if the potential benefit to the mother outweighs the potential risk to the fetus.[32676] [36875] [61771]
It is not known if ganciclovir is excreted into breast milk. Due to the potential for serious adverse reactions in nursing infants, the manufacturer recommends instructing mothers to stop or not to start breast-feeding if they are receiving ganciclovir. Additionally, ganciclovir 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. It is not known if topically administered ophthalmic ganciclovir could result in sufficient systemic absorption to produce detectable quantities in breast milk; therefore, the manufacturer recommends caution if ophthalmic ganciclovir is administered to breast-feeding women. 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 maternally ingested or administered drug, health care providers are encouraged to report the adverse effect to the FDA.[32676] [36875] [46675]
Contact lenses should be removed prior to administration of ganciclovir ophthalmic gel. Ganciclovir ophthalmic gel contains the preservative benzalkonium chloride, which may be absorbed by soft contact lenses. Patients should not wear contact lenses if they have signs or symptoms of herpetic keratitis or during the course of therapy with ganciclovir ophthalmic gel. Ganciclovir ophthalmic gel is indicated for topical ophthalmic use only.[36875]
Ganciclovir is a synthetic analog of 2'-deoxyguanosine and inhibits the replication of human cytomegalovirus (CMV). In CMV-infected cells, ganciclovir is initially phosphorylated to ganciclovir monophosphate by the viral protein kinase pUL97. Further phosphorylation by protein kinases produces ganciclovir triphosphate. Ganciclovir triphosphate inhibits viral DNA synthesis by competitive inhibition of viral DNA polymerases and incorporation into viral DNA resulting in eventual termination of viral DNA elongation. Since phosphorylation is dependent upon viral protein kinases, ganciclovir is preferentially metabolized in virus-infected cells. Ganciclovir triphosphate concentrations may be 100-fold greater in CMV-infected cells than in uninfected cells. As sensitivity tests vary due to many factors, the concentration of ganciclovir to inhibit the growth of virus in cell culture by 50% (IC50) ranges from 0.02—3.48 mcg/mL. Ganciclovir inhibits mammalian cell proliferation (CIC50) in vitro at higher concentrations ranging from 30—725 mcg/mL; however, bone marrow cells are more sensitive (CIC50 0.028—0.7 mcg/mL).
Resistance to ganciclovir may occur after prolonged treatment with valganciclovir by selection of mutations in either the viral protein kinase (UL97) and/or in the viral polymerase gene (UL54). Virus with mutations in the UL97 gene is resistant to ganciclovir alone, whereas virus with mutations in the UL54 gene may show cross-resistance to other antiviral agents with a similar mechanism of action. The current definition of CMV resistance to ganciclovir in vitro is IC50 >= 1.5 mcg/mL. CMV resistance to ganciclovir has been observed in individuals with AIDS and CMV retinitis who have never received ganciclovir therapy.
Revision Date: 03/19/2024, 01:37:00 AMGanciclovir is administered intravenously, by topical ophthalmic administration, and by intravitreal injection. Ganciclovir crosses the blood-brain barrier, producing CSF concentrations that average about 40% (range 24% to 70%) of plasma concentrations. Ganciclovir crosses the placenta. It is not known if ganciclovir is excreted into breast milk. Protein binding is roughly 1% to 2%. Ganciclovir undergoes little or no metabolism. Ganciclovir is excreted primarily in the urine, with about 90% excreted unchanged by glomerular filtration and active tubular secretion.[32676]
Affected cytochrome P450 isoenzymes: none
Following IV administration of ganciclovir, distribution into body tissues and fluids is extensive including significant intraocular penetration. The half-life in patients with normal renal function is about 3.5 hours following IV administration.[32676]
Ophthalmic Route
Minimal systemic exposure is expected with topical ophthalmic administration of ganciclovir gel.[36875]
Half-life of ganciclovir increases in patients with impaired renal function. Patients with an estimated creatinine clearance < 25 mL/minute achieved a mean half-life of 10.7 hours. Hemodialysis reduces ganciclovir concentrations by about 50%.[32676]
The pharmacokinetics of IV ganciclovir in pediatric patients are similar to those seen in adults.
Infants, Children, and Adolescents
The Cmax, systemic clearance, and half-life of ganciclovir in 10 infants and children (9 months to 12 years of age) after doses of 5 mg/kg IV were 7.9 mcg/mL, 4.7 mL/minute/kg, and 2.4 hours, respectively.[32676]
Neonates
The Cmax, systemic clearance, and half-life of ganciclovir in 27 neonates (2 to 49 days postnatal age, gestational age not specified) after doses of 4 to 6 mg/kg IV were 5.5 to 7 mcg/mL, 3.14 to 3.56 mL/minute/kg, and 2.4 hours, respectively.[32676]
There are no adequate and well-controlled human studies evaluating use of ganciclovir during pregnancy; however, based on data from animal studies, ganciclovir may be teratogenic or embryotoxic at doses recommended for human use. If considering use of ganciclovir in a pregnant female, consider that most maternal CMV infections are subclinical or may be associated with mononucleosis-like syndrome. However, in immunocompromised patients, CMV infections are often symptomatic and associated with significant morbidity and mortality. Also consider that the risk and severity of congenital CMV infection appear to be higher in infants born to mother with primary CMV infection than in those born to mothers with reactivation of the disease. Of the newborns who are infected with CMV, only 10% are symptomatic at birth and the mortality rate among symptomatic infants is about 10%; however, approximately 50% to 90% of the surviving infants may experience significant problems, including sensorineural hearing loss, mental retardation, and other neurologic defects. It is not known if topically administered ophthalmic ganciclovir could result in significant systemic absorption; therefore, the manufacturer recommends the administration of ophthalmic ganciclovir to pregnant women only if the potential benefit to the mother outweighs the potential risk to the fetus.[32676] [36875] [61771]
It is not known if ganciclovir is excreted into breast milk. Due to the potential for serious adverse reactions in nursing infants, the manufacturer recommends instructing mothers to stop or not to start breast-feeding if they are receiving ganciclovir. Additionally, ganciclovir 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. It is not known if topically administered ophthalmic ganciclovir could result in sufficient systemic absorption to produce detectable quantities in breast milk; therefore, the manufacturer recommends caution if ophthalmic ganciclovir is administered to breast-feeding women. 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 maternally ingested or administered drug, health care providers are encouraged to report the adverse effect to the FDA.[32676] [36875] [46675]
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