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  • CLASSES

    Nucleoside and Nucleotide DNA Polymerase Inhibitor Antivirals
    Ophthalmological Antiviral Agents

    BOXED WARNING

    Anemia, bone marrow suppression, chemotherapy, leukopenia, neutropenia, radiation therapy, thrombocytopenia

    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.

    Accidental exposure, neoplastic disease, ocular exposure

    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.

    Contraception requirements, infertility, male-mediated teratogenicity, pregnancy testing, reproductive risk

    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.
     

    Pregnancy

    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.

    DEA CLASS

    Rx

    DESCRIPTION

    Synthetic purine nucleoside analog antiviral
    Used for prevention and treatment of CMV; ophthalmic gel approved for acute herpetic keratitis
    Dose adjustment may be required for hematological toxicity (neutropenia, thrombocytopenia)
    .

    COMMON BRAND NAMES

    Cytovene, Zirgan

    HOW SUPPLIED

    Cytovene/Ganciclovir/Ganciclovir Sodium Intravenous Inj Pwd F/Sol: 500mg
    Ganciclovir Intravenous Inj Sol: 1mL, 2mg, 50mg
    Vitrasert Intravitreal Imp: 4.5mg
    Zirgan Ophthalmic Gel: 0.15%

    DOSAGE & INDICATIONS

    For induction treatment of cytomegalovirus (CMV) retinitis in immunocompromised patients, including persons with HIV.
    Intravenous dosage
    Adults and Adolescents†

    5 mg/kg/dose IV every 12 hours for 14 to 21 days as an initial therapy. Systemic therapy may be combined with intravitreal injections of ganciclovir (2 mg/injection) or foscarnet (2.4 mg/injection) for immediate sight-threatening lesions (i.e., within 1,500 microns of the fovea). Following induction therapy, give chronic maintenance therapy.

    Infants† and Children†

    5 mg/kg/dose IV every 12 hours for 14 to 21 days; may increase to 7.5 mg/kg/dose IV every 12 hours if needed. For children with sight-threatening disease, the addition of IV foscarnet may also be considered. CMV is not eradicated once contracted; follow induction treatment with secondary prophylaxis (chronic maintenance therapy).

    Intravitreal dosage†
    Adults and Adolescents

    For patients with immediate sight-threatening lesions (i.e., within 1,500 microns of the fovea), give 2 mg intravitreal injections once weekly until lesion inactivity is achieved. Intravitreal injections are given to achieve rapid high intraocular drug concentrations and should be administered in combination with systemic induction therapy.

    For cytomegalovirus (CMV) disease prophylaxis in patients at risk for CMV disease.
    For prophylaxis in allogeneic hematopoietic cell transplant (HCT) recipients.
    Intravenous dosage
    Adults

    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. Other studies have examined similar doses starting 5 to 7 days prior to transplantation. Regimens are transplant center and recipient specific; high dose acyclovir or other co-therapies may be utilized.

    Infants†, Children†, and Adolescents†

    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. Regimens are transplant center and recipient specific; consult local protocols.

    For solid organ transplant recipients who are CMV-seropositive or CMV-seronegative receiving an organ from a CMV-seropositive donor.
    NOTE: Treatment regimens are organ, transplant center, and recipient specific; CMV hyperimmune globulin may be added to the ganciclovir regimen and/or the duration of IV therapy may vary from 14 days to 6 months, with total ganciclovir treatment duration of 3 to 6 months.
    Intravenous dosage
    Adults

    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. 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.

    Children† and Adolescents†

    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.

    For solid organ transplant recipients who are CMV-seropositive and receiving immunosuppressive induction therapy (i.e., transplant rejection treatment) with antithymocyte globulin (ATG)†.
    Intravenous dosage
    Adults

    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.

    For preemptive therapy in hematopoietic cell transplant (HCT) recipients who are less than 100 days post HCT†.
    Intravenous dosage
    Adults

    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). Regimens are transplant center and recipient specific; consult local protocols.

    Infants, Children, and Adolescents

    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). Regimens are transplant center and recipient specific; consult local protocols.

    For preemptive therapy in hematopoietic cell transplant (HCT) recipients who are more than 100 days post HCT†.
    Intravenous dosage
    Adults

    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. Regimens are transplant center and recipient specific; consult local protocols.

    Infants, Children, and Adolescents

    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. Regimens are transplant center and recipient specific; consult local protocols.

    For the treatment of acute herpes simplex keratitis (dendritic keratitis).
    NOTE: Ganciclovir ophthalmic gel is an FDA-designated orphan drug for this indication.
    Ophthalmic dosage (Zirgan 0.15% ophthalmic gel)
    Adults, Adolescents, and Children >= 2 years

    1 drop in the affected eye(s) 5 times per day (approximately every 3 hours while awake) until corneal ulcer heals, and then 1 drop in the affected eye(s) 3 times per day for 7 days.  In an open-label, randomized, controlled multicenter trial (n = 164) and in randomized, single-masked, controlled, multicenter trials (total n = 213), ganciclovir ophthalmic gel was non-inferior to acyclovir 3% ointment with clinical resolution (healed ulcers) at day 7 in 72—77% of ganciclovir patients and 69—72% of acyclovir patients.

    For chronic suppressive therapy of cytomegalovirus (CMV) disease, including CMV retinitis (i.e., secondary cytomegalovirus (CMV) retinitis prophylaxis) in patients with HIV.
    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. In infants and children, chronic suppressive therapy is recommended after disseminated disease, neurologic disease, retinitis, or gastrointestinal disease with relapse.
    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.
    Intravenous dosage
    Adults

    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).

    Adolescents†

    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).

    Infants† and Children†

    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.

    Intravitreal injection dosage†
    Adults

    2 mg intravitreally twice weekly for 3 weeks then weekly thereafter; alternately, 5 mg intravitreal injection once weekly has been studied.

    For the treatment of viral encephalitis†.
    For varicella-zoster (herpes zoster) encephalitis† as an alternative to acyclovir.
    Intravenous dosage
    Adults

    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.

    Infants 4 months and older, Children, and Adolescents

    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.

    Neonates and Infants 1 to 3 months

    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.

    For the treatment of cytomegalovirus (CMV) encephalitis† and for the treatment of cytomegalovirus (CMV) neurological disease† (including encephalitis†) in HIV-infected patients.
    Intravenous dosage
    Adults and Adolescents

    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.

    Infants and Children

    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.

    Neonates

    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.

    For encephalitis† due to B virus (cercopithecine herpesvirus) infection† as an alternative to valacyclovir.
    Intravenous dosage
    Adults, Adolescents, Children, and Infants

    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.

    For the treatment of cytomegalovirus (CMV)-associated gastrointestinal disease† (e.g., esophagitis†, gastroenteritis†, or colitis†).
    In HIV-infected patients.
    Intravenous dosage
    Adults

    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.

    Adolescents

    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.

    Infants and Children

    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.

    In patients who have undergone a bone marrow transplant (BMT).
    Intravenous dosage
    Adults

    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.

    For the treatment of cytomegalovirus (CMV) pneumonitis†.
    Intravenous dosage
    Adults

    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. 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. 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.

    Adolescents

    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. 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.

    Infants and Children

    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. 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.

    For the treatment of symptomatic congenital cytomegalovirus (CMV) disease†.
    Intravenous dosage
    Neonates and Infants

    6 mg/kg/dose IV every 12 hours for 6 weeks. Dosage adjustments for the development of neutropenia may be required. 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. Clinical practice guidelines recommend antiviral treatment only for symptomatic neonates (first 30 days of life) with severe symptomatic focal organ disease or CNS disease.

    For the treatment of progressive outer retinal necrosis (PORN)† due to varicella zoster virus (VZV)† in HIV-infected patients.
    Intravenous dosage
    Adults

    5 mg/kg/dose IV every 12 hours plus ganciclovir intravitreal injection twice weekly AND/OR foscarnet intravitreal injection twice weekly, is recommended by the HIV guidelines. The optimal duration has not been defined; duration should be determined clinically in consultation with an ophthalmologist.

    Adolescents

    5 mg/kg/dose IV every 12 hours plus ganciclovir intravitreal injection twice weekly AND/OR foscarnet intravitreal injection twice weekly, is recommended by the HIV guidelines. The optimal duration has not been defined; duration should be determined clinically in consultation with an ophthalmologist.

    Infants and Children

    5 mg/kg/dose IV every 12 hours plus IV foscarnet plus ganciclovir intravitreal injection twice weekly AND/OR foscarnet intravitreal injection twice weekly is recommended by the HIV guidelines. The optimal duration has not been defined; duration should be determined clinically in consultation with an ophthalmologist.

    Intravitreal dosage
    Adults

    2 mg/0.05 mL intravitreal injection twice weekly, with or without foscarnet 1.2 mg/0.05 mL intravitreal injection twice weekly, in combination with systemic therapy (i.e., ganciclovir or acyclovir) is recommended by the HIV guidelines. The optimal duration has not been defined; duration should be determined clinically in consultation with an ophthalmologist.

    Adolescents

    2 mg/0.05 mL intravitreal injection twice weekly, with or without foscarnet 1.2 mg/0.05 mL intravitreal injection twice weekly, in combination with systemic therapy (i.e., ganciclovir or acyclovir) is recommended by the HIV guidelines. The optimal duration has not been defined; duration should be determined clinically in consultation with an ophthalmologist.

    Infants and Children

    2 mg/0.05 mL intravitreal injection twice weekly, with or without foscarnet 1.2 mg/0.05 mL intravitreal injection twice weekly, in combination with systemic therapy is recommended by the HIV guidelines. The optimal duration has not been defined; duration should be determined clinically in consultation with an ophthalmologist.

    For the treatment of severe human herpesvirus 8 (HHV-8) infection† and associated diseases in HIV-infected patients, including multicentric Castleman disease† (MCD) and primary effusion lymphoma† (PEL).
    For multicentric Castleman disease (MCD)†.
    Intravenous dosage
    Adults, Adolescents, Children, and Infants

    5 mg/kg/dose IV every 12 hours for 3 weeks is recommended by the HIV guidelines.

    Primary effusion lymphoma† (PEL).
    Intravenous dosage
    Adults, Adolescents, Children, and Infants

    5 mg/kg/dose IV every 12 hours may be useful as an adjunct to chemotherapy and antiretroviral therapy.

    For the treatment of acute retinal necrosis (ARN)† due to varicella-zoster virus in patients with HIV.
    Intravitreal dosage
    Adults

    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.

    Adolescents

    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.

    For the treatment of herpes simplex virus infection† or varicella (chickenpox) infection† due to varicella-zoster virus in hospitalized immunocompromised patients unable to take oral therapy.
    NOTE: For CNS disease, see encephalitis.
    Intravenous dosage
    Infants 4 months and older, Children, and Adolescents

    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.

    Neonates and Infants 1 to 3 months

    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.

    For the treatment of neonatal herpes simplex virus infection†.
    Intravenous dosage
    Neonates and Infants 1 to 3 months

    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.

    For the treatment of encephalitis caused by human herpesvirus 6 (HHV-6) infection† in immunocompromised patients.
    Intravenous dosage
    Adults

    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. Ganciclovir alone or in combination with foscarnet is suggested as reasonable by the IDSA due to the lack of other therapeutic options.

    Infants, Children, and Adolescents

    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. Higher doses of ganciclovir (18 to 24 mg/kg/day) have also been used in children, without side effects. Ganciclovir alone or in combination with foscarnet is suggested as reasonable by the IDSA due to the lack of other therapeutic options.

    †Indicates off-label use

    MAXIMUM DOSAGE

    Adults

    10 mg/kg/day IV; 5 drops/day ophthalmic gel in each affected eye.

    Geriatric

    10 mg/kg/day IV; 5 drops/day ophthalmic gel in each affected eye.

    Adolescents

    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.

    Children

    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.

    Infants

    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.

    Neonates

    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.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    No dosage adjustment necessary.

    Renal Impairment

    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.
     
    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.
     
    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.
     
    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.
     
    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.
     
    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.

    ADMINISTRATION

     
    Perform frequent hematologic monitoring in patients during treatment and do not administer if the absolute neutrophil count (ANC) is less than 500 cells/mm3, hemoglobin is less than 8 g/dL, or the platelet count is less than 25,000 cells/mm3.
    Use caution when handling and preparing parenteral solutions. Consider handling and disposing of 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.

    Injectable Administration

    Use caution when preparing and administering the product to avoid direct contact with skin. If contact occurs, wash the area thoroughly with soap and water. Ganciclovir solution for injection is alkaline and may cause irritation.
    Do NOT administer by rapid infusion or injection; toxicity may be increased.
    Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit; the solution should be colorless. Discard if discoloration or particulate matter is observed.

    Intravenous Administration

    Reconstitution
    Reconstitute 500 mg vials with 10 mL of Sterile Water for Injection. Do NOT use Bacteriostatic Water for Injection containing parabens or precipitation may occur.
    Gently swirl vial until a clear reconstituted solution is obtained.
    Storage: Reconstituted vials are stable at room temperature 25 degrees C (77 degrees F) for 12 hours. Do not refrigerate or freeze. Discard any unused portion of the reconstituted solution.
     
    Dilution
    Withdraw appropriate dose of reconstituted solution and dilute with 50 to 250 mL of a compatible IV infusion solution including 0.9% Sodium Chloride Injection, 5% Dextrose Injection, Ringer's Solution for Injection, or Lactated Ringer's Injection. Infusion concentrations greater than 10 mg/mL are not recommended.
    Storage: Once further diluted in an IV solution, use within 24 hours to reduce the risk of bacterial contamination. Refrigerate the diluted infusion solution at 2 to 8 degrees C (36 to 46 degrees F). Do not freeze.
     
    Premixed IV solution
    Dilution is not required.
    Solution does not contain preservatives and is for single use only. Any unused portion must be discarded.
     
    Intermittent IV Infusion
    Infuse slowly over 1 hour at a constant rate via a large peripheral or central vein with adequate blood flow to permit rapid dilution and distribution. The infusion should be accompanied by adequate hydration.
    A controlled-infusion device is recommended for highly concentrated solutions.

    Other Injectable Administration

    Intravitreal injection†
    NOTE: Ganciclovir is not approved by the FDA for administration via intravitreal injection.
    Reconstitute and dilute ganciclovir IV powder in 0.9% NaCl Injection to a concentration of 2 mg/0.04 mL to 2 mg/0.1 mL. Doses of 5 mg/0.1 mL have also been used in adults.
    Inject appropriate dose intravitreally using a tuberculin syringe.

    Ophthalmic Administration

    Ganciclovir ophthalmic gel is for topical ophthalmic use only.
    To avoid contamination or the spread of infection, do not use dropper for more than 1 person.
    Do not to touch the tip of the dropper to the eye, fingertips, or other surface to prevent contamination.
    Instruct patient on proper instillation of eye gel (see Patient Information).
    Wash hands before and after use. Tilt the head back slightly and pull the lower eyelid down with the index finger to form a pouch. Squeeze the prescribed number of drops into the pouch. Close eyes to spread drops.
    Patients should not wear contact lenses while using ganciclovir ophthalmic gel.

    STORAGE

    Generic:
    - Store at 77 degrees F; excursions permitted to 59-86 degrees F
    Cytovene:
    - Diluted product if not used immediately can be stored at 36 to 46 degrees F for up to 24 hours
    - Discard unused portion. Do not store for later use.
    - Do not freeze
    - Do not refrigerate reconstituted product
    - Store reconstituted product at room temperature (77 degrees F)
    - Store unreconstituted product at 77 degrees F; excursions permitted to 59-86 degrees F
    - Use within 12 hours after reconstitution
    Vitrasert:
    - Avoid direct heat and sunlight
    - Protect from freezing
    - Store at room temperature (between 59 to 86 degrees F)
    Zirgan:
    - Do not freeze
    - Store between 59 to 77 degrees F

    CONTRAINDICATIONS / PRECAUTIONS

    Acyclovir hypersensitivity, famciclovir hypersensitivity, ganciclovir hypersensitivity, penciclovir hypersensitivity, valacyclovir hypersensitivity, valganciclovir hypersensitivity

    Ganciclovir is contraindicated in patients with a significant ganciclovir hypersensitivity, valganciclovir hypersensitivity, or acyclovir hypersensitivity. 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.

    Anemia, bone marrow suppression, chemotherapy, leukopenia, neutropenia, radiation therapy, thrombocytopenia

    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.

    Intramuscular administration, subcutaneous administration

    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.

    Dehydration, geriatric, renal failure, renal impairment

    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.

    Accidental exposure, neoplastic disease, ocular exposure

    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.

    Children, infants, neonates

    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.

    Contraception requirements, infertility, male-mediated teratogenicity, pregnancy testing, reproductive risk

    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.
     

    Antimicrobial resistance

    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.

    Pregnancy

    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.

    Breast-feeding

    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.   

    Contact lenses

    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.

    ADVERSE REACTIONS

    Severe

    retinal detachment / Delayed / 8.0-11.0
    hemolytic anemia / Delayed / 0-1.0
    cranial nerve palsies / Delayed / 0-1.0
    stroke / Early / 0-1.0
    increased intracranial pressure / Early / 0-1.0
    hemolytic-uremic syndrome / Delayed / 0-1.0
    Stevens-Johnson syndrome / Delayed / 0-1.0
    exfoliative dermatitis / Delayed / 0-1.0
    anaphylactoid reactions / Rapid / 0-1.0
    hepatic failure / Delayed / 0-1.0
    bronchospasm / Rapid / 0-1.0
    pulmonary fibrosis / Delayed / 0-1.0
    rhabdomyolysis / Delayed / 0-1.0
    cardiac arrest / Early / 0-1.0
    torsade de pointes / Rapid / 0-1.0
    vasculitis / Delayed / 0-1.0
    keratitis / Delayed / 5.0
    pancytopenia / Delayed / Incidence not known
    agranulocytosis / Delayed / Incidence not known
    GI perforation / Delayed / Incidence not known
    pancreatitis / Delayed / Incidence not known
    seizures / Delayed / Incidence not known
    renal failure (unspecified) / Delayed / Incidence not known
    new primary malignancy / Delayed / Incidence not known
    teratogenesis / Delayed / Incidence not known
    hearing loss / Delayed / Incidence not known
    arrhythmia exacerbation / Early / Incidence not known
    ventricular tachycardia / Early / Incidence not known
    visual impairment / Early / Incidence not known
    macular edema / Delayed / Incidence not known
    SIADH / Delayed / Incidence not known

    Moderate

    blurred vision / Early / 60.0-60.0
    thrombocytopenia / Delayed / 3.0-57.0
    leukopenia / Delayed / 29.0-41.0
    neutropenia / Delayed / 3.0-29.0
    anemia / Delayed / 2.0-26.0
    peripheral neuropathy / Delayed / 8.0-9.0
    conjunctival hyperemia / Early / 5.0-5.0
    hallucinations / Early / 0-1.0
    memory impairment / Delayed / 0-1.0
    aphasia / Delayed / 0-1.0
    cholelithiasis / Delayed / 0-1.0
    elevated hepatic enzymes / Delayed / 0-1.0
    cholestasis / Delayed / 0-1.0
    hepatitis / Delayed / 0-1.0
    dyspnea / Early / 0-1.0
    metabolic acidosis / Delayed / 0-1.0
    hypertriglyceridemia / Delayed / 0-1.0
    hyponatremia / Delayed / 0-1.0
    hypercalcemia / Delayed / 0-1.0
    bleeding / Early / Incidence not known
    bone marrow suppression / Delayed / Incidence not known
    stomatitis / Delayed / Incidence not known
    constipation / Delayed / Incidence not known
    depression / Delayed / Incidence not known
    dysphagia / Delayed / Incidence not known
    confusion / Early / Incidence not known
    urinary retention / Early / Incidence not known
    hematuria / Delayed / Incidence not known
    phlebitis / Rapid / Incidence not known
    clastogenesis / Delayed / Incidence not known
    infertility / Delayed / Incidence not known
    candidiasis / Delayed / Incidence not known
    edema / Delayed / Incidence not known
    chest pain (unspecified) / Early / Incidence not known
    testicular atrophy / Delayed / Incidence not known
    myasthenia / Delayed / Incidence not known
    hypotension / Rapid / Incidence not known
    hypertension / Early / Incidence not known
    peripheral vasodilation / Rapid / Incidence not known
    conjunctivitis / Delayed / Incidence not known
    cataracts / Delayed / Incidence not known

    Mild

    fever / Early / 38.0-48.0
    diarrhea / Early / 41.0-44.0
    ocular irritation / Rapid / 20.0-20.0
    anorexia / Delayed / 14.0-15.0
    infection / Delayed / 0-15.0
    vomiting / Early / 13.0-13.0
    diaphoresis / Early / 11.0-12.0
    chills / Rapid / 7.0-10.0
    pruritus / Rapid / 5.0-6.0
    irritability / Delayed / 0-1.0
    dysesthesia / Delayed / 0-1.0
    cough / Delayed / 0-1.0
    xerophthalmia / Early / 0-1.0
    xerostomia / Early / Incidence not known
    dysgeusia / Early / Incidence not known
    eructation / Early / Incidence not known
    flatulence / Early / Incidence not known
    dyspepsia / Early / Incidence not known
    abdominal pain / Early / Incidence not known
    nausea / Early / Incidence not known
    weight loss / Delayed / Incidence not known
    paresthesias / Delayed / Incidence not known
    drowsiness / Early / Incidence not known
    headache / Early / Incidence not known
    fatigue / Early / Incidence not known
    anxiety / Delayed / Incidence not known
    hypoesthesia / Delayed / Incidence not known
    tremor / Early / Incidence not known
    insomnia / Early / Incidence not known
    dizziness / Early / Incidence not known
    increased urinary frequency / Early / Incidence not known
    rash / Early / Incidence not known
    alopecia / Delayed / Incidence not known
    urticaria / Rapid / Incidence not known
    xerosis / Delayed / Incidence not known
    injection site reaction / Rapid / Incidence not known
    spermatogenesis inhibition / Delayed / Incidence not known
    influenza / Delayed / Incidence not known
    malaise / Early / Incidence not known
    anosmia / Delayed / Incidence not known
    otalgia / Early / Incidence not known
    tinnitus / Delayed / Incidence not known
    myalgia / Early / Incidence not known
    arthralgia / Delayed / Incidence not known
    muscle cramps / Delayed / Incidence not known
    back pain / Delayed / Incidence not known
    ocular pain / Early / Incidence not known

    DRUG INTERACTIONS

    Abacavir; Lamivudine, 3TC; Zidovudine, ZDV: (Major) Coadministration of ganciclovir and zidovudine may increase the hematologic toxicity (e.g., neutropenia, anemia) of zidovudine. Some patients may not tolerate concomitant therapy with these drugs at full dosage. If concomitant use is necessary, monitor hematologic parameters closely.
    Aldesleukin, IL-2: (Moderate) Aldesleukin may cause nephrotoxicity. Concurrent administration of drugs possessing nephrotoxic effects, such as ganciclovir, with Aldesleukin, IL-2 may increase the risk of kidney dysfunction.
    Aminoglycosides: (Major) Concurrent use of nephrotoxic agents, such as the aminoglycosides, with ganciclovir should be done cautiously to avoid additive nephrotoxicity.
    Amlodipine; Celecoxib: (Minor) Concurrent use of nephrotoxic agents, such as NSAIDs, with ganciclovir should be done cautiously to avoid additive nephrotoxicity. Monitor renal function carefully if concomitant therapy is required.
    Amphotericin B cholesteryl sulfate complex (ABCD): (Moderate) Use caution and monitor renal function when ganciclovir is coadministered with amphotericin B because of the potential increase in serum creatinine. Acute renal failure may occur in patients concomitantly receiving potential nephrotoxic drugs.
    Amphotericin B lipid complex (ABLC): (Moderate) Use caution and monitor renal function when ganciclovir is coadministered with amphotericin B because of the potential increase in serum creatinine. Acute renal failure may occur in patients concomitantly receiving potential nephrotoxic drugs.
    Amphotericin B liposomal (LAmB): (Moderate) Use caution and monitor renal function when ganciclovir is coadministered with amphotericin B because of the potential increase in serum creatinine. Acute renal failure may occur in patients concomitantly receiving potential nephrotoxic drugs.
    Amphotericin B: (Moderate) Use caution and monitor renal function when ganciclovir is coadministered with amphotericin B because of the potential increase in serum creatinine. Acute renal failure may occur in patients concomitantly receiving potential nephrotoxic drugs.
    Aprotinin: (Moderate) The manufacturer recommends using aprotinin cautiously in patients that are receiving drugs that can affect renal function, such as ganciclovir, as the risk of renal impairment may be increased.
    Bacitracin: (Minor) Concurrent use of nephrotoxic agents, including systemic bacitracin, with ganciclovir should be done cautiously to avoid additive nephrotoxicity.
    Bictegravir; Emtricitabine; Tenofovir Alafenamide: (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 ganciclovir. Consider the potential for drug interaction prior to and during concurrent use of these medications. Both emtricitabine and ganciclovir 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.
    Bupivacaine; Meloxicam: (Minor) Concurrent use of nephrotoxic agents, such as NSAIDs, with ganciclovir should be done cautiously to avoid additive nephrotoxicity. Monitor renal function carefully if concomitant therapy is required.
    Capreomycin: (Major) Since capreomycin is eliminated by the kidney, coadministration with other potentially nephrotoxic drugs, including ganciclovir, 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.
    Celecoxib: (Minor) Concurrent use of nephrotoxic agents, such as NSAIDs, with ganciclovir should be done cautiously to avoid additive nephrotoxicity. Monitor renal function carefully if concomitant therapy is required.
    Chlorpheniramine; Ibuprofen; Pseudoephedrine: (Minor) Concurrent use of nephrotoxic agents, such as NSAIDs, with ganciclovir should be done cautiously to avoid additive nephrotoxicity. Monitor renal function carefully if concomitant therapy is required.
    Cidofovir: (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.
    Cisplatin: (Moderate) Concomitant use of cisplatin and ganciclovir should be considered only if the potential benefits outweigh the risks of increased treatment-related toxicities. If coadministration is necessary, closely monitor for treatment-related adverse reactions. Ganciclovir is eliminated renally and cisplatin can cause nephrotoxicity, which may result in increased plasma concentrations of ganciclovir. Side effects such as nephrotoxicity and myelosuppression may be additive.
    Clofarabine: (Moderate) Concomitant use of clofarabine and ganciclovir may result in altered clofarabine levels because both agents are a substrate of OCT1. Therefore, monitor for signs of clofarabine toxicity such as gastrointestinal toxicity (e.g., nausea, vomiting, diarrhea, mucosal inflammation), hematologic toxicity, and skin toxicity (e.g. hand and foot syndrome, rash, pruritus) in patients also receiving OCT1 substrates.
    Colistimethate, Colistin, Polymyxin E: (Major) Theoretically, chronic coadministration may increase the risk of developing nephrotoxicity, even in patients who have normal renal function. Monitor patients for changes in renal function during concurrent use. Since colistimethate sodium is eliminated by the kidney, coadministration with other potentially nephrotoxic drugs, including ganciclovir, may increase serum concentrations of either drug.
    Cyclosporine: (Moderate) Use caution and monitor renal function when ganciclovir is coadministered with cyclosporine because of the potential increase in serum creatinine. Acute renal failure may occur in patients concomitantly receiving potential nephrotoxic drugs.
    Dapsone: (Moderate) Use ganciclovir and dapsone together only if the potential benefits outweigh the risks; bone marrow suppression, spermatogenesis inhibition, skin toxicity, and gastrointestinal toxicity may be additive as both drugs inhibit rapidly dividing cells.
    Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (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 ganciclovir. Consider the potential for drug interaction prior to and during concurrent use of these medications. Both emtricitabine and ganciclovir 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.
    Dichlorphenamide: (Major) Use of dichlorphenamide and ganciclovir is not recommended because of an increased risk of ganciclovir-related adverse effects. Monitor closely for signs of drug toxicity if use together cannot be avoided. For example, the main toxicities of ganciclovir are myelosuppresion or nephrotoxicity. Monitor blood counts and renal function, since increased ganciclovir exposure is possible. Dichlorphenamide inhibits OAT1. Ganciclovir is an OAT1 substrate. Additionally, metabolic acidosis is associated with the use of dichlorphenamide and has been reported with the postmarketing use of ganciclovir. 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.
    Diclofenac: (Minor) Concurrent use of nephrotoxic agents, such as NSAIDs, with ganciclovir should be done cautiously to avoid additive nephrotoxicity. Monitor renal function carefully if concomitant therapy is required.
    Diclofenac; Misoprostol: (Minor) Concurrent use of nephrotoxic agents, such as NSAIDs, with ganciclovir should be done cautiously to avoid additive nephrotoxicity. Monitor renal function carefully if concomitant therapy is required.
    Didanosine, ddI: (Moderate) Ganciclovir can increase the AUC and Cmax of didanosine, ddI when given concurrently. Patients should be monitored closely for didanosine toxicity when receiving ganciclovir concurrently.
    Diflunisal: (Minor) Concurrent use of nephrotoxic agents, such as NSAIDs, with ganciclovir should be done cautiously to avoid additive nephrotoxicity. Monitor renal function carefully if concomitant therapy is required.
    Diphenhydramine; Ibuprofen: (Minor) Concurrent use of nephrotoxic agents, such as NSAIDs, with ganciclovir should be done cautiously to avoid additive nephrotoxicity. Monitor renal function carefully if concomitant therapy is required.
    Diphenhydramine; Naproxen: (Minor) Concurrent use of nephrotoxic agents, such as NSAIDs, with ganciclovir should be done cautiously to avoid additive nephrotoxicity. Monitor renal function carefully if concomitant therapy is required.
    Doravirine; Lamivudine; Tenofovir disoproxil fumarate: (Moderate) Concurrent use of nephrotoxic agents with ganciclovir should be done cautiously to avoid additive nephrotoxicity. Other nephrotoxic agents include tenofovir.
    Doxorubicin: (Moderate) Use ganciclovir and doxorubicin together only if the potential benefits outweigh the risks; bone marrow suppression, spermatogenesis inhibition, skin toxicity, and gastrointestinal toxicity may be additive as both drugs inhibit rapidly dividing cells.
    Efavirenz; Emtricitabine; Tenofovir: (Moderate) Concurrent use of nephrotoxic agents with ganciclovir should be done cautiously to avoid additive nephrotoxicity. Other nephrotoxic agents include tenofovir. (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 ganciclovir. Consider the potential for drug interaction prior to and during concurrent use of these medications. Both emtricitabine and ganciclovir 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.
    Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Moderate) Concurrent use of nephrotoxic agents with ganciclovir should be done cautiously to avoid additive nephrotoxicity. Other nephrotoxic agents include tenofovir.
    Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (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 ganciclovir. Consider the potential for drug interaction prior to and during concurrent use of these medications. Both emtricitabine and ganciclovir 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.
    Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Concurrent use of nephrotoxic agents with ganciclovir should be done cautiously to avoid additive nephrotoxicity. Other nephrotoxic agents include tenofovir. (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 ganciclovir. Consider the potential for drug interaction prior to and during concurrent use of these medications. Both emtricitabine and ganciclovir 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.
    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 ganciclovir. Consider the potential for drug interaction prior to and during concurrent use of these medications. Both emtricitabine and ganciclovir 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.
    Emtricitabine; Rilpivirine; Tenofovir alafenamide: (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 ganciclovir. Consider the potential for drug interaction prior to and during concurrent use of these medications. Both emtricitabine and ganciclovir 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.
    Emtricitabine; Rilpivirine; Tenofovir disoproxil fumarate: (Moderate) Concurrent use of nephrotoxic agents with ganciclovir should be done cautiously to avoid additive nephrotoxicity. Other nephrotoxic agents include tenofovir. (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 ganciclovir. Consider the potential for drug interaction prior to and during concurrent use of these medications. Both emtricitabine and ganciclovir 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.
    Emtricitabine; Tenofovir alafenamide: (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 ganciclovir. Consider the potential for drug interaction prior to and during concurrent use of these medications. Both emtricitabine and ganciclovir 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.
    Emtricitabine; Tenofovir disoproxil fumarate: (Moderate) Concurrent use of nephrotoxic agents with ganciclovir should be done cautiously to avoid additive nephrotoxicity. Other nephrotoxic agents include tenofovir. (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 ganciclovir. Consider the potential for drug interaction prior to and during concurrent use of these medications. Both emtricitabine and ganciclovir 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.
    Entecavir: (Moderate) Entecavir may affect renal function and should be used cautiously in combination with other drugs that may also affect renal function including ganciclovir.
    Etodolac: (Minor) Concurrent use of nephrotoxic agents, such as NSAIDs, with ganciclovir should be done cautiously to avoid additive nephrotoxicity. Monitor renal function carefully if concomitant therapy is required.
    Famotidine; Ibuprofen: (Minor) Concurrent use of nephrotoxic agents, such as NSAIDs, with ganciclovir should be done cautiously to avoid additive nephrotoxicity. Monitor renal function carefully if concomitant therapy is required.
    Fenoprofen: (Minor) Concurrent use of nephrotoxic agents, such as NSAIDs, with ganciclovir should be done cautiously to avoid additive nephrotoxicity. Monitor renal function carefully if concomitant therapy is required.
    Flucytosine: (Moderate) Use ganciclovir and flucytosine together only if the potential benefits outweigh the risks; bone marrow suppression, spermatogenesis inhibition, skin toxicity, and gastrointestinal toxicity may be additive as both drugs inhibit rapidly dividing cells.
    Flurbiprofen: (Minor) Concurrent use of nephrotoxic agents, such as NSAIDs, with ganciclovir should be done cautiously to avoid additive nephrotoxicity. Monitor renal function carefully if concomitant therapy is required.
    Gallium Ga 68 Dotatate: (Major) Avoid use of mannitol and ganciclovir, if possible. Concomitant administration of nephrotoxic drugs, such as ganciclovir, increases the risk of renal failure after administration of mannitol.
    Gallium: (Contraindicated) Concurrent use of gallium nitrate with other potentially nephrotoxic drugs, such as ganciclovir, may increase the risk for developing severe renal insufficiency. If use of ganciclovir is indicated, gallium nitrate administration should be discontinued, and hydration for several days after administration of ganciclovir is recommended. Serum creatinine concentrations and urine output should be closely monitored during and subsequent to this period. Gallium nitrate should be discontinued if the serum creatinine concentration exceeds 2.5 mg/dl.
    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 ganciclovir. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function.
    Hydrocodone; Ibuprofen: (Minor) Concurrent use of nephrotoxic agents, such as NSAIDs, with ganciclovir should be done cautiously to avoid additive nephrotoxicity. Monitor renal function carefully if concomitant therapy is required.
    Hydroxyurea: (Moderate) Use ganciclovir and hydroxyurea together only if the potential benefits outweigh the risks; bone marrow suppression, spermatogenesis inhibition, skin toxicity, and gastrointestinal toxicity may be additive as both drugs inhibit rapidly dividing cells.
    Ibuprofen: (Minor) Concurrent use of nephrotoxic agents, such as NSAIDs, with ganciclovir should be done cautiously to avoid additive nephrotoxicity. Monitor renal function carefully if concomitant therapy is required.
    Ibuprofen; Oxycodone: (Minor) Concurrent use of nephrotoxic agents, such as NSAIDs, with ganciclovir should be done cautiously to avoid additive nephrotoxicity. Monitor renal function carefully if concomitant therapy is required.
    Ibuprofen; Pseudoephedrine: (Minor) Concurrent use of nephrotoxic agents, such as NSAIDs, with ganciclovir should be done cautiously to avoid additive nephrotoxicity. Monitor renal function carefully if concomitant therapy is required.
    Imipenem; Cilastatin: (Major) Avoid concomitant use of imipenem; cilastatin and ganciclovir unless the potential benefits outweigh the risks. Generalized seizures have occurred in patients who were receiving imipenem; cilastatin concomitantly with ganciclovir.
    Imipenem; Cilastatin; Relebactam: (Major) Avoid concomitant use of imipenem; cilastatin and ganciclovir unless the potential benefits outweigh the risks. Generalized seizures have occurred in patients who were receiving imipenem; cilastatin concomitantly with ganciclovir.
    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 ganciclovir. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function.
    Indomethacin: (Minor) Concurrent use of nephrotoxic agents, such as NSAIDs, with ganciclovir should be done cautiously to avoid additive nephrotoxicity. Monitor renal function carefully if concomitant therapy is required.
    Inotersen: (Moderate) Use caution with concomitant use of inotersen and ganciclovir due to the risk of glomerulonephritis and nephrotoxicity.
    Ketoprofen: (Minor) Concurrent use of nephrotoxic agents, such as NSAIDs, with ganciclovir should be done cautiously to avoid additive nephrotoxicity. Monitor renal function carefully if concomitant therapy is required.
    Ketorolac: (Minor) Concurrent use of nephrotoxic agents, such as NSAIDs, with ganciclovir should be done cautiously to avoid additive nephrotoxicity. Monitor renal function carefully if concomitant therapy is required.
    Lamivudine, 3TC; Zidovudine, ZDV: (Major) Coadministration of ganciclovir and zidovudine may increase the hematologic toxicity (e.g., neutropenia, anemia) of zidovudine. Some patients may not tolerate concomitant therapy with these drugs at full dosage. If concomitant use is necessary, monitor hematologic parameters closely.
    Lamivudine; Tenofovir Disoproxil Fumarate: (Moderate) Concurrent use of nephrotoxic agents with ganciclovir should be done cautiously to avoid additive nephrotoxicity. Other nephrotoxic agents include tenofovir.
    Lansoprazole; Naproxen: (Minor) Concurrent use of nephrotoxic agents, such as NSAIDs, with ganciclovir should be done cautiously to avoid additive nephrotoxicity. Monitor renal function carefully if concomitant therapy is required.
    Mannitol: (Major) Avoid use of mannitol and ganciclovir, if possible. Concomitant administration of nephrotoxic drugs, such as ganciclovir, increases the risk of renal failure after administration of mannitol.
    Meclofenamate Sodium: (Minor) Concurrent use of nephrotoxic agents, such as NSAIDs, with ganciclovir should be done cautiously to avoid additive nephrotoxicity. Monitor renal function carefully if concomitant therapy is required.
    Mefenamic Acid: (Minor) Concurrent use of nephrotoxic agents, such as NSAIDs, with ganciclovir should be done cautiously to avoid additive nephrotoxicity. Monitor renal function carefully if concomitant therapy is required.
    Meloxicam: (Minor) Concurrent use of nephrotoxic agents, such as NSAIDs, with ganciclovir should be done cautiously to avoid additive nephrotoxicity. Monitor renal function carefully if concomitant therapy is required.
    Mycophenolate: (Moderate) The systemic concentration of ganciclovir and the glucuronide metabolite of mycophenolate are increased in the presence of renal impairment. Concomitant use may result in competition for tubular secretion, which could further increase the systemic exposures. Thus, adverse effects from increased serum concentrations may be anticipated; blood cell count monitoring is recommended.
    Nabumetone: (Minor) Concurrent use of nephrotoxic agents, such as NSAIDs, with ganciclovir should be done cautiously to avoid additive nephrotoxicity. Monitor renal function carefully if concomitant therapy is required.
    Naproxen: (Minor) Concurrent use of nephrotoxic agents, such as NSAIDs, with ganciclovir should be done cautiously to avoid additive nephrotoxicity. Monitor renal function carefully if concomitant therapy is required.
    Naproxen; Esomeprazole: (Minor) Concurrent use of nephrotoxic agents, such as NSAIDs, with ganciclovir should be done cautiously to avoid additive nephrotoxicity. Monitor renal function carefully if concomitant therapy is required.
    Naproxen; Pseudoephedrine: (Minor) Concurrent use of nephrotoxic agents, such as NSAIDs, with ganciclovir should be done cautiously to avoid additive nephrotoxicity. Monitor renal function carefully if concomitant therapy is required.
    Nitisinone: (Moderate) Monitor for increased ganciclovir-related adverse effects. Coadministration may increase ganciclovir exposure resulting in increased adverse effects. Nitisinone inhibits OAT1. Ganciclovir is an OAT1 substrate.
    Nonsteroidal antiinflammatory drugs: (Minor) Concurrent use of nephrotoxic agents, such as NSAIDs, with ganciclovir should be done cautiously to avoid additive nephrotoxicity. Monitor renal function carefully if concomitant therapy is required.
    Oxaprozin: (Minor) Concurrent use of nephrotoxic agents, such as NSAIDs, with ganciclovir should be done cautiously to avoid additive nephrotoxicity. Monitor renal function carefully if concomitant therapy is required.
    Pentamidine: (Moderate) Use ganciclovir with pentamidine only if the potential benefits are judged to outweigh the risks. Concurrent use of agents that inhibit rapidly dividing cell populations (i.e., bone marrow, spermatogonia, germinal layers of the skin, gastrointestinal mucosa) with ganciclovir should be done cautiously, in order to avoid additive toxicity. Additive nephrotoxicity may be seen with the combination of pentamidine and other agents that cause nephrotoxicity, including ganciclovir.
    Piroxicam: (Minor) Concurrent use of nephrotoxic agents, such as NSAIDs, with ganciclovir should be done cautiously to avoid additive nephrotoxicity. Monitor renal function carefully if concomitant therapy is required.
    Polymyxin B: (Minor) Concurrent use of nephrotoxic agents, such as polymyxin b, with ganciclovir should be done cautiously to avoid additive nephrotoxicity.
    Polymyxins: (Major) Theoretically, chronic coadministration may increase the risk of developing nephrotoxicity, even in patients who have normal renal function. Monitor patients for changes in renal function during concurrent use. Since colistimethate sodium is eliminated by the kidney, coadministration with other potentially nephrotoxic drugs, including ganciclovir, may increase serum concentrations of either drug.
    Probenecid: (Moderate) Ganciclovir should be used with probenecid with caution. Probenecid can inhibit renal tubular secretion of ganciclovir, possibly potentiating ganciclovir toxicity. Patients should be monitored for increased ganciclovir toxicity when taking probenecid with ganciclovir.
    Probenecid; Colchicine: (Moderate) Ganciclovir should be used with probenecid with caution. Probenecid can inhibit renal tubular secretion of ganciclovir, possibly potentiating ganciclovir toxicity. Patients should be monitored for increased ganciclovir toxicity when taking probenecid with ganciclovir.
    Rofecoxib: (Minor) Concurrent use of nephrotoxic agents, such as NSAIDs, with ganciclovir should be done cautiously to avoid additive nephrotoxicity. Monitor renal function carefully if concomitant therapy is required.
    Sulfamethoxazole; Trimethoprim, SMX-TMP, Cotrimoxazole: (Moderate) Use ganciclovir and sulfamethoxazole; trimethoprim together only if the potential benefits outweigh the risks; bone marrow suppression, spermatogenesis inhibition, skin toxicity, and gastrointestinal toxicity may be additive as both drugs inhibit rapidly dividing cells.
    Sulindac: (Minor) Concurrent use of nephrotoxic agents, such as NSAIDs, with ganciclovir should be done cautiously to avoid additive nephrotoxicity. Monitor renal function carefully if concomitant therapy is required.
    Sumatriptan; Naproxen: (Minor) Concurrent use of nephrotoxic agents, such as NSAIDs, with ganciclovir should be done cautiously to avoid additive nephrotoxicity. Monitor renal function carefully if concomitant therapy is required.
    Tacrolimus: (Moderate) Use ganciclovir and tacrolimus together only if the potential benefits outweigh the risks. Monitor renal function when ganciclovir is coadministered with tacrolimus because of the potential increase in serum creatinine. Acute renal failure may occur in patients concomitantly receiving potential nephrotoxic drugs.
    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.
    Telavancin: (Moderate) Concurrent or sequential use of telavancin with other potentially nephrotoxic drugs such as ganciclovir may lead to additive nephrotoxicity. Closely monitor renal function and adjust telavancin doses based on calculated creatinine clearance.
    Telbivudine: (Moderate) Drugs that alter renal function such as ganciclovir may alter telbivudine plasma concentrations because telbivudine is eliminated primarily by renal excretion. Monitor renal function before and during telbivudine treatment.
    Tenofovir Alafenamide: (Moderate) Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with drugs that are eliminated by active tubular secretion may increase concentrations of tenofovir and/or the co-administered drug. Drugs that decrease renal function may also increase concentrations tenofovir. Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir, with a majority of the cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Tenofovir-containing products should be avoided with concurrent or recent use of a nephrotoxic agent, such as ganciclovir. Monitor patients receiving concomitant nephrotoxic agents for changes in serum creatinine and phosphorus, and urine glucose and protein.
    Tenofovir, PMPA: (Moderate) Concurrent use of nephrotoxic agents with ganciclovir should be done cautiously to avoid additive nephrotoxicity. Other nephrotoxic agents include tenofovir.
    Tolmetin: (Minor) Concurrent use of nephrotoxic agents, such as NSAIDs, with ganciclovir should be done cautiously to avoid additive nephrotoxicity. Monitor renal function carefully if concomitant therapy is required.
    Trimethoprim: (Moderate) Use ganciclovir and sulfamethoxazole; trimethoprim together only if the potential benefits outweigh the risks; bone marrow suppression, spermatogenesis inhibition, skin toxicity, and gastrointestinal toxicity may be additive as both drugs inhibit rapidly dividing cells.
    Valdecoxib: (Minor) Concurrent use of nephrotoxic agents, such as NSAIDs, with ganciclovir should be done cautiously to avoid additive nephrotoxicity. Monitor renal function carefully if concomitant therapy is required.
    Vancomycin: (Moderate) Concurrent use of nephrotoxic agents, such as vancomycin, with ganciclovir should be done cautiously to avoid additive nephrotoxicity. Renal function should be monitored closely and vancomycin doses should be adjusted according to vancomycin serum concentrations.
    Vinca alkaloids: (Moderate) Use ganciclovir and vinca alkaloids together only if the potential benefits outweigh the risks; bone marrow suppression, spermatogenesis inhibition, skin toxicity, and gastrointestinal toxicity may be additive as both drugs inhibit rapidly dividing cells.
    Voclosporin: (Moderate) Concomitant use of voclosporin and ganciclovir may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required.
    Zidovudine, ZDV: (Major) Coadministration of ganciclovir and zidovudine may increase the hematologic toxicity (e.g., neutropenia, anemia) of zidovudine. Some patients may not tolerate concomitant therapy with these drugs at full dosage. If concomitant use is necessary, monitor hematologic parameters closely.

    PREGNANCY AND LACTATION

    Pregnancy

    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.

    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.
     

    MECHANISM OF ACTION

    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.

    PHARMACOKINETICS

    Ganciclovir 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.
     
    Affected cytochrome P450 isoenzymes: none

    Intravenous Route

    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.

    Other Route(s)

    Ophthalmic Route
    Minimal systemic exposure is expected with topical ophthalmic administration of ganciclovir gel.