Ganciclovir Sodium

Brand names: Cytovene
Drug class: Antineoplastic Agents

Usage of Ganciclovir Sodium

Cytomegalovirus (CMV) Retinitis

Initial treatment (induction therapy) and maintenance therapy (secondary prophylaxis) of CMV retinitis in immunocompromised patients, including HIV-infected adults. Also used for management of CMV retinitis in HIV-infected pediatric patients† [off-label].

Like other antivirals, ganciclovir is not a cure for CMV retinitis; stabilization or improvement of ocular manifestations may occur, but relapse and/or progression of CMV retinitis possible during or following ganciclovir therapy.

Retinitis is the most common clinical manifestation of CMV end-organ disease in HIV-infected patients; ideally should be managed in consultation with an ophthalmologist familiar with diagnosis and treatment of retinal diseases.

Select antiviral regimen for initial treatment of CMV retinitis in HIV-infected individuals based on location and severity of CMV retinal lesions, severity of underlying immunosuppression, concomitant drug therapy, and patient’s ability to adhere to the treatment regimen. Select antiviral regimen for maintenance therapy based on location of CMV retinal lesions, vision in contralateral eye, patient's immunologic and virologic status, and patient's response to antiretroviral therapy.

For management of immediate sight-threatening CMV retinal lesions (e.g., within 1.5 mm of the fovea) in HIV-infected adults and adolescents, CDC, NIH, and IDSA state that the preferred regimen is initial treatment (induction therapy) with intravitreal ganciclovir or intravitreal foscarnet (1–4 doses given over a period of 7–10 days) in conjunction with oral valganciclovir (twice daily for 14–21 days) followed by maintenance therapy (secondary prophylaxis) with oral valganciclovir (once daily). One alternative regimen recommended by these experts for sight-threatening CMV retinitis in HIV-infected adults and adolescents is intravitreal ganciclovir† [off-label] or intravitreal foscarnet (1–4 doses given over a period of 7–10 days) in conjunction with IV ganciclovir (twice daily for 14–21 days) followed by maintenance therapy (secondary prophylaxis) with oral valganciclovir (once daily). Systemic antivirals (without an intravitreal antiviral) usually adequate for management of CMV retinitis in patients with only small peripheral lesions.

For management of CMV retinitis in HIV-infected pediatric patients† [off-label], CDC, NIH, IDSA, and others state that IV ganciclovir is drug of choice for initial treatment (induction therapy) and one of several options for maintenance therapy (secondary prophylaxis). These experts state that oral valganciclovir may be considered in older children† [off-label] and adolescents† [off-label] transitioning from IV ganciclovir to oral valganciclovir to complete treatment and/or for maintenance therapy following improvement of retinitis. Data are limited regarding use of intravitreal antivirals in children; intravitreal injections are impractical in most children.

Because of risk of relapse, chronic maintenance therapy (secondary prophylaxis) of CMV retinitis usually continued until immune reconstitution occurs as a result of effective antiretroviral therapy. CDC, NIH, and IDSA state that discontinuance of maintenance therapy of CMV retinitis can be considered in HIV-infected adults and adolescents if CMV lesions have been treated for ≥3–6 months and are inactive and there has been a sustained (i.e., 3–6 months) increase in CD4+ T-cell count to >100/mm3 in response to antiretroviral therapy. Although safety of discontinuing maintenance therapy of CMV retinitis in HIV-infected pediatric patients not well studied, discontinuance of such therapy can be considered in those receiving antiretroviral therapy who have a sustained (i.e., >6 months) increase in CD4+ T-cell percentage to >15% (children <6 years of age) or increase in CD4+ T-cell count to >100/mm3 (children ≥6 years of age).

If maintenance therapy of CMV is discontinued, continue regular ophthalmologic monitoring (optimally every 3–6 months) for early detection of CMV relapse or immune reconstitution uveitis. If CD4+ T-cell count decreases to <100/mm3 (adults, adolescents, children ≥6 years of age) or CD4+ T-cell percentage decreases to <15% (children <6 years of age), reinitiate CMV retinitis maintenance therapy.

Extraocular CMV Infections

Although safety and efficacy not established for management of extraocular CMV infections, has been used in immunocompromised patients for management of CMV GI disease†, pneumonitis†, encephalitis†, or other CMV infections†.

CDC, NIH, and IDSA state that IV ganciclovir usually is the preferred antiviral for initial management of CMV GI disease† in HIV-infected adults and transition to oral valganciclovir may be considered when patient can tolerate and absorb oral drugs.

For management of well-documented CMV pneumonitis† in HIV-infected adults, CDC, NIH, and IDSA state that either IV ganciclovir or IV foscarnet is a reasonable choice.

A combination regimen of IV ganciclovir and IV foscarnet has been used for management of CMV neurologic disease† (e.g., CMV encephalitis or myelitis), and is recommended by CDC, NIH, IDSA, and others for such infections in HIV-infected individuals.

Congenital CMV Disease

Although safety and efficacy not established, has been used for management of symptomatic congenital CMV disease†.

Transmission of CMV from infected mothers to their fetuses occurs as a result of maternal viremia and transplacental infection; perinatal infection also can occur from exposure to CMV shedding in mother's genital tract. Approximately 10% of neonates with congenital CMV infection are symptomatic at birth; mortality is about 10% and approximately 50–90% of symptomatic surviving neonates experience substantial morbidity (e.g., mental retardation, sensorineural hearing loss, microcephaly, seizures). Risk of congenital CMV infection resulting from primary maternal CMV infection may be higher and the disease more severe than that resulting from Reactivation of maternal CMV infection.

AAP and others recommend that oral valganciclovir be considered in neonates with moderate to severe symptomatic congenital CMV disease (with or without CNS involvement) when an antiviral indicated. Regimen of IV ganciclovir either alone or followed by oral valganciclovir also has been used in neonates with symptomatic congenital CMV disease†.

CDC, NIH, IDSA, and others state that IV ganciclovir can be considered for initial treatment of symptomatic congenital CMV disease with CNS involvement in HIV-exposed or HIV-infected infants†.

Antivirals not usually recommended for neonates with asymptomatic congenital CMV infection or only mildly symptomatic infection without evidence of CNS involvement.

Prevention of CMV Infection and Disease

Prophylaxis to prevent CMV infection and disease in solid organ transplant recipients, bone marrow transplant (BMT) recipients, and hematopoietic stem cell transplant (HSCT) recipients at high risk for the disease.

Has been used for preemptive treatment of CMV infection and disease† in transplant recipients.

VaricElla-Zoster Virus (VZV) Infections

Although optimal regimens for management of progressive outer retinal necrosis caused by VZV† not identified, CDC, NIH, and IDSA recommend that such infections in HIV-infected adults and adolescents be treated with at least one IV antiviral (acyclovir, ganciclovir, foscarnet, cidofovir) used in conjunction with at least one intravitreal antiviral (ganciclovir or foscarnet). Some experts recommend IV ganciclovir and/or IV foscarnet used in conjunction with intravitreal ganciclovir† and/or intravitreal foscarnet. Prognosis for visual preservation in patients with progressive outer retinal necrosis caused by VZV is poor; such infections should be managed in consultation with an ophthalmologist.

Relate drugs

How to use Ganciclovir Sodium

General

  • Test females of childbearing potential for pregnancy prior to initiation of ganciclovir. (See Pregnancy under Cautions.)
  • Assess renal function prior to and during ganciclovir therapy; adjust dosage as needed. (See Renal Effects Under Cautions.)
  • Frequently monitor CBCs with differential and platelet counts during ganciclovir therapy, especially in those who developed cytopenias during previous therapy with ganciclovir or other nucleoside analogs and in those with Neutrophil counts <1000/mm3 prior to initiation of the drug. (See Hematologic Effects under Cautions.)
  • Ensure that patients are adequately hydrated.
  • Do not exceed recommended ganciclovir dosage or recommended frequency and rate of administration.

    • Administration

    Administer by IV infusion.

    Do not administer by rapid IV infusion or direct IV injection since potentially toxic plasma ganciclovir concentrations may result.

    Do not administer by IM or sub-Q injection.

    Has been administered by intravitreal injection†; ganciclovir preparation specifically for intravitreal administration not commercially available in US.

    Has been administered orally; oral preparations of ganciclovir no longer commercially available in US.

    IV Infusion

    For solution and drug compatibility information, see Compatibility under Stability.

    Handle ganciclovir lyophilized powder and solutions of the drug cautiously because of the high pH of some preparations and because of the mUTAgenic and/or carcinogenic potential of the drug (see Mutagenicity and Carcinogenicity under Cautions). Use of disposable gloves recommended.

    Since ganciclovir shares some of the properties of cytotoxic drugs, consider consulting specialized references for procedures for proper handling and disposal of cytotoxic drugs.

    To avoid phlebitis and pain at IV infusion site, select a vein with adequate blood flow to allow for rapid dilution and distribution of ganciclovir.

    Reconstitution and Dilution

    For IV infusion, reconstitute single-dose vial containing 500 mg of ganciclovir by adding 10 mL of preservative-free sterile water for injection to provide a solution containing 50 mg/mL. Do not use bacteriostatic water for injection containing parabens. Gently swirl vial until drug is completely wetted and a clear reconstituted solution is obtained. Withdraw appropriate dose of reconstituted solution from the vial and dilute in a compatible IV infusion solution (usually 100 mL). Solutions containing ganciclovir concentrations >10 mg/mL not recommended for IV infusion.

    Alternatively, if single-dose vials of solution containing 500 mg of ganciclovir (50 mg/mL) are used, shake vial containing the solution and withdraw appropriate dose and dilute in a compatible IV infusion solution (usually 100 mL). Solutions containing ganciclovir concentrations >10 mg/mL not recommended for IV infusion.

    Alternatively, commercially available single-dose IV bags containing 500 mg of ganciclovir in 250 mL of 0.8% sodium chloride (2 mg/mL) can be used for IV infusion without further dilution. The solution in the bag should appear clear. If any crystals have formed in the solution, gently shake the bag to redissolve the crystals prior to use. Discard any unused portions of the premixed solution.

    Rate of Administration

    Administer by IV infusion at a constant rate over 1 hour.

    Dosage

    Available as ganciclovir and ganciclovir sodium; dosage expressed in terms of ganciclovir.

    Pediatric Patients

    CMV Retinitis in HIV-infected Pediatric Patients† IV

    Initial treatment (induction therapy) in children†: CDC, NIH, IDSA, and others recommend 5 mg/kg every 12 hours for 14–21 days (may be increased to 7.5 mg/kg every 12 hours if needed).

    Maintenance therapy (secondary prophylaxis) in children†: CDC, NIH, IDSA, and others recommend 5 mg/kg once daily for 5–7 days each week.

    Make decisions regarding discontinuance of CMV retinitis maintenance therapy in consultation with an ophthalmologist. (See Cytomegalovirus [CMV] Retinitis under Uses.)

    CNS or Disseminated CMV Infections in HIV-infected Pediatric Patients† IV

    Initial treatment (induction therapy) of CMV CNS infections in children†: CDC, NIH, IDSA, and others recommend 5 mg/kg every 12 hours in conjunction with IV foscarnet. Continue initial treatment until symptomatic improvement.

    Initial treatment (induction therapy) of disseminated CMV infections in children†: CDC, NIH, IDSA, and others recommend 5 mg/kg IV every 12 hours (may be increased to 7.5 mg/kg every 12 hours if needed). Continue initial treatment for 14–21 days.

    Maintenance therapy (secondary prophylaxis) of CNS or disseminated CMV infections in children†: CDC, NIH, IDSA, and others recommend 5 mg/kg once daily for 5–7 days each week.

    Congenital CMV Disease† IV

    Symptomatic congenital CMV disease†: AAP and others recommend 6 mg/kg twice daily; transition to oral valganciclovir when infant is able to tolerate and absorb oral drugs.

    Initiate antiviral treatment within first month of life and continue for a total of 6 months.

    Prevention of CMV Infection and Disease in Pediatric Transplant Recipients† IV

    Prophylaxis of CMV in children†: Some clinicians recommend 5 mg/kg every 12 hours for 5–7 days (or 7–14 days), followed by 5 mg/kg once daily 7 days each week or 6 mg/kg once daily 5 days each week. Continue for 100–120 days posttransplantation.

    Prophylaxis of CMV in children†: Other clinicians recommend 5 mg/kg once daily continued for ≥3 months Depending on immune status of the recipient and type of transplant.

    Preemptive treatment of CMV infection in high-risk pediatric patients†: 5 mg/kg twice daily for 7–14 days followed by 5 mg/kg once daily recommended.

    VZV Infections† IV

    Progressive outer retinal necrosis caused by VZV in HIV-infected pediatric patients†: CDC, NIH, IDSA, and others state 5 mg/kg every 12 hours (used with IV foscarnet) in conjunction with intravitreal ganciclovir† (used with or without intravitreal foscarnet) can be considered.

    Adults

    CMV Retinitis IV

    Initial treatment (induction therapy): 5 mg/kg every 12 hours for 14–21 days. If patient has immediate sight-threatening CMV retinal lesions, CDC, NIH, and IDSA recommend that initial treatment also include an appropriate intravitreal antiviral. (See Cytomegalovirus [CMV] Retinitis under Uses.)

    Maintenance therapy (secondary prophylaxis): 5 mg/kg once daily 7 days each week or 6 mg/kg once daily 5 days each week.

    Make decisions regarding discontinuance of CMV retinitis maintenance therapy in consultation with an ophthalmologist. (See Cytomegalovirus [CMV] Retinitis under Uses.)

    CMV Esophagitis† or Colitis† IV

    CMV GI infections†: 5 mg/kg every 12 hours for 14–21 days has been used for initial treatment (induction); alternatively, 2.5 mg/kg IV every 8 hours has been used. If maintenance therapy required, dosages comparable to those used for maintenance therapy of CMV retinitis have been used.

    CMV esophagitis† or colitis† in HIV-infected adults: CDC, NIH, and IDSA recommend 5 mg/kg every 12 hours for 21–42 days or until signs and symptoms have resolved. Maintenance therapy (secondary prophylaxis) usually not necessary, but consider if relapse occurs.

    CMV Pneumonitis† IV

    5 mg/kg IV every 12 hours for 14–21 days has been used for initial treatment (induction); alternatively, 2.5 mg/kg IV every 8 hours has been used. If maintenance therapy required, dosages comparable to those used for maintenance therapy of CMV retinitis have been used.

    Well-documented CMV pneumonitis† in HIV-infected adults: CDC, NIH, and IDSA recommend SAMe dosage used for management of CMV retinitis in HIV-infected adults. Optimal duration of treatment not established.

    CMV Neurologic Disease† IV

    CMV neurologic disease† in HIV-infected adults: CDC, NIH, and IDSA recommend same dosage used for management of CMV retinitis in HIV-infected adults. Use in conjunction with IV foscarnet. Optimal duration of treatment not established.

    Prevention of CMV Infection and Disease in Transplant Recipients IV

    Prophylaxis of CMV: Manufacturers recommend 5 mg/kg every 12 hours for 7–14 days, followed by 5 mg/kg once daily 7 days each week or 6 mg/kg once daily 5 days each week. Continue until 100–120 days posttransplantation.

    Prophylaxis of CMV: Some experts recommend 5 mg/kg once daily. Continue antiviral prophylaxis for 3 months in CMV-seropositive recipients of solid organs (kidney, pancreas, kidney/pancreas, liver, heart) and for 3–6 months in CMV-seronegative recipients of solid organs (kidney, pancreas, kidney/pancreas, liver, heart) from CMV-seropositive donors.

    Preemptive treatment of CMV infection in solid organ transplant recipients†: 5 mg/kg twice daily recommended.

    VZV Infections† IV

    Progressive outer retinal necrosis caused by VZV in HIV-infected adults†: CDC, NIH, IDSA, and others state 5 mg/kg every 12 hours (used with or without IV foscarnet) in conjunction with intravitreal ganciclovir† (used with or without intravitreal foscarnet) can be considered.

    Special Populations

    Renal Impairment

    In patients with impaired renal function, doses and/or frequency of administration of ganciclovir must be modified in response to the degree of impairment.

    Base dosage on the patient’s measured or estimated Clcr.

    CMV Retinitis IV

    Adults with renal impairment: Manufacturers recommend the following dosage for initial treatment (induction therapy) and maintenance therapy (secondary prophylaxis) based on Clcr. (See Table 1.)

    Table 1. Dosage of IV Ganciclovir for Management of CMV Retinitis in Adults with Renal Impairment1214

    Clcr (mL/minute)

    Initial Treatment (Induction) Dosage

    Maintenance Dosage

    50–69

    2.5 mg/kg every 12 hours

    2.5 mg/kg every 24 hours

    25–49

    2.5 mg/kg every 24 hours

    1.25 mg/kg every 24 hours

    10–24

    1.25 mg/kg every 24 hours

    0.625 mg/kg every 24 hours

    <10

    1.25 mg/kg 3 times weekly

    0.625 mg/kg 3 times weekly

    Adults undergoing hemodialysis: Do not exceed initial treatment (induction therapy) dosage of 1.25 mg/kg 3 times weekly and do not exceed maintenance therapy dosage of 0.625 mg/kg 3 times weekly. Because hemodialysis may reduce ganciclovir plasma concentrations by approximately 50% (see Elimination under Pharmacokinetics), time doses on dialysis days to give them shortly after completion of dialysis.

    Geriatric Patients

    Select dosage with caution because of age-related decreases in renal function. Assess renal function before and during ganciclovir therapy and adjust dosage as necessary. (See Renal Impairment under Dosage and Administration.)

    Warnings

    Contraindications

  • Clinically important hypersensitivity reaction (e.g., anaphylaxis) to ganciclovir, valganciclovir, or any component of the formulation.

    • Warnings/Precautions

    Warnings

    Hematologic Effects

    Hematologic toxicity, including granulocytopenia (neutropenia), anemia, thrombocytopenia, and pancytopenia, reported in patients receiving ganciclovir.

    Neutropenia (ANC <1000/mm3) frequently occurs and is most common dose-limiting adverse effect of ganciclovir.

    Granulocytopenia (neutropenia) usually develops early in treatment (e.g., during the first or second week of induction therapy), but can occur at any time.

    In most cases, interruption of ganciclovir therapy will result in increased neutrophil counts, usually evident within 3–7 days; however, prolonged or irreversible neutropenia has occurred. Neutropenia has recurred following reinitiation of ganciclovir therapy, occasionally even with reduced dosage.

    Carefully monitor CBCs with differential and platelet counts in all patients, especially in those with renal impairment, baseline neutrophil counts <1000/mm3, or history of leukopenia during treatment with ganciclovir or other nucleoside analogs and in those receiving myelosuppressive drugs or radiation treatments.

    Not recommended in patients with ANC <500/mm3, platelet count <25,000/mm3, or hemoglobin concentration <8 g/dL.

    Impairment of Fertility

    Animal data from studies using ganciclovir and limited data from patients receiving valganciclovir (prodrug of ganciclovir) indicate ganciclovir may cause temporary or permanent inhibition of spermatogenesis in males and may cause suppression of fertility in females.

    In a small clinical study in adult male renal transplant patients receiving CMV prophylaxis with valganciclovir for up to 200 days posttransplantation, mean sperm density in evaluable patients at end-of-treatment visit was decreased by 11 million/mL from baseline; among evaluable patients in an untreated control group, mean sperm density increased by 33 million/mL. At final follow-up visit 6 months after the drug was discontinued, mean sperm density in evaluable patients in the valganciclovir group was comparable to that in evaluable patients in untreated control group (mean sperm density increased by 41 or 43 million/mL from baseline, respectively).

    Advise patients that ganciclovir may be associated with infertility.

    Teratogenicity

    Animal data indicate that ganciclovir may cause fetal toxicity when administered to pregnant women.

    In studies in pregnant mice and rabbits, ganciclovir at dosages 2 times human exposure resulted in maternal toxicity and embryofetal toxicity (e.g., fetal resorptions, embryofetal mortality). In addition, teratogenic effects (cleft palate, anophthalmia/microphthalmia, hydrocephalus, brachygnathia, aplastic organs [kidney, pancreas]) reported in rabbits.

    Perform pregnancy testing before initiating ganciclovir in females of childbearing potential. Advise females of childbearing potential to use an effective method of contraception during and for ≥30 days after ganciclovir discontinued. Advise male patients to use a reliable method of barrier contraception during and for ≥90 days after ganciclovir discontinued. (See Pregnancy under Cautions.)

    Mutagenicity and Carcinogenicity

    Animal studies indicate that ganciclovir is mutagenic and carcinogenic.

    Consider ganciclovir a potential carcinogen in humans.

    Other Warnings/Precautions

    Renal Effects

    Increased Scr concentrations reported in geriatric patients and in transplant recipients receiving ganciclovir concomitantly with other nephrotoxic drugs (e.g., cyclosporine, amphotericin B).

    Patients should be adequately hydrated during ganciclovir therapy.

    Renal function monitoring is essential in all patients, especially in geriatric patients and transplant recipients receiving concomitant nephrotoxic drugs.

    Specific Populations

    Pregnancy

    Ganciclovir caused maternal and fetal toxicity, embryofetal mortality, and teratogenic effects in animal studies. (See Teratogenicity under Cautions.)

    Data regarding use of ganciclovir in pregnant women inadequate to establish whether the drug poses a risk to pregnancy outcomes. Placental transfer of ganciclovir observed in ex vivo experiments with human placenta and in at least one case report in a pregnant woman.

    Perform pregnancy testing in females of childbearing potential prior to initiating ganciclovir.

    Advise females of childbearing potential to use an effective method of contraception during and for ≥30 days after ganciclovir therapy.

    Advise male patients to use a reliable method of barrier contraception during and for ≥90 days after ganciclovir therapy.

    Lactation

    Not known whether distributes into human milk, affects the breast-fed infant, or affects milk production. Distributed into milk in rats.

    Because of potential for serious adverse effects in the infant, women should not breast-feed infants while receiving ganciclovir.

    Instruct HIV-infected women not to breast-feed because of risk of HIV transmission.

    Pediatric Use

    Safety and efficacy not established in pediatric patients.

    In clinical trials in pediatric patients†, granulocytopenia and thrombocytopenia were most commonly reported adverse effects.

    Although pharmacokinetics reported in pediatric patients are similar to those reported in adults (see Pharmacokinetics), safety and efficacy of such ganciclovir exposures in pediatric patients not established.

    Geriatric Use

    Insufficient experience in patients ≥65 years of age to determine whether geriatric patients respond differently than younger adults.

    Select dosage with caution because of age-related decreases in hepatic, renal, and/or cardiac function and potential for concomitant disease and drug therapy.

    Assess renal function before and during therapy; make appropriate dosage adjustments as necessary. (See Renal Impairment under Dosage and Administration.)

    Hepatic Impairment

    Safety and efficacy not evaluated.

    Renal Impairment

    Use with caution in patients with impaired renal function.

    Dosage adjustment necessary in patients with renal impairment. (See Renal Impairment under Dosage and Administration.)

    Common Adverse Effects

    Hematologic effects (leukopenia, neutropenia, thrombocytopenia, anemia), pyrexia, GI effects (diarrhea, nausea, decreased appetite, abdominal pain), catheter-associated effects (sepsis), hyperhidrosis, asthenia, headache, cough, dyspnea, increased creatinine concentrations.

    What other drugs will affect Ganciclovir Sodium

    Drug interaction studies were performed in patients with normal renal function. In patients with renal impairment, concomitant use of ganciclovir and other drugs eliminated by renal excretion may increase concentrations of ganciclovir and the concomitant drug; closely monitor for toxicity associated with ganciclovir and the concomitant drug.

    Specific Drugs

    Drug

    Interaction

    Comments

    Amphotericin B

    Possible increased Scr

    Monitor renal function

    Antineoplastic agents (doxorubicin, hydroxyUrea, vinblastine, vincristine)

    Possible increased toxicity

    Use concomitantly only if potential benefits outweigh risks

    Co-trimoxazole

    Possible increased toxicity

    Use concomitantly only if potential benefits outweigh risks

    Dapsone

    Possible increased toxicity

    Use concomitantly only if potential benefits outweigh risks

    Didanosine

    Increased peak plasma concentrations and AUC of didanosine; no effect on ganciclovir pharmacokinetics

    Some in vitro evidence that ganciclovir antagonizes antiretroviral activity of didanosine

    If used concomitantly, monitor closely for didanosine toxicity

    Flucytosine

    Possible increased toxicity

    Use concomitantly only if potential benefits outweigh risks

    Foscarnet

    No apparent effect on pharmacokinetics of either drug

    Physically incompatible

    No in vitro evidence of antagonistic antiviral effects; in vitro evidence of additive or synergistic antiviral activity against CMV and herpes simplex virus type 2 (HSV-2)

    Do not admix

    Imipenem and cilastatin

    Seizures reported with concomitant use

    Concomitant use not recommended

    Immunosuppressive agents (azathioprine, corticosteroids, cyclosporine, mycophenolate mofetil, tacrolimus)

    Immunosuppressive agents: Possible increased risk of myelosuppression or nephrotoxicity

    Cyclosporine: Possible increased Scr; no effect on cyclosporine whole blood concentrations

    Mycophenolate mofetil: No effect on pharmacokinetics of either drug; possible increased toxicity

    Tacrolimus: Possible increased toxicity

    Immunosuppressive agents: Consider need for decreased dosage or temporary withdrawal of the immunosuppressive agent

    Cyclosporine: Monitor renal function

    Mycophenolate mofetil: Monitor for hematologic and renal toxicity

    Tacrolimus: Use concomitantly only if potential benefits outweigh risks

    Letermovir

    No in vitro evidence of antagonistic anti-CMV effects

    Pentamidine

    Possible increased toxicity

    Use concomitantly only if potential benefits outweigh risks

    Probenecid

    Possible increased ganciclovir concentrations

    Monitor for ganciclovir-associated toxicity; ganciclovir dosage may need to be reduced

    Sulfamethoxazole

    Possible increased toxicity

    Use concomitantly only if potential benefits outweigh risks

    Tenofovir

    Tenofovir alafenamide or tenofovir disoproxil fumarate: Possible increased concentrations of ganciclovir and tenofovir

    Tenofovir alafenamide or tenofovir disoproxil fumarate: Monitor for tenofovir toxicities

    Trimethoprim

    No effect on pharmacokinetics of either drug; possible increased toxicity

    Use concomitantly only if potential benefits outweigh risks

    Zidovudine

    Increased risk of hematologic toxicity

    Some in vitro evidence that ganciclovir antagonizes antiretroviral activity of zidovudine

    Use concomitantly only if potential benefits outweigh risks

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