Ganciclovir

Generalized seizures reported with coadministration. Concomitant use not recommended unless potential benefits outweigh risks.

Coadministration may increase hematologic toxicity of zidovudine.

Increased risk of nephrotoxicity and potential increase in serum creatinine. Monitor renal function.

Increased risk of nephrotoxicity and potential increase in serum creatinine. Monitor renal function.

7 DRUG INTERACTIONS Ganciclovir: Avoid concomitant use. ( 7.2 ) 7.1 Ganciclovir Generalized seizures have been reported in patients who received ganciclovir concomitantly with imipenem/cilastatin, a component of RECARBRIO. Ganciclovir should not be used concomitantly with RECARBRIO unless the potential benefits outweigh the risks.

May increase hematologic toxicity of zidovudine when coadministered.

LIVTENCITY may antagonize the antiviral activity of ganciclovir by inhibiting human CMV pUL97 kinase, which is required for activation/phosphorylation of ganciclovir. Coadministration is not recommended.

Increased risk of hematological and renal toxicity. Monitor for toxicity in patients with normal and impaired renal function.

Coadministration may increase the hematologic toxicity of zidovudine.

Eliminated by active tubular secretion; coadministration may increase tenofovir and ganciclovir concentrations, increasing adverse reaction risk.

Coadministration may increase concentrations of ganciclovir and renally eliminated drugs, increasing risk of adverse reactions.

Associated with myelosuppression or nephrotoxicity. Coadministration considered only if benefits outweigh risks.

Ganciclovir may increase didanosine concentrations. Monitor closely for didanosine toxicity including pancreatitis.

Associated with myelosuppression or nephrotoxicity. Coadministration considered only if benefits outweigh risks.

Eliminated by active tubular secretion; may increase concentrations of ganciclovir and/or emtricitabine/tenofovir.

Coadministration may increase concentrations of tenofovir and/or ganciclovir due to competition for active tubular secretion in the kidneys.

Ganciclovir is eliminated by active tubular secretion; coadministration may increase concentrations of ganciclovir and emtricitabine/tenofovir, increasing risk of adverse reactions.

Coadministration may increase concentrations of FTC, tenofovir, and ganciclovir due to competition for active tubular secretion.

Coadministration may increase concentrations of ganciclovir and/or tenofovir due to competition for renal tubular secretion. Monitor for tenofovir toxicity.

Coadministration may increase serum concentrations of emtricitabine, tenofovir, and/or ganciclovir due to competition for renal tubular secretion.

Coadministration may increase serum concentrations of FTC, tenofovir, and/or ganciclovir due to competition for active tubular secretion.

Coadministration may increase concentrations of FTC, tenofovir, and/or ganciclovir due to competition for active tubular secretion in kidneys.

Associated with myelosuppression or nephrotoxicity. Coadministration considered only if benefits outweigh risks.

Associated with myelosuppression or nephrotoxicity. Coadministration considered only if benefits outweigh risks.

May increase serum tenofovir concentrations and/or increase concentrations of other renally eliminated drugs.

( 5.2 , 7.8 ) Acyclovir, Valacyclovir, Ganciclovir, Valganciclovir, and Other Drugs that Undergo Renal Tubular Secretion: May increase concentrations of mycophenolic acid glucuronide (MPAG) and coadministered drug; monitor blood cell counts. 7.9 Acyclovir (Valacyclovir), Ganciclovir (Valganciclovir), and Other Drugs That Undergo Renal Tubular Secretion The coadministration of MMF and acyclovir or ganciclovir may increase plasma concentrations of mycophenolic acid glucuronide (MPAG) and acyclovir/valacyclovir/ganciclovir/valganciclovir as their coexistence competes for tubular secretion. Both acyclovir/valacyclovir/ganciclovir/valganciclovir and MPAG concentrations will be also increased in the presence of renal impairment.

OAT1/OAT3 Substrates (e.g., adefovir, ganciclovir, methotrexate) Clinical Impact Increased exposure of the interacting drug [see Clinical Pharmacology ( 12.3 )] Intervention Monitor for potential adverse reactions related to the co-administered drug.

Associated with myelosuppression or nephrotoxicity. Coadministration considered only if benefits outweigh risks.

Increases ganciclovir concentrations. Ganciclovir dose may need reduction. Monitor for toxicity.

Associated with myelosuppression or nephrotoxicity. Coadministration considered only if benefits outweigh risks.

Associated with myelosuppression or nephrotoxicity. Coadministration considered only if benefits outweigh risks.

Coadministration may increase tenofovir concentrations due to active tubular secretion competition. Monitor for evidence of tenofovir toxicity.

Associated with myelosuppression or nephrotoxicity. Coadministration considered only if benefits outweigh risks.

Associated with myelosuppression or nephrotoxicity. Coadministration considered only if benefits outweigh risks.

Established and Other Potentially Significant Drug Interactions with Ganciclovir Name of the Concomitant Drug Change in the Concentration of Ganciclovir or Concomitant Drug Clinical Comment Imipenem-cilastatin Unknown Coadministration with imipenem­-cilastatin is not recommended because generalized seizures have been reported in patients who received ganciclovir and imipenem-cilastatin. Imipenem-cilastatin: Seizures were reported in patients receiving ganciclovir and imipenem-cilastatin.

Some examples of drugs that are eliminated by active tubular secretion include, but are not limited to, acyclovir, cidofovir, ganciclovir, valacyclovir, valganciclovir, aminoglycosides (e.g., gentamicin), and high-dose or multiple NSAIDs [see Warnings and Precautions (5.6) ] .

Some examples of drugs that are eliminated by active tubular secretion include, but are not limited to, acyclovir, cidofovir, ganciclovir, valacyclovir, valganciclovir, aminoglycosides (e.g., gentamicin), and high-dose or multiple NSAIDs [see Warnings and Precautions (5.3) and Clinical Pharmacology (12.3) ] .

Some examples of drugs that are eliminated by active tubular secretion include, but are not limited to, acyclovir, cidofovir, ganciclovir, valacyclovir, valganciclovir, aminoglycosides (e.g., gentamicin), and high-dose or multiple NSAIDs [see Warnings and Precautions (5.4) ] .

Some examples of drugs that are eliminated by active tubular secretion include, but are not limited to, acyclovir, cidofovir, ganciclovir, valacyclovir, valganciclovir, aminoglycosides (e.g., gentamicin), and high-dose or multiple NSAIDs [see Warnings and Precautions (5.5) ] .

Patients with impaired renal function may have increased concentrations of ganciclovir and the coadministered drug following concomitant administration of Ganciclovir Injection Drug-drug interaction studies were conducted in patients with normal renal function. Patients with impaired renal function may have increased concentrations of ganciclovir and the coadministered drug following concomitant administration of Ganciclovir Injection and drugs excreted by the same pathway as ganciclovir. Therefore, these patients should be closely monitored for toxicity of ganciclovir and the coadministered drug.

Examples Acyclovir, ganciclovir, probenecid, valacyclovir, valganciclovir Combination Oral Contraceptives Clinical Impact Concomitant use with Mycophenolate Mofetil decreased the systemic exposure to levonorgestrel, but did not affect the systemic exposure to ethinylestradiol [see Clinical Pharmacology (12.3) ] , which may result in reduced combination oral contraceptive effectiveness.

Other drugs associated with myelosuppresion or nephrotoxicity (e.g., dapsone, doxorubicin, flucytosine, hydroxyurea, pentamidine, tacrolimus, trimethoprim/ sulfamethoxazole, vinblastine, vincristine and zidovudine) Unknown Because of potential for higher toxicity, coadministration with ganciclovir should be considered only if the potential benefits are judged to outweigh the risks.

7 DRUG INTERACTIONS In vivo drug-drug interaction studies were not conducted with valganciclovir. However, because valganciclovir is rapidly and extensively converted to ganciclovir, drug-drug interactions associated with ganciclovir will be expected for valganciclovir tablets. Established and other potentially significant drug interactions conducted with ganciclovir are listed in Table 9.

7 DRUG INTERACTIONS In vivo drug-drug interaction studies were not conducted with valganciclovir. However, because valganciclovir is rapidly and extensively converted to ganciclovir, drug-drug interactions associated with ganciclovir will be expected for valganciclovir. Drug-drug interaction studies with ganciclovir were conducted in patients with normal renal function.