Valganciclovir

Generalized seizures have been reported in patients receiving ganciclovir and imipenem-cilastatin. Coadministration is not recommended.

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

Risk of nephrotoxicity may be increased when coadministered with valganciclovir. Monitor renal function closely.

Risk of nephrotoxicity may be increased when coadministered with valganciclovir. Monitor renal function closely.

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

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

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

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

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

Risk of hematological and renal toxicity may be increased. Monitor for ganciclovir and MMF toxicity.

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

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

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

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

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

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

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

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

Table 9 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 imipenem­cilastatin is not recommended because generalized seizures have been reported in patients who received ganciclovir and imipenemcilastatin Cyclosporine or amphotericin B Unknown Monitor renal function when Valganciclovir hydrochloride is coadministered with cyclosporine or amphotericin B because of potential increase in serum creatinine [see Warningsand Precautions (5.2) ]. Imipenem-cilastatin: Seizures were reported in patients receiving ganciclovir and imipenem-cilastatin.

Valganciclovir may increase didanosine concentrations. Patients should be closely monitored for didanosine toxicity.

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

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

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

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

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

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

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

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

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.

Probenecid increases ganciclovir concentrations. Monitor patients for evidence of ganciclovir toxicity.

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

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) ] .

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.

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 myelosuppression or nephrotoxicity (e.g., adriamycin, dapsone, doxorubicin, flucytosine, hydroxyurea, pentamidine, tacrolimus, trimethoprim/ sulfamethoxazole, vinblastine, vincristine, and zidovudine) Unknown Because of potential for higher toxicity, coadministration with valganciclovir 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. Following concomitant administration of valganciclovir and other renally excreted drugs, patients with impaired renal function may have increased concentrations of ganciclovir and the coadministered drug.