General VEMLIDY should not be coadministered with products containing tenofovir alafenamide (GENVOYA®, DESCOVY®, ODEFSEY®, BIKTARVY®, Symtuza®), tenofovir disoproxil fumarate (ATRIPLA®, COMPLERA®, STRIBILD®, TRUVADA®, VIREAD®), or adefovir dipivoxil (HEPSERA®) (see DRUG INTERACTIONS, Drug-Drug Interactions).
Hepatic/Biliary/Pancreatic Hepatic Impairment No dosage adjustment of VEMLIDY is required in patients with mild hepatic impairment (Child- Pugh A). VEMLIDY is not recommended in patients with decompensated (Child-Pugh B or C) hepatic impairment (see DOSAGE AND ADMINISTRATION and ACTION AND CLINICAL PHARMACOLOGY).
Exacerbation of Hepatitis after Discontinuation of Treatment Discontinuation of anti-hepatitis B therapy, including VEMLIDY, may be associated with severe acute exacerbations of hepatitis. Patients who discontinue VEMLIDY should be closely monitored with both clinical and laboratory follow-up for at least several months after stopping treatment.
If appropriate, resumption of anti-hepatitis B therapy may be warranted. In patients with advanced liver disease or cirrhosis, discontinuation of anti-hepatitis B therapy is not recommended since post-treatment exacerbation of hepatitis may lead to hepatic decompensation.
Lactic acidosis and severe hepatomegaly with steatosis Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogs, including tenofovir disoproxil fumarate, another prodrug of tenofovir, alone or in combination with other antiretrovirals.
Treatment with VEMLIDY should be suspended in any patient who develops clinical or laboratory findings suggestive of lactic Serious Warnings and Precautions Post-treatment Exacerbation of Hepatitis B Discontinuation of anti-hepatitis B therapy, including VEMLIDY, may be associated with severe acute exacerbations of hepatitis B.
Hepatic function should be monitored closely with both clinical and laboratory follow-up for at least several months in patients who discontinue anti-hepatitis B therapy, including VEMLIDY. If appropriate, resumption of anti-hepatitis B therapy may be warranted (see WARNINGS AND PRECAUTIONS, Hepatic).
VEMLIDY (tenofovir alafenamide*) tablets *as tenofovir alafenamide hemifumarate Product Monograph Page 5 of 33 acidosis or pronounced hepatotoxicity (which may include hepatomegaly and steatosis even in the absence of marked transaminase elevations).
Renal Renal Impairment Renal impairment, including cases of acute renal failure and Fanconi syndrome (renal tubular injury with severe hypophosphatemia), has been reported with the use of tenofovir prodrugs in both animal toxicology studies and human trials.
In clinical trials of VEMLIDY, there have been no cases of Fanconi syndrome or proximal renal tubulopathy. Patients taking tenofovir prodrugs who have impaired renal function and those taking nephrotoxic agents including non-steroidal anti-inflammatory drugs are at increased risk of developing renal-related adverse reactions (see DOSAGE AND ADMINISTRATION, Testing Prior to Initiation and During Treatment with VEMLIDY).
No dosage adjustment of VEMLIDY is required in patients with mild, moderate, or severe renal impairment (estimated creatinine clearance of ≥ 15 mL/min). VEMLIDY is not recommended in patients with end stage renal disease (estimated creatinine clearance of < 15 mL/min) (see DOSAGE AND ADMINISTRATION and ACTION AND CLINICAL PHARMACOLOGY, Special Populations).
Special Populations Patients Coinfected with HBV and HIV-1 Due to the risk of development of HIV resistance, VEMLIDY is not recommended for the treatment of HIV-1 infection. The safety and efficacy of VEMLIDY have not been established in patients co-infected with HIV-1 and HBV.
HIV antibody testing should be offered to all HBV- infected patients before initiating therapy with VEMLIDY, and, if positive, an appropriate antiretroviral combination regimen that is recommended for patients co-infected with HIV-1 should be used.
Patients should be informed that if they have HIV infection and are not receiving effective HIV treatment, VEMLIDY may increase the risk of development of resistance to HIV treatment (see DOSAGE AND ADMINISTRATION). Pregnant Women There are no adequate and well-controlled studies in pregnant women.
Because animal reproduction studies are not always predictive of human response, VEMLIDY should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Embryonic fetal development studies performed in rats and rabbits revealed no evidence of impaired fertility or harm to the fetus.
The embryo-fetal NOAELs in rats and rabbits occurred at VEMLIDY (tenofovir alafenamide*) tablets *as tenofovir alafenamide hemifumarate Product Monograph Page 6 of 33 tenofovir alafenamide exposures similar to and 53 times higher than, respectively, the exposure in humans at the recommended daily dose.
Tenofovir alafenamide is rapidly converted to tenofovir; the observed tenofovir exposure in rats and rabbits were 54 and 85 times higher than human tenofovir exposures at the recommended daily doses, respectively.
Antiretroviral Pregnancy Registry:
To monitor fetal outcomes of pregnant women exposed to VEMLIDY, an Antiretroviral Pregnancy Registry has been established. com Telephone: 1-800-258-4263 Fax: (800) 800-1052 Nursing Women Animal studies have demonstrated that tenofovir is secreted in milk after administration of tenofovir disoproxil fumarate.
There is no information regarding the presence of tenofovir alafenamide in human milk. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for VEMLIDY and any potential adverse effects on the breastfed infant from VEMLIDY or from the underlying maternal condition.
Geriatrics (≥ 65 years of age) Clinical trials of VEMLIDY did not include sufficient […]