HIV infection in combination with other antiretroviral drugs | Chronic hepatitis B infection with compensated liver disease (with evidence of viral replication,and histologically documented active liver inflammation or fibrosis) | Chronic hepatitis B infection with decompensated liver disease
Potential for Other Drugs to Affect Tenofovir alafenamide: Tenofovir alafenamide is a substrate of P-glycoprotein (P-gp) and BCRP. Drugs that strongly affect P-gp and BCRP activity may lead to changes in tenofovir alafenamide absorption. Drugs that induce P-gp activity are expected to decrease the absorption of tenofovir alafenamide resulting in decreased plasma concentrations of tenofovir alafenamide which may lead to loss of therapeutic effect of Tenofovir alafenamide. Coadministration of Tenofovir alafenamide with other drugs that inhibit P-gp and BCRP may increase the absorption & plasma concentration of tenofovir alafenamide.
Drugs Affecting Renal Function: Tenofovir is primarily excreted by the kidneys by a combination of glomerular filtration and active tubular secretion, coadministration of Tenofovir alafenamide with drugs that reduce renal function or compete for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs and this may increase the risk of adverse reactions. 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.
Recommended dose for the treatment of HIV-1 or chronic hepatitis B in adults and pediatric patients 12 years of age and older (35 kg or more): 300 mg once daily taken orally without regard to food. Recommended dose for the treatment of HIV-1 in pediatric patients (2 to less than 12 years of age): Tablets: for pediatric patients weighing greater than or equal to 17 kg who can swallow an intact tablet,one tablet (150,200,250 or 300 mg based on body weight) once daily taken orally without regard to food. Oral powder: 8 mg/kg oral powder (up to a maximum of 300 mg) once daily with food. Dose recommended in renal impairment in adults: Creatinine clearance 30-49 mL/min: 300 mg every 48 hours. Creatinine clearance 10-29 mL/min: 300 mg every 72 to 96 hours.Hemodialysis: 300 mg every 7 days or after approximately 12 hours of dialysis.
Potential for Other Drugs to Affect Tenofovir alafenamide: Tenofovir alafenamide is a substrate of P-glycoprotein (P-gp) and BCRP. Drugs that strongly affect P-gp and BCRP activity may lead to changes in tenofovir alafenamide absorption. Drugs that induce P-gp activity are expected to decrease the absorption of tenofovir alafenamide resulting in decreased plasma concentrations of tenofovir alafenamide which may lead to loss of therapeutic effect of Tenofovir alafenamide. Coadministration of Tenofovir alafenamide with other drugs that inhibit P-gp and BCRP may increase the absorption & plasma concentration of tenofovir alafenamide.
Drugs Affecting Renal Function: Tenofovir is primarily excreted by the kidneys by a combination of glomerular filtration and active tubular secretion, coadministration of Tenofovir alafenamide with drugs that reduce renal function or compete for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs and this may increase the risk of adverse reactions. 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.
New onset or worsening renal impairment: Can include acute renal failure and Fanconi syndrome. Assess creatinine clearance (CrCl) before initiating treatment with it. Monitor CrCl and serum phosphorus in patients at risk. Avoid administering it with concurrent or recent use of nephrotoxic drugs. ?Coadministration with Other Products: Do not use with other tenofovir-containing products (e.g.,ATRIPLA,COMPLERA,and TRUVADA). Do not administer in combination with HEPSERA. ?HIV testing: HIV antibody testing should be offered to all HBV-infected patients before initiating therapy with it. VIREAD should only be used as part of an appropriate antiretroviral combination regimen in HIV-infected patients with or without HBV coinfection. (5.5) ?Decreases in bone mineral density (BMD): Consider assessment of BMD in patients with a history of pathologic fracture or other risk factors for osteoporosis or bone loss. ?Redistribution/accumulation of body fat: Observed in HIV-infected patients receiving antiretroviral combination therapy. ?Immune reconstitution syndrome: Observed in HIV-infected patients. May necessitate further evaluation and treatment. ?Triple nucleoside-only regimens: Early virologic failure has been reported in HIV-infected patients. Monitor carefully and consider treatment modification.
In HIV-infected adult subjects: Most common adverse reactions (incidence greater than or equal to 10%,Grades 2?4) are rash,diarrhea,headache,pain,depression,asthenia,and nausea. In HBV-infected subjects with compensated liver disease: most common adverse reaction (all grades) was nausea (9%). In pediatric subjects: Adverse reactions in pediatric subjects were consistent with those observed in adults. In HBV-infected subjects with decompensated liver disease: most common adverse reactions (incidence greater than or equal to 10%,all grades) were abdominal pain,nausea,insomnia,pruritus,vomiting,dizziness,and pyrexia.
Pregnancy Category B There are no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response,It should be used during pregnancy only if clearly needed. Women infected with HIV should be instructed not to breast feed.
If overdose occurs, monitor patient for evidence of toxicity. Treatment of overdosage with Tenofovir alafenamide consists of general supportive measures including monitoring of vital signs as well as observation of the clinical status of the patient. Tenofovir is efficiently removed by hemo- dialysis with an extraction coefficient of approximately 54%.
Store below 30°C. Keep it in its original container. protect from light. Keep out of children’s reach.
Tenofovir alafenamide is a phosphonamidate prodrug of tenofovir (2’-deoxyadenosine monophosphate analog). Tenofovir alafenamide as a lipophilic cell-permeant compound enters primary hepatocytes by passive diffusion and by the hepatic uptake transporters OATP1B1 and OATP1B3. Tenofovir alafenamide is then converted to tenofovir through hydrolysis primarily by carboxylesterase 1 (CES1) in primary hepatocytes. Intracellular tenofovir is subsequently phosphorylated by cellular kinases to the pharmacologically active metabolite tenofovir diphosphate. Tenofovir diphosphate inhibits HBV replication through incorporation into viral DNA by the HBV reverse transcriptase, which results in DNA chain termination. Tenofovir diphosphate is a weak inhibitor of mammalian DNA polymerases that include mitochondrial DNA polymerase γ and there is no evidence of toxicity to mitochondria in cell culture.
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