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Tenofovir Alafenamide

Pronunciation

(ten OF oh vir al a FEN a mide)

Index Terms

  • GS-7340
  • Tenofovir Alafenamide Fumarate

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral:

Vemlidy: 25 mg

Brand Names: U.S.

  • Vemlidy

Pharmacologic Category

  • Antihepadnaviral, Reverse Transcriptase Inhibitor, Nucleotide (Anti-HBV)

Pharmacology

Tenofovir alafenamide, an analog of adenosine 5'-monophosphate, is converted intracellularly by hydrolysis to tenofovir and subsequently phosphorylated to the active tenofovir diphosphate. The active moiety inhibits replication of HBV by inhibiting HBV polymerase.

Metabolism

Tenofovir alafenamide (TAF) is converted intracellularly by hydrolysis to tenofovir, then phosphorylated to the active tenofovir diphosphate.

Excretion

Feces (31.7%) and urine (<1%)

Time to Peak

Serum: 0.48 hours

Half-Life Elimination

Serum: 0.51 hours

Protein Binding

80% to plasma proteins

Special Populations: Renal Function Impairment

Tenofovir alafenamide and tenofovir systemic exposures were 1.9-fold and 5.7-fold higher, respectively, in severe renal impairment.

Special Populations: Hepatic Function Impairment

Tenofovir alafenamide and tenofovir systemic exposures were 7.5% and 11% lower, respectively, in mild hepatic impairment.

Use: Labeled Indications

Chronic hepatitis B: Treatment of chronic hepatitis B virus (HBV) infection in adults with compensated liver disease

Contraindications

There are no contraindications listed in the manufacturer's labeling.

Dosing: Adult

Chronic hepatitis B: Oral: 25 mg once daily

Dosing: Geriatric

Refer to adult dosing.

Dosing: Renal Impairment

CrCl ≥15 mL/minute: No dosage adjustment necessary.

CrCl <15 mL/minute: Use is not recommended.

Dosing: Hepatic Impairment

Child-Pugh class A: No dosage adjustment necessary.

Child-Pugh class B or C: Use is not recommended.

Administration

Oral: Administer with food.

Storage

Store below 30°C (86°F). Keep container tightly closed; dispense in original container.

Drug Interactions

Acyclovir-Valacyclovir: May increase the serum concentration of Tenofovir Products. Tenofovir Products may increase the serum concentration of Acyclovir-Valacyclovir. Monitor therapy

Adefovir: May diminish the therapeutic effect of Tenofovir Products. Adefovir may increase the serum concentration of Tenofovir Products. Tenofovir Products may increase the serum concentration of Adefovir. Avoid combination

Aminoglycosides: May increase the serum concentration of Tenofovir Products. Tenofovir Products may increase the serum concentration of Aminoglycosides. Monitor therapy

Cabozantinib: MRP2 Inhibitors may increase the serum concentration of Cabozantinib. Monitor therapy

CarBAMazepine: May decrease the serum concentration of Tenofovir Alafenamide. Avoid combination

Cidofovir: May increase the serum concentration of Tenofovir Products. Tenofovir Products may increase the serum concentration of Cidofovir. Monitor therapy

Cobicistat: May enhance the adverse/toxic effect of Tenofovir Products. More specifically, cobicistat may impair proper tenofovir monitoring and dosing. Monitor therapy

Diclofenac (Systemic): May enhance the nephrotoxic effect of Tenofovir Products. Management: Seek alternatives to this combination whenever possible. Avoid use of tenofovir with multiple NSAIDs or any NSAID given at a high dose. Consider therapy modification

Fosphenytoin-Phenytoin: May decrease the serum concentration of Tenofovir Alafenamide. Avoid combination

Ganciclovir-Valganciclovir: Tenofovir Products may increase the serum concentration of Ganciclovir-Valganciclovir. Ganciclovir-Valganciclovir may increase the serum concentration of Tenofovir Products. Monitor therapy

Nonsteroidal Anti-Inflammatory Agents: May enhance the nephrotoxic effect of Tenofovir Products. Management: Seek alternatives to these combinations whenever possible. Avoid use of tenofovir with multiple NSAIDs or any NSAID given at a high dose. Consider therapy modification

Orlistat: May decrease the serum concentration of Antiretroviral Agents. Monitor therapy

OXcarbazepine: May decrease the serum concentration of Tenofovir Alafenamide. Avoid combination

PHENobarbital: May decrease the serum concentration of Tenofovir Alafenamide. Avoid combination

Primidone: May decrease the serum concentration of Tenofovir Alafenamide. Avoid combination

Rifabutin: May decrease the serum concentration of Tenofovir Alafenamide. Avoid combination

RifAMPin: May decrease the serum concentration of Tenofovir Alafenamide. Avoid combination

Rifapentine: May decrease the serum concentration of Tenofovir Alafenamide. Avoid combination

St John's Wort: May decrease the serum concentration of Tenofovir Alafenamide. Avoid combination

Tipranavir: May decrease the serum concentration of Tenofovir Alafenamide. Avoid combination

Adverse Reactions

1% to 10%:

Central nervous system: Headache (9%), fatigue (6%)

Endocrine & metabolic: Increased LDL cholesterol (4%), glycosuria, increased amylase

Gastrointestinal: Abdominal pain (7%), nausea (5%)

Hepatic: Increased serum ALT, increased serum AST

Neuromuscular & skeletal: Decreased bone mineral density (3% to 6%), back pain (5%), increased serum creatine phosphokinase

Respiratory: Cough (6%)

ALERT: U.S. Boxed Warning

Lactic acidosis/severe hepatomegaly with steatosis:

Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogs.

Post-treatment severe acute exacerbation of hepatitis B

Discontinuation of anti-hepatitis B therapy, including tenofovir alafenamide, may result in 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 tenofovir alafenamide. If appropriate, resumption of anti-hepatitis B therapy may be warranted.

Warnings/Precautions

Concerns related to adverse effects:

• Lactic acidosis/hepatomegaly: [US Boxed Warning]: Lactic acidosis and severe hepatomegaly with steatosis have been reported with nucleoside analogues (eg, tenofovir), including fatal cases; use with caution in patients with risk factors for liver disease (risk may be increased with female gender, obesity or prolonged nucleoside exposure) and suspend treatment in any patient who develops clinical or laboratory findings suggestive of lactic acidosis or hepatotoxicity (transaminase elevation may/may not accompany hepatomegaly and steatosis). Some cases of hepatotoxicity have occurred in patients with no known risk factors for hepatic disease prior to treatment.

Disease-related concerns:

• Hepatic impairment: Use is not recommended in patients with Child-Pugh class B or C hepatic impairment.

• Hepatitis B acute exacerbation: [US Boxed Warning]: Discontinuation of anti-hepatitis B therapy may result in severe acute exacerbations of hepatitis B. Monitor clinical and laboratory data closely for several months after treatment discontinuation. If clinically indicated, anti-hepatitis B therapy may be resumed.

• HIV-1 and HBV coinfection: Should not be used as a single agent for the treatment of HIV-1 due to resistance development risk.

• Renal impairment: Use is not recommended in patients with CrCl <15 mL/minute.

• Renal toxicity: Cases of acute renal failure and/or Fanconi syndrome have been reported with use of tenofovir prodrugs; patients with preexisting renal impairment and those taking nephrotoxic agents (including NSAIDs) are at increased risk. Assess estimated creatinine clearance, serum phosphorus, urine protein, and urine glucose prior to initiation of therapy and during therapy. Discontinue therapy in patients that develop clinically significant decreases in renal function or evidence of Fanconi syndrome.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Other warnings/precautions:

• HIV testing: HIV antibody testing should be offered to all HBV infected patients prior to treatment initiation. If HIV testing is positive, institute an appropriate antiretroviral (HIV-1) combination regimen.

Monitoring Parameters

Serum creatinine, serum phosphorus, urine glucose, urine protein (prior to initiation and as clinically indicated during therapy); HIV testing (prior to initiation); hepatic function tests; monitor clinical and laboratory data closely for several months following therapy discontinuation.

Pregnancy Considerations

Adverse events were not observed in animal reproduction studies. Tenofovir alafenamide is rapidly converted to tenofovir. There have been no data reported to the antiretroviral registry related to the use of this drug in pregnancy. The Health and Human Services (HHS) Perinatal HIV Guidelines note data are insufficient to recommend tenofovir alafenamide for initial therapy in antiretroviral-naive pregnant women (HHS [perinatal] 2016).

Health care providers are encouraged to enroll pregnant women exposed to antiretroviral medications as early in pregnancy as possible in the Antiretroviral Pregnancy Registry (1-800-258-4263 or www.APRegistry.com).

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience headache, abdominal pain, loss of strength and energy, cough, nausea, or back pain. Have patient report immediately to prescriber signs of kidney problems (urinary retention, hematuria, change in amount of urine passed, or weight gain), signs of liver problems (dark urine, fatigue, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or jaundice), signs of lactic acidosis (fast breathing, tachycardia, abnormal heartbeat, vomiting, fatigue, shortness of breath, severe loss of strength and energy, severe dizziness, feeling cold, or muscle pain or cramps), bone pain, muscle pain, muscle weakness, or pain in the extremities (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.

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