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.
Chronic hepatitis B: Oral: 25 mg once daily.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Note: Renal function may be estimated using the Cockcroft-Gault formula for dosage adjustment purposes
CrCl ≥15 mL/minute: No dosage adjustment necessary.
CrCl <15 mL/minute: Use is not recommended.
ESRD requiring hemodialysis: No dosage adjustment necessary; administer postdialysis on hemodialysis days.
Mild impairment (Child-Pugh class A): No dosage adjustment necessary.
Decompensated cirrhosis (Child-Pugh class B or C): Use is not recommended.
Refer to adult dosing.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Vemlidy: 25 mg
No
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Vemlidy: 25 mg
Oral: Administer with food.
Chronic hepatitis B: Treatment of chronic hepatitis B virus (HBV) infection in adults with compensated liver disease
This medication is in a class the Institute for Safe Medication Practices (ISMP) includes among its list of drug classes that have a heightened risk of causing significant patient harm when used in error.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%:
Nervous system: Headache (12%)
Neuromuscular & skeletal: Decreased bone mineral density (≥5% at lumbar spine: 11%; ≥7% at femoral neck: 5%)
1% to 10%:
Cardiovascular: Increased serum creatine kinase (grades 3/4: 3%)
Dermatologic: Skin rash (<5%)
Endocrine & metabolic: Glycosuria (grades 3/4: 5%), increased amylase (grades 3/4: 3%), increased LDL cholesterol (grades 3/4: 6%)
Gastrointestinal: Abdominal pain (9%), diarrhea (5%), dyspepsia (5%), flatulence (<5%), nausea (6%), vomiting (<5%)
Hepatic: Increased serum alanine aminotransferase (grades 3/4: 8%), increased serum aspartate aminotransferase (grades 3/4: 3%)
Nervous system: Fatigue (6%)
Neuromuscular & skeletal: Arthralgia (5%), back pain (6%)
Respiratory: Cough (8%)
Frequency not defined:
Endocrine & metabolic: Decreased HDL cholesterol, increased serum triglycerides
Hepatic: Exacerbation of hepatitis B
Postmarketing:
Dermatologic: Urticaria
Endocrine & metabolic: Fanconi’s syndrome
Genitourinary: Proximal tubular nephropathy
Hypersensitivity: Angioedema
Renal: Acute kidney injury, renal tubular necrosis
There are no contraindications listed in the US manufacturer's labeling.
Canadian labeling: Additional contraindications (not in US labeling): Hypersensitivity to tenofovir alafenamide or any component of the formulation
Concerns related to adverse effects:
• Lactic acidosis/hepatomegaly: Lactic acidosis and severe hepatomegaly with steatosis, sometimes fatal, have been reported with the use of nucleoside analogs, alone or in combination with other antiretrovirals. Suspend treatment in any patient who develops clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity (marked transaminase elevation may/may not accompany hepatomegaly and steatosis).
• Renal toxicity: Renal toxicity (acute renal failure, Fanconi syndrome, and/or proximal renal tubulopathy) has been reported with use of tenofovir prodrugs; patients with impaired renal function and those with concurrent or recent nephrotoxic therapy (including nonsteroidal anti-inflammatory drug use) are at an increased risk. Discontinue use in patients who develop clinically significant decreases in renal function or evidence of Fanconi syndrome.
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 who are not receiving hemodialysis.
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.
Substrate of BCRP/ABCG2, OATP1B1/1B3 (SLCO1B1/1B3), P-glycoprotein/ABCB1 (major); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Inhibits MRP2
Acyclovir-Valacyclovir: May increase the serum concentration of Tenofovir Products. Tenofovir Products may increase the serum concentration of Acyclovir-Valacyclovir. Risk C: 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. Risk X: Avoid combination
Aminoglycosides: May increase the serum concentration of Tenofovir Products. Tenofovir Products may increase the serum concentration of Aminoglycosides. Risk C: Monitor therapy
Cabozantinib: MRP2 Inhibitors may increase the serum concentration of Cabozantinib. Risk C: Monitor therapy
CarBAMazepine: May decrease the serum concentration of Tenofovir Alafenamide. Risk X: Avoid combination
Cidofovir: May increase the serum concentration of Tenofovir Products. Tenofovir Products may increase the serum concentration of Cidofovir. Risk C: Monitor therapy
Cladribine: Agents that Undergo Intracellular Phosphorylation may diminish the therapeutic effect of Cladribine. Risk X: Avoid combination
Cobicistat: May increase the serum concentration of Tenofovir Alafenamide. Risk C: Monitor therapy
Fosphenytoin-Phenytoin: May decrease the serum concentration of Tenofovir Alafenamide. Risk X: Avoid combination
Ganciclovir-Valganciclovir: Tenofovir Products may increase the serum concentration of Ganciclovir-Valganciclovir. Ganciclovir-Valganciclovir may increase the serum concentration of Tenofovir Products. Risk C: Monitor therapy
Lumacaftor and Ivacaftor: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates (High risk with Inhibitors or Inducers). Lumacaftor and Ivacaftor may decrease the serum concentration of P-glycoprotein/ABCB1 Substrates (High risk with Inhibitors or Inducers). Risk C: 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 due to a potential risk of acute renal failure. Diclofenac appears to confer the most risk. Risk D: Consider therapy modification
Nonsteroidal Anti-Inflammatory Agents (Topical): May enhance the nephrotoxic effect of Tenofovir Products. Risk C: Monitor therapy
Orlistat: May decrease the serum concentration of Antiretroviral Agents. Risk C: Monitor therapy
OXcarbazepine: May decrease the serum concentration of Tenofovir Alafenamide. Risk X: Avoid combination
P-glycoprotein/ABCB1 Inducers: May decrease the serum concentration of Tenofovir Alafenamide. Management: Consider alternatives to the use of P-gp inducers with tenofovir alafenamide. If combined, monitor for reduced tenofovir alafenamide concentrations and efficacy, and for the development of resistance. Risk D: Consider therapy modification
PHENobarbital: May decrease the serum concentration of Tenofovir Alafenamide. Risk X: Avoid combination
Primidone: May decrease the serum concentration of Tenofovir Alafenamide. Risk X: Avoid combination
Rifabutin: May decrease the serum concentration of Tenofovir Alafenamide. Risk X: Avoid combination
RifAMPin: May decrease the serum concentration of Tenofovir Alafenamide. Risk X: Avoid combination
Rifapentine: May decrease the serum concentration of Tenofovir Alafenamide. Risk X: Avoid combination
Ritonavir: May increase the serum concentration of Tenofovir Alafenamide. Risk C: Monitor therapy
St John's Wort: May decrease the serum concentration of Tenofovir Alafenamide. Risk X: Avoid combination
Tipranavir: May decrease the serum concentration of Tenofovir Alafenamide. Risk X: Avoid combination
The Health and Human Services perinatal HIV guidelines consider tenofovir alafenamide an alternative nucleoside reverse transcriptase inhibitor in patients living with HIV who are not yet pregnant but are trying to conceive.
Tenofovir alafenamide is not approved for preexposure prophylaxis in persons with vaginal exposure to HIV.
Viral suppression sustained below the limits of detection with antiretroviral therapy (ART) and modification of therapy (if needed) is recommended in patients of all genders who are living with HIV and planning a pregnancy. Optimization of the health of the person who will become pregnant and a discussion of the potential risks and benefits of ART during pregnancy is also recommended prior to conception.
Health care providers caring for couples planning a pregnancy when one or both partners are living with HIV may contact the National Perinatal HIV Hotline (1-888-448-8765) for clinical consultation (HHS [perinatal] 2020).
Tenofovir alafenamide has a low level of transfer across the human placenta.
According to the Health and Human Services perinatal HIV guidelines, data collected by the antiretroviral registry related to the use of tenofovir alafenamide in pregnancy are insufficient to evaluate teratogenicity.
Maternal antiretroviral therapy (ART) may be associated with adverse pregnancy outcomes, including preterm delivery, stillbirth, low birth weight, and small-for-gestational-age infants. Actual risks may be influenced by maternal factors such as disease severity, gestational age at initiation of therapy, and specific ART regimen; therefore, close fetal monitoring is recommended. Because there is clear benefit to appropriate treatment, maternal ART should not be withheld due to concerns for adverse neonatal outcomes. Long-term follow-up is recommended for all infants exposed to antiretroviral medications; children not diagnosed with HIV infection but who were exposed to ART in utero or as a neonate and develop significant organ system abnormalities of unknown etiology (particularly of the CNS or heart) should be evaluated for potential mitochondrial dysfunction.
The Health and Human Services perinatal HIV guidelines consider tenofovir alafenamide an alternative nucleoside reverse transcriptase inhibitor (NRTI) for pregnant patients living with HIV who are antiretroviral naive, who have had ART therapy in the past but are restarting, or who require a new ART regimen (due to poor tolerance or poor virologic response of current regimen). Patients who become pregnant while taking tenofovir alafenamide may continue if viral suppression is effective and the regimen is well tolerated. The guidelines also consider tenofovir alafenamide plus emtricitabine or lamivudine as an alternative dual NRTI backbone for HIV/hepatitis B virus coinfected patients who are pregnant.
ART is recommended for all patients who are pregnant and living with HIV to maintain the viral load below the limit of detection and reduce the risk of perinatal transmission. Therapy should be individualized following a discussion of the potential risks and benefits of treatment during pregnancy. Monitoring of patients who are pregnant is more frequent than in patients who are not pregnant. ART should be continued postpartum for all patients living with HIV and can be modified after delivery.
Health care providers are encouraged to enroll patients exposed to antiretroviral medications as early in pregnancy as possible in the Antiretroviral Pregnancy Registry (1-800-258-4263 or www.APRegistry.com). Health care providers caring for pregnant patients who are living with HIV and their infants may contact the National Perinatal HIV Hotline (1-888-448-8765) for clinical consultation (HHS [perinatal] 2020).
It is not known if tenofovir alafenamide is present in breast milk.
Breastfeeding is not contraindicated in patients with hepatitis B; however, if nipples are cracked or bleeding, breastfeeding is not recommended (Tran 2016).
Maternal or infant antiretroviral therapy does not completely eliminate the risk of postnatal HIV transmission. In addition, multiclass-resistant virus has been detected in breastfeeding infants despite maternal therapy. In the United States, where formula is accessible, affordable, safe, and sustainable, and the risk of infant mortality due to diarrhea and respiratory infections is low, the Health and Human Services perinatal HIV guidelines do not recommend breastfeeding for patients who are living with HIV. Information is available for counseling and managing patients living with HIV who are considering breastfeeding (HHS [perinatal] 2020).
Serum creatinine, estimated CrCl, serum phosphorus (in patients with chronic kidney disease), 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.
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.
Protein binding: 80% to plasma proteins.
Metabolism: Tenofovir alafenamide (TAF) is converted intracellularly to tenofovir, then phosphorylated to the active tenofovir diphosphate.
Bioavailability: Increases ~65% with a high-fat meal
Half-life elimination: 0.51 hours
Time to peak, serum: 0.48 hours
Excretion: Feces (31.7%) and urine (<1%)
Renal function impairment: In patients with CrCl 15 to 29 mL/minute or with end-stage renal disease requiring dialysis, Cmax and AUC of tenofovir were increased.
Tablets (Vemlidy Oral)
25 mg (per each): $51.91
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