Dosing & Uses
Dosage Forms & Strengths
tablet
- 25mg
Chronic Hepatitis B Infection
Indicated for treatment of chronic hepatitis B virus (HBV) infection in patients aged ≥12 years with compensated liver disease
25 mg PO qDay with food
Dosage Modifications
Renal impairment
- Mild, moderate, or severe: No dosage adjustment required
- ESRD (CrCl <15 mL/min: Not recommended in patients who are not receiving hemodialysis; in patients receiving chronic hemodialysis, administer drug after completion of hemodialysis
Hepatic impairment
- Mild (Child-Pugh A): No dosage adjustment required
- Decompensated (Child-Pugh B or C): Not recommended
Dosing Considerations
Test for HIV-1 infection before initiating; do not use tenofovir alone in patients coinfected with HIV infection
Assess serum creatinine, phosphorous, estimated CrCl, urine glucose, and urine protein before initiating and periodically throughout treatment
Dosage Forms & Strengths
tablet
- 25mg
Chronic Hepatitis B Infection
Indicated for treatment of chronic hepatitis B virus (HBV) infection in patients age ≥12 years with compensated liver disease
<12 years: Safety and efficacy not established
≥12 years: 25 mg PO qDay with food
Dosage Modifications
Renal impairment
- Mild, moderate, or severe: No dosage adjustment required
- ESRD (CrCl <15 mL/min): Not recommended in patients who are not receiving hemodialysis; in patients receiving chronic hemodialysis, administer drug after completion of hemodialysis
Hepatic impairment
- Mild (Child-Pugh A): No dosage adjustment required
- Decompensated (Child-Pugh B or C): Not recommended
Dosing Considerations
Test for HIV-1 infection before initiating; do not use tenofovir alone in patients coinfected with HIV infection
Assess serum creatinine, phosphorous, estimated CrCl, urine glucose, and urine protein before initiating and periodically throughout treatment
Interactions
Interaction Checker
No Results
Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor
Contraindicated (0)
Serious - Use Alternative (4)
- leniolisib
leniolisib will increase the level or effect of tenofovir AF by Other (see comment). Avoid or Use Alternate Drug. Leniolisib, a BCRP inhibitor, may increase systemic exposure of BCRP substrates
- letermovir
tenofovir AF will decrease the level or effect of letermovir by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. Coadministration of letermovir with P-gp inducers is not recommended.
- sotorasib
sotorasib will decrease the level or effect of tenofovir AF by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. If use is unavoidable, refer to the prescribing information of the P-gp substrate for dosage modifications.
- tepotinib
tepotinib will increase the level or effect of tenofovir AF by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. If concomitant use unavoidable, reduce the P-gp substrate dosage if recommended in its approved product labeling.
Monitor Closely (26)
- acalabrutinib
acalabrutinib increases levels of tenofovir AF by Other (see comment). Use Caution/Monitor. Comment: Acalabrutinib may increase exposure to coadministered BCRP substrates by inhibition of intestinal BCRP.
- apalutamide
apalutamide will decrease the level or effect of tenofovir AF by increasing elimination. Use Caution/Monitor. Apalutamide weakly induces BCRP and may decrease systemic exposure of drugs that are BCRP substrates.
- berotralstat
berotralstat will increase the level or effect of tenofovir AF by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor or titrate P-gp substrate dose if coadministered.
- cabozantinib
tenofovir AF will increase the level or effect of cabozantinib by Other (see comment). Use Caution/Monitor. MRP2 inhibitors increase cabozantinib toxicity
- darolutamide
darolutamide will increase the level or effect of tenofovir AF by Other (see comment). Modify Therapy/Monitor Closely. Darolutamide is a BCRP inhibitor. Avoid coadministration with BCRP inhibitors. If use is unavoidable, closely monitor for adverse reactions and consider dose reduction of BCRP substrate drug (refer BCRP substrate prescribing information).
- duvelisib
tenofovir AF will decrease the level or effect of duvelisib by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- elagolix
elagolix will increase the level or effect of tenofovir AF by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- encorafenib
encorafenib will increase the level or effect of tenofovir AF by Other (see comment). Modify Therapy/Monitor Closely. Encorafenib (a BCRP inhibitor) may increase the concentration and toxicities of BCRP substrates. Closely monitor for signs and symptoms of increased exposure and consider adjusting the dose of these substrates.
- fostamatinib
fostamatinib will increase the level or effect of tenofovir AF by decreasing metabolism. Use Caution/Monitor. Concomitant use of fostamatinib may increase concentrations of BCRP substrate drugs. Monitor for toxicities of BCRP substrate drug that may require dosage reduction when given concurrently with fostamatinib.
- glecaprevir/pibrentasvir
glecaprevir/pibrentasvir will increase the level or effect of tenofovir AF by decreasing metabolism. Use Caution/Monitor. Glecaprevir/pibrentasvir may increase plasma concentration of BCRP substrates.
- ifosfamide
ifosfamide, tenofovir AF. Either increases toxicity of the other by nephrotoxicity and/or ototoxicity. Modify Therapy/Monitor Closely. Monitor electrolytes and renal function.
- istradefylline
istradefylline will increase the level or effect of tenofovir AF by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Istradefylline 40 mg/day increased peak levels and AUC of P-gp substrates in clinical trials. Consider dose reduction of sensitive P-gp substrates.
- lonafarnib
lonafarnib will increase the level or effect of tenofovir AF by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. Lonafarnib is a weak P-gp inhibitor. Monitor for adverse reactions if coadministered with P-gp substrates where minimal concentration changes may lead to serious or life-threatening toxicities. Reduce P-gp substrate dose if needed.
- momelotinib
momelotinib increases toxicity of tenofovir AF by plasma protein binding competition. Modify Therapy/Monitor Closely. Momelotinib (BCRP inhibitor) may increase exposure of BCRP substrates, which may increase the risk of BCRP substrate adverse reactions. Dose adjustment of other BCRP substrates may necessary.
- nirmatrelvir
nirmatrelvir will increase the level or effect of tenofovir AF by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration may increase tenofovir systemic exposures.
- nirmatrelvir/ritonavir
nirmatrelvir/ritonavir will increase the level or effect of tenofovir AF by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration may increase tenofovir systemic exposures.
- orlistat
orlistat will decrease the level or effect of tenofovir AF by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor. Loss of virological control reported in HIV-infected patients taking orlistat concomitantly. Exact mechanism is unclear, but may include a drug-drug interaction that inhibits systemic absorption of the antiretroviral drug. Monitor HIV RNA levels frequently and if increased HIV viral load confirmed, discontinue orlistat.
- oteseconazole
oteseconazole will increase the level or effect of tenofovir AF by Other (see comment). Modify Therapy/Monitor Closely. Otesezonale, a BCRP inhibitor, may increase the effects and risk of toxicities of BCRP substrates. Use lowest starting dose of BCRP substrate, or consider reducing BCRP substrate dose.
- regorafenib
regorafenib will increase the level or effect of tenofovir AF by Other (see comment). Modify Therapy/Monitor Closely. Regorafenib likely inhibits BCRP (ABCG2) transport. Coadministration with a BCRP substrate may increase systemic exposure to the substrate and related toxicity.
- safinamide
safinamide will increase the level or effect of tenofovir AF by Other (see comment). Use Caution/Monitor. Safinamide and its major metabolite may inhibit intestinal BCRP. Monitor BCRP substrates for increased pharmacologic or adverse effects.
- sarecycline
sarecycline will increase the level or effect of tenofovir AF by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor for toxicities of P-gp substrates that may require dosage reduction when coadministered with P-gp inhibitors.
- stiripentol
stiripentol will increase the level or effect of tenofovir AF by Other (see comment). Use Caution/Monitor. Stiripentol is a BCRP transport inhibitor. Consider dosage reduction for BCRP substrates if adverse effects are experienced when coadministered.
- tafamidis
tafamidis will increase the level or effect of tenofovir AF by Other (see comment). Use Caution/Monitor. Tafamidis inhibits breast cancer resistant protein (BCRP) in vitro and may increase exposure of BCRP substrates following tafamidis or tafamidis meglumine administration. Dosage adjustment of these BCRP substrates may be necessary.
- tafamidis meglumine
tafamidis meglumine will increase the level or effect of tenofovir AF by Other (see comment). Use Caution/Monitor. Tafamidis inhibits breast cancer resistant protein (BCRP) in vitro and may increase exposure of BCRP substrates following tafamidis or tafamidis meglumine administration. Dosage adjustment of these BCRP substrates may be necessary.
- tucatinib
tucatinib will increase the level or effect of tenofovir AF by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Consider reducing the dosage of P-gp substrates, where minimal concentration changes may lead to serious or life-threatening toxicities.
- voclosporin
voclosporin, tenofovir AF. Either increases toxicity of the other by nephrotoxicity and/or ototoxicity. Modify Therapy/Monitor Closely. Coadministration with drugs associated with nephrotoxicity may increase the risk for acute and/or chronic nephrotoxicity.
Minor (0)
Adverse Effects
>10%
Headache (9-12%)
Bone mineral density decline (5-11%)
1-10%
Abdominal pain (7-9%)
ALT >5 x ULN (8%)
Cough (8%)
Fatigue (6%)
Nausea (6%)
LDL-cholesterol fasted >190 mg/dL (6%)
Back pain (6%)
Glycosuria ≥3+ (5%)
Nausea (5%)
Arthralgia (5%)
Diarrhea (5%)
Dyspepsia (5%)
AST >5 x ULN (3%)
Creatine kinase ≥10 x ULN (3%)
Serum amylase >2 x ULN (3%)
Frequency Not Defined
Severe acute exacerbation of hepatitis B in patients with HBV infection
Postmarketing Reports
Skin and subcutaneous tissue disorders: Angioedema, urticaria
Acute renal failure, acute tubular necrosis, proximal renal tubulopathy, and Fanconi syndrome
Warnings
Black Box Warnings
Hepatitis B exacerbation
- Severe acute exacerbations of hepatitis B reported in patients who have discontinued therapy for hepatitis B
- Hepatic function should be monitored closely with both clinical and laboratory follow-up for at least several months in patients who discontinue therapy
- Resumption of therapy for hepatitis B may be warranted
Contraindications
None
Cautions
Lactic acidosis and severe hepatomegaly with steatosis, including fatalities, reported with nucleoside analogs, including tenofovir disoproxil fumarate in combination with other antiretrovirals; most were reported in women; obesity and prolonged nucleoside exposure may be risks factors (see Black Box Warnings)
Discontinuation of antihepatitis B drugs may result in severe acute exacerbations of hepatitis B (see Black Box Warnings); all patients should be tested for presence of chronic hepatitis B virus (HBV) before or when initiating therapy
Resumption of anti-hepatitis B therapy may be warranted, in patients with advanced liver disease or cirrhosis, since posttreatment exacerbation of hepatitis may lead to hepatic decompensation and liver failure
Due to risk of development of HIV-1 resistance, tenofovir AF alone is not recommended for treatment of HIV-1 infection; safety and efficacy have not been established in patients coinfected with HBV and HIV-1; perform HIV antibody testing on all HBV-infected patients before initiating therapy; if positive, use an appropriate antiretroviral combination regimen recommended for patients coinfected with HIV-1
Persistent or worsening bone pain, pain in extremities, fractures and/or muscular pain or weakness may be manifestations of proximal renal tubulopathy and should prompt an evaluation of renal function in patients at risk of renal dysfunction
Renal impairment
- Renal impairment, including cases of acute renal failure and Fanconi syndrome (renal tubular injury with severe hypophosphatemia), reported with use of tenofovir prodrugs; this has not been observed with tenofovir AF in clinical trials
- 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
- Prior to or when initiating therapy, and during treatment on a clinically appropriate schedule, assess serum creatinine, estimated creatinine clearance, urine glucose, and urine protein in all patients
- In patients with chronic kidney disease, also assess serum phosphorus; discontinue therapy in patients who develop clinically significant decreases in renal function or evidence of Fanconi syndrome
- Lactic acidosis: Treatment should be suspended in any patient who develops clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity (which may include hepatomegaly and steatosis even in the absence of marked transaminase elevations)
Drug interaction overview
-
P-gp and BCRP
- P-gp and BCRP substrate; drugs that strongly affect these transporters may lead to changes in tenofovir AF absorption
- Drugs that induce P-gp result in decreased tenofovir AF absorption and plasma concentrations, which may lead to loss of therapeutic effect (eg, carbamazepine, oxcarbazepine, phenobarbital, phenytoin, rifabutin, rifampin, rifapentine, St John’s wort)
- Drugs that inhibit P-gp and BCRP may increase tenofovir AF absorption and plasma concentration
-
Drugs affecting renal function
- Postmarketing cases of renal impairment, including acute renal failure, proximal renal tubulopathy (PRT), and Fanconi syndrome reported with tenofovir AF-containing products
- Tenofovir is primarily excreted by the kidneys by a combination of glomerular filtration and active tubular secretion
- Coadministration of tenofovir AF 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 include acyclovir, cidofovir, ganciclovir, valacyclovir, valganciclovir, aminoglycosides, high-dose or long-term NSAD use
Pregnancy & Lactation
Pregnancy
There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to drug during pregnancy; healthcare providers are encouraged to register patients by calling the Antiretroviral Pregnancy Registry (APR) at 1-800-258- 4263
Available data from the APR show no significant difference in overall risk of birth defects for tenofovir alafenamide (TAF) compared with background rate for major birth defects of 2.7% in U.S. reference population of the Metropolitan Atlanta Congenital Defects Program (MACDP); the rate of miscarriage is not reported in the APR
In animal studies, no adverse developmental effects were observed when tenofovir alafenamide was administered during the period of organogenesis at exposure equal to or 51 times (rats and rabbits, respectively) the tenofovir alafenamide exposure at the recommended daily dose
Lactation
Unknown if distributed in human breast milk
Consider the developmental and health benefits of breastfeeding along with the mother’s clinical need for the drug, and any potential adverse effects on the breastfed infant from the drug or from the underlying maternal condition
Pregnancy Categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available.Pharmacology
Mechanism of Action
Tenofovir alafenamide (AF) is a nucleotide reverse transcriptase inhibitor (NRTI) and a phosphonamidate prodrug of tenofovir
Compared with tenofovir disoproxil fumarate (tenofovir DF, Viread), tenofovir AF is a more targeted form of tenofovir that has demonstrated high antiviral efficacy at a dose that is 10 times lower than tenofovir DF, as well as an improved renal and bone safety profile
Tenofovir AF as a lipophilic cell-permeant compound enters primary hepatocytes by passive diffusion and by the hepatic uptake transporters OATP1B1 and OATP1B3 and is converted to tenofovir diphosphate
Tenofovir diphosphate inhibits HBV replication through incorporation into viral DNA by the HBV reverse transcriptase, which results in DNA chain-termination
Absorption
Peak plasma time: ~30 minutes
Distribution
Protein bound: 80%
Metabolism
Converted from tenofovir AF to tenofovir through hydrolysis primarily by carboxyesterase 1 (CES1) in primary hepatocytes
Intracellular tenofovir is subsequently phosphorylated by cellular kinases to the pharmacologically active metabolite tenofovir diphosphate
Also metabolized by Cathepsin A in peripheral blood mononuclear cells (PBMCs)
CYP3A: Minimal
Elimination
Half-life: 0.5 hr
Excretion: <1% urine; 31.7% feces
Administration
Oral Administration
Take with food
Inform patients to take on a regular dosing schedule and to avoid missing doses, as it can result in development of resistance
Storage
Store at controlled room temperature <30°C (86°F)
Keep container tightly closed
Dispense only in original container
Images
| BRAND | FORM. | UNIT PRICE | PILL IMAGE |
|---|---|---|---|
| Vemlidy oral - | 25 mg tablet |  |
Copyright © 2010 First DataBank, Inc.
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