Alenvir25 mg

Alenvir is a nucleotide analog reverse transcriptase inhibitor (NtRTI) prodrug of tenofovir, approved for the following uses:

Established / FDA-approved uses

• Chronic Hepatitis B Virus (HBV) infection - as a standalone 25 mg once-daily tablet, in adults and pediatric patients aged 6 years and older weighing at least 25 kg, with compensated liver disease.
• HIV-1 infection - Alenvir is not used alone for HIV-1; it is a component of fixed-dose combination antiretroviral regimens (with other agents such as emtricitabine plus an integrase inhibitor or non-nucleoside reverse transcriptase inhibitor) for treatment of HIV-1 infection in adults and pediatric patients, and for HIV-1 pre-exposure prophylaxis (PrEP) in at-risk adults and adolescents as part of an approved combination product.

Important notes on evidence and combination requirement

• Alenvir must always be used in combination with other antiretroviral agents for HIV-1 treatment or prevention; it is never given as HIV-1 monotherapy because of the risk of resistance development.
• Before starting Alenvir for the hepatitis B indication, patients should be tested for HIV-1 infection; if HIV-1 is undiagnosed and untreated, Alenvir alone may allow HIV-1 resistance to develop.

Tenofovir Alafenamide is supplied as oral tablets, most commonly as a 25 mg tablet for the chronic hepatitis B indication, and as a fixed-dose component (typically 10 mg or 25 mg per tablet depending on the co-formulated agents) in combination antiretroviral products for HIV-1. Tenofovir Alafenamide is a phosphonoamidate prodrug that is converted intracellularly to the active moiety, tenofovir diphosphate.

Alenvir is an antiviral medicine belonging to the nucleotide analog reverse transcriptase inhibitor class. It is a next-generation prodrug of tenofovir, designed to deliver the active drug more efficiently into lymphoid cells and hepatocytes at a lower circulating plasma tenofovir concentration than the older prodrug, tenofovir disoproxil fumarate. This lower systemic tenofovir exposure is associated with reduced effects on the kidneys and bone mineral density while maintaining antiviral efficacy.

Alenvir is used to treat chronic hepatitis B virus infection and, as part of combination regimens, HIV-1 infection.

Antiviral agent - Nucleotide Analog Reverse Transcriptase Inhibitor (NtRTI); Alenvir is a prodrug of tenofovir used as an anti-hepadnaviral and antiretroviral agent.

Tenofovir Alafenamide is a phosphonoamidate prodrug of tenofovir. After absorption, Tenofovir Alafenamide is taken up preferentially into hepatocytes and lymphoid cells, where it is hydrolyzed by carboxylesterase 1 (hepatocytes) or cathepsin A (lymphoid cells) to release tenofovir. Tenofovir is then phosphorylated by cellular kinases to the active metabolite, tenofovir diphosphate.

Tenofovir diphosphate inhibits:

• Hepatitis B virus (HBV) reverse transcriptase (DNA polymerase), by competing with the natural substrate deoxyadenosine 5'-triphosphate and causing DNA chain termination after incorporation into viral DNA.
• HIV-1 reverse transcriptase, by the same competitive-inhibition and chain-termination mechanism, which is why Tenofovir Alafenamide contributes antiretroviral activity when used in combination HIV-1 regimens.

Because Tenofovir Alafenamide concentrates the active metabolite intracellularly at target sites, it achieves antiviral efficacy at roughly one-tenth the dose of tenofovir disoproxil fumarate, resulting in substantially lower circulating plasma tenofovir levels.

Alenvir tablets should be swallowed whole with food; do not chew, crush, or split the tablet unless a specific formulation is labeled for that use. Taking Alenvir with food increases its absorption. Doses should be taken at approximately the same time each day to maintain consistent drug levels, and patients should not stop or interrupt treatment without consulting their physician (see Precautions and Warnings regarding hepatitis B exacerbation on discontinuation).

Clinically significant interactions with Alenvir generally involve drugs that strongly affect P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) transporters, which alter absorption of Alenvir:

• Strong P-gp inducers (e.g., rifampin, rifabutin, rifapentine, carbamazepine, phenobarbital, phenytoin, St. John's wort): significantly decrease plasma concentrations of Alenvir, which may result in loss of therapeutic effect and development of viral resistance. Co-administration is generally not recommended; if unavoidable with carbamazepine, dose adjustment of the combination product may be required per that product's label.
• Strong P-gp/BCRP inhibitors (e.g., ketoconazole, cobicistat, certain HIV protease inhibitors): can increase Alenvir plasma concentrations; used cautiously and only in combination products specifically labeled for such co-administration.
• Other nephrotoxic or renally-adjusted drugs: concurrent use of drugs that reduce renal function may increase concentrations of tenofovir; renal function should be monitored.

Always inform the prescribing physician of all other medicines, herbal products, and supplements being taken before starting Alenvir.

Most patients tolerate Alenvir well. Reported adverse effects include:

Common

• Headache
• Nausea and abdominal pain
• Fatigue
• Cough
• Back pain
• Diarrhea

Less common but serious

• Severe acute exacerbation of hepatitis B after stopping treatment (see boxed warning under Precautions and Warnings)
• Lactic acidosis and severe hepatomegaly with steatosis (class effect of nucleoside/nucleotide analogs)
• New-onset or worsening renal impairment
• Decreases in bone mineral density
• Immune reconstitution syndrome (when used as part of HIV-1 combination therapy)

Pregnancy: Data from an antiretroviral pregnancy registry involving over a thousand first-trimester exposures to Alenvir-containing regimens have not shown an increase in overall birth defects compared with the background rate. However, this information is not sufficient to consider Alenvir definitively safe in pregnancy. Alenvir should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus, and only under close medical supervision; consult a physician before use.

Lactation: It is not known whether Alenvir passes into breast milk in clinically significant amounts. Because of the potential for HIV transmission (in HIV-exposed infants) and unknown effects on the nursing infant, a decision to breastfeed while taking Alenvir should be made only in consultation with a physician, weighing the mother's clinical need against potential infant risk.

Boxed Warning: Post-treatment exacerbation of Hepatitis B

Severe acute exacerbations of hepatitis B have been reported in patients who have discontinued anti-hepatitis B therapy, including Alenvir. Hepatic function should be monitored closely with both clinical and laboratory follow-up for at least several months after stopping Alenvir in patients with HBV infection. If appropriate, resumption of anti-hepatitis B therapy may be warranted.

Lactic acidosis / severe hepatomegaly with steatosis

This class effect of nucleoside/nucleotide analogs has been reported with tenofovir-containing products, including Alenvir, and can be fatal. Treatment should be suspended if clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity develop.

Renal effects

New-onset or worsening renal impairment can occur. Renal function (creatinine, estimated creatinine clearance, urine glucose and urine protein) should be assessed before starting and periodically during treatment, particularly in patients with pre-existing renal risk factors.

Bone effects

Decreases in bone mineral density have been observed with Alenvir, although generally less pronounced than with tenofovir disoproxil fumarate. Consider bone monitoring in patients with a history of pathologic fracture or other risk factors for osteoporosis or bone loss.

HIV-1 resistance risk

Alenvir must never be used as HIV-1 monotherapy. Patients being treated for chronic hepatitis B should be tested for HIV-1 infection before starting Alenvir, because unrecognized or untreated HIV-1 infection can develop resistance to Alenvir if it is used alone for the hepatitis B indication.

Combination use only for HIV-1

For the HIV-1 indication, Alenvir is used only as part of an approved multi-drug combination product, never alone.

There is limited clinical experience with acute overdose of Alenvir. If overdose is suspected, the patient should seek immediate medical attention or contact a poison control center or emergency services promptly. Management should be supportive, with monitoring of vital signs and renal function; Alenvir's active metabolite (tenofovir) can be efficiently removed by hemodialysis, which may be considered by treating physicians in cases of significant overdose with renal compromise. Do not attempt to manage a suspected overdose at home without professional medical guidance.

Store at room temperature (below 30°C), away from light and moisture. Keep in the original container, tightly closed. Keep out of reach of children.

Renal impairment

No dose adjustment of Alenvir is needed for estimated creatinine clearance ≥15 mL/min. Use is not recommended in patients with CrCl below 15 mL/min who are not on chronic hemodialysis; in patients on hemodialysis, Alenvir may be used, dosed after dialysis. See Dosage and Administration.

Hepatic impairment

No adjustment is needed for mild (Child-Pugh A) impairment. Alenvir is not recommended in moderate-to-severe (decompensated, Child-Pugh B or C) hepatic disease, as safety and efficacy have not been established.

Elderly

Clinical studies did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently from younger patients; use with caution, considering the greater frequency of decreased renal, hepatic, or cardiac function and concomitant disease in this population.

Pediatric use

See Pediatric Uses below.

HIV/HBV coinfection

Patients should be tested for HIV-1 before starting Alenvir for hepatitis B, since Alenvir used alone in an unrecognized HIV-1 infection can lead to HIV-1 resistance.

Alenvir for chronic hepatitis B is typically administered long-term/indefinitely, as chronic HBV suppression generally requires ongoing therapy; the optimal duration is determined by the treating physician based on virologic, biochemical, and serologic response. For HIV-1, Alenvir-containing combination regimens are continued indefinitely as part of lifelong antiretroviral therapy, or for the duration prescribed for pre-exposure prophylaxis. Treatment should not be stopped abruptly without medical advice, given the risk of hepatitis B exacerbation on discontinuation.

Nucleotide Analog Reverse Transcriptase Inhibitor (NtRTI); Antiretroviral agent; Anti-hepadnaviral agent. Tenofovir Alafenamide is a prodrug of tenofovir.

Tenofovir Alafenamide is a prodrug that is preferentially taken up by hepatocytes and lymphoid cells and converted intracellularly to tenofovir, which is then phosphorylated to its active form, tenofovir diphosphate. Tenofovir diphosphate competitively inhibits HBV reverse transcriptase and HIV-1 reverse transcriptase by acting as a chain terminator when incorporated into viral DNA, thereby suppressing viral replication.

Chronic Hepatitis B: Alenvir (25 mg tablet) is approved for pediatric patients aged 6 years and older weighing at least 25 kg with compensated liver disease, at the same dose as adults (one 25 mg tablet once daily with food). Safety and efficacy have not been established in children younger than 6 years or weighing less than 25 kg, and Alenvir is not recommended in this younger/lighter group.

HIV-1: Pediatric use of Alenvir for HIV-1 is only through specific combination products that have their own pediatric approvals, weight bands, and dosing; Alenvir alone is not used for HIV-1 in any age group.