Avifanz600 mg

Avifanz is a non-nucleoside reverse transcriptase inhibitor (NNRTI) indicated for the treatment of HIV-1 infection.

Established/Approved Use

• Treatment of HIV-1 infection in adults and pediatric patients (weighing at least 3.5 kg), always used in combination with other antiretroviral agents (for example, with two nucleoside reverse transcriptase inhibitors). Avifanz must never be used as monotherapy, as this leads to rapid development of viral resistance.

Not Indicated / Off-label

Avifanz is not indicated for HIV-2 infection, as NNRTIs are generally not active against HIV-2. There is no well-established, guideline-supported off-label indication for Avifanz outside combination antiretroviral therapy for HIV-1.

Each tablet/capsule contains Efavirenz as the active pharmaceutical ingredient, commonly available in strengths such as 50 mg, 200 mg, and 600 mg, either alone or as part of a fixed-dose combination with other antiretroviral agents (e.g., emtricitabine and tenofovir disoproxil fumarate). Excipients vary by manufacturer and formulation.

Avifanz is a synthetic non-nucleoside reverse transcriptase inhibitor (NNRTI) used in the management of HIV-1 infection. It is available as film-coated tablets and capsules, and also as part of fixed-dose combination products with other antiretroviral drugs. Avifanz works by directly binding to and inhibiting the HIV-1 reverse transcriptase enzyme, which is essential for viral replication.

Avifanz belongs to the class of Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs), a group of antiretroviral medicines used in combination regimens for HIV-1 infection.

Mechanism of Action

Efavirenz is a non-nucleoside reverse transcriptase inhibitor of HIV-1. It inhibits HIV-1 replication by binding directly to reverse transcriptase, causing a disruption of the enzyme's catalytic site, which blocks RNA-dependent and DNA-dependent DNA polymerase activities. Efavirenz does not inhibit HIV-1 protease or human cellular DNA polymerases, and it has no significant activity against HIV-2 reverse transcriptase.

Pharmacokinetics

Efavirenz is well absorbed orally, extensively bound to plasma proteins (approximately 99.5-99.75%), and is primarily metabolized by the hepatic cytochrome P450 system, mainly CYP2B6 (with contribution from CYP3A4), to hydroxylated metabolites that undergo further glucuronidation. It has a long elimination half-life (approximately 40-55 hours after multiple dosing), allowing once-daily dosing. Efavirenz is also a mixed inducer and inhibitor of certain CYP enzymes, which underlies many of its drug interactions.

Take Avifanz orally, once daily, on an empty stomach, preferably at bedtime (especially during the first few weeks of treatment) to help reduce dizziness, drowsiness, and other CNS side effects. Swallow tablets/capsules whole; do not take with a high-fat meal, as this increases absorption and side effects.

Avifanz is metabolized by and affects the CYP450 enzyme system, resulting in clinically significant interactions:

• Contraindicated combinations: Drugs highly dependent on CYP3A4 for clearance with a narrow therapeutic index, including certain antiarrhythmics (e.g., pimozide), ergot derivatives (ergotamine, dihydroergotamine), triazolam, and oral midazolam — Avifanz can significantly increase their plasma concentrations, risking serious or life-threatening reactions.
• St. John's Wort (Hypericum perforatum): Co-administration can substantially reduce Avifanz plasma concentrations, potentially leading to loss of virologic response and resistance; concurrent use is not recommended.
• Other antiretrovirals: Avifanz may alter concentrations of certain protease inhibitors (e.g., requiring dose adjustment of some boosted regimens) and should not be combined with certain other NNRTIs.
• Hormonal contraceptives: Avifanz may reduce the efficacy of some hormonal contraceptives; an additional or alternative barrier method of contraception is recommended.
• CNS depressants and alcohol: May increase sedation and CNS side effects when combined with Avifanz.

Inform your physician of all medicines, herbal products, and supplements you are taking before starting Avifanz.

Common

• Central nervous system effects: dizziness, insomnia, impaired concentration, drowsiness, abnormal dreams (usually diminish after the first 2-4 weeks)
• Skin rash (usually mild to moderate)
• Headache, fatigue
• Nausea, diarrhea

Less Common / Serious

• Severe psychiatric symptoms, including severe depression, suicidal ideation or attempts, aggressive behavior, and rarely psychosis or paranoia — seek prompt medical attention if these occur.
• Severe skin reactions, including Stevens-Johnson syndrome (rare).
• Hepatotoxicity, including elevated liver enzymes, hepatitis, and rarely liver failure (see Precautions and Warnings).
• False-positive results on some cannabinoid (marijuana) urine screening tests have been reported.

Pregnancy: Avifanz should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus, and only after careful consultation with a physician experienced in managing HIV in pregnancy. Current guidance on the use of Avifanz in pregnancy, including in early pregnancy, has evolved over time; a physician should be consulted for the latest recommendations and to weigh individual risks and benefits. Women of childbearing potential should use effective contraception, as Avifanz may reduce the efficacy of some hormonal contraceptive methods (see Interactions).

Lactation: Due to the potential for HIV transmission through breast milk and possible transfer of Avifanz into breast milk, breastfeeding is generally not recommended for mothers with HIV in settings where safe, affordable replacement feeding is available; follow current national/WHO guidance and consult a physician.

• Psychiatric and CNS symptoms: Avifanz is associated with CNS side effects (dizziness, impaired concentration, abnormal dreams) and, less commonly, serious psychiatric symptoms including severe depression, suicidal ideation, and psychosis. Use with caution in patients with a history of mental illness or substance abuse, and counsel patients on symptoms to watch for.
• Hepatotoxicity: Hepatic events, including some fatal cases, have been reported. Use with caution and monitor liver function tests in patients with underlying hepatic disease (including chronic hepatitis B or C coinfection) or significant transaminase elevations.
• Skin reactions: Rash is common, usually mild to moderate; discontinue if severe rash occurs, especially if accompanied by blistering, mucosal involvement, fever, or Stevens-Johnson syndrome is suspected.
• Immune reconstitution syndrome: May occur during initial combination antiretroviral treatment, including inflammatory reactions to residual opportunistic infections or autoimmune disorders.
• Antiretroviral stewardship: Take exactly as prescribed by your physician; do not stop, extend, skip doses, or share this medicine with others without medical advice, as this may lead to development of drug resistance and treatment failure. Always use Avifanz as part of a complete combination antiretroviral regimen, never alone.
• Lipid and metabolic changes: Increases in cholesterol and triglycerides have been observed with antiretroviral therapy, including Avifanz; periodic monitoring may be advised.

There is limited clinical experience with acute overdosage of Avifanz. Reported symptoms with higher-than-recommended doses include increased CNS symptoms such as heightened confusion, somnolence, and involuntary muscle contractions. There is no specific antidote for Avifanz overdose. If overdose is suspected, seek immediate medical attention or contact a poison control center; supportive treatment should be administered, with monitoring for adverse effects, under medical supervision. Since Avifanz is highly protein-bound, dialysis is unlikely to significantly remove the drug.

Store at room temperature (below 30°C), away from light and moisture. Keep out of reach of children.

Pediatric Use

Avifanz is approved for use in pediatric patients weighing at least 3.5 kg, in combination with other antiretroviral agents, with weight-based dosing. Safety and efficacy have not been established below this weight threshold.

Elderly

Clinical studies of Avifanz have not included sufficient numbers of patients aged 65 and over to determine whether they respond differently from younger patients; use with caution given the greater likelihood of decreased hepatic function and concomitant disease/medication use in this age group.

Hepatic Impairment

Use with caution in mild hepatic impairment; avoid use in moderate to severe hepatic impairment where possible, as Avifanz has not been adequately studied in this population (see Dosage and Administration).

Renal Impairment

No dosage adjustment is generally required, as renal excretion is a minor elimination pathway.

Avifanz is used long-term as part of lifelong combination antiretroviral therapy for HIV-1 infection. Duration is determined by the treating physician based on virologic response, tolerability, and current HIV treatment guidelines; it should not be stopped or interrupted without medical advice.

Antiretroviral agent; Non-Nucleoside Reverse Transcriptase Inhibitor (NNRTI)

Efavirenz binds directly to HIV-1 reverse transcriptase and blocks its RNA-dependent and DNA-dependent DNA polymerase activities by disrupting the enzyme's catalytic site, thereby inhibiting viral replication. It does not require intracellular activation (unlike nucleoside analogues) and has no significant inhibitory effect on human cellular DNA polymerases or HIV-1 protease.

Avifanz is indicated for HIV-1 infection in pediatric patients weighing at least 3.5 kg, always in combination with other antiretroviral agents, using weight-based dosing per current pediatric HIV guidelines. Safety and efficacy below this weight have not been established. Children should be monitored for the same CNS, psychiatric, hepatic, and dermatologic effects seen in adults.