Efavirenz (Adverse effects)

Efavirenz is an antiretroviral drug from the group of non-nucleoside reverse transcriptase inhibitors (NNRTIs). All NNRTIs specifically interfere with HIV-1 reverse transcriptase function by preventing the formation of double-stranded viral DNA from the single-stranded RNA viral genome.

This antiretroviral agent is used in the treatment of human immunodeficiency virus (HIV) and is recommended to be combined with two reverse transcriptase antagonist drugs. The efficacy of combination therapy has been demonstrated through numerous clinical trials. This type of treatment is used in adults, adolescents and children older than 3 months and weighing more than 3kg.

Efavirenz is characterized by a long plasma half-life, which allows it to be administered once a day. This drug is metabolized mainly by the hepatic CYP2B6 enzyme, resulting in two hydroxylated and inactive metabolites. The CYP2B6 gene can present several polymorphisms, which have some implication in the dosage and adverse reactions of the drug.

CONTRAINDICATIONS

Hypersensitivity to the active ingredient or any of its excipients.

Contraindicated in concomitant treatment with astemizole, cisapride, ergot derivatives, oral midazolam, pimozide, St. John's wort or St. John's wort and triazolam.

PRECAUTIONS

Use efavirenz with caution in patients with a history of psychiatric illness or excessive drug use. Monitor for the development of psychiatric disorders such as depression or suicide attempts.

Nervous system symptoms (dizziness, insomnia, nightmares, drowsiness) may occur on the first day or two of treatment and disappear after 2-4 weeks of treatment.

Consider whether the patient has a history of seizures or is an epileptic patient.

Consider whether the patient has a history of liver disease, as patients with chronic hepatitis B or C who are treated with antiretroviral drugs are at high risk of serious and even fatal adverse effects.

Take efavirenz with caution if QT prolongation occurs.

Children have a higher incidence of skin rash than adults. Discontinue treatment if severe skin rash symptoms such as blistering, fever or scaling occur.

It is recommended to avoid treatment with efavirenz in adolescent women with a high probability of pregnancy, since a potential risk of teratogenicity has been detected in the first trimester of pregnancy.

Avoid efavirenz if you are lactose intolerant, since both capsules and tablets contain lactose.

Dyslipidemia may occur during treatment with efavirenz, so it is recommended to monitor triglycerides and cholesterol.

In some patients with advanced HIV and a history of opportunistic infection, signs of inflammation or infection may occur. Inform your doctor immediately.

SIDE EFFECTS

The most frequent side effects are skin rash and alterations of the central nervous system: drowsiness, insomnia, dizziness, headache, problems with coordination or balance, difficulty concentrating, hallucinations and abnormal dreams, convulsions or euphoria. It also causes increased levels of transaminases, as well as diarrhea, vomiting and fatigue.

Rare reactions are nervousness, prolongation of the QT interval, blurred vision, abdominal pain, vertigo, mood disturbance, tremor, flushing, breast enlargement in men, hypersensitivity, yellowish skin and eyes due to liver inflammation or ringing in the ears. Suicidal ideation is among the very rare side effects.

DRUG INTERACTIONS

The administration of efavirenz together with other drugs that are metabolized mainly by the 2C9, CYP2C19, CYP2B6 or CYP3A isoenzymes of the cytochrome P450 (CYP), may cause alteration of the plasma concentrations of the co-administered drugs. Those drugs that induce CYP3A and CYP2B6 activity are expected to reduce plasma concentrations of efavirenz.

Rifampicin is an even more potent CYP3A inducer than efavirenz. Therefore, in adults, increasing the dose of efavirenz to 800 mg/day should be considered if it is well tolerated.

Efavirenz causes a decrease in plasma levels of HIV protease inhibitor drugs (atazanavir, indinavir, lopinavir, nelfinavir, saquinavir, darunavir, ritonavir). In adults, there are different ways to proceed: do not administer without boosting with ritonavir, increase the dose of protease inhibitor or increase the dose of ritonavir.

The effect of oral anticoagulants can be affected, so it is important to monitor the prothrombin time.

In the case of antiepileptics such as carbamazepine, phenytoin and phenobarbital, it is recommended to monitor plasma levels of antiepileptic and efavirenz.

Antifungal drugs such as itraconazole or posaconazole should be avoided and replaced by other antifungal drugs with fewer interactions.

Statin therapy may be affected, so an increase in dose or a substitution/addition of another drug to the therapy may be necessary.

Regarding immunosuppressants, it is recommended to monitor the levels and efficacy of cyclosporine, sirolimus and tracolimus. Efavirenz causes plasma depletion of these drugs.

Methadone metabolism is also affected by efavirenz, therefore it is necessary to monitor for signs and symptoms of withdrawal.

Drugs used to reduce blood clots such as warfarin or acenocoumarol may require dosage modification.

BRAND NAMES

• Atripla®
• Stocrin®
• Sustiva®
• Symfi®