Viranz Special Precautions

Efavirenz must not be used as a single agent to treat HIV or added on as a sole agent to a failing regimen. Patients with chronic hepatitis B or C and treated with combination antiretroviral therapy are at increased risk for severe and potentially fatal hepatic adverse events.
When prescribing drugs concomitantly with Efavirenz, physicians should refer to the corresponding manufacturer's product circular.
If any antiretroviral medication in a combination regimen is interrupted because of suspected intolerance, serious consideration should be given to simultaneous discontinuation of all antiretroviral medications. The antiretroviral medications should be restarted at the same time upon resolution of the intolerance symptoms. Intermittent monotherapy and sequential reintroduction of antiretroviral agents is not advisable because of the increased potential for selection of drug-resistant mutant virus.
Malformations have been observed in foetuses from efavirenz-treated animals; therefore, pregnancy should be avoided in women receiving Efavirenz. Barrier contraception should always be used in combination with other methods of contraception (e.g., oral or other hormonal contraceptives).
Rash: Mild-to-moderate rash has been reported in clinical trials with Efavirenz and usually resolves with continued therapy. Appropriate antihistamines and/or corticosteroids may improve the tolerability and hasten the resolution of rash. The incidence of erythema multiforme or Stevens-Johnson syndrome was approximately 0.14%. Efavirenz should be discontinued in patients developing severe rash associated with blistering, desquamation, mucosal involvement or fever. If therapy with Efavirenz is discontinued, consideration should also be given to interrupting therapy with other antiretroviral agents to avoid development of drug resistant virus.
Psychiatric symptoms: Psychiatric adverse experiences have been reported in patients treated with efavirenz. Patients with a history of psychiatric disorders appear to be at greater risk of these serious psychiatric adverse experiences. There have also been post-marketing reports of death by suicide, delusions and psychosis-like behaviour, although a causal relationship to the use of efavirenz cannot be determined from these reports. Patients should be advised that if they experience these symptoms they should contact their doctor immediately to assess the possibility that the symptoms may be related to the use of efavirenz, and if so, to determine whether the risks of continued therapy outweigh the benefits.
Nervous system symptoms: Symptoms including, but not limited to, dizziness, insomnia, somnolence, impaired concentration and abnormal dreaming are frequently reported undesirable effects in patients receiving efavirenz 600 mg daily in clinical studies. Nervous system symptoms usually begin during the first one or two days of therapy and generally resolve after the first 2 - 4 weeks. Patients should be informed that if they do occur, these common symptoms are likely to improve with continued therapy and are not predictive of subsequent onset of any of the less frequent psychiatric symptoms.
Seizures: Convulsions have been observed rarely in patients receiving efavirenz, generally in the presence of known medical history of seizures. Patients who are receiving concomitant anticonvulsant medicinal products primarily metabolised by the liver, such as phenytoin, carbamazepine and phenobarbital, may require periodic monitoring of plasma levels. In a drug interaction study, carbamazepine plasma concentrations were decreased when carbamazepine was co-administered with efavirenz. Caution must be taken in any patient with a history of seizures.
Effect of food: The administration of Efavirenz with food may increase efavirenz exposure and may lead to an increase in the frequency of undesirable effects. This effect may be more evident for the tablets than for the hard capsules. Taking Efavirenz on an empty stomach, preferably at bedtime, can be considered.
Immune Reconstitution Syndrome: Immune reconstitution syndrome has been reported in patients treated with combination antiretroviral therapy (CART), including Efavirenz. During the initial phase of treatment, a patient whose immune system responds to CART may mount an inflammatory response to indolent or residual opportunistic infections, which may necessitate further evaluation and treatment.
Special populations: Because of the extensive cytochrome P450-mediated metabolism of efavirenz and limited clinical experience in patients with chronic liver disease, caution should be exercised in administering Efavirenz to patients with liver disease.
The pharmacokinetics of efavirenz has not been studied in patients with renal insufficiency; however, less than 1% of an efavirenz dose is excreted unchanged in the urine, so the impact of renal impairment on efavirenz elimination should be minimal.
Insufficient numbers of elderly patients have been evaluated in clinical studies to determine whether they respond differently than younger patients.
Efavirenz has not been evaluated in children below 3 years of age or who weigh less than 13 kg. Evidence exists indicating that efavirenz may have altered pharmacokinetics in very young children. For this reason, efavirenz oral solution should not be given to children less than 3 years of age.
Liver enzymes: In patients with known or suspected history of Hepatitis B or C infection and in patients treated with other medications associated with liver toxicity monitoring of liver enzymes is recommended. In patients with persistant elevations of serum transaminases to greater than 5 times the upper limit of the normal range, the benefit of continued therapy with Efavirenz needs to be weighed against the unknown risks of significant liver toxicity.
Lipids: Monitoring of lipid levels should be considered in patients treated with Efavirenz.