A new formulation of efavirenz, making it a once a day 600mg tablet, should be widely available by the end of the year, as Tracy Barnes explains.
Drug Name:
Efavirenz
Drug Class:
Non-nucleoside reverse transcriptase inhibitors (NNRTIs), also known as non-nucleoside analogues or "non nukes"
Brand Name:
Sustiva®
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How efavirenz works:
Efavirenz belongs to the group of drugs referred to as non-nucleoside reverse transcriptase inhibitors (NNRTIs) or non-nucleoside analogues.
This class of drugs combats viral replication of HIV by disrupting the essential transcription process of HIV genetic material (RNA) into DNA.
Efavirenz binds to the reverse transcriptase enzyme and changes its shape so that it is no longer effective in converting the viral RNA to DNA. How non-nucleosides achieve this is poorly understood.
Efavirenz is usually taken in combination with other anti-retroviral drugs, predominantly drugs from the nucleoside analogue class of HIV anti-retrovirals.
History:
Efavirenz was formerly known as DMP 266. It was approved in the USA in 1998 and received its European licence in June 1999. In the UK, Ireland, France, Germany, Italy and Spain efavirenz is branded as Sustiva(r), but in all other European countries, Brazil, Australia and South Africa it is known as Stocrin® and is marketed by a different pharmaceutical company.
Combination therapy:
Efavirenz is an established component of combination anti-retroviral therapy for both treatment-naïve patients and those who are treatment-experienced. When used in first line therapies its efficacy is equal or superior to that of protease inhibitors.
Efavirenz is most commonly prescribed in regimes that include two nucleoside analogues and is often considered an effective alternative to a protease inhibitor. Efavirenz also has proven efficacy in patients who are highly treatment-experienced, including those with protease inhibitor experience. When efavirenz was used alongside protease inhibitors and nucleoside reverse transcriptase inhibitors viral suppression was achieved on most patients who had experienced treatment failure.
Efavirenz provides very little treatment benefit to patients who have already experienced non-nucleoside transcriptase inhibitors in their regimes.
Efavirenz dosing:
Efavirenz is produced in 200mg capsules. The recommended adult dose is three capsules to be taken once a day. An oral suspension is being developed and will soon be available in the UK.
Dosing restrictions:
There are no dietary restrictions with efavirenz; the capsules can be taken with or without food. However, it has been demonstrated that high fat foods may increase drug absorption resulting in increased risk of side effects.
To decrease the effect of central nervous system side effects, patients are usually advised to administer efavirenz just prior to bedtime.
St. John's Wort (hypericum) is known to reduce the levels of efavirenz in the blood and is therefore contraindicated for use with efavirenz.
There are some dosing considerations for patients who have tuberculosis (TB). For those who are prescribed rifampicin, an increased daily dose of efavirenz to 800mg is recommended; for those prescribed rifabutin it should be noted that efavirenz is known to reduce rifabutin levels necessitating a 50% increase of rifabutin to ensure therapeutic efficacy.
Side effects of efavirenz:
The most commonly reported side effects of efavirenz are those that affect the central nervous system (CNS). These are experienced in 14-50% of patients. They include:
Dizziness
Headache
Drowsiness or insomnia
Vivid dreams and/or nightmares
Confusion
Poor concentration
Amnesia
Agitation
Hallucinations
Depression
Euphoria or mania
Most CNS side effects diminish after the first two weeks of treatment, although reports of persistent anxiety have been made. Taking efavirenz before bedtime is usually recommended to reduce the impact of CNS side effects.
Less common side effects to efavirenz include:
Alcohol intolerance
Fever
Aches and pains
Fluid retention
Elevated blood fats
Dry mouth
Seizures (rare)
Rash
Asthma
Changes to taste and vision
Fatigue
Most of the above side effects appear in the first few weeks of treatment and are easily remedied with dietary change and/or over the counter medications to alleviate symptoms. It is always wise to check with your physician before taking any other medication in case it interferes with the efficacy of your treatment.
Pre-existing conditions:
Efavirenz should never be used in patients with severe liver failure.
Increased incidence of liver toxicity has been associated with patients who have a history of raised ALT or AST levels and/or hepatitis B and hepatitis C.
Patients who are co-infected with hepatitis B and hepatitis C should have their liver enzymes monitored. If levels are 5 times above the normal range then efavirenz might not be suitable.
Paediatric use of efavirenz:
Efavirenz is suitable for use in children over the age of 3 years and more than 13kg in weight. Dosing is weight-based with multiples of 50mg, 100mg and 200mg capsules as follows.
13kg-15kg 200mg once a day
15kg-20kg 250mg once a day
20kg-25kg 300mg once a day
25kg-32.5kg 350mg once a day
32.5kg-40kg 400mg once a day
over 40kg 600mg once a day
Efavirenz treatment during pregnancy:
Efavirenz should not be used to treat pregnant women. Studies undertaken in rats and monkeys showed a number of birth defects were reported.
Because of the high incidence in animals and the unknown effect on humans, men and women taking efavirenz are advised to use two forms of birth control, a barrier method alongside the contraceptive pill.
Women taking efavirenz are advised not to breastfeed.
Efavirenz-resistant HIV:
The non-nucleoside analogues are highly cross resistant. Resistance to one drug in this class is likely to eliminate any other as an effective future treatment option.
In order to minimise the risk of drug resistant HIV developing, it is very important that efavirenz is used in combination with drugs that will be effective in suppressing viral load below detectable levels.
Future developments:
A new formulation of efavirenz is currently in development. A once daily 600mg tablet, the same size and with no known additional side effects, should be available by the end of this year (2002).
