Nonnucleoside Reverse Transcriptase Inhibitors

Efavirenz has a long duration of action and need be taken only once per day (t/ 52 h). Rash is relatively common during the first 2 weeks of therapy, but resolution usually occurs within a further 2 weeks; the drug should be stopped if the rash is severe or if there is blistering, desquamation, mucosal involvement or fever. Neurological adverse reactions occur and may be reduced by taking the drug; gastrointestinal side effects, hepatitis and pancreatitis have also been reported.

Nevirapine is used in combination with at least two other antiretroviral drugs, usually for progressive or advanced HIV infection, although it appears effective also in pregnancy. It penetrates the CSF well, and undergoes hepatic metabolism (tV2 28 h). It is taken once daily, increasing to twice daily if rash is not seen. Rash and hepatitis are the commonest side effects.

Anti-HIV drugs are the subject of intense research and development and several new agents belonging to one or other of the above classes are to be expected.

Influenza A


Amantadine is effective only against influenza A; it acts by interfering with the uncoating and release of viral genome into the host cell. It is well absorbed from the gastrointestinal tract and is eliminated in the urine (t'/2 3 h). Amantadine may be used orally for the prevention and treatment of infection with influenza A (but not influenza B) virus. Those most likely to benefit include the debilitated, persons with respiratory disability and people living in crowded conditions, especially during an influenza epidemic.

Adverse reactions include dizziness, nervousness, lightheadedness and insomnia. Drowsiness, hallucinations, delirium and coma may occur in patients with impaired renal function. Convulsions may be induced, and amantadine should be avoided in epileptic patients.

Amantadine for Parkinson's disease: see page 404.

Zanamivir (Relenza)

Zanamivir is a neuraminidase inhibitor which blocks entry of the influenza A and B viruses to target cells and the release of their progeny. It is administered as 5 mg of a dry powder twice daily in 5-day course via a special inhaler. Controlled trials have shown that the duration of symptoms is reduced from about 6 to 5 days, with a smaller reduction in the mean time taken to return to normal activities. In high-risk groups the reduction in duration of symptoms is a little greater, and fewer patients need antibiotics.

Zanamivir was one of the first medicines to be the subject of a technology appraisal by the National Institute for Clinical Excellence (NICE) in the UK. NICE recommends that it be reserved for: at-risk patients (those with chronic respiratory or cardiovascular disease, immunosuppression or diabetes mellitus, or over the age of 65); when virological surveillance in the community indicates that influenza virus is circulating; and only for those who present within 48 h of the onset of influenza-like symptoms.

Unwanted effects are uncommon, butbronchospasm may be precipitated in asthmatics and gastrointestinal disturbance and rash are occasionally seen.

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