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Phosphorylated aciclovir inhibits DNA polymerase and so prevents viral DNA being formed. It effectively treats susceptible herpes viruses if started early in the course of infection, but it does not eradicate persistent infection. Taken orally about 20% is absorbed from the gut, but this is sufficient for the systemic treatment of some infections. It distributes widely in the body; the concentration in CSF is approximately half that of plasma, and the brain concentration may be even less. These differences are taken into account in dosing for viral encephalitis (for which aciclovir must be given i.v.). The drug is excreted in the urine (t /2 3 h). For oral and topical use the drug is given x 5/d.

Indications for aciclovir include: Herpes simplex virus:

• skin infections, including initial and recurrent labial and genital herpes (as a cream), most effectively when new lesions are forming; skin and mucous membrane infections (as tablets or oral suspension)

• ocular keratitis (as an ointment)

• prophylaxis and treatment in the immunocompromised (oral, as tablets or suspension)

• encephalitis, disseminated disease (i.v.).

Aciclovir-resistant herpes simplex virus has been reported in patients with AIDS; foscarnet (see p. 262) has been used in these cases. Varicella-zoster virus:

chickenpox, particularly in the immunocompromised (i.v.) or in the immunocompetent with pneumonitis or hepatitis (i.v.)

shingles in immunocompetent persons (as tablets or suspension, and best within 48 h of the appearance of the rash). Immunocompromised persons will often have more severe symptoms and require i.v. administration.

Adverse reactions are remarkably few. The ophthalmic ointment causes a mild transient stinging sensation and a diffuse superficial punctate keratopathy which clears when the drug is stopped. Oral or i.v. use may cause gastrointestinal symptoms, headache and neuropsychiatrie reactions. Extravasation with i.v. use causes severe local inflammation.

Valaciclovir is a prodrug (ester) of aciclovir, i.e. after oral administration the parent aciclovir is released. The higher bioavailability of valaciclovir (about 60%) allows dosing only 8-hourly. It is used for treating herpes zoster infections and herpes simplex infections of the skin and mucous membranes.

Famciclovir is a prodrug of penciclovir which is similar to aciclovir; it is used for herpes zoster and genital herpes simplex infections. It need be given only 8-hourly. Penciclovir is also available as a cream for treatment of labial herpes simplex.

Idoxuridine was the first widely used antivirus drug. It is superseded by aciclovir and is variably effective topically for ocular and cutaneous herpes simplex with few adverse reactions.

HUMAN IMMUNODEFICIENCY VIRUS (HIV)

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