The effect of acyclovir is based on a selective inhibition of the replication of herpes viruses. The drug is phosphorylated by viral thymidine kinase. As a triphosphate acyclovir inhibits the DNA polymerase and thus the formation of viral DNA. The host cells are not considerably affected. Varicella-zoster viruses are not as sensitive as herpes simplex viruses. Resistant herpes viruses, that lack the thymidine kinase, have been observed almost exclusively in immunocompromised subjects.

Indications
For the treatment of immunocompetent subjects acyclovir only plays a minor role. Herpes simplex: For genital primary infections, oral acyclovir entails a considerably faster healing rate than a placebo or an acyclovir ointment. For herpes simplex keratitis, local or oral therapy is successful. Herpes simplex encephalitis and herpes simplex neonatorum must be treated intravenously. Patients with frequently relapsing herpes simplex (labial or genital) benefit from long-term, prophylactic acyclovir administration. However, treatment of an isolated (labial or genital) herpes relapse is not indicated.

The effect of acyclovir against most forms of the varicella-zoster disease is marginal. A herpes zoster of the cornea should be treated as early as possible with high doses of acyclovir. Acyclovir only brings limited benefit for zosters (and varicella) in other localisations. Specialists do not agree on its advantages as far as post-herpetic neuralgias are concerned.

The case is different for immunocompromised subjects (chemotherapy, HIV infection, lymphoma) whose herpes simplex and varicella-zoster infections should all be treated with oral or parenteral acyclovir.
Adverse Reactions
Acyclovir occasionally causes nausea or vomiting, upper abdominal pain, headaches, or exanthema. In approximately 1% of the treated patients, an encephalopathy (lethargy, confusion, agitation, cramps) can be observed after intravenous administration. An increase of the liver enzymes has been reported occasionally.

High dose acyclovir treatment (especially intravenous) can lead to the rise of plasma creatinine and plasma urea or even to acute renal failure. The problem lies in crystal depositions in the renal tubules.

The ointments can cause topical reactions (itching, burning). Paravenous injections cause severe topical inflammations, possibly with skin lesions.

燙ontraindications
None except hypersensitivity to acyclovir

Cautions
Always ensure ample fluid supply! (Example: for a daily dose of 4 g, at least 3 litres/day).

Do not inject intravenously as bolus (duration of infusion is at least 1 hour).

Risk Groups

燩regnant women:
Allowed despite certain doubts. No unequivocal danger has yet been demonstrated for children.牋
?Nursing mothers:
There are high concentrations in breast milk. It is better avoided.牋
?Children:
Oral administration: up to two years of age, half of the adult dose; older children take the adult dose. Intravenous administration: 3 X daily 250 mg (max. 500 mg) per m?/sup>.牋
?Elderly people:
Mind the potential reduction of renal function.?BR>?Renal failure:
Reduce the intravenous dose when the creatinine clearance (GFR) drops below 50 ml/min:
GFR 25-50 ml/min: 5-10 mg/kg every 12 hours
GFR 10-25 ml/min: 5-10 mg/kg every 24 hours
GFR below 10 ml/min: 2.5-5 mg/kg/day
Oral dose: Only reduce when GFR drops below 10 ml/min: 2 X daily 200 mg.
?BR>燣iver insufficiency:
No dose adjustment is necessary.

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