Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard.

4.9 Overdose
Symptoms and signs

Aciclovir is only partly absorbed in the gastrointestinal tract.

Patients have ingested overdoses of up to 20 g aciclovir on a single occasion, usually without toxic effects. Accidental, repeated overdoses of oral aciclovir over several days have been associated with gastrointestinal effects (eg nausea and vomiting) and neurological effects (eg headache and confusion).

Overdosage of i.v. aciclovir has resulted in elevations of serum creatinine, blood urea nitrogen and subsequent renal failure. Neurological effects including confusion, hallucinations, agitation, seizures and coma have been described in association with overdosage.

Treatment

Patients should be observed closely for signs of toxicity. Haemodialysis significantly enhances the removal of aciclovir from the blood and may, therefore, be considered a management option in the event of symptomatic overdose.

5. Pharmacological properties
5.1 Pharmacodynamic properties
Pharmacotherapeutic group - ATC code: J05A B

Aciclovir is an antiviral agent which is highly active in vitro against herpes simplex virus (HSV) types I and II and varicella zoster virus. Toxicity to mammalian host cells is low.

Aciclovir is phosphorylated after entry into herpes infected cells to the active compound aciclovir triphosphate. The first step in this process is dependant on the presence of the HSV-coded thymidine kinase. Aciclovir triphosphate acts as an inhibitor of, and substrate for, the herpes-specified DNA polymerase, preventing further viral DNA synthesis without affecting the normal cellular processes.

Herpes simplex virus develops resistance to aciclovir by selection of mutants deficient in thymidine kinase which are usually of diminished virulence with reduced infectivity and latency. Resistance is rare in immunocompetent patients on short courses of oral therapy but it is more preva lent in immunocompromised patients who have often received prolonged courses of treatment. Herpes zoster resistance develops by a similar mechanism and has been reported in immunocompromised patients undergoing prolonged therapy with aciclovir.

5.2 Pharmacokinetic properties
Absorption

Aciclovir is slowly and incompletely absorbed from the gastrointestinal tract. The peak plasma concentration occurs about 2 hours following ingestion.

Distribution

There is a wide distribution to various tissues, including the CSF where concentrations achieved are about 50% of those achieved in plasma. Protein binding is reported to range from 9-33%. Aciclovir crosses the placenta and is excreted in breast milk in concentrations approximately 3 times higher than those in maternal serum.

Metabolism and Elimination

Renal excretion is the major route of elimination by both glomerular filtration and tubular secretion. The terminal or beta-phase half-life is reported to be about 2-3 hours for adults without renal impairment. As aciclovir persists in the plasma of patients with renal insufficiency, in chron