atients and patients with renal impairment are at increased risk of developing neurological side effects and should be closely monitored for evidence of these effects. In the reported cases, these reactions were generally reversible on discontinuation of treatment (see 4.8 Undesirable Effects). Prolonged or repeated courses of aciclovir in severely immune-compromised individuals may result in the selection of virus strains with reduced sensitivity, which may not respond to continued aciclovir treatment (see section 5.1).
Hydration status: Care should be taken to maintain adequate hydration in patients receiving high oral doses of aciclovir.
This risk of renal impairment is increased by use with other nephrotoxic drugs.
The data currently available from clinical studies is not sufficient to conclude that treatment with aciclovir reduces the incidence of chickenpox-associated complications in immunocompetent patients.
This medicinal product contains sorbitol liquid (non-crystallising) (E420). Patients with rare hereditary problems of fructose intolerance should not take this medicine. It also contains methyl parahydroxybenzoate (E218). This may cause an allergic reaction (possibly delayed).
4.5 Interaction with other medicinal products and other forms of interaction
Aciclovir is eliminated primarily unchanged in the urine via active renal tubular secretion. Any drugs administered concurrently that compete with this mechanism may increase aciclovir plasma concentrations. Probenecid and cimetidine increase the AUC of aciclovir by this mechanism, and reduce aciclovir renal clearance. Similarly increases in plasma AUCs of aciclovir and of the inactive metabolite of mycophenolate mofetil, an immunosuppressant agent used in transplant patients have been shown when the drugs are coadministered. However no dosage adjustment is necessary because of the wide therapeutic index of aciclovir.
When aciclovir is administered concomitantly with theophylline close monitoring of theophylline concentrations and possible theophylline dose reduction is recommended. A study has shown that when theophylline was given as a single 320mg doses before and with the sixth dose of aciclovir 800mg five times daily for 2 days, the AUC of the theophylline was increased by 45% (189.9 to 274.9 micrograms .h/ml) and total body clearance was reduced by 30%.
4.6 Fertility, pregnancy and lactation
Pregnancy:
The use of acyclovir should be considered only when the potential benefits outweigh the possibility of unknown risks.
A post-marketing aciclovir pregnancy registry has documented pregnancy outcomes in women exposed to any formulation of Aciclovir suspension. The registry findings have not shown an increase in the number of birth defects amongst aciclovir exposed subjects compared with the general population, and any birth defects showed no uniqueness or consistent pattern to suggest a common cause.
Lactation:
Following oral administration of 200mg aciclovir five times a day, aciclovir has been detected in breast milk at concentrations ranging from 0.6 to 4.1 times the corresponding plasma levels. These levels would potentially expose nursing infants to aciclovir dosages of up to 0.3mg/kg/day. Caution is therefore advised if Aciclovir suspension is to be administered to a nursing woman.
Fertility:
See Section 5.3
4.7 Effects on ability to drive and use machines
The clinical status of the pa
