, therefore the dose must be reduced in patients with renal impairment (see section 4.2). Elderly patients are likely to have reduced renal function and therefore the need for dose reduction must be considered in this group of patients. Both elderly patients 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 section 4.8).
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.
Aciclovir should also be used with caution in patients with underlying neurological abnormalities, severe hepatic or electrolyte abnormalities or significant hypoxia.
Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
4.5 Interaction with other medicinal products and other forms of interaction
No clinically significant interactions have been identified.
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 co-administered. However, no dosage adjustment is necessary because of the wide therapeutic index of aciclovir.
The risk of renal impairment is increased by the concomitant use of other nephrotoxic drugs.
Antivirals: fatigue has been associated with the combined use of aciclovir and zidovudine.
Aciclovir may increase serum theophylline levels.
4.6 Pregnancy and lactation
Pregnancy
The use of aciclovir 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. 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 0.3 mg/kg/day. Caution is therefore advised if aciclovir is to be administered to a nursing woman.
4.7 Effects on ability to drive and use machines
The clinical status of the patient and the adverse event profile of aciclovir should be borne in mind when considering the patients' ability to drive or operate machinery.
There have been no studies to investigate the effects of aciclovir on driving performance or the ability to operate machinery. Further, a detrimental effect on such activities cannot be predicted from the pharm
