Administration: Patients who experience difficulty in swallowing the tablets may disperse them in a minimum of 50ml water which should be stirred before drinking.

For oral administration.

4.3 Contraindications
• Hypersensitivity to the active substance, valaciclovir or to any of the excipients listed in section 6.1.

4.4 Special warnings and precautions for use
Use in patients with renal impairment and in elderly patients:

The risk of renal impairment is increased by use with other nephrotoxic drugs.

Aciclovir is eliminated by renal clearance, 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 (see section 5.1).

Hydration status: Care should be taken to maintain adequate hydration in patients receiving higher dose oral regimens or i.v., e.g. for the treatment of herpes zoster infection (4g daily), in order to avoid the risk of possible renal toxicity.

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.

• Ciclosporin: There has been a small number of transplant patients with increased serum levels of ciclosporin and signs of nephrotoxicity when aciclovir is given concurrently. Renal function should be monitored closely in patients taking both drugs.

• Cimetidine and probenecid: Cimetidine and probenecid increase the AUC of aciclovir by competing for active secretion by the renal tubules and reduce aciclovir renal clearance. Dosage adjustment is usually not necessary because of the wide therapeutic index of aciclovir.

• Mycophenolate mofetil: 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.

• An experimental study on five male subjects indicates that concomitant therapy with aciclovir increases AUC of totally administered theophylline with approximately 50%. It is recommended to measure plasma concentrations during concomitant therapy with aciclovir.

• Zidovudine: Although co-administration of zidovudine and aciclovir is not usually associated with toxicity, there is a single case report of overwhelming fatigue developing in a patient when given the two drugs together. This did not occur when zidovudine and aciclovir were given alone.

4.6 Fertility, pregnancy and lactation
Pregnancy

Experience in humans is limited so the use of aciclovir should be consi