When a pharmaceutical company changes an SPC or PIL, a new version is published on medicines.ie. For each version, we show the dates it was published on medicines.ie and the reasons for change.
4.2 Posology and method of administration
Under the subheading ‘Dosage in the elderly’ updated the wording to read:
The possibility of renal impairment in the elderly must be considered and the dosage should be adjusted accordingly (see Dosage in renal impairment below). Adequate hydration should be maintained.
Under the subheading ‘Dosage in renal impairment’ added the following warning:
Caution is advised when administering aciclovir to patients with impaired renal function. Adequate hydration should be maintained.
4.4 Special warnings and precautions for use
Under the new subheading ‘Use in patients with renal impairment and in elderly patients’ added the following warning:
Aciclovir is eliminated by renal clearance, therefore the dose must be adjusted in patients with renal impairment (see section 4.2). Elderly patients are likely to have reduced renal function and therefore the need for dose adjustment 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).
4.8 Undesirable Effects
Regarding the adverse events listed under ‘Psychiatric and nervous system disorders’, updated the wording to read:
The above events are generally reversible and usually reported in patients with renal impairment, or with other predisposing factors (see section 4.4).
Section 4.8: Addition of renal pain as a very rare undesirable effect with the following statement added: 'Renal pain may be associated with renal failure'.
5.3 Preclinical safety data
There is no information on the effect of aciclovir oral formulations or i.v. for infusion on human female fertility. In a study of 20 male patients with normal sperm count, oral aciclovir administered at doses of up to 1g per day for up to six months has been shown to have no clinically significant effect on sperm count, motility or morphology.
NON-CLINICAL INFORMATION
Mutagenicity
The results of a wide range of mutagenicity tests in vitro and in vivo indicate that acyclovir does not is unlikely to pose a genetic risk to man.
Carcinogenicity
Aciclovir was not found to be carcinogenic in long-term studies in the rat and the mouse.
Fertility
Largely reversible adverse effects on spermatogenesis in association with overall toxicity in rats and dogs have been reported only at systemic doses of aciclovir greatly in excess of those employed therapeutically. Two-generation studies in mice did not reveal any effect of (orally administered) aciclovir on fertility.