n decreases, a greater percentage of the drug is eliminated by metabolic conversion to carboxymethoxymethyl guanine. During haemodialysis the half-life is reduced to 5.7 hours, with 60% of a dose of aciclovir being removed in 6 hours. Faecal excretion may account for about 2% of a dose.
In neonates and young infants (0 to 3 months of age) treated with doses of 10 mg/kg administered by infusion over a one-hour period every 8 hours the Cssmax was found to be 61.2 microMol (13.8 micrograms/ml) and Cssmin to be 10.1 microMol (2.3 micrograms/ml). A separate group of neonates treated with 15 mg/kg every 8 hours showed approximate dose proportional increases, with a Cmax of 83.5 micromolar (18.8 microgram/ml) and Cmin of 14.1 micromolar (3.2 microgram/ml).
5.3 Preclinical safety data
Systemic administration of aciclovir in internationally accepted standard tests did not produce embryotoxic or teratogenic effects in rats, rabbits or mice. In a non-standard test in rats, foetal abnormalities were observed, but only following such high subcutaneous doses that maternal toxicity was produced. The clinical relevance of these findings is uncertain.
Two generation studies in mice do not reveal any effect of aciclovir on fertility.
The results of a wide range of mutagenicity tests in vitro and in vivo indicate that aciclovir does not pose a genetic risk to man. Aciclovir was not found to be carcinogenic in long term studies in the rat and the mouse. Largely reversible adverse effects on spermatogenesis in association with overall toxicity in rats and dogs have been reported only at doses of aciclovir greatly in excess of those employed therapeutically. Aciclovir has been shown to have no definite effect upon sperm count, morphology or motility in man.
6. Pharmaceutical particulars
6.1 List of excipients
Also contains: colloidal anhydrous silica, magnesium stearate, polyvidone, sodium starch glycollate, E172, E460
6.2 Incompatibilities
None known.
6.3 Shelf life
Shelf-life
Three years from the date of manufacture.
Shelf-life after dilution/reconstitution
Not applicable.
Shelf-life after first opening
Not applicable.
6.4 Special precautions for storage
Store below 25°C in a dry place.
6.5 Nature and contents of container
The product containers are rigid injection moulded polypropylene or injection blow-moulded polyethylene containers with polyfoam wad or polyethylene ullage filler and snap-on polyethylene lids; in case any supply difficulties should arise the alternative is amber glass containers with screw caps and polyfoam wad or cotton wool.
The product may also be supplied in blister packs in cartons:
a) Carton: Printed carton manufactured from white folding box board.
b) Blister pack: (i) 250µm white rigid PVC. (ii) Surface printed 20µm hard temper aluminium foil with 5-7g/M2 PVC and PVdC compatible heat seal lacquer on the reverse side.
The product may be contained in blister packs which enhances security of the pack increasing resistance to deliberate contamination, pilfering, etc.
Pack sizes: 20s, 25s, 28s, 30s, 35s, 56s, 60s, 100s.
Product may also be supplied in bulk packs, for reassembly purposes only, in polybags contained in tins, skillets or polybuckets filled with suitable cushioning material. Bulk packs are included for temporary storage of the finished product before final packaging into the proposed marketing co
