rams/ml), 43.6 microMol (9.8 micrograms/ml) and 92 microMol (20.7 micrograms/ml), respectively. The corresponding trough levels (Cssmin) 7 hours later were 2.2 microMol (0.5 micrograms/ml), 3.1 microMol (0.7 micrograms/ml) and 10.2 microMol (2.3 micrograms/ml), respectively. In children over 1 year of age similar mean peak (Cssmax) and trough (Cssmin) levels were observed when a dose of 250 mg/m2 was substituted for 5 mg/kg and a dose of 500 mg/m2 was substituted for 10 mg/kg. 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). The terminal plasma half-life in these patients was 3.8 hours. 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). In the elderly, total body clearance falls with increasing age associated with decreases in creatinine clearance although there is little change in the terminal plasma half-life.
In patients with chronic renal failure the mean terminal half-life was found to be 19.5 hours. The mean Aciclovir half-life during haemodialysis was 5.7 hours. Plasma Aciclovir levels dropped approximately 60% during dialysis.
Cerebrospinal fluid levels are approximately 50% of corresponding plasma levels. Plasma protein binding is relatively low (9 to 33%) and drug interactions involving binding site displacement are not anticipated.
5.3 Preclinical safety data
Mutagenicity:- The results of a wide range of mutagenicity tests in vitro and in vivo indicate that aciclovir 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.
Teratogenicity:- 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.
Fertility:- 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. Two generation studies in mice did not reveal any effect of aciclovir on fertility.
6. Pharmaceutical particulars
6.1 List of excipients
Microcrystalline Cellulose
Aluminium Magnesium Silicate
Sodium Starch Glycollate
Povidone (K30)
Magnesium Stearate
Filmcoat
Hypromellose
Titanium Dioxide
Polyethylene glycol 400
Polish
Polyethylene Glycol 8000
6.2 Incompatibilities
None known
6.3 Shelf life
36 months
6.4 Special precautions for storage
Do not store above 30°C
Store in the original package.
6.5 Nature and contents of container
PVC/Aluminium foil blisterpack (5 tablets per blister strip)
Pack size : 35 tablets
Polypropylene container with polyethylene snap-on lid.
Pack size : 35 and 800 tablets
PVC/Aluminium foil blister sample pack.
Pack size: 5 and 2 tablets
Polyethylene bag in a ri
