Indications:
It is mainly used for the treatment of herpes simplex virus and varicella zoster virus infections, including:
● Genital herpes simplex (treatment and prevention)
● Herpes simplex labialis (cold sores)
● Shingles
● Chickenpox
● Herpes simplex encephalitis
● Acute mucocutaneous HSV infections in immunocompromised patients
● Herpes of the eye and herpes simplex blepharitis (a chronic (long-term) form of herpes eye infection)
● Prophylaxis or prevention of herpes viruses in immunocompromised people (such as people undergoing cancer chemotherapy)
Pharmacodynamic properties:
Acyclovir belongs to a direct acting antiviral class of drugs. It is a synthetic purine nucleoside analog that inhibits the action of viral DNA polymerase and DNA replication of different herpes virus including herpes simplex virus (HSV) types I and II and varicella zoster virus (VZV), acting as a reverse transcriptase inhibitors.
Mechanism of Action:
Due to the affinity of acyclovir for the enzyme thymidine kinase (TK) encoded by HSV and VZV its inhibitory activity is highly selective. This viral enzyme converts acyclovir into acyclovir monophosphate which is further converted into diphosphate by cellular guanylate kinase and into triphosphate by a number of cellular enzymes such as nucleoside diphosphate kinase, pyruvate kinase, creatine kinase, phosphoglycerate kinase, succinyl-CoA synthetase, phosphoenolpyruvate carboxykinase and adenylosuccinate synthetase. In vitro, acyclovir triphosphate stops replication of herpes viral DNA in 3 ways:
1) competitive inhibition of viral DNA polymerase,
2) incorporation into and termination of the growing viral DNA chain, and
3) inactivation of the viral DNA polymerase.
Pharmacokinetics Properties:
Aciclovir is poorly water-soluble and is partially absorbed from the gastrointestinal tract having poor oral bioavailability (15–30%), hence intravenous administration is necessary if high concentrations are required. When orally administered, peak plasma concentration occurs after 1–2 hours. Aciclovir has a high distribution rate and plasma protein binding is reported to be relatively low ranging from 9 to 33%. The terminal plasma half-life (t1/2) of aciclovir depends according to age group; neonates have a t1/2 of 4 hours, children 1–12 years have a t1/2 of 2–3 hours whereas adults have a t1/2 of 3 hours.
Side Effects:
Some of the more common side effects associated with acyclovir oral tablet include:
● nausea
● vomiting
● diarrhea
● headache
● Weakness
Few other adverse effects include:
● extreme tiredness
● slow/fast/irregular heartbeat
● easy bruising/bleeding
● bloody/dark urine
● severe stomach/abdominal pain
● yellowing eyes/skin
● sudden vision changes
● loss of consciousness
● seizures
● renal failure
Precautions & Warning:
For patients with renal impairment and in elderly patients: Dosage adjustment is recommended when administering acyclovir to patients with renal impairment or elederly patients with low renal function since this may increase the risk of renal dysfunction and/or neurological side effects.
Hydration status: Care should be taken to maintain adequate hydration in patients receiving high oral doses of aciclovir. Adequate hydration should be maintained.
For pregnant women: 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. Systemic administration of aciclovir in internationally accepted standard tests did not produce embryotoxic or teratogenic effects in rabbits, rats 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.
For women who are breastfeeding: Acyclovir may pass into breast milk and may cause side effects in a child who is breastfed. Talk to your doctor if you breastfeed your baby. You may need to decide whether to stop breastfeeding or stop taking this medication.
Contraindications:
Acyclovir is contraindicated for patients who develop hypersensitivity to acyclovir or valacyclovir.
Storage:
● Keep out of the reach of children
● Store in a cool, dry place, away from direct heat and light.