Each gram contains: Aciclovir 50 mg.
Pharmacology: Pharmacokinetics: Absorption of Aciclovir is usually slight after topical application to intact skin, although it may be increased by changes in formulation. Average daily urinary excretion of Aciclovir was approximately 0.04% of the daily applied dose. Systemic absorption is minimal in adults.
Microbiology: Antiviral Action: Aciclovir is active against herpes simplex virus type 1 and type 2 and against varicella-zoster virus. This activity is due to intracellular conversion of Aciclovir by viral thymidine kinase to the monophosphate with subsequent conversion by cellular enzymes to the diphosphate and the active triphosphate. This active form inhibits viral DNA synthesis and replication by inhibiting the herpes virus DNA polymerase enzyme as well as being incorporated into viral DNA. This process is highly selective for infected cells. Studies in animals and in vitro have found various sensitivities but show that these viruses are inhibited by concentrations of Aciclovir that are readily achieved clinically. Herpes simplex virus type I appears to be the most susceptible, then type 2, followed by varicella-zoster virus. The Epstein-Barr virus and CMV are also susceptible to Aciclovir to a lesser extent. However, for CMV it does not appear to be activated by thymidine kinase and may act via a different mechanism. Epstein-Barr virus may have reduced thymidine kinase activity but its DNA polymerase is very sensitive to inhibition by Aciclovir triphosphate, which may account for the partial activity. Aciclovir has no activity against latent viruses, but there is some evidence that it inhibits latent herpes simplex virus at an early stage of reactivation.
Resistance: Herpes simplex virus develops resistance to Aciclovir in vitro and in vivo by selection of mutants deficient in thymidine kinase. Other mechanisms of resistance include altered substrate specificity of thymidine kinase and reduced sensitivity of viral DNA polymerase. Resistance has also been reported with varicella-zoster virus, probably by similar mechanisms. Although occasional treatment failures have been reported, resistance has not yet emerged as a major problem in treating herpes simplex infections. However, resistant viruses are more likely to be a problem in patients with a suppressed immune response; AIDS patients may be particularly prone to Aciclovir-resistant mucocutaneous herpes simplex virus infections. Viruses resistant to Aciclovir because of absence of thymidine kinase may be cross-resistant to other antivirals phosphorylated by this enzyme, such as Brivudine, Idoxuridine, and Ganciclovir. Viruses resistant because of altered substrate specificity of thymidine kinase may display cross-resistance to brivudine; those with altered DNA polymerase sensitivity may be resistant to Brivudine and Vidarabine. However, those viruses with altered enzyme specificity or sensitivity tend to have variable cross-resistance patterns and may be relatively susceptible to the aforementioned antivirals.
Treatment of viral infections due to Herpes Simplex Virus (types 1 and 2) and Varicella-Zoster virus (herpes zoster and chickenpox).
In herpes simplex infections of the skin, including genital herpes and herpes labialis, topical treatment with cream containing Aciclovir 5% may be applied 5 or 6 times daily for periods of 5 to 10 days. Or as prescribed by the physician.
Prophylactic use of aciclovir and routine use for treatment of recurrent herpes infections should be avoided since indiscriminate use may result to resistance. Do not use in eyes, nose or mouth. No evidence that topically applied Aciclovir will either prevent transmission of HSV infections to other individuals or prevent recurrent HSV infections when applied in the absence of signs and symptoms of disease. Do not use to prevent recurrent HSV infection.
Use in pregnancy: No adequate and controlled studies to date.
Use in lactation: Not known if aciclovir is distributed into milk; Aciclovir should be administered in caution.
Use in Children: Safety and efficacy in pediatric patients less than 12 years of age has not been established.
Pregnant women: No adequate and controlled studies to date.
Nursing women: Not known if aciclovir is distributed into milk; Aciclovir should be administered in caution.
Aciclovir appears to have low order of toxicity when applied topically to the skin. Mild pain, with or without transient burning and stinging, occurs in about 30% of patients following topical application of the drug to the ulcerated genital lesions. Pruritus, rash or vulvitis occurs rarely. Accelerated diffuse hair loss has also been reported.
Probenecid is reported to block the renal clearance of Aciclovir. The risk of renal impairment is increased by use with other nephrotoxic drugs.
Store at temperatures not exceeding 30°C.
D06BB03 - aciclovir ; Belongs to the class of topical antivirals used in the treatment of dermatological diseases.