Zylovir

Aciclovir.

Each tablet contains: Aciclovir 200 mg or Aciclovir 800 mg.

Pharmacology: Pharmacokinetics: Aciclovir is excreted through the kidney by both glomerular filtration and tubular secretion. The terminal or beta-phase half-life is reported to be about 2 to 3 hours for adults without renal impairment. In chronic renal failure, this value is increased and may be up to 19.5 hours in anuric patients. During haemodialysis the half-life has been reported to be reduced to 5.7 hours, with 60% of a dose of aciclovir being removed. Faecal excretion may account for about 2% of a dose. There is wide distribution, including into the CSF where concentrations achieved are about 50% of those achieved in plasma. Protein binding is reported to range from 9 to 33%. Probenecid increases the half-life and the area under the plasma concentration-time curve of aciclovir. About 15 to 30% of an oral dose of aciclovir is considered to be absorbed from the gastrointestinal tract. Orally active prodrugs such as valaciclovir have been developed to overcome this poor absorption. Aciclovir crosses the placenta and is distributed into breast milk in concentrations about 3 times higher than those in maternal serum.
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.

It is used for the treatment and prophylaxis of viral infection due to the herpes simplex virus types 1 and 2, and varicella zoster virus (herpes zoster and chicken pox).

Oral doses of aciclovir vary according to indication. For treatment of primary herpes simplex infections, including genital herpes, the usual oral dose is 200 mg five times daily (usually every 4 hours while awake) for 5 to 10 days. Severely immunocompromised patients or those with impaired absorption may be given 400 mg five times daily for 5 days. For suppression of recurrent herpes simplex in immunocompetent patients, the oral dose is 800 mg daily in two to four divided doses; dosage reduction to 400 to 600 mg daily can be tried. Higher doses of 1 g daily have also been used. Therapy should be interrupted every 6 to 12 months for reassessment of the condition. For prophylaxis of herpes simplex in immunocompromised patients, the dose is 200 to 400 mg four times daily. Chronic suppressive treatment is not suitable for mild or infrequent recurrences of herpes simplex. In such cases episodic treatment of recurrences may be more beneficial; a dose of 200 mg five times daily for 5 days has been recommended, preferably initiated during the prodromal period. The usual oral dose of aciclovir for treatment of chickenpox is 800 mg four or five times daily for 5 to 7 days; for herpes zoster 800 mg five times daily may be given for 7 to 10 days. Or as prescribed by the physician.

Aciclovir should be used with caution in patients with renal impairment and doses should be adjusted according to creatinine clearance. The risk of renal impairment is increased by use with other nephrotoxic drugs.

Renal impairment may be associated with systemic use of aciclovir in some patients; it is usually reversible and is reported to respond to hydration and/or dosage reduction or withdrawal, but may progress to acute renal failure. The risk of renal toxicity is increased by conditions favouring deposition of aciclovir crystals in the tubules such as when the patient is poorly hydrated, has existing renal impairment, or when the drug is given at a high dosage. Some patients receiving systemic aciclovir may experience transient increases in blood concentrations of urea and creatinine although this is more acute with intravenous administration.
Occasional adverse effects after systemic administration include increased serum bilirubin and liver enzymes, haematological changes, skin rashes (including erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis), fever, headache, dizziness, and gastrointestinal effects such as nausea, vomiting, and diarrhea. Anaphylaxis has been reported. Hepatitis and jaundice have been reported rarely. Neurological effects including lethargy, somnolence, confusion, hallucinations, agitation, tremors, psychosis, convulsions, and coma have been reported in a small number of patients, particularly in those given intravenous aciclovir and with predisposing factor, such as renal impairment; these effects may be more marked in older patients. Thrombotic thrombocytopenic purpura and hemolytic uraemic syndrome, sometimes resulting in death, have occurred in immunocompromised patients given high parenteral doses of aciclovir. 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.

Antivirals

J05AB01 - aciclovir ; Belongs to the class of nucleosides and nucleotides excluding reverse transcriptase inhibitors. Used in the systemic treatment of viral infections.

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