Acylete

Acyclovir.

Tablet: An orange color shield-shaped tablet, one surface with CCP, other surface with score.
Name and Strength of Active Ingredient: Acyclovir, Antiviral Agent, 400 mg.
Cream: An off white to creamy white cream.
Each gm contains: Acyclovir 50 mg.
Excipients/Inactive Ingredients: Contains preservatives: Propylparaben 0.02%w/w, Methylparaben 0.18%w/w.

Pharmacology: Pharmacodynamics: Acyclovir is an antiviral agent which is highly active in vitro against herpes simplex virus (HSV) type I and II and varicella zoster virus. Acyclovir is phosphorylated after entry into herpes-infected cells to the active compound acyclovir triphosphate. Acyclovir triphosphate acts as an inhibitor of and substrate for the herpes-specified DNA-polymerase preventing further viral DNA synthesis without affecting normal cellulose processes.
Pharmacokinetics: Acyclovir is only partially absorbed from the gut. It is estimated that 15 ~ 30% of an oral dose of the drug is absorbed. Steady-state peak and trough plasma acyclovir concentrations were not dose proportional over the oral dosing range of 200 ~ 800 mg 6 times daily. Mean steady state peak plasma concentrations following doses of 400 mg administered 4-hourly were 1.21 ug/ml and the equivalent trough plasma levels were 0.63 ug/ml.
Acyclovir is widely distributed into body tissues and fluids including the brain, kidney, saliva, lung, liver, muscle, spleen, uterus, vaginal mucosa and secretions, CSF and herpetic vesicular fluid. The drug is also distributed into semen, achieving concentrations about 1.4 and 4 times those in plasma during chronic oral therapy at dosage of 400 mg and 1 g daily, respectively. Acyclovir crosses the placenta. Limited data indicate that the drug is distributed into milk, generally in concentrations greater than concurrent maternal plasma concentrations, possibly via an active transport mechanism.
From studies with intravenous acyclovir, the terminal plasma half-life has been determined as about 2.9 hours. Most of the drug is excreted unchanged by the kidney. Renal clearance of acyclovir is substantially greater than creatinine clearance indicating that tubular secretion in addition to glomerular filtration contributes to the renal elimination of the drug 9-carboxymethoxymethylguanine is the only significant metabolite of acyclovir and accounts for 10 ~ 15% of the total amount of drug recovered in the urine. In patients with chronic renal failure, the mean terminal half-life was found to be 19.5 hours. The mean acyclovir half-life during haemodialysis was 5.7 hours. Plasma acyclovir levels dropped approximately 60% during dialysis. 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.

Tablet: Acylete tablets are indicated for: The treatment of herpes simplex virus infections of the skin and mucous membranes including initial and recurrent genital herpes.
The suppression (prevention of recurrences) of recurrent herpes simplex infections in immune-competent patients.
The prophylaxis of herpes simplex infections in immune-compromised patients.
The treatment of herpes zoster infections.
Cream: Acylete Cream is indicated for the treatment of herpes simplex virus infections of the skin including initial and recurrent genital herpes and herpes labialis.

Tablet: Adults, children and geriatric: Acylete Tablets should be applied to the lesions or impending lesions as early as possible after the start of an infection.
Dosage for treatment of herpes simplex in adults: For treatment of herpes simplex infections, 200 mg Acyclovir should be taken 5 times daily at approximately 4-hourly intervals omitting the night-time dose. Treatment should continue for 5 days, but in severe initial infections, treatment may have to be extended. In severely immune-compromised patients (e.g. after marrow transplant) or patients with impaired absorption from the gut, the dose can be doubled to 400 mg or alternatively intravenous dosing could be considered. Dosing should begin as early as possible after the start of an infection; for recurrent episodes this should preferably be during the prodromal period or when lesions first appear.
Dosage for suppression of herpes simplex in adults: For suppression of herpes simplex infections in immune-competent patients, 200 mg Acyclovir should be taken 4 times daily at approximately 6-hourly intervals. Many patients may be conveniently managed on a regimen of 400 mg Acyclovir taken twice daily at approximately 12-hourly intervals.
Dosage titration down to 200 mg Acyclovir taken thrice daily at approximately 8-hourly intervals or even twice daily at approximately 12-hourly intervals may prove effective. Some patients may experience break-through infections on total daily doses of 800 mg Acyclovir, Therapy should be interrupted periodically at intervals of 6~12 months, in order to observe possible changes in the natural history of the disease.
Dosage for prophylaxis of herpes simplex in adults: For prophylaxis of herpes simplex infections in immune-compromised patients, 200 mg Acyclovir should be taken 4 times daily at approximately 6 hourly intervals.
In severely immune-compromised patients (e.g. after marrow transplant) or in patients with impaired absorption from the gut, the dose can be doubled to 400 mg or alternatively intravenous dosing could be considered.
The duration of prophylactic administration is determined by the duration of the period at risk.
Dosage for treatments of herpes zoster in adults: For treatment of herpes zoster infections, 800 mg Acyclovir should be taken 5 times daily at approximately 4-hourly intervals, omitting the night-time dose, Treatment should continue for 7 days. In severely immune-compromised patients (e.g. after marrow transplant) or in patients with impaired absorption from the gut, consideration should be given to intravenous dosing. Dosing should begin as early as possible after the start of an infection; treatment yields better results if initiated as soon as possible after onset of the rash.
Dosage in children: For treatment of herpes simplex infections, and for prophylactics of herpes simplex infections in the immune-compromised, children over the age of 2 years should be given adult dosage and children below the age of 2 years should be given half the adult dose.
No specific data are available on the suppression of herpes simplex infections or the treatment of herpes zoster infections in immune-competent children.
Dosage in the elderly: In the elderly, total Acyclovir body clearance declines in parallel with creatinine clearance. Adequate hydration of elderly patients taking high oral doses of Acyclovir should be maintained. Special attention should be given to dosage reduction in elderly patients with impaired renal function.
Dosage in renal impairment: In the management of herpes simplex infections in patients with impaired renal function, the recommended oral dosage will not lead to accumulation of acyclovir above levels that have been established safe by intravenous infusions. However, for patients with severe renal impairment (creatinine clearance less than 10 ml/minute) an adjustment of dosage to 200 mg twice daily at approximately 12-hourly intervals is recommended.
In the treatment of herpes zoster infections, it is recommended to adjust the dosage 800 mg twice daily at approximately 12-hourly intervals for patients with severe renal impairment (creatinine clearance less than 10 ml/minute), and to 800 mg 3 times daily at intervals of approximately 6 hours for patients with moderate renal impairment (creatinine clearance in the range 10~25 ml/minute).
Route of Administration: Oral.
Cream: Topical application.
Adults, children and geriatric: Acylete Cream should be applied five times daily at approximately 4-hourly intervals omitting the night-time dose. Acylete Cream should be applied to the lesions or impending lesions as early as possible after the start of an infection. It is particularly important to start treatment of recurrent episodes during the prodromal period or when the lesions first appear. Treatment should be continued for 5 days. If healing has not occurred, treatment may be continued for up to 10 days.

Tablet: Symptoms: Acyclovir is only partly absorbed in the gastrointestinal tract. It is unlikely that serious toxic effects would occur if a dose of up to 5 g were taken on a single occasion. No data are available on the consequences of the ingestion of higher doses.
Single intravenous doses of up to 80 mg/kg have been inadvertently administered without adverse effects.
Treatment: Ingestion of doses of acyclovir in excess of 5 g warrants close observation of the patient.
Acyclovir is dialysable.
Cream: Overdosage by topical application of Acylete cream is unlikely because of limited transcutaneous absorption.

Tablet: Acylete Tablets are contraindicated in patients known to be hypersensitivity to acyclovir.
Cream: Acylete Cream is contraindicated for patients who develop hypersensitivity or chemical intolerance to the components of the formulation.

Tablet: Effects on Ability to Drive and Use Machines: They have been no studies to investigate the effect of Acyclovir on driving performance or the ability to operate machinery. Further, a detrimental effect on such activities cannot be predicted from the pharmacology of the active substance.
Mutagenicity: The results of a wide range of mutagenicity test in vitro and in vivo indicates that acyclovir does not pose a genetic risk to man.
In severely immune-compromized patients (e.g. AIDS patients or bone marrow transplant recipients), oral acyclovir should be considered. Such patients should be encouraged to consult a physician concerning the treatment of any infection.
Cream: The recommended dosage, frequency of applications, and length of treatment should not be exceeded.
Acylete Cream is not recommended for application to mucous membranes, such as in the mouth, eye or vagina. Particular care should be taken to avoid accidental introduction into the eye.
In severely immune compromised patients (e.g. AIDS patients or bone marrow transplant recipients), oral acyclovir should be considered. Such patients should be encouraged to consult a physician concerning the treatment of any infection.
Teratogenic Effects: Acyclovir was not teratogenic in mouse, rabbit or in standard tests in the rat. There are no adequate and well-controlled studies in pregnant women. Acyclovir should not be used during pregnancy unless the potential benefit justifies the potential risk to the fetus.
Carcinogenesis, Mutagenesis, Impairment of Fertility: No chromosome damage was observed at maximum tolerated parenteral doses of 100 mg/kg acyclovir in rats or chinese hamsters. No evidence of mutagenicity was observed in mammalin cell. Acyclovir does not impair fertility or reproduction in mice at subcutaneous doses up to 25 mg/kg/day.
Use in Lactation: It is not known whether topically applied acyclovir is excreted in breast milk. Caution should be exercised when Acyclovir cream is administered to a nursing woman.

Systemic administration of acyclovir did not produce embryotoxic or teratogenic effects in rabbits or rats. Experience in humans is limited, so the use of Acylete Tablets should be considered only when the potential benefits outweigh the possibility of unknown risks. Limited human data show that the drug does pass into breast milk.

Tablet: Skin rashes have been reported in a few patient receiving Acylete Tablets; the rashes have resolved on withdrawal of the drug. Gastrointestinal effects, including nausea vomiting, diarrhea and abdominal pains, have been reported in some patients receiving Acylete Tablets. In double-blind, placebo-controlled trials the incidence of gastrointestinal events has not been found to differ between placebo and acyclovir recipients. Other events reported rarely in patients receiving oral formulations of Acyclovir include mild, transient rises in bilirubin an liver-related enzymes, small increase in blood urea and creatinine, small decrease in haematological indices, mild reversible neurological reactions and fatigue.
Cream: Because ulcerated genital lesions are characteristically tender and sensitive to any contact manipulation, patients may experience discomfort upon application of cream. In the controlled clinical trials, main pain (including transient burring and stinging) was reported. Other local reactions among acyclovir treated patients included pruritus, rash and vulvitis.

Probenecid increases the mean half-life and area under the plasma concentration curve of systemically administered acyclovir. Other drugs affecting renal physiology could potentially influence the pharmacokinetics of acyclovir. However, clinical experience has not identified other drug interactions with acyclovir.

Store at room temperature below 30°C.
Shelf Life: 3 years.

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