Indications/Uses
For the treatment of herpes simplex virus infections of the skin and mucous membranes including initial and recurrent genital herpes zoster (shingles) infections; chicken pox (varicella) in children over the age of two years old.
Dosage/Direction for Use
Dosage in Adults: Treatment of herpes simplex infections: 200 mg (1 tsp) should be taken 5 times daily at approximately 4 hour intervals omitting the night time dose for 5 days. But in severe initial infections, this may have to be extended.
In severely immunocompromised patients (e.g. after marrow transplant) or in patients with impaired absorption from the gut, the dose can be doubled to 400 mg (2 tsp) ACICLOVIR 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.
Suppression of herpes simplex infections in immunocompetent patients: 200 mg (1 tsp) should be taken 4 times daily at approximately 6 hour intervals.
Many patients may be conveniently managed on a regimen of 400 mg (2 tsp) twice daily at approximately 12 hour intervals.
Dosage titration down to 200 mg (1 tsp) taken thrice daily at approximately 8 hour intervals or even twice daily at approximately 12 hour intervals, may prove effective.
Therapy should be interrupted periodically at intervals of 6-12 months, in order to observe possible changes in the natural history of the disease.
Prophylaxis of herpes simplex infections in immunocompromised patients: 200 mg (1 tsp) should be taken 4 times daily at approximately 6 hour intervals.
In severely immunocompromised patients (e.g. after marrow transplant) or in patients with impaired absorption from the gut, the dose can be doubled to 400 mg (2 tsp) or alternatively, intravenous dosing could be considered.
The duration of prophylactic administration is determined by the duration of the period at risk.
Treatment of herpes zoster infections: 800 mg (4 tsp) Aciclovir should be taken 5 times daily at approximately 4 hour intervals omitting the night time dose. Treatment should continue for 7 days.
In severely immunocompromised patients 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 rash onset.
Dosage in Children: Treatment of herpes simplex infections, and prophylaxis of herpes simplex infections in the immunocompromised: >2 yrs: should be given adult dosages.
<2 yrs: should be given half the adult dose of Aciclovir.
No specific data are available on the suppression of herpes simplex infections in immunocompetent children.
Treatment of chicken pox in children up to 2 yrs: Aciclovir is administered 20 mg/kg on the basis of body weight 4 times daily for 5 days. Dosing should begin as early as possible after the start of a chicken pox rash, treatment yields better results if initiated within 24 hours after rash onset.
Patients with renal impairment: Treatment of herpes simplex infections: In the management of herpes simplex infections in patients with impaired renal functions, the recommended oral doses will not lead to accumulation of Aciclovir above levels that have been established by intravenous infusion.
For patients with severe renal impairment (creatinine clearance less than 10 mL/minute) an adjustment of dosage to 200 mg (1 tsp) Aciclovir twice daily at approximately 12 hour intervals is recommended.
Treatment of herpes zoster infections: For patients with severe renal impairment (creatinine clearance less than 10 mL/minute) an adjustment of dosage to 800 mg (4 tsp) Aciclovir 3-4 times daily at approximately 6 to 8 hour intervals is recommended.
Dosage in Elderly: In the elderly, total Aciclovir body clearance declined in parallel with creatinine clearance. Adequate hydration of elderly patients taking high oral doses of Aciclovir should be maintained.
Special attention should be given to dosage reduction in elderly patients with impaired renal function. Or as prescribed by a physician.Overdosage
Aciclovir is only partly absorbed in the gastrointestinal tract.
Patients have ingested overdoses of up to 20 grams Aciclovir on a single occasion, usually without toxic effects. Accidental, repeated overdoses of oral Aciclovir over several days have been associated with gastrointestinal effects (such as nausea and vomiting) and neurological effects (headache and confusion).
Overdosage of intravenous Aciclovir has resulted in elevations of serum creatinine, blood urea nitrogen and subsequent renal failure. Neurological effects including confusion, hallucinations, agitation, seizures and coma have been described in association with intravenous overdosage.
Management: patients should be observed closely for signs of toxicity. Haemodialysis significantly enhances the removal of Aciclovir from the blood and may, therefore, be considered a management option in the event of symptomatic overdose.Administration
May be taken with or without food: May be taken w/ meals to reduce GI discomfort.
Contraindications
Aciclovir is contraindicated in patients known to be hypersensitive to the drug.
Warnings
Change to another treatment if the illness and symptoms worsen five days after using Aciclovir. Treatment yields better results if initiated as soon as possible after onset of symptoms.
Special Precautions
Aciclovir is administered cautiously in the following: Patients with renal impairment and infants.
Use In Pregnancy & Lactation
Use in Pregnancy: Administration of Aciclovir produces embryotoxic or teratogenic effects in rats, rabbits or mice. Limited data are available on the use of Aciclovir during pregnancy. Caution should therefore be exercised by balancing the potential benefit of treatment against any possible hazard.
Adverse Reactions
Psychoneurotic: Somnolence and dizziness have occurred.
Renal: There have been reported elevations of BUN and red blood cells in urine precipitation occasionally.
Hematologic: Increasing and reduction of white blood cell, and eosinophilia have occurred.
Hepatic: Abnormal hepatic function test level (Elevation of GOT, GPT, LDH, AL-P, total bilirubin level) has occurred.
Gastrointestinal: Diarrhea, vomiting, nausea, gastrodynia and epigastralgia have occurred in patients given Aciclovir occasionally. In case of this effect, administration is controlled.
Cutaneous toxicity: Rash, blister, erythema and urticaria have occurred occasionally, therefore, administration is controlled cautiously.
General symptom: Fatigue and headache.
Skeletal muscle: Arthralgia.
Others: Elevation of total cholesterol, triglyceride, serum K level.Drug Interactions
Probenecid increases the Aciclovir mean half-life and area under the plasma concentration curve. Other drugs affecting renal physiology could potentially influence the pharmacokinetics of Aciclovir.
Storage
Store at temperatures not exceeding 30°C.
Action
Pharmacology: Pharmacodynamics: Aciclovir is a synthetic purine nucleotide analogue with in vitro and in vivo inhibitory activity against human herpes viruses, including herpes simplex virus (HSV) types I and II and varicella zoster virus (VZV). The inhibitory activity of Aciclovir for HSV I and HSV II and VZV is highly selective. The enzyme thymidine kinase (TK) of normal, uninfected cells does not use Aciclovir effectively as a substrate, hence toxicity to mammalian host cells is low; however, TK encoded by HCV and VZV converts Aciclovir to Aciclovir monophosphate, a nucleoside analogue which is further converted to the diphosphate and finally to the triphosphate by cellular enzymes. Aciclovir triphosphate interferes with the viral DNA polymerase and inhibits viral DNA replication with resultant chain termination following its incorporation into the viral DNA.
Prolonged or repeated courses of Aciclovir in severely immune-compromised individuals may result in the selection of virus strains with reduced sensitivity, which may not respond to continued Aciclovir treatment. Most of the clinical isolates with reduced sensitivity have been relatively deficient in viral TK, however, strains with altered viral TK or viral DNA polymerase have also been reported. In vitro exposure of HSV isolates to Aciclovir can also lead to the emergence of less sensitive strains. The relationship between the in-vitro determined sensitivity of HSV isolates and clinical response to Aciclovir therapy is not clear.
Pharmacokinetics: About 15 to 30% of a dose of Aciclovir given by mouth is considered to be absorbed from the gastrointestinal tract. A dose of 200 mg Aciclovir every 4 hours by mouth is reported to produce maximum and minimum steady-state plasma concentrations of 0.7 and 0.4 mcg per mL respectively; equivalent values following 400 mg doses are 1.2 and 0.6 mcg per mL. Aciclovir crosses the placenta and is excreted in breast milk in concentrations approximately 3 times higher than those in maternal serum.MedsGo Class
Antivirals
Features
- Aciclovir