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Virless
Acyclovir is a synthetic purine nucleoside analogue with in vitro and in
vivo inhibitory activity against human herpes viruses including Herpes
Simplex Types 1 (HSV-1) and 2 (HSV-2), Varicella-Zoster Virus (VZV),
Epstein-Barr virus (EBV), and Cytomegalovirus (CMV). In cell culture,
Acyclovir has the highest antiviral activity against HSV-1, followed in
decreasing order of potency against HSV-2, VZV, EBV and CMV.
Presentation(s)
Virless Tablet 200mg
Each tablet contains: Acyclovir 200mg
Virless Tablet 800mg
Each tablet
contains:
Acyclovir 800mg
Pharmacology (Summary of Pharmacodynamic and Pharmacokinetics)
Acyclovir is preferentially taken up and selectively converted to the active
triphosphate form by Herpes Virus – infected cells. Thus, Acyclovir is much
less toxic in vitro for normal unaffected cells because: (1) less is taken
up; (2) less is converted to the active form; (3) cellular a-DNA polymerase
is less sensitive to the effects of the active form.
Acyclovir is slowly and poorly absorbed from the gastrointestinal tract and
the time to reach peak concentration is 1.5 to 2 hours. With multiple
administration, steady-state plasma concentrations are achieved by the
second day. The estimated bioavailability is 13-21% and appears to
decrease with decreasing dosage. Following oral administration in adult
patients with normal renal function the plasma half-life is 3.3 hours.
It is widely distributed in tissue and body fluids including brain, kidney,
lung, liver, muscle, spleen, uterus, vaginal mucosa, vaginal secretions,
cerebrospinal fluid and herpetic vesicular fluid. Concentration in kidney
and lung were 10 - 13 times plasma concentrations after multiple dose
therapy and 25 - 75% of the plasma level was found in brain, spinal cord and
cerebrospinal fluid. Limited human data shows that Acyclovir passes into
breast milk and levels can be 3 - 4 times higher than in serum.
Renal excretion is the major route of elimination in individuals with normal
renal function. The renal clearance for Acyclovir, which is approximately
three-fold greater than the creatinine clearance, indicates that the drug
removed by tubular secretion as well as glomerular filtration. Acyclovir
persist in the plasma of patients with renal insufficiency and the mean
terminal plasma half-life recorded in patients with end stage renal disease
is 19.5 hours. Acyclovir is readily removed by hemodialysis. As renal
function decreases, a greater percentage of the drug is eliminated by
metabolic conversion to carboxymethoxymethyl guanine.
Indication(s)
1. Infections caused by Varicella-Zoster Virus.
2. Skin and mucous membrane infections due to Herpes Simplex Virus.
3.Prophylaxis of Herpes Simplex infection in patients who are
immunocompromised including those with bone marrow transplant
and leukemia.
4.Suppression of recurrent Herpes Simplex Virus infections.
Dosage and Administration
I. Adult dose:
Treatment of Herpes Simplex Infection:
200mg (400mg in the immunocompromised patient) 5 times daily, usually for 5
days.
Prevention of recurrent Herpes Simplex Infection:
200mg to be taken 4 times daily, or 400mg twice daily, possibly reduced to
200mg 2 or 3 times daily.
Therapy should be interrupted periodically at interval 6 - 12 months in
order to observe possible changes in the nature history of the disease.
Prophylaxis of Herpes Simplex Infection in immunocompromised patients:
200mg to be taken 4 times daily at approximately 6 hours interval. In
situation of severe immunocompromised, eg., after bone marrow
transplantation, or in patients with impaired gastrointestinal absorption,
the dose may be doubled to 400mg.
Treatment of Varicella and Herpes Zoster infection:
800mg, 5 times daily for 7 days.
II. Pediatric Dose:
For treatment of Herpes Simplex Infection and for Prophylaxis of Herpes
Simplex Infection in immunocompromised, children 2 years and over
should be given adult dosage, and children < 2 years should be given half
the adult dose.
For treatment of Varicella Infection,
Children > 6 years : 800mg 4 times a day.
2 - 6 years : 400mg 4 times a day.
Below 2 years : 200mg 4 times a day.
Dosing may be calculated as
20mg/kg body weight ( not to exceed 800mg ), 4 times daily.
Treatment should be continued for 5 days.
No specific data are available on the treatment of Herpes Simplex Infection
in immune-competent children.
III. Dosage in Elderly
Elderly patients are more likely to have an age-related decrease in renal
function, which may required an adjustment of dosage or dosing interval.
IV. Dosage in Renal Impairment
For patient with renal impairment ( creatinine clearance < 10ml/min ), the
dosage should be decreased to 200mg every 12 hours for treatment of Herpes
Simplex Infection, and 800mg twice daily for treatment of Varicella and
Zoster Infection.
Contraindication(s)
Contraindicated in patients who develop hypersensitivity or intolerance to
any of the components of the formulation.
Precaution(s)/Warning(s)
1. Acyclovir should be administered with caution to patients with renal
impairment and doses should be adjusted according to creatinine clearance.
The risk of renal impairment is increased by dehydration and by the
concomitant use of other nephrotoxic drugs.
2. Use in pregnancy and lactation:
Acyclovir crosses placenta, caution should be exercised by balancing the
potential benefits of treatment against any possible hazard.
Acyclovir passes into breast milk at concentration from 0.2 - 4.1 times the
corresponding plasma levels.
Therefore, caution is advised if it is to be administered to a nursing
woman.
Drug Interaction(s)
Probenecid is reported to block the renal clearance of Acyclovir.
Side Effects)/Adverse Reaction(s)
1.Skin rashes, only a few cases reported. The rashes have resolved on
withdrawal of drug.
2.Gastrointestinal effect: nausea, vomiting, abdominal pains.
3. Neurological: occasionally dizziness and hallucination, somnolence.
4.Rises in bilirubin and
liver-related enzyme.
5.lncrease in blood urea and creatinine.
6. Decrease in haematological indices.
Symptoms and Treatment for Overdosage, and Antidote(s)
Since there is no specific antidote, treatment of adverse effects and/or
overdose should be symptomatic and supportive with possible utilization of
the following:
• Adequate hydration to prevention precipitation of Acyclovir in the renal
tubules.
• Hemodialysis to aid in the removal of Acyclovir from the blood, especially
in patients with acute renal failure and anuria.
Shelf-Life
3 years from the date of manufacture.
Storage Condition(s)
Keep in a container. Store at temperature below 30°C. Protect from light and
moisture.
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