(Acyclovir USP 200mg / Tablet)
COMPOSITION:
Each tablet contains 200mg of the active ingredient, Acyclovir USP.
CLINICAL PHARMACOLOGY
Acyclovir is a pharmacologically inactive guanosine analogue that only becomes virustatic agent after penetrating into a cell infected by herpes simplex virus or varicella zooster virus.
Acyclovir preferentially penetrates into cells infected with the herpes virus. The enzyme thymidine kinase of these cells converts acyclovir to acyclovir monophosphate. Cellular enzymes further convert acyclovir monophosphate to the virustatic agent acyclovir triphosphate.
The affinity of acyclovir triphosphate to viral DNA polymerase is 10 to 30 times higher than its affinity to cellular DNA polymerase. It thus selectively inhibits viral enzyme activity.
PHARAMACOKINETICS
Acyclovir is only partly absorbed from the gastrointestinal tract. Mean steady state peak plasma levels following repeated oral administration of 200mg, 400mg and 800mg acyclovir every four hours (five times per day ) were 3.02± 0.5µmol/L (`200mg), 5.21±1.32 µmol / L (400mg ) and 8.16± 1.98µmol/L (800mg), respectively.
The distribution volume in adults (steady state) is 50± 8.7L / 1.73m2, in new-born and infants up to three months is 28.8± 9.3L /1.73m2. Protein binding ranged between 9% and 33%. In patients with normal renal function Acyclovir is renally eliminated as unchanged drug (62 – 91%) and as 9 – carboxymethoxymethyl-guanine (10 – 15%).
In patients suffering from chronic renal insufficiency, average plasma half-life is about 19.5 hours. Mean plasma half-life during haemodialysis is 5.7 hours. During haemodialysis a decrease of Acyclovir plasma levels of about 60% occurs.
INDICATIONS AND USAGE
Acyclovir is used for the treatment of initial and prophylaxis of recurrent mucosal and cutaneous herpes simplex (HSV -1 and HSV- 2) infections, herpes simplex encephalitis, herpes zoster, genital herpes infections, varicella-zooster infections in healthy, nonpregnant persons > 13 years of age, children >12months of age who have a chronic skin or lung disorder and immunocompromised patients.
CONTRAINDICATIONS:
Acyclovir tablets should not be given to patients with hypersensitivity to acyclovir. There are no adequate studies concerning the prophylactic use of acyclovir tablets in patients with renal impairment or anuria and acyclovir should not be used in these patients.
INTERACTIONS:
Probenecid has been shown to reduce the renal clearance of acyclovir by approximately 30% resulting in an increase of its mean elimination half life. Overwhelming fatigue has been associated with the use of acyclovir and zidovudine.
WARNINGS:
PREGNANCY
There is little experience with oral administration of acyclovir during pregnancy. The use of Acyclovir tablets in women who are, or may become pregnant requires that an expected benefit is weighed against the possible risks, particularly in the first trimester. Systemic administration (oral and intravenous administration) of acyclovir during the second and third trimester of pregnancy has been described in at least 72 cases without any harm to the foetus.
LACTATION
After oral administration of 200mg acyclovir, five times daily, acyclovir concentrations found in breast milk were 0.6 – 4.1 times the corresponding acyclovir plasma concentrations.
The infant would then receive up to 0.3 mg /kg/day.
Mothers should stop breastfeeding during treatment with Acyclovir tablets.
KEEP OUT OF THE REACH OF CHILDREN
PRECAUTIONS
Acyclovir should be administered with caution to patients with renal impairment and doses should be adjusted according to creatinine clearance.
ADVERSE REACTIONS
Gastrointestinal disorders such as nausea, vomiting, diarrhea and abdominal pain.
Occasionally: Neurological reactions such as vertigo confusion and hallucinations. The side effects disappear after cessation of therapy and are usually observed in patients suffering from renal impairment or other diseases favouring the occurrence of these side effects.
SYMPTOMS OF OVERDOSE AND ANTIDOTE:
Symptoms include seizures, confusion, elevated serum creatinine, and renal failure. In the event of an overdose, sufficient urine flow must be maintained to avoid drug precipitation within the renal tubules. Haemodialysis has resulted in up to 60% reductions in serum acyclovir levels.
DOSAGE ADMINISTRATION
DOSAGE
Adults
Genital herpes infections
Initial therapy: Oral, 200 mg 5 times a day for 10 days.
-Creatinine clearance > 10 ml/min : Oral, 200 mg 5 times a day for 10 days.
-Creatinine clearance 0- 10 ml/min: Oral, 200 mg 5 twice a day for 10 days.
Intermittent therapy: Oral, 200 mg 5 times a day for 5 days.
-Creatinine clearance > 10 ml/min : Oral, 200 mg 5 times a day for 5 days.
-Creatinine clearance 0- 10 ml/min: Oral, 200 mg 5 twice a day for 5 days.
Chronic suppressive therapy: Oral, 400 mg twice a day; or 200 mg
2 to 5 times a days.
-Creatinine clearance > 10 ml/min : Oral, 400 mg twice a day.
-Creatinine clearance 0- 10 ml/min: Oral, 200 mg twice a day.
Herpes zoster
Oral, 800 mg 5 times a day for 7 to 10 days.s
Creatinine clearance > 25ml/min, 800mg 5times a day for 7 to 10 days.
Creatinine clearance 10-25ml/min, 800 mg 5 times a day for 7 to 10 days.
Creatinine clearance 0-10 ml/min, 800 mg twice a day for 7 to 10 days.
Varicella
Oral, 20 mg per kg of body weight, up to 800 mg per dose, 4 times a day for 5 days. Treatment should be initiated at the earliest sign or symptoms of chickenpox
Herpes Simplex
Oral, 200 to 400 mg 5 times a day for 10 days in immunocompromised patients.
Pediatrics
Children < 2 years: Dosage has not been established in children up to 2 years of age. However, no unusual toxicity or pediatric-specific problems have been observed in studies done in children using doses of up to 3000mg/m2/day and 80 mg/kg/day.
Children 2 to 12 years : Varicella: Oral 20 mg per kg of body weight, up to 800mg per dose, 4 times a day for 5 days. Treatment should be initiated at the earliest sign or symptoms of chickenpox
NOTE:
– For herpes zoster: Acyclovir should be started within 72 hours of the appearance of the
rash to be effective.
– Patients suffering from renal impairment (particularly elderly patients) should drink sufficient quantities of fluid during treatment with acyclovir tablets.
PRESENTATION
Acyclovir tablets are presented as a 200mg tablet in a blister of 5×10’s per pack.
STORAGE CONDITION
Store below 250C. Protect from light.
Manufactured by:
DRUGFIELD PHARMACEUTICALS LIMITED
Lynson Chemical Avenue
Km 38, Lagos-Abeokuta Expressway
Sango-Ota, Ogun State, Nigeria.