VIRAVAL – 500

For the use of a registered medical practitioner, a Hospital or laboratory only.

COMPOSITION:

• Each film coated tablet contains:
• Valacyclovir Hydrochloride U.S.P  equivalent to 500mg Valacyclovir.

CLINICAL PHARMACOLOGY:
Valacyclovir is a prodrug, an esterified version of acyclovir that has greater oral bioavailability (about 55%) than acyclovir (10-20%). It is converted by esterases to the active drug acyclovir, as well as the amino acid valine, via hepatic first-pass metabolism. Acyclovir is selectively converted into a monophosphate form by viral thymidine kinase, which is far more effective (3000 times) in phosphorylation than cellular thymidine kinase. Subsequently, the monophosphate form is further phosphorylated into the active triphosphate form, aciclo-GTP, by cellular kinases. Aciclo-GTP is a very potent inhibitor of viral DNA polymerase; it has approximately 100 times higher affinity to viral than cellular polymerase. Its monophosphate form also incorporates into the viral DNA, resulting in chain termination.

It has also been shown that the viral enzymes cannot remove aciclo-GMP from the chain, which results in inhibition of further activity of DNA polymerase. Aciclo-GTP is fairly rapidly metabolised within the cell, possibly by cellular phosphatases.

PHARMACOKINETICS:
Absorption:
Valacyclovir is rapidly absorbed in the gastrointestinal tract; it is then converted to the active compound, acyclovir, by first-pass intestinal and hepatic metabolism. Administration of valacyclovir with food was not found to alter the bioavailability     of acyclovir.
The bioavailability of acyclovir following oral administration of valacyclovir is approximately 54%, which is three to five times greater than its bioavailability following oral administration of acyclovir.

Distribution:
Acyclovir is widely distributed to tissues and body fluids, including brain, kidneys, lungs, liver, aqueous humor, tears, intestines, muscle, spleen, breast milk, uterus, vaginal mucosa, vaginal secretions, semen, amniotic fluid, cerebrospinal fluid (CSF), and vesicular fluid. Highest concentrations are found in the kidneys, liver, and intestines. In addition, acyclovir crosses the placenta.

Elimination:
Less than 1% of valacyclovir is recovered unchanged in the urine over 24 hours.

INDICATIONS:
Valacyclovir is an antiviral agent used in the treatment of shingles (herpes zoster) or genital herpes. This medication may also be used for cold sores (herpes simplex).

Adult Patients:

• Cold Sores (Herpes Labialis): Valacyclovir is indicated for treatment of cold sores (herpes labialis).
• Genital Herpes: Initial Episode: Valacyclovir is indicated for treatment of the initial episode of genital herpes in immune competent adults.
• Recurrent Episodes: Valacyclovir is indicated for treatment of recurrent episodes of genital herpes in immune competent adults. Suppressive Therapy: Valacyclovir is indicated for chronic suppressive therapy of recurrent episodes of genital herpes in immune competent and in HIV-infected adults.
• Reduction of Transmission: Valacyclovir is indicated for the reduction of transmission of genital herpes in immune competent adults.
• Herpes Zoster: Valacyclovir is indicated for the treatment of herpes zoster (shingles) in immune competent adults.

Pediatric Patients:

• Cold Sores (Herpes Labialis): Valacyclovir is indicated for the treatment of cold sores (herpes labialis) in paediatric patients’ = 12 years of age.
• Chickenpox: Valacyclovir is indicated for the treatment of chickenpox in immune competent paediatric patients 2 to < 18 years of age.

DOSAGE AND ADMINISTRATION:

• Treatment of herpes zoster:
• The dosage in adults is 1000mg of valacyclovir to be taken three times a day for 7 days.
• Treatment of herpes simplex infection:
• The dosage in adults is 500mg of valacyclovir to be taken twice daily. For recurrent episodes, treatment should be for 3 or 5 days. For initial episodes, which can be more severe, treatment may have to be extended from 5 to 10 days. Dosing should begin as early as possible. For recurrent episodes of herpes simplex, this should be ideally during the prodromal period or immediately the first sign or symptoms appear. Alternatively, for herpes liabialis (cold sore), valacyclovir 2g twice daily for 1 day is effective treatment. The second dose should be taken about 12 hours (no sooner than 6 hours) after the first dose. When using this dosing regimen, treatment should not exceed one day, since this has shown not to provide additional clinical benefit. Therapy should be initiated at the earliest symptom of a cold sore (e.g tingling, itching or burning).
• Prevention (suppression) of recurrences of herpes simplex infections:
• In immune competent adult patients, 500mg of valacyclovir to be taken once daily. Some patients with very frequent recurrences (e.g. 10 or more per day) may gain additional benefit from the daily dose of 500mg being taken as a divided dose (250mg twice daily).
• For immune compromised patients the dose is 500mg twice daily.
• Reduction of transmission of genital herpes:
• In immuno competent heterosexual adults with 9 or fewer recurrences per year 500mg of valacyclovir to be taken once daily by the infected partner.
• Prophylaxis of cytomegalovirus infection (CMV) and disease:
• Dosage in adults and adolescents (from 12 years of age).
• The dosage of 2g four times daily is recommended for prophylaxis of cytomegalovirus infection in renal transplant recipient; prophylaxis should begin within 72 hours and is usually continued for 90 days.

Dosage of renal impairment:

• Herpes zoster treatment and herpes simplex treatment, prevention (suppression) and reduction of transmission.
• In patients of haemodialysis, valacyclovir recommended for patients with creatinine clearance of less than 15ml/ min should be used.
• This should be administered after haemodialysis has been performed.
• CMV Prophylaxis: The dose should be adjusted in patients with impaired renal function
• The creatinine clearance should be cleared frequently, especially during periods when renal clearance is changing rapidly e.g. immediately after transplantation or engraftment. The dosage should be adjusted accordingly.

Dosage in hepatic impairment:
Dose modification is not required in patients with mild or moderate cirrhosis; patients with advanced cirrhosis need dosage adjustment.

DOSAGE IN CHILDREN:

• Cold Sores (Herpes Labialis): The recommended dosage of Valacyclovir for the treatment of cold sores in paediatric patients 12 years of age is 2 grams twice daily for 1 day taken 12 hours apart. Therapy should be initiated at the earliest symptom of a cold sore (e.g., tingling, itching, or burning).
• Chickenpox: The recommended dosage of Valacyclovir for treatment of chickenpox in immunocompetent paediatric patients 2 to < 18 years of age is 20 mg/kg administered 3 times daily for 5 days. The total dose should not exceed 1 gram 3 times daily. Therapy should be initiated at the earliest sign or symptoms.
• Dosage in the elderly :Dosage modification is not required unless renal function is significantly impaired.

CONTRAINDICATIONS:
Valacyclovir is contra-indicated in patients known to be hypersensitive to valacyclovir, acyclovir or any of the components in the product.

SIDE EFFECTS:
Nausea, vomiting, headache, loss of appetite, weakness, stomach pain, or dizziness may occur the first several days as your body adjusts to the medication. If any of these effects continue or become bothersome, inform your doctor.

PRECAUTION:

• Hydration status: Care should be taken to ensure adequate fluid intake with patients who are at risk of dehydration, particularly the elderly.
• Use in renal impairment: Dosage should be adjusted in patients with renal impairment. Patients with history of renal impairment are at great risk of developing neurological effects.
• Use in genital herpes: Does not cure genital herpes completely but eliminate the risk of transmission. In addition to the therapy it is recommended that patient use safer sex practices.

DRUG INTERACTION:

• Valacyclovir   can potentially interact with many drugs which include: Cimetidine, Probenecid and Tenofovir.
• Taking any of the above medication together with valacyclovir increases the level of valacyclovir in your blood by increasing AUC and reduces acyclovir renal clearance. For most people, this interaction will not cause any problems, and the doses of these medications do not need to be adjusted.

OVERDOSAGE:    
Caution should be exercised to prevent inadvertent overdose. Precipitation of acyclovir in renal tubules may occur when the solubility (2.5 mg/ml) is exceeded in the intra tubular fluid. The patient may benefit from hemodialysis until renal function is restored.

PRESENTATION:
Blister packs of 10`s in unit boxes.
STORAGE: Do not store above 30oC.Store in a dry place. Protect from direct sunlight. Keep all medicines away from children.
LEGAL CATEGORY: Prescription only medicine (P.O.M).