Zostravel (Tablets) Instructions for Use

Marketing Authorization Holder

Bright Way, LLC (Russia)

Manufactured By

Velpharm, LLC (Russia)

ATC Code

J05AB01 (Aciclovir)

Active Substance

Aciclovir (Rec.INN registered by WHO)

Dosage Forms

	Zostravel	Tablets 200 mg: 5, 7, 10, 14, 15, 20, 21, 25, 28, 30, 35, 40, 42, 45, 49, 50, 56, 60, 63, 70, 80, 90 or 100 pcs.
		Tablets 400 mg: 5, 7, 10, 14, 15, 20, 21, 25, 28, 30, 35, 40, 42, 45, 49, 50, 56, 60, 63, 70, 80, 90 or 100 pcs.

Dosage Form, Packaging, and Composition

Tablets white or almost white, round, flat-cylindrical, with a bevel and a score.

Excipients : lactose monohydrate, potato starch, magnesium stearate, povidone (low molecular weight medical polyvinylpyrrolidone 12600±2700, Plasdone K-17), sodium carboxymethyl starch (sodium starch glycolate, Primogel).

5 pcs. – contour cell packs – cardboard packs.
5 pcs. – contour cell packs (2) – cardboard packs.
5 pcs. – contour cell packs (3) – cardboard packs.
5 pcs. – contour cell packs (4) – cardboard packs.
5 pcs. – contour cell packs (5) – cardboard packs.
5 pcs. – contour cell packs (6) – cardboard packs.
5 pcs. – contour cell packs (7) – cardboard packs.
5 pcs. – contour cell packs (8) – cardboard packs.
5 pcs. – contour cell packs (9) – cardboard packs.
5 pcs. – contour cell packs (10) – cardboard packs.
7 pcs. – contour cell packs – cardboard packs.
7 pcs. – contour cell packs (2) – cardboard packs.
7 pcs. – contour cell packs (3) – cardboard packs.
7 pcs. – contour cell packs (4) – cardboard packs.
7 pcs. – contour cell packs (5) – cardboard packs.
7 pcs. – contour cell packs (6) – cardboard packs.
7 pcs. – contour cell packs (7) – cardboard packs.
7 pcs. – contour cell packs (8) – cardboard packs.
7 pcs. – contour cell packs (9) – cardboard packs.
7 pcs. – contour cell packs (10) – cardboard packs.
10 pcs. – contour cell packs – cardboard packs.
10 pcs. – contour cell packs (2) – cardboard packs.
10 pcs. – contour cell packs (3) – cardboard packs.
10 pcs. – contour cell packs (4) – cardboard packs.
10 pcs. – contour cell packs (5) – cardboard packs.
10 pcs. – contour cell packs (6) – cardboard packs.
10 pcs. – contour cell packs (7) – cardboard packs.
10 pcs. – contour cell packs (8) – cardboard packs.
10 pcs. – contour cell packs (9) – cardboard packs.
10 pcs. – contour cell packs (10) – cardboard packs.
5 pcs. – jars – cardboard packs.
7 pcs. – jars – cardboard packs.
10 pcs. – jars – cardboard packs.
14 pcs. – jars – cardboard packs.
15 pcs. – jars – cardboard packs.
20 pcs. – jars – cardboard packs.
21 pcs. – jars – cardboard packs.
25 pcs. – jars – cardboard packs.
28 pcs. – jars – cardboard packs.
30 pcs. – jars – cardboard packs.
35 pcs. – jars – cardboard packs.
40 pcs. – jars – cardboard packs.
42 pcs. – jars – cardboard packs.
45 pcs. – jars – cardboard packs.
49 pcs. – jars – cardboard packs.
50 pcs. – jars – cardboard packs.
56 pcs. – jars – cardboard packs.
60 pcs. – jars – cardboard packs.
63 pcs. – jars – cardboard packs.
70 pcs. – jars – cardboard packs.
80 pcs. – jars – cardboard packs.
90 pcs. – jars – cardboard packs.
100 pcs. – jars – cardboard packs.

Tablets white or almost white, biconvex, oval in shape, with a score.

Excipients : lactose monohydrate, potato starch, magnesium stearate, povidone (low molecular weight medical polyvinylpyrrolidone 12600±2700, Plasdone K-17), sodium carboxymethyl starch (sodium starch glycolate, Primogel).

5 pcs. – contour cell packs – cardboard packs.
5 pcs. – contour cell packs (2) – cardboard packs.
5 pcs. – contour cell packs (3) – cardboard packs.
5 pcs. – contour cell packs (4) – cardboard packs.
5 pcs. – contour cell packs (5) – cardboard packs.
5 pcs. – contour cell packs (6) – cardboard packs.
5 pcs. – contour cell packs (7) – cardboard packs.
5 pcs. – contour cell packs (8) – cardboard packs.
5 pcs. – contour cell packs (9) – cardboard packs.
5 pcs. – contour cell packs (10) – cardboard packs.
7 pcs. – contour cell packs – cardboard packs.
7 pcs. – contour cell packs (2) – cardboard packs.
7 pcs. – contour cell packs (3) – cardboard packs.
7 pcs. – contour cell packs (4) – cardboard packs.
7 pcs. – contour cell packs (5) – cardboard packs.
7 pcs. – contour cell packs (6) – cardboard packs.
7 pcs. – contour cell packs (7) – cardboard packs.
7 pcs. – contour cell packs (8) – cardboard packs.
7 pcs. – contour cell packs (9) – cardboard packs.
7 pcs. – contour cell packs (10) – cardboard packs.
10 pcs. – contour cell packs – cardboard packs.
10 pcs. – contour cell packs (2) – cardboard packs.
10 pcs. – contour cell packs (3) – cardboard packs.
10 pcs. – contour cell packs (4) – cardboard packs.
10 pcs. – contour cell packs (5) – cardboard packs.
10 pcs. – contour cell packs (6) – cardboard packs.
10 pcs. – contour cell packs (7) – cardboard packs.
10 pcs. – contour cell packs (8) – cardboard packs.
10 pcs. – contour cell packs (9) – cardboard packs.
10 pcs. – contour cell packs (10) – cardboard packs.
5 pcs. – jars – cardboard packs.
7 pcs. – jars – cardboard packs.
10 pcs. – jars – cardboard packs.
14 pcs. – jars – cardboard packs.
15 pcs. – jars – cardboard packs.
20 pcs. – jars – cardboard packs.
21 pcs. – jars – cardboard packs.
25 pcs. – jars – cardboard packs.
28 pcs. – jars – cardboard packs.
30 pcs. – jars – cardboard packs.
35 pcs. – jars – cardboard packs.
40 pcs. – jars – cardboard packs.
42 pcs. – jars – cardboard packs.
45 pcs. – jars – cardboard packs.
49 pcs. – jars – cardboard packs.
50 pcs. – jars – cardboard packs.
56 pcs. – jars – cardboard packs.
60 pcs. – jars – cardboard packs.
63 pcs. – jars – cardboard packs.
70 pcs. – jars – cardboard packs.
80 pcs. – jars – cardboard packs.
90 pcs. – jars – cardboard packs.
100 pcs. – jars – cardboard packs.

Clinical-Pharmacological Group

Antiviral drug

Pharmacotherapeutic Group

Systemic antiviral agents; direct-acting antiviral agents; nucleosides and nucleotides, excluding reverse transcriptase inhibitors

Pharmacological Action

An antiviral agent, a synthetic analogue of a purine nucleoside.

It has the ability to inhibit in vitro and in vivo Herpes simplex virus types 1 and 2, Varicella zoster virus, Epstein-Barr virus, and cytomegalovirus. In cell culture, Aciclovir has the most pronounced antiviral activity against Herpes simplex virus type 1, followed in descending order of activity by: Herpes type 2 virus, Varicella zoster virus, Epstein-Barr virus, and cytomegalovirus. The inhibitory effect of acyclovir on these viruses is characterized by high selectivity.

Aciclovir is not a substrate for the thymidine kinase enzyme of uninfected cells, therefore Aciclovir has low toxicity to mammalian cells. The high selectivity of action and low toxicity for humans are due to the absence of the necessary enzyme for the formation of acyclovir triphosphate in intact cells of the macroorganism.

Thymidine kinase of cells infected with Herpes simplex viruses types 1 and 2, Varicella zoster virus, Epstein-Barr virus or cytomegalovirus converts Aciclovir into Aciclovir monophosphate – a nucleoside analogue, which is then sequentially converted into diphosphate and triphosphate under the action of cellular enzymes. Acyclovir triphosphate is incorporated into the viral DNA chain and blocks its synthesis through competitive inhibition of viral DNA polymerase. Thus, “defective” viral DNA is formed, which leads to the suppression of the replication of new generations of viruses.

Pharmacokinetics

Aciclovir is only partially absorbed from the intestine. After taking 200 mg of acyclovir every 4 hours, the average C_ss,max was 0.7 µg/ml, and the average C_ss,min was 0.4 µg/ml. Aciclovir binds to plasma proteins to a small extent (9-33%). The concentration of acyclovir in the cerebrospinal fluid is approximately 50% of the concentration in plasma. In adults after oral administration of acyclovir, T_1/2 from plasma is about 3 hours. Most of the drug is excreted unchanged in the urine. The renal clearance of acyclovir significantly exceeds the creatinine clearance, which indicates that acyclovir is excreted not only by glomerular filtration but also by tubular secretion. 9-carboxymethoxymethylguanine is the main metabolite of acyclovir and accounts for about 10-15% of the dose excreted in the urine.

Indications

Treatment of infections of the skin and mucous membranes caused by Herpes simplex virus types 1 and 2, including primary and recurrent genital herpes; prevention of recurrences of infections caused by Herpes simplex virus types 1 and 2 in patients with normal immune status; prevention of infections caused by Herpes simplex virus types 1 and 2 in immunodeficient patients; treatment of chickenpox and herpes zoster (early treatment of herpes zoster with acyclovir has an analgesic effect and may reduce the incidence of postherpetic neuralgia).

ICD codes

Dosage Regimen

Administer orally with a full glass of water.

Adjust the dosage regimen based on the specific diagnosis, clinical severity, and patient age.

For treatment of herpes simplex infections in adults, administer 200 mg five times daily at approximately 4-hour intervals, omitting the night-time dose.

Continue treatment for 5 days; for severe primary infections or immunocompromised patients, extend the treatment course as directed.

For prophylaxis of recurrent herpes simplex in immunocompetent adults, administer 400 mg twice daily.

Re-evaluate prophylaxis therapy at 6-12 month intervals.

For herpes zoster (shingles) treatment in adults, administer 800 mg five times daily for 7-10 days.

Initiate zoster treatment at the earliest sign or symptom for maximum efficacy.

For chickenpox treatment in adults and children over 6 years, administer 20 mg/kg per dose (up to 800 mg) four times daily for 5 days.

For children aged 2 to 5 years, administer 400 mg four times daily for chickenpox.

This medication is contraindicated for children under 3 years of age.

For all patients, initiate therapy as early as possible following the onset of signs and symptoms.

In patients with renal impairment, adjust the dosing interval according to creatinine clearance.

For creatinine clearance 10-25 mL/min, administer the standard dose every 12 hours.

For creatinine clearance less than 10 mL/min, administer the standard dose every 24 hours.

For hemodialysis patients, administer a standard dose after each dialysis session.

Ensure adequate hydration, particularly during high-dose therapy, to prevent precipitation in renal tubules.

For elderly patients, assess renal function prior to initiation and adjust dose accordingly.

Adverse Reactions

From the immune system rarely – anaphylaxis.

From the hematopoietic system very rarely – anemia, leukopenia, thrombocytopenia.

From the nervous system frequently – headache, dizziness; very rarely – agitation, confusion, tremor, ataxia, dysarthria, hallucinations, psychotic symptoms, convulsions, drowsiness, encephalopathy, coma.

From the respiratory system rarely – dyspnea.

From the digestive system frequently – nausea, vomiting, diarrhea, abdominal pain.

From the liver and biliary tract rarely – transient increase in blood bilirubin concentration and activity of liver enzymes; very rarely – hepatitis, jaundice.

From the urinary system rarely – increased plasma urea, creatinine concentration; very rarely – acute renal failure, renal colic.

From the skin and subcutaneous tissues frequently – itching, rash, incl. photosensitivity; infrequently – urticaria, rapid diffuse hair loss; rarely – angioedema; very rarely – toxic epidermal necrolysis, multiform exudative erythema, incl. Stevens-Johnson syndrome.

Other frequently – fever, fatigue.

Contraindications

Hypersensitivity to acyclovir or valacyclovir; children under 3 years of age.

With caution pregnancy, breastfeeding period, elderly age, renal failure, dehydration, simultaneous use with other nephrotoxic drugs.

Use in Pregnancy and Lactation

Caution should be exercised when prescribing acyclovir to women during pregnancy and breastfeeding, and the intended benefit to the mother and the possible risk to the fetus or child should be assessed.

Use in Renal Impairment

Aciclovir should be prescribed with caution in renal failure.

Pediatric Use

Contraindicated for use in children under 3 years of age.

Geriatric Use

The likelihood of renal failure in elderly patients should be taken into account; doses should be adjusted according to the degree of renal failure.

Special Precautions

The risk of developing renal failure increases with simultaneous use with other nephrotoxic drugs.

Patients taking Aciclovir in high doses should receive sufficient fluids.

Since Aciclovir is excreted in the urine, doses should be reduced for patients with renal failure. In elderly patients, renal function may be reduced, therefore, for this group of patients, a dose reduction may also be required. Both elderly patients and patients with impaired renal function are at increased risk of developing side effects from the nervous system and, accordingly, should be under close medical supervision.

Long-term or repeated courses of acyclovir treatment in patients with severe immunodeficiency may lead to the emergence of virus strains with reduced sensitivity to acyclovir, which will not respond to continued acyclovir therapy.

Drug Interactions

Aciclovir is excreted unchanged in the urine by active tubular secretion. All drugs with a similar route of excretion may increase the plasma concentration of acyclovir.

Aciclovir increases the AUC of theophylline by approximately 50% when taken simultaneously, so it is recommended to measure plasma theophylline concentrations when acyclovir is co-administered.

Probenecid and cimetidine increase the AUC of acyclovir and reduce its renal clearance.

An increase in the plasma AUC for acyclovir and the inactive metabolite of mycophenolate mofetil was observed with the simultaneous use of both drugs.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.