Medovir (Powder) Instructions for Use

Marketing Authorization Holder

Medochemie, Ltd. (Cyprus)

Manufactured By

Laboratorio Italiano Biochimico Farmaceutico Lisapharma, S.p.A. (Italy)

ATC Code

J05AB01 (Aciclovir)

Active Substance

Aciclovir (Rec.INN registered by WHO)

Dosage Form

Medovir

Powder for solution for infusion 250 mg: fl. 10 pcs.

Dosage Form, Packaging, and Composition

Powder for solution for infusion from white to almost white, hygroscopic.

250 mg – vials of colorless glass (10) – cardboard packs.

Clinical-Pharmacological Group

Antiviral drug

Pharmacotherapeutic Group

Antiviral agent

Pharmacological Action

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 virus type 2, 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 for 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 virus 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 widely distributed in body tissues and fluids. Plasma protein binding is 9-33%. The concentration in the cerebrospinal fluid is about 50% of the corresponding concentration in the blood plasma at equilibrium. In adults after IV administration, the terminal T_1/2 is about 2.9 hours. In newborns (from 0 to 3 months) when acyclovir is administered at a dose of 10 mg/kg as a 1-hour infusion every 8 hours, the terminal T_1/2 is about 3.8 hours. It is excreted primarily unchanged in the urine. The only known metabolite in urine is 9-[(carboxymethoxy)methyl]guanine, which accounts for 10-15% of the dose excreted in the urine.

Indications

Treatment of infections caused by Herpes simplex virus types 1 and 2; prevention of infections caused by Herpes simplex virus types 1 and 2 in immunocompromised patients; treatment of infections caused by Varicella zoster virus, including chickenpox and herpes zoster; treatment of infections caused by Herpes simplex virus types 1 and 2 in newborns; prevention of cytomegalovirus infection in bone marrow transplant recipients.

ICD codes

Dosage Regimen

Administer as a slow intravenous infusion over at least one hour to prevent renal tubular damage.

For Herpes simplex virus infections in immunocompromised adults, administer 5 mg/kg every 8 hours (15 mg/kg/day).

For Herpes simplex encephalitis in adults, administer 10 mg/kg every 8 hours (30 mg/kg/day).

For Varicella-zoster virus infections in immunocompromised adults, administer 10 mg/kg every 8 hours (30 mg/kg/day).

For prophylaxis of cytomegalovirus infection post-bone marrow transplant, administer 500 mg/m² every 8 hours.

For neonates (0-3 months) with Herpes simplex infections, administer 10 mg/kg every 8 hours.

For pediatric patients over 3 months, use the adult dosing regimen of 250 mg/m² every 8 hours for Herpes simplex or 500 mg/m² every 8 hours for severe Varicella-zoster.

Adjust dosage for renal impairment based on creatinine clearance. For CrCl >50 mL/min, use standard dosing every 8 hours.

For CrCl 25-50 mL/min, administer standard dose every 12 hours. For CrCl 10-25 mL/min, administer standard dose every 24 hours.

For CrCl <10 mL/min, administer 50% of the standard dose every 24 hours.

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

Reconstitute the 250 mg vial with 10 mL of Water for Injections or Sodium Chloride 0.9% to yield a concentration of 25 mg/mL.

Further dilute the reconstituted solution in at least 50 mL of compatible infusion fluid such as Sodium Chloride 0.9% or 0.45%, or Glucose 5%.

Do not administer as a bolus injection or intramuscularly. Maintain adequate patient hydration during infusion.

The usual treatment duration is 5-10 days, but may be extended for severe or disseminated infections.

Adverse Reactions

From the hematopoietic system infrequently – anemia, leukopenia, thrombocytopenia.

From the immune system very rarely – anaphylaxis.

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

From the cardiovascular system frequently – phlebitis.

From the respiratory system very rarely – dyspnea.

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

From the liver: frequently – transient increase in the activity of hepatic transaminases; very rarely – transient increase in bilirubin concentration, jaundice, hepatitis.

From the skin and subcutaneous tissues frequently – itching, urticaria, rash (including photosensitivity); very rarely – angioedema.

From the urinary system frequently – increased blood urea and creatinine concentration; very rarely – renal function impairment, acute renal failure, renal colic.

Other very rarely – general weakness, fever, local inflammatory reactions. When acyclovir was accidentally administered into the extracellular space during IV infusion, severe local inflammatory reactions were detected, which can lead to destructive skin changes.

Contraindications

Hypersensitivity to acyclovir, valacyclovir.

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

Use in Pregnancy and Lactation

Use during pregnancy is possible only in cases where the intended benefit to the mother outweighs the potential risk to the fetus.

Caution should be exercised when using acyclovir in nursing women.

Use in Renal Impairment

Aciclovir should be prescribed with caution to patients with renal failure.

Pediatric Use

Use in children is possible strictly according to indications, in doses and regimens recommended according to age.

Geriatric Use

The likelihood of impaired renal function in elderly patients should be taken into account; the dose should be adjusted according to the degree of renal impairment.

Special Precautions

Adequate hydration should be maintained in patients receiving Aciclovir intravenously.

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

Aciclovir is excreted in the urine, therefore, reduced doses of acyclovir should be used in patients with impaired renal function. In elderly patients, renal function may be reduced, so the need to reduce the dose of acyclovir for this group of patients should be assessed. Both in elderly patients and in patients with impaired renal function, the risk of adverse reactions from the central nervous system increases, so such patients should be under careful medical supervision for the timely detection of relevant symptoms.

In patients receiving higher doses of acyclovir (for example, for herpes encephalitis), renal function should be carefully monitored, especially against the background of dehydration or pre-existing renal impairment.

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

Caution should be exercised when co-administering with drugs that compete with acyclovir for the elimination pathway, due to the possible increase in plasma concentration of one or both drugs, or their metabolites.

An increase in the AUC of acyclovir and the inactive metabolite of mycophenolate mofetil – an immunosuppressive agent used in patients after transplantation – was observed with the simultaneous use of medicinal products containing these substances.

Caution is required (and monitoring of changes in renal function should be carried out) during IV infusion of acyclovir together with drugs that affect other aspects of renal physiology (for example, cyclosporine, tacrolimus).

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.