Orvirem^® (Syrup) Instructions for Use

Marketing Authorization Holder

Zentiva Pharma LLC (Russia)

Manufactured By

Pharmstandard-Lexredstva OJSC (Russia)

ATC Code

J05AC02 (Rimantadine)

Active Substance

Rimantadine (Rec.INN WHO registered)

Dosage Form

Orvirem®

Syrup for children 2 mg/1 ml: 100 ml bottle

Dosage Form, Packaging, and Composition

Syrup for children as a thick liquid of pink or light red color.

Excipients: sucrose (white sugar) – 770 mg, sodium alginate – 3.2 mg, dye azorubine (E122) (carmoisine) – 0.013 mg, purified water – up to 1 ml.

100 ml – dark glass bottles (1) – cardboard packs.

Clinical-Pharmacological Group

Antiviral drug

Pharmacotherapeutic Group

Systemic antiviral agent; direct-acting antiviral agent; cyclic amines

Pharmacological Action

Antiviral agent, an adamantane derivative; active against various strains of influenza A virus (especially type A₂). The polymeric structure provides long-term circulation of rimantadine in the body, which allows its use not only for therapeutic but also for prophylactic purposes.

It suppresses the early stage of specific reproduction (after the virus enters the cell and before initial RNA transcription).

Being a weak base, Rimantadine acts by increasing the pH of endosomes – membrane-bound vacuoles that surround viral particles after they enter the cell.

Preventing acidification in these vacuoles blocks the fusion of the viral envelope with the endosome membrane, thus preventing the transfer of viral genetic material into the cell cytoplasm.

Rimantadine also inhibits the release of viral particles from the cell, i.e., interrupts the transcription of the viral genome.

Pharmacokinetics

After oral administration, it is slowly, almost completely absorbed in the intestine.

Plasma protein binding is about 40%.

V_d in adults is 17-25 l/kg, in children – 289 l.

The concentration in nasal secretion is 50% higher than plasma concentration.

The C_max value when taking 100 mg once/day is 181 ng/ml, when taking 100 mg twice/day is 416 ng/ml.

It is metabolized in the liver.

T_1/2 is 24-36 hours; it is excreted by the kidneys (15% unchanged, 20% as hydroxyl metabolites).

Indications

Early treatment and prevention of influenza A in adults and children (depending on the dosage form).

ICD codes

Dosage Regimen

Administer Orvirem^® syrup orally after meals.

For treatment of influenza type A, initiate therapy within 24-48 hours of symptom onset.

For children aged 1 to 3 years: give 10 ml (20 mg) three times on the first day. On the second and third days: give 10 ml twice daily. On the fourth day: give 10 ml once.

For children aged 3 to 7 years: give 15 ml (30 mg) three times on the first day. On the second and third days: give 15 ml twice daily. On the fourth day: give 15 ml once.

For children aged 7 to 14 years: give 20 ml (40 mg) three times on the first day. On the second and third days: give 20 ml twice daily. On the fourth day: give 20 ml once.

The total treatment course is 4 days.

For prophylaxis of influenza type A, administer once daily for 10-15 days.

For children aged 1 to 3 years: give 10 ml (20 mg) once daily.

For children aged 3 to 7 years: give 15 ml (30 mg) once daily.

For children aged 7 to 14 years: give 20 ml (40 mg) once daily.

For post-exposure prophylaxis, administer for 10 days. For seasonal prophylaxis during an epidemic, administer for up to 15 days.

Use the supplied measuring spoon for accurate dosing. Shake the bottle well before each use.

Do not exceed the recommended daily dose or duration of therapy.

Adverse Reactions

From the cardiovascular system tachycardia, heart failure, heart block, palpitations, arterial hypertension, cerebrovascular accident, loss of consciousness.

From the nervous system: insomnia, dizziness, headache, irritability, feeling of fatigue, impaired concentration, movement disorders, drowsiness, depressed mood, euphoria, hyperkinesia, tremor, hallucinations, confusion, convulsions.

From the sensory organs tinnitus, change or loss of smell.

From the respiratory system: shortness of breath, bronchospasm, cough.

From the digestive system: nausea, vomiting, loss of appetite, dry oral mucosa, abdominal pain, diarrhea, dyspepsia.

From the skin and subcutaneous tissues: rash.

Other allergic reactions.

Contraindications

Hypersensitivity to rimantadine; acute liver diseases, acute and chronic kidney diseases, thyrotoxicosis; pregnancy, breastfeeding period; childhood – depending on the dosage form used.

With caution in arterial hypertension, epilepsy (including in history), cerebral atherosclerosis, in hepatic insufficiency, in gastrointestinal diseases; in elderly patients.

Use in Pregnancy and Lactation

Contraindicated for use during pregnancy. If it is necessary to use during lactation, the issue of discontinuing breastfeeding should be decided.

Use in Hepatic Impairment

Contraindicated in acute liver diseases.

Use in Renal Impairment

Contraindicated in acute and chronic kidney diseases.

Pediatric Use

It is possible to use in children of the appropriate age categories strictly according to the indications, in recommended doses and dosage forms. It is necessary to strictly follow the instructions in the rimantadine drug leaflets regarding contraindications for the use of specific rimantadine dosage forms in children of different ages.

Geriatric Use

In elderly patients with arterial hypertension, the risk of hemorrhagic stroke increases.

Special Precautions

When using rimantadine, an exacerbation of chronic concomitant diseases is possible.

In elderly patients with arterial hypertension, the risk of hemorrhagic stroke increases.

If there is a history of epilepsy and anticonvulsant therapy, the risk of an epileptic seizure increases while using rimantadine.

In such cases, Rimantadine is used at a dose of up to 100 mg/day simultaneously with anticonvulsant therapy.

Prophylactic use is effective in case of contact with sick people, when the infection spreads in closed groups, and when there is a high risk of disease during an influenza epidemic.

The appearance of viruses resistant to the drug is possible.

The appearance of viruses resistant to rimantadine is possible.

In influenza caused by virus B, Rimantadine has an antitoxic effect.

Influence on the ability to drive vehicles and mechanisms

Patients who experience dizziness, headache, or other side effects from the central nervous system while using rimantadine should be cautious when driving vehicles and mechanisms, as well as when engaging in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions.

Drug Interactions

With simultaneous use, Rimantadine reduces the effectiveness of anticonvulsant drugs.

Adsorbents, astringents, and coating agents reduce the absorption of rimantadine.

Agents that acidify urine (ammonium chloride, ascorbic acid) reduce the effectiveness of rimantadine (due to increased renal excretion).

Agents that alkalize urine (acetazolamide, sodium bicarbonate) increase its effectiveness (by reducing renal excretion).

Paracetamol and acetylsalicylic acid reduce the C_max of rimantadine by 11%.

Cimetidine reduces the clearance of rimantadine by 18%.

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.