Remavir

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT REMAVIR (REMAVIR)

Composition:

Active substance: rimantadine;

1 capsule contains rimantadine hydrochloride 100 mg;

Excipients: lactose monohydrate; potato starch; stearic acid; titanium dioxide (E 171); colourant "Yellow Sunset FCF" (E 110); gelatin.

Pharmaceutical form. Capsules.

Main physico-chemical characteristics: solid, white gelatin capsules containing an orange-coloured powder with a shade ranging from slightly pinkish to brownish, with white inclusions.

Pharmacotherapeutic group.

Antiviral agents for systemic use. Rimantadine.

ATC code J05A C02.

Pharmacological Properties

Pharmacodynamics.

Rimantadine hydrochloride is an amantadine derivative with pronounced antiviral activity. It is effective against various influenza A viruses and also exhibits antitoxic effects in influenza caused by type B virus. Remavir inhibits viral replication at early stages of the cycle by disrupting the formation of the viral envelope. Genetic studies have shown that the specific M2 gene protein of the virion plays a significant role in the antiviral action of rimantadine against influenza A virus. In vitro, rimantadine inhibits replication of all three antigenic subtypes (H1N1, H2N2, H3N2) of influenza virus identified in humans. Remavir does not affect the immunogenic properties of inactivated influenza A vaccine.

Pharmacokinetics.

After single or repeated administration of the drug to patients of different age groups, a correlation between the concentration of Remavir in blood plasma and its antiviral activity has not been established.

Absorption. After oral administration, the drug is almost completely absorbed in the intestine and provides high bioavailability.

Distribution. After a single oral dose of Remavir at 100 mg, maximum plasma concentration – 74 ng/mL (range from 45 to 138 ng/mL) – is reached within 5–7 hours in healthy subjects aged 20–44 years.

Approximately 40% of Remavir binds to plasma proteins, primarily to albumins. The elimination half-life of a single dose in this study group averages 25 hours, while in patients aged 71–79 years it averages 32 hours.

Concentration in nasal secretion is about 50% higher than in plasma.

Metabolism. Remavir is extensively metabolized in the liver via hydroxylation, conjugation, and glucuronidation.

Excretion. Three hydroxylated metabolites of Remavir are detected in blood plasma. These and other metabolites account for up to 74 ± 10% of a single 200 mg dose. The drug is excreted in metabolized form in urine over 72 hours. Less than 25% of the drug is excreted unchanged in urine.

In renal insufficiency, plasma concentrations of Remavir metabolites increase.

The pharmacokinetics of the drug in children is close to that in adults.

Clinical characteristics.

Indications.

Early treatment of disease caused by influenza A viruses in adults and children aged 10 years and older.

Prophylaxis of influenza A during epidemics in adults and children aged 10 years and older.

Contraindications.

Hypersensitivity to rimantadine, derivatives of the adamantane group, or excipients of the medicinal product.

Severe impairment of liver and kidney function.

Acute and chronic liver and kidney diseases.

Thyrotoxicosis.

Pregnancy and breastfeeding.

Interaction with other medicinal products and other forms of interaction.

Paracetamol and acetylsalicylic acid reduce the effectiveness of Remavir.

Remavir reduces the effectiveness of antiepileptic agents.

Remavir enhances the stimulant effect of caffeine.

Cimetidine may enhance the action of Remavir.

Alcoholic beverages should be avoided, as adverse reactions involving the central nervous system may occur.

Special precautions for use

Remavir should be prescribed with caution to patients with gastrointestinal disorders, hepatic and/or renal dysfunction of mild to moderate severity, severe heart diseases including cardiac rhythm disturbances, and elderly patients. In such cases, dose reduction of the drug is recommended.

In patients with epilepsy and in patients receiving anticonvulsant therapy during Remavir treatment, the risk of epileptic seizures increases. In these cases, the dose of Remavir should be reduced to 100 mg per day.

If a seizure occurs, the drug should be discontinued.

Patients with hepatic and/or renal dysfunction

Available data on the use of Remavir in patients with acute or chronic hepatic and/or renal dysfunction are limited. Dose adjustment is required before prescribing Remavir, with careful assessment of expected benefit versus potential risk. Close monitoring of patients is necessary, as Remavir is extensively metabolized in the liver, and accumulation of its metabolites after repeated administration may lead to adverse reactions.

To prevent development of drug resistance, influenza treatment should be discontinued as soon as possible, usually approximately 5 days after initiation of therapy or within 24–48 hours after symptom resolution.

The medicinal product contains lactose; therefore, patients with rare hereditary forms of galactose intolerance, lactase deficiency, or glucose-galactose malabsorption syndrome should not use this product.

The medicinal product contains the colorant "Yellow Sunset FCF" (E 110), which may cause allergic reactions.

Use during pregnancy or breastfeeding

Remavir crosses the placental barrier and is excreted in breast milk; therefore, the use of this drug during pregnancy and breastfeeding is contraindicated.

Ability to affect reaction rate while driving or operating machinery

Patients should refrain from driving or operating machinery during treatment with Remavir, as dizziness, headache, or other central nervous system adverse effects may occur.

Method of Administration and Dosage.

Take orally, after meals, with water. The capsule must not be chewed.

Treatment with Remavir should be initiated as early as possible, immediately after the onset of the first flu symptoms. The therapeutic effect is more pronounced if administration of the drug is started within the first 48 hours after the onset of flu symptoms.

Treatment of influenza: for adults and children aged 10 years and older – 100 mg twice daily.

Always consult a physician before administering the drug to children.

For elderly patients (over 65 years of age) – 100 mg once daily.

Duration of treatment course – 5 days.

Influenza prophylaxis: for adults and children aged 10 years and older – 100 mg twice daily.

For elderly patients or those at high risk of complications – 100 mg once daily.

Drug administration should be initiated at the beginning of an influenza epidemic and continued during the epidemic period, but not for longer than 2 weeks.

For patients with mild to moderate hepatic and/or renal impairment, the dose may be adjusted to 100 mg once daily, if necessary. Close monitoring of such patients is required.

Children.

The drug may be administered to children aged 10 years and older following consultation with a physician.

Overdose.

In cases of overdose – symptomatic therapy to support vital functions.

Information is available regarding poisoning with a chemical analogue – amantadine.

Symptoms: agitation, hallucinations, cardiac arrhythmia, fever, chills, sweating, arrhythmia, hypoesthesia, increased lacrimation, dysphagia, constipation, increased urination, stomatitis, eye pain.

Treatment: discontinue the drug, gastric lavage, intravenous administration of physostigmine: 1–2 mg for adults, 0.5 mg for children; repeated administration may be necessary, but not exceeding 2 mg per hour. Rimantadine and amantadine are not removed by hemodialysis.

Adverse Reactions

The medicinal product is generally well tolerated.

Classification of adverse reactions by frequency of occurrence: very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥ 1/1,000 to < 1/100); rare (≥ 1/10,000 to < 1/1,000); very rare (< 1/10,000).

In a clinical trial involving 1027 patients who received a daily dose of rimantadine 200 mg, the most frequently reported adverse events were gastrointestinal and nervous system disorders.

Gastrointestinal system: common – nausea, vomiting; uncommon – anorexia, dry mouth, abdominal pain, diarrhea, dyspepsia.

Nervous system: common – insomnia; uncommon – impaired concentration, dizziness, headache, tremor, seizures, confusion, ataxia (impaired coordination of movements), somnolence, increased excitability, hyperkinesia (involuntary movements), altered/loss of taste, parosmia.

Psychiatric disorders: uncommon – hallucinations, depression, euphoria.

Cardiovascular system: uncommon – palpitations, arterial hypertension, heart failure, cardiac conduction disorders (heart blocks), tachycardia, syncope (fainting), cerebrovascular disorders.

Reproductive system and mammary glands: uncommon – galactorrhea.

Vestibular apparatus and auditory system: uncommon – tinnitus (ringing in the ears).

Respiratory system: uncommon – cough, dyspnea (shortness of breath), bronchospasm.

Skin and subcutaneous tissues: uncommon – pallor; frequency not known – pruritus, papular rash, generalized rash, urticaria.

General disorders: uncommon – asthenia (weakness), edema, fatigue.

The incidence of adverse effects, particularly those affecting the gastrointestinal and nervous systems, increases with doses exceeding the recommended dose.

In individual cases, after exceeding the recommended doses, lacrimation, increased urination, chills, constipation, sweating, stomatitis, hypesthesia, and eye pain have been observed.

Adverse reactions usually resolve after discontinuation of the drug.

There are conflicting data on the adverse effects of rimantadine in elderly patients. In a clinical study conducted during the 1997–1998 influenza epidemic involving 156 elderly patients, adverse effects were observed in only 1.9% of patients, mainly disturbances of consciousness.

In another controlled study involving 83 elderly patients requiring home care, central nervous system adverse effects were reported in 8.3% of patients in the placebo group and in 10.6% of patients in the rimantadine group. The observed events included insomnia, increased excitability, impaired concentration, and dizziness.

Shelf life.

2 years.

Storage conditions.

Store in a dry, light-protected place at a temperature not exceeding 25°C.

Keep out of reach of children.

Packaging.

10 capsules per blister. 1 or 3 blisters per cardboard box.

Supply category.

Over-the-counter (without prescription).

Manufacturer.

JSC «Olfa» / Olpha AS.

Manufacturer's address and location of business activity.

5 Rupnicu Street, Olaine, Olaine district, LV-2114, Latvia / Rupnicu iela 5, Olaine, Olaines novads, LV - 2114, Latvia.