Rimantadine-darnitsa

INSTRUCTION FOR MEDICAL USE OF THE MEDICINAL PRODUCT RIMANTADINE-DARNITSA (RIMANTADINE-DARNITSA)

Composition:

Active substance: rimantadine;

1 tablet contains rimantadine hydrochloride 50 mg;

Excipients: lactose monohydrate, corn starch, povidone, colloidal anhydrous silicon dioxide, magnesium stearate.

Pharmaceutical form. Tablets.

Main physical and chemical properties: white or white with yellowish tint tablets, flat cylindrical in shape, with bevel and groove.

Pharmacotherapeutic group. Antiviral agents for systemic use. Cyclic amines.

ATC code J05A C02.

Pharmacological Properties

Pharmacodynamics

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

Rimantadine-Darnitsia is also effective against arboviruses, which are causative agents of tick-borne encephalitis.

Pharmacokinetics

After single and multiple doses administered to patients of various age groups, no correlation has been established between plasma concentrations of rimantadine and its antiviral activity.

Following oral administration, the drug is almost completely absorbed. Absorption is slow. Plasma protein binding is approximately 40%. Volume of distribution is 17−25 L/kg in adults and 289 L/kg in children. The concentration in nasal secretions is 50% higher than in plasma. Maximum plasma concentration of the active substance is 181 ng/mL after a single 100 mg dose once daily, and 416 ng/mL after 100 mg twice daily.

The drug is metabolized in the liver. Elimination half-life ranges from 24 to 36 hours. 75−85% of the administered dose is excreted by the kidneys, mainly as metabolites, and 15% in unchanged form.

In chronic renal failure, the elimination half-life is doubled. In patients with renal impairment and in elderly individuals, the concentration of the active substance may increase to toxic levels.

Dose reduction is not required for patients with chronic liver diseases, including those with compensated liver cirrhosis, as the pharmacokinetics after a single 200 mg dose do not significantly differ from those in healthy individuals. However, in patients with severe hepatic impairment, administration of a 200 mg dose results in AUC values three times higher, elimination half-life twice as long, and clearance 50% lower compared to healthy adults.

The pharmacokinetic profile of rimantadine in children corresponds to that observed in healthy 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 to excipients of the medicinal product.

Acute and chronic liver and kidney diseases.

Thyrotoxicosis.

Interaction with other medicinal products and other forms of interaction.

Agents that alkalinize urine (acetazolamide, sodium bicarbonate) and cimetidine increase the concentration of rimantadine in plasma.

Agents that acidify urine (ammonium chloride, ascorbic acid), paracetamol, and acetylsalicylic acid reduce the efficacy of rimantadine.

Rimantadine diminishes the effectiveness of antiepileptic drugs and enhances the stimulant effect of caffeine.

During treatment, consumption of alcoholic beverages should be avoided, as adverse reactions from the central nervous system may occur.

Special precautions.

The maximum therapeutic effect is achieved when the medicinal product is used within the first 2 days from the onset of illness.

Rimantadine should be administered with caution in patients with gastrointestinal disorders, impaired liver function, severe heart diseases, cardiac arrhythmias, and in elderly individuals. In these cases, a reduced dose of the medicinal product is recommended.

In patients with a history of epilepsy or those receiving anticonvulsant therapy, the risk of epileptic seizures may increase during rimantadine treatment. In such cases, the dose should be reduced to 100 mg per day. If a seizure occurs, the medicinal product should be discontinued.

Development of resistant viruses may occur.

During treatment, alcohol consumption should be avoided, as it may lead to undesirable adverse effects on the central nervous system.

Rimantadine-Darnitsia contains lactose; therefore, the medicinal product is contraindicated in patients with rare hereditary forms of galactose intolerance, lactase deficiency, or glucose-galactose malabsorption syndrome.

Use during pregnancy or breastfeeding.

Rimantadine-Darnitsia should not be used during pregnancy. If use of the medicinal product is necessary, breastfeeding should be discontinued.

Ability to affect reaction rate while driving or operating machinery.

When using this medicinal product, patients should refrain from driving vehicles or operating potentially hazardous machinery.

Method of Administration and Dosage

Take tablets orally after meals with water.

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

Treatment of influenza: Adults and children aged 10 years and older: 100 mg (2 tablets) twice daily.

Always consult a physician before administering the drug to children.

For elderly patients (over 65 years of age): 100 mg (2 tablets) once daily.

Duration of treatment course: 5 days.

Influenza prophylaxis: Adults and children aged 10 years and older: 100 mg (2 tablets) twice daily.

For elderly patients or those at high risk of complications: 100 mg (2 tablets) once daily.

Administration of the drug should begin at the start of an influenza epidemic and continue during the epidemic period, but not for longer than 2 weeks.

Children

Rimantadine-Darnitsia may be administered to children aged 10 years and older.

Overdose

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

There is information regarding poisoning with a chemical analogue—amantadine.

Symptoms: Excitation, hallucinations, cardiac arrhythmia, fever, chills, sweating, arrhythmia, hypesthesia, increased lacrimation, dysphagia, constipation, increased frequency of urination, stomatitis, eye pain.

Treatment: Discontinue the drug, gastric lavage, intravenous administration of physostigmine; initial dose for children and adults: 0.5 mg; if necessary, repeat administration, but not exceeding 2 mg per hour. Rimantadine and amantadine are not removed by hemodialysis.

Adverse reactions.

Usually adverse effects disappear after discontinuation of the medicinal product.

Sense organs: altered/loss of taste, parosmia.

Ear and labyrinth disorders: tinnitus.

Respiratory, thoracic and mediastinal disorders: cough, dyspnoea (shortness of breath), bronchospasm.

Gastrointestinal disorders: dyspepsia, nausea, vomiting, dry mouth, abdominal pain, diarrhoea, indigestion, anorexia.

Nervous system disorders: headache, dizziness, tremor, ataxia (impaired coordination of movements), hyperkinesia (involuntary movements), convulsions, insomnia, increased fatigue, somnolence, difficulty concentrating, confusion, increased excitability, nervousness, restlessness, depression, euphoria, hallucinations.

Cardiovascular disorders: palpitations, tachycardia, hypertension, cerebrovascular disorders, heart failure, oedema, cardiac conduction disturbances (blockades), syncope; in elderly patients with hypertension, increased risk of haemorrhagic stroke.

Immune system disorders: urticaria.

Skin and subcutaneous tissue disorders: skin rash, pruritus, pallor.

Other: galactorrhoea, exacerbation of concomitant chronic diseases, asthenia (weakness).

Shelf life.

3 years.

Do not use the medicinal product after the expiry date stated on the packaging.

Storage conditions.

Store in the original packaging, out of reach of children, at a temperature not exceeding 25 °C.

Packaging.

10 tablets in a blister pack; 2 blisters per carton.

Prescription status.

Over-the-counter.

Manufacturer.

JSC "Pharmaceutical company "Darnytsia".

Manufacturer's name and address of the place of business.

13, Boryspylska Street, Kyiv, 02093, Ukraine.