Amantin film-coated tablets 100 mg blister No. 60

Instructions for use Amantin film-coated tablets 100 mg blister No. 60

Composition

active ingredient: amantadine sulfate;

1 tablet contains amantadine sulfate 100 mg;

excipients: lactose monohydrate, microcrystalline cellulose, potato starch, gelatin, povidone, croscarmellose sodium, talc, colloidal anhydrous silica, magnesium stearate, Opadry II White (polyethylene glycol, polyvinyl alcohol, talc, titanium dioxide (E 171)).

Dosage form

Film-coated tablets.

Main physicochemical properties: round tablets, with a biconvex surface, with a score, covered with a white film coating.

Pharmacotherapeutic group

Antiparkinsonian drugs. Dopaminergic drugs. ATX code N04B B01.

Pharmacological properties

Pharmacodynamics

Amantadine has various pharmacological properties. It exhibits indirect striatal dopamine receptor agonist properties. Animal studies have shown that amantadine increases extracellular dopamine concentrations both by increasing dopamine release and by blocking reuptake in presynaptic nerve cells. At therapeutic concentrations, amantadine inhibits NMDA receptor-mediated acetylcholine release and may thus exert anticholinergic effects. Amantadine has a synergistic effect with L-dopa.

Pharmacokinetics

After oral administration, amantadine is rapidly and completely absorbed from the gastrointestinal tract. Peak plasma concentrations (Cmax) are reached approximately 2 to 8 hours after a single dose. The readily soluble amantadine hydrochloride produces higher plasma concentrations than the less soluble amantadine sulfate, which has a later peak plasma concentration (Cmax) than the hydrochloride. A Cmax of 0.5 μg/ml is achieved after a single oral dose of 250 mg amantadine hydrochloride.

When taking the drug at a dose of 200 mg/day, the equilibrium concentration is reached after 4-7 days with a plasma concentration of 400-900 ng/ml. After taking 100 mg of amantadine sulfate Cmax is 0.15 μg/ml. Plasma clearance is determined to be identical to renal clearance and is 17.7±10 l/hour in healthy adult volunteers. The conditional volume of distribution is 4.2±1.9 l/kg and depends on the patient's age; in adults - 6 l/kg.

The elimination half-life is 10-30 hours (mean 15 hours) and is largely dependent on the patient's age. In elderly male patients (62-72 years) the half-life is 30 hours. In patients with renal insufficiency the terminal plasma half-life may be significantly prolonged (up to 68±10 hours).

Amantadine is approximately 67% bound to plasma proteins (in vitro); approximately 33% is found in plasma in an unbound form. Penetrates the blood-brain barrier by saturable transport systems. Excreted in urine practically unchanged (90% of a single dose), a small amount is excreted in feces.

The dialyzability of amantadine is low, approximately 5% per dialysis.

Amantadine is not metabolized in the human body.

Indication

Parkinson's syndrome: treatment of symptoms of Parkinson's disease, such as rigidity, tremor, hypokinesia and akinesia.

Extrapyramidal side effects of neuroleptics and other drugs: tardive dyskinesia, akathisia, and parkinsonism.

Contraindication

Hypersensitivity to amantadine or to any component of the drug;

epilepsy and other seizures;

severe renal failure;

peptic ulcer;

decompensated heart failure (stage IV according to the classification developed by the New York Heart Association – NYHA);

cardiomyopathy and myocarditis;

atrioventricular block II and III degree;

bradycardia (less than 55 beats/min);

prolonged QT interval (Bazett QTc > 420 ms) with either prominent U-waves or a family history of congenital long QT syndrome;

severe ventricular arrhythmia, including chaotic polymorphic ventricular tachycardia;

simultaneous treatment with budipine or other drugs that prolong the QT interval (see section "Interaction with other medicinal products and other types of interactions");

low levels of potassium or magnesium in the blood.

Special safety precautions

Patients taking neuroleptics and amantadine concurrently are at risk of developing neuroleptic malignant syndrome if amantadine is abruptly discontinued.

Intoxication may occur in patients with kidney damage.

Particular caution should be exercised when prescribing the drug to patients with organic brain syndrome or patients prone to seizures, as seizures and exacerbation of existing symptoms may occur (see sections “Method of administration and dosage” and “Adverse reactions”).

Patients with cardiovascular disorders require medical supervision during treatment with amantadine.

An ophthalmologist should be consulted if symptoms of visual loss or blurred vision occur to rule out corneal edema. If corneal edema is diagnosed, amantadine should be discontinued. Corneal edema caused by amantadine usually resolves within a month of discontinuation of treatment.

Patients should inform their doctor if they experience difficulty urinating.

Interaction with other medicinal products and other types of interactions

Before starting to take other medicines together with amantadine, it is necessary to carefully read the instructions for medical use regarding the possible interaction of these medicines with amantadine, which may lead to prolongation of the QT interval. Combination of amantadine with other antiparkinsonian drugs is possible. To avoid side effects (such as psychotic reactions), the dose of other drugs or their combinations should be reduced.

It is known that special interaction studies after simultaneous administration of amantadine and other antiparkinsonian drugs (such as levodopa, bromocriptine, memantine, trihexylphenidyl, etc.) have not been conducted (pay attention to side effects).

Taking amantadine at the same time as any other type of medicine or active ingredient listed below may lead to these types of interactions.

Anticholinergics. Increased adverse reactions (confusion and hallucinations) of anticholinergics (such as trihexylphenidyl, benztropine, scopolamine, biperiden, orphenadrine, etc.).

Sympathomimetics with direct action on the CNS. Enhancement of the main action of amantadine.

Alcohol. Decreased alcohol tolerance.

Levodopa (antiparkinsonian drug). Mutual enhancement of therapeutic effects. Therefore, levodopa can be administered simultaneously with amantadine.

Other antiparkinsonian agents: Memantine may potentiate the effects and side effects of amantadine (see section "Special warnings and precautions for use"), so concomitant use with memantine should be avoided.

Other medicinal products: Concomitant use of diuretics such as triamterene/hydrochlorothiazide may reduce the clearance of amantadine from plasma, leading to toxic plasma concentrations of amantadine. Therefore, concomitant use of this combination should be avoided.

Concomitant use of amantadine and drugs that prolong the QT interval is contraindicated. These include:

certain class IA (e.g. quinidine, disopyramide, procainamide) and class III (e.g. amiodarone, sotalol) antiarrhythmics;

certain neuroleptics (e.g. thioridazine, chlorpromazine, haloperidol, pimozide);

certain tricyclic and tetracyclic antidepressants (e.g. amitriptyline);

certain antihistamines (e.g. astemizole, terfenadine);

certain macrolide antibiotics (e.g. erythromycin, clarithromycin);

certain gyrase inhibitors (e.g. sparfloxacin);

azole antifungals and other drugs such as budipine, halofantrine, cotrimoxazole, pentamidine, cisapride, and bepridil.

Application features

Special caution should be exercised when administering the drug to patients with:

psychoses;

liver dysfunction;

thyrotoxicosis;

recurrent eczema;

prostatic hypertrophy;

narrow-angle glaucoma;

renal failure (of varying severity); there is a risk of amantadine accumulation due to impaired renal filtration (see also section "Method of administration and dosage");

agitation or confusion;

delirium syndrome or exogenous psychosis in history;

with simultaneous treatment with memantine (see section "Interaction with other medicinal products and other types of interactions");

when used simultaneously with drugs that affect the CNS (see section "Interaction with other medicinal products and other types of interactions").

An ECG (50 mm/s) and a manually determined Bazett-corrected QT interval (QTc) should be performed before initiation of treatment and after 1 and 3 weeks of treatment. This ECG should be performed before any subsequent dose increase and 2 weeks thereafter. ECGs should be performed at least annually thereafter. Treatment should not be initiated or discontinued if the baseline QTc value exceeds 420 ms, if the QT increases by more than 60 ms during treatment with the drug, or if the QTc value exceeds 480 ms, or if U waves are visible on the ECG.

Patients at risk of electrolyte imbalance due to, for example, diuretic treatment, frequent vomiting and/or diarrhea, patients taking insulin in crisis situations, or patients with renal or anorexic disorders should undergo examination and monitoring of laboratory parameters and appropriate replenishment of electrolytes, especially potassium and magnesium.

If symptoms such as palpitations, dizziness, or fainting occur, amantadine treatment should be discontinued immediately and the patient should be monitored for QT prolongation for 24 hours. If QT prolongation is absent, treatment with the drug can be resumed, taking into account contraindications and interactions.

The additional use of amantadine for the prevention and treatment of influenza A is not recommended due to the risk of overdose.

Amantadine treatment should not be stopped abruptly, as this may lead to worsening of Parkinson's disease, the appearance of symptoms characteristic of neuroleptic malignant syndrome, as well as the development of cognitive disorders, such as: catatonia, confusion, disorientation, deterioration of mental status, delirium.

Amantadine should not be abruptly discontinued in patients who are concomitantly taking neuroleptics due to the possible risk of developing neuroleptic-induced catatonia.

Suicide attempts and suicidal thoughts have been reported in patients receiving amantadine. In order to prevent the emergence of suicidal thoughts and intentions, the drug should be prescribed in the minimum effective dose.

Some patients may develop peripheral edema with prolonged use of the drug. This should be taken into account in patients with chronic heart failure.

The drug should not be used in patients with angle-closure glaucoma.

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

Use during pregnancy or breastfeeding

Amantadine is contraindicated in pregnant women and women planning to become pregnant. The drug is contraindicated during breastfeeding, as it passes into breast milk. If necessary, breastfeeding should be discontinued.

Ability to influence reaction speed when driving vehicles or other mechanisms

Amantadine may reduce concentration and reaction speed, cause dizziness, and decrease visual acuity, so patients should be warned about the potential danger when driving a car or operating other mechanisms.

Method of administration and doses

Tablets should be taken by adults orally, with a small amount of liquid, after meals, preferably in the morning and/or afternoon. Due to the possible activating effect on the central nervous system (CNS), the last dose of the drug is recommended to be taken no later than 4 p.m.

Single and daily dose.

By following the above precautions and considering contraindications, you can prevent the life-threatening adverse reaction of chaotic polymorphic ventricular tachycardia.

Treatment of patients with Parkinson's syndrome and drug-induced motor disorders should be carried out gradually, adhering to the dosage according to the therapeutic effect.

Treatment should be initiated by taking 1 tablet (100 mg of amantadine sulfate) of Amantin per day for the first 4-7 days, with a subsequent increase in the daily dose by 1 tablet once a week until an effective therapeutic dose is reached.

The usual effective dose is 1-3 tablets twice daily (200-600 mg of amantadine sulfate).

For elderly patients, particularly in cases of agitation, confusion or delirium, a daily dose of 100 mg (1 tablet) is recommended. If this dose is not effective, it can be carefully increased to 200 mg per day under medical supervision.

In combination treatment with other antiparkinsonian agents, the dose should be selected individually.

For patients previously treated with amantadine, solution for injection, the initial dose should be higher.

In case of a sharp deterioration of parkinsonian symptoms during an akinetic crisis, it is necessary to prescribe the administration of amantadine sulfate solution.

Patients with renal failure.

Doses for patients with renal insufficiency should be adapted according to glomerular filtration rate (GFR), as shown in the table:

* Achieved by taking alternately 1 tablet once and 2 tablets of 100 mg of amantadine sulfate once.

Glomerular filtration rate (GFR) can be approximately calculated using the following equation:

cr

where,

Clcr – creatinine clearance in ml/min;

creatinine – serum creatinine in mg/100 ml.

Creatinine clearance calculated according to this expression is applicable only to men (the corresponding value for women is 85% of this value) and can be equated to insulin clearance for determining GFR (120 ml/min for adults).

Amantadine is poorly dialyzed (approximately 5%).

The duration of treatment depends on the nature and severity of the disease and is determined by the doctor. Patients should not interrupt treatment on their own.

Children

Experience with the use of amantadine in children is insufficient, so the drug is not used in this age category.

Overdose

The possibility of multiple intoxication, such as taking more than one drug for the purpose of suicide, must always be considered.

Symptoms. Symptoms of acute toxic psychosis in the form of confusion with visual hallucinations, sometimes including coma and myoclonus, occupy a significant place in amantadine overdose. Excessive excitement, tremor, ataxia, blurred vision, lethargy, depression, dysarthria, neuromuscular disorders, hyperreflexia, restlessness, convulsions, extrapyramidal phenomena, torsion spasms, mydriasis, dysphagia, confusion, disorientation, delirium, myoclonus, nausea, vomiting, dry mouth, hyperventilation, pulmonary edema, respiratory failure, respiratory distress syndrome, hypertension, cardiac arrhythmia, tachycardia, angina pectoris, cardiac arrest.

Renal dysfunction, including increased urea nitrogen and decreased creatinine clearance, and urinary retention, is possible.

Treatment. No specific medical treatment or antidote is known. To prevent absorption, induce vomiting and/or gastric lavage (if the patient is conscious), administer activated charcoal. In case of life-threatening intoxication, resuscitation measures are necessary. Therapeutic measures should be taken, including support of vital functions, adequate hydration, possibly sedation, and measures against seizures and arrhythmias. For the treatment of the neurotoxic symptoms described above, intravenous physostigmine can be used at a dose of 1–2 mg every 2 hours for adults and 2 × 0.5 mg at intervals of 5–10 minutes to a maximum dose of 2 mg for children.

Close monitoring is recommended in patients at risk of QT prolongation and torsades de pointes, such as those with electrolyte imbalance (including hypokalemia and hypomagnesemia) or bradycardia. Due to the low dialyzability of amantadine (approximately 5%), hemodialysis is not recommended.

Side effects

Adverse reactions to amantadine, which are more often mild and transient, usually appear within 2 to 4 days of starting treatment and quickly resolve after stopping the drug.

The frequency of adverse reactions was assessed using the following criteria:

very common (> 1/10); common (> 1/100 to < 1/10); uncommon (> 1/1000 to < 1/100); rare (> 1/10,000 to < 1/1000); very rare (< 1/10,000); frequency unknown (cannot be estimated from the available data).

On the part of the psyche: often - sleep disorders and mental agitation.

In patients (especially the elderly) prone to mental disorders, when used concomitantly with anticholinergic drugs, paranoid exogenous psychoses may occur, accompanied by visual hallucinations. Adverse reactions of this type may be observed more often if Amantine is taken in combination with other antiparkinsonian drugs (such as levodopa, bromocriptine or memantine).

Blood and lymphatic system disorders: very rarely – thrombocytopenia, leukopenia.

Nervous system: often - movement disorders; infrequently - dizziness, orthostatic disorders; rarely - blurred vision; very rarely - epileptic seizures, usually after treatment with doses exceeding the recommended ones, symptoms of myoclonus and peripheral neuropathy, anxiety, headache, drowsiness, insomnia, weakness, fever, ataxia, slurred speech, impaired concentration, irritability, depression, paresthesia, confusion, disorientation, tremor, dyskinesia, stupor, suicidal thoughts and intentions, neuroleptic malignant syndrome, delirium, hypomania and mania, hallucinations, nightmares.

On the part of the organs of vision: rarely - blurred vision *; very rarely - temporary loss of vision *, increased sensitivity to light, corneal damage (punctate subepithelial opacification, which may be associated with superficial punctate keratitis), corneal epithelial edema, decreased visual acuity, oculogyric crises, mydriasis; unknown - corneal edema, disappears after discontinuation of treatment.

Cardiac system: very rarely - cardiac arrhythmia (ventricular tachycardia, ventricular fibrillation, chaotic polymorphic ventricular tachycardia and QT interval prolongation), orthostatic hypotension, tachycardia, peripheral edema, heart failure. The cause of most of these cases was overdose, concomitant use of certain drugs or other risk factors (see sections "Contraindications" and "Interaction with other drugs and other types of interactions"). Cardiac arrhythmia with tachycardia.

From the vascular system: often - orthostatic dysregulation.

On the part of the digestive tract: often - nausea, dry mouth; infrequently - anorexia, vomiting, constipation, diarrhea, reversible increase in liver enzyme activity.

Musculoskeletal and connective tissue disorders: Rhabdomyolysis may occur. Patients should be closely monitored. If symptoms occur, including myalgia, weakness, elevated creatine kinase (creatine phosphokinase) or elevated myoglobin levels in blood and urine, the medicinal product should be discontinued and appropriate measures should be taken. In addition, caution should be exercised due to the possibility of acute renal failure secondary to rhabdomyolysis.

From the genitourinary system: often - urinary retention in patients with prostatic hyperplasia, urinary incontinence, change in libido.

Others: hypersensitivity reactions in case of intolerance to any component of the drug.

*An ophthalmologist should be consulted as soon as symptoms of loss of visual acuity or blurred vision appear, in order to rule out possible corneal edema (see section "Special precautions").

Expiration date

3 years.

Storage conditions

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

Packaging

10 tablets in a blister; 3 or 6 blisters in a cardboard pack.

Vacation category

According to the recipe.

Producer

"Pharma Start" LLC.

Location of the manufacturer and address of the place of implementation of its activities

Ukraine, 03124, Kyiv, Vaclav Havel Boulevard, 8.

In case of side effects and questions regarding the safety of the medicinal product, please contact the Pharmacovigilance Department of ASINO UKRAINE LLC at the address: Vaclav Havel Boulevard, 8, Kyiv, 03124, tel/fax: +38 044 281 2333.