Neomidantan capsules 100 mg blister No. 50

Instructions Neomidantan capsules 100 mg blister No. 50

Composition

active ingredient: amantadine hydrochloride;

1 capsule contains amantadine hydrochloride 100 mg;

Excipients: lactose monohydrate; potato starch; stearic acid.

Dosage form

Capsules.

Main physicochemical properties: hard gelatin capsules No. 0, white/white in color, containing white or almost white powder.

Pharmacotherapeutic group

Dopaminergic agents, adamantane derivatives. ATX code N04B B01.

Pharmacological properties

Pharmacodynamics

Antiparkinsonian drug. Neomidantan is believed to act by enhancing dopamine release from central neurons and by inhibiting its reuptake into synaptic vesicles. The drug may also exhibit mild anticholinergic activity.

When used as monotherapy or in combination therapy, Neomidantan improves the main symptoms of Parkinson's disease. This effect largely depends on the age and sex of the patient, as well as the duration and severity of the disease. Neomidantan has a therapeutic effect in akinesia, rigidity, tremor and bradyphrenia. Often, mood improvement, relaxation of facial muscles, regulation of excessive sebaceous gland secretion and salivation are observed. Improvement of symptoms usually occurs 24–48 hours, but no later than 1 week after the start of treatment. The optimal therapeutic effect is achieved after a period of several days to several weeks.

Virostatic anti-influenza drug. Neomidantan at low concentrations specifically inhibits the replication of influenza A virus. According to the results of the plaque reduction susceptibility test, Neomidantan inhibits human influenza A virus, including subtypes H1N1, H2N2 and H3N2, at a concentration of 0.4 μg/ml or less. Neomidantan blocks the ion channel activity of the viral M2 protein of influenza A virus by allosteric inhibition, thus preventing virus decapsidation, which leads to inhibition of viral replication.

In some subtypes of avian influenza, a late-stage replication effect with impaired virus assembly has been observed.

The antiviral effect appears within 1–2 hours after taking Neomidantan, while the effectiveness of influenza vaccination appears after 8–14 days.

Pharmacokinetics

Absorption.

Amantadine is absorbed slowly but completely. Peak plasma concentrations of approximately 250 ng/mL and 500 ng/mL are reached within 3–4 hours after a single oral dose of 100 mg and 200 mg of amantadine, respectively. After repeated administration of amantadine at a dose of 25 mg, 100 mg, or 150 mg twice daily, steady-state plasma concentrations of 110 ng/mL, 302 ng/mL, or 588 ng/mL, respectively, are reached within 3 days.

Distribution.

In vitro, approximately 67% of amantadine binds to plasma proteins. A significant portion of amantadine binds to erythrocytes. The concentration of amantadine in erythrocytes in healthy volunteers is 2.66 times higher than the concentration in plasma.
The apparent volume of distribution of amantadine is 5–10 l/kg, indicating extensive distribution in body tissues. The volume of distribution decreases with increasing dose. The concentration of amantadine in the lungs, heart, kidneys, liver and spleen is higher than in the blood. After a few hours, amantadine accumulates in the serous secretion of the nasal mucosa.

Amantadine crosses the blood-brain barrier. The half-life of amantadine from brain tissue (6.5 days) is significantly longer than from blood plasma. The average ratio of amantadine concentrations in cerebrospinal fluid to serum is about 0.76. Amantadine penetrates into breast milk and crosses the placental barrier.

Metabolism.
Amantadine is metabolized to a minor extent. Eight metabolites of amantadine have been identified. The major metabolite is the N-acetylated metabolite, which accounts for 5 to 15% of the administered dose. The pharmacological activity of the metabolites is unknown. The effect of specific acetylators on the metabolism of amantadine has not yet been established.

Elimination.
In healthy young adults, amantadine is eliminated with a mean half-life of 15 hours (10–31 hours).

Total plasma clearance is approximately equal to renal clearance (250 ml/min). Renal clearance of amantadine is significantly higher than creatinine clearance, indicating tubular secretion of amantadine.

A single dose of amantadine is excreted within 72 hours as follows: 65–85% unchanged, 5–15% as the N-acetylated metabolite in the urine, 1% excreted in the feces. After 4–5 days, 90% of the dose is found in the urine unchanged. The pH of the urine significantly affects the rate of elimination. An increase in the pH value can lead to a significant decrease in the elimination of amantadine.

Dose dependence.

Amantadine exhibits dose-dependent pharmacokinetics in the dose range of 100 mg to 200 mg. Pharmacokinetics in special patient groups.

Elderly patients.

In elderly patients with impaired renal function, the use of amantadine at a dose of 100 mg/day for 14 days may lead to an increase in plasma concentrations to toxic levels.

Kidney failure.

Amantadine is primarily excreted by the kidneys, so in patients with renal insufficiency, accumulation of amantadine is possible, which can lead to serious adverse reactions. Creatinine clearance less than 40 ml/min × [1.73 m2] leads to a three- to five-fold increase in half-life, as well as a five-fold decrease in total and renal clearance. Even in renal insufficiency, amantadine is primarily excreted by the kidneys.

Elderly patients or patients with renal insufficiency should have their dose reduced and adjusted according to individual creatinine clearance. Plasma amantadine concentrations should not exceed a maximum of 300 ng/ml.

Hemodialysis.

A small amount of amantadine is removed by hemodialysis. This is probably due to the extensive tissue binding of amantadine. Less than 5% of the dose is removed 4 hours after the start of hemodialysis. The average half-life reaches 24 hours of dialysis.

Liver failure.

The effect of hepatic insufficiency on the pharmacokinetics of amantadine is unknown. The majority of an administered dose of amantadine is excreted unchanged in the urine. Only a small portion of amantadine is metabolized in the liver (see Pharmacokinetics, Metabolism).

Eating.

Food intake does not significantly affect the pharmacokinetics of amantadine. If Neomidantan is taken with food, this may lead to a slight delay in the absorption of the active substance.

Ethnic influence.

There is currently no information on the influence of genetic factors on the distribution of amantadine. No studies have been conducted on the influence of ethnicity and race on the pharmacokinetic properties of amantadine.

Indication

Parkinson's disease. Parkinson's disease (Paralysis agitans), symptomatic (postencephalitic, cerebrovascular) and drug-induced parkinsonism in adults. Influenza A virus. Individual and group prophylaxis in case of risk of infection, treatment in the initial stages (1-2 days of illness) of adults and children aged 10 years and older. Neomidantan should be taken only under medical supervision.

Contraindication

Known hypersensitivity to amantadine or other components of the drug. Disorders and confusion of consciousness. Refractory epilepsy, psychosis or delirium syndrome. Pregnancy.

Relative contraindications are benign prostatic hyperplasia and angle-closure glaucoma.

Concomitant use of memantine.

Interaction with other medicinal products and other types of interactions

Concomitant administration of Neomidantan and anticholinergics, dopamine agonists, or levodopa may increase confusion, hallucinations, nightmares, gastrointestinal disorders, or other atropine-like side effects (see section "Overdose").

Isolated cases of psychotic decompensation have been reported following concomitant use of amantadine and neuroleptics or levodopa.

Concomitant use of Neomidantan and drugs or substances that act on the central nervous system (e.g. alcohol) may increase the toxic effect on the central nervous system. In such cases, careful monitoring of the patient is recommended (see section "Overdose").

Concomitant use of Neomidantan and combined diuretics (hydrochlorothiazide and potassium-sparing diuretics) reduces the renal clearance of amantadine, leading to increased plasma concentrations and toxic effects (confusion, hallucinations, ataxia and myoclonus).

Application features

In patients with organic cerebral psychosyndrome or existing seizure disorders, an increased frequency of epileptic seizures or exacerbation of disease symptoms has been reported when taking Neomidantan (see sections "Side effects" and "Dosage and administration"). The risk decreases with dose reduction. These patients should be carefully monitored.

Patients with mental disorders are more likely to experience adverse reactions such as hallucinations, confusion, and nightmares.

About 50% of patients with Parkinson's disease experience symptoms of depression, which increases the risk of suicidal thoughts and possible suicide attempts. A number of suicide attempts have been reported in association with the use of Neomidantan, some of which were fatal. Therefore, it is very important to use the lowest effective dose of the drug and to ensure close monitoring and care of the patient.

Caution should be exercised in patients with severe hepatic impairment, myasthenia gravis, recurrent eczema, gastric ulcer, prostatic hyperplasia or cardiovascular disorders, as well as in patients with a history of such conditions. In case of combination therapy with anticholinergics or levodopa, the contraindications for these drugs should be taken into account.

Patients with impaired renal function should be dosed with caution due to the risk of intoxication (see sections “Method of administration and dosage” and “Overdose”).

In about 20% of patients receiving Neomidantan, a partial decrease in the effect is possible after 2 to 8 weeks of treatment.

Additional use of Neomidantan for the prevention and treatment of influenza A virus is not advisable and should be avoided due to the risk of overdose.

Hypothermia has been observed in children, so special care should be taken when prescribing the drug for the prevention of influenza A virus.

Do not prescribe Neomidantan to children under 10 years of age. Since the drug has an anticholinergic effect and can provoke mydriasis, it is contraindicated in patients with untreated angle-closure glaucoma.

Impulse control disorders.

Patients should be monitored regularly for signs of impulse control disorders. Patients and caregivers should be alerted to the possibility of behavioral symptoms of impulse control disorders. These symptoms include excessive gambling, increased libido, hypersexuality, compulsive spending or buying, and binge or compulsive eating. If these symptoms occur, the dose of the drug should be reduced or treatment should be gradually discontinued.

Discontinuation of treatment.

Abrupt discontinuation of Neomidantan may lead to exacerbation of Parkinson's disease symptoms or the development of symptoms similar to neuroleptic malignant syndrome (NMS), as well as symptoms such as catatonia or manifestations of cognitive impairment (e.g. confusion, disorientation, deterioration of mental status or delirium).

There have been isolated reports of a possible association between exacerbation of neuroleptic malignant syndrome or catatonia induced by neuroleptics and discontinuation of Neomidantan in patients receiving concomitant neuroleptic treatment and Neomidantan. Therefore, amantadine treatment should not be discontinued abruptly.

Resistance.

Resistance to amantadine and rimantadine develops relatively rapidly upon repeated exposure to influenza virus strains in vitro and in vivo. Influenza A viruses resistant to amantadine and rimantadine can cause disease even when these active substances are used to treat influenza. Transmission of drug-resistant viruses may result in ineffective home-based prophylaxis, but there is no evidence that infection with drug-resistant viruses is different from infection with drug-susceptible viruses.

Ability to influence reaction speed when driving vehicles or other mechanisms

Patients who experience side effects from the central nervous system (nervousness, impaired concentration, sleep disturbances, dizziness, seizures, confusion, hallucinations, paranoid psychosis, blurred vision) should refrain from driving or operating other mechanisms.

Use during pregnancy or breastfeeding

The use of Neomidantan is contraindicated in pregnant women and women who may become pregnant. Women of reproductive age are strongly advised to use effective methods of contraception for up to 5 days after the last dose of Neomidantan.

Neomidantan passes into breast milk. Adverse reactions have been reported in breastfed infants. Neomidantan is contraindicated during breast-feeding.

Method of administration and doses

The drug should be taken orally with food, preferably in the morning (to avoid stomach complaints). The capsule should be swallowed whole with a small amount of water Parkinson's disease.

The initial dose for 4–7 (maximum 15) days is 100 mg once a day (to determine individual response).

Long-term treatment (usual dose) – 100 mg twice a day.

In exceptional cases (if an improvement in the therapeutic effect can be expected with good tolerability) - 100 mg three times a day.

These regular doses are recommended for both previously treated and untreated patients. A lower initial dose helps to determine individual response. The usual dose can usually be given after 4–7 days. A dose of 100 mg 3 times a day may provide additional improvement, but this may be associated with increased toxicity. In these cases, the dose should be increased gradually, at intervals of at least one week.

The effect of Neomidantan occurs after a few days, however, after continuous use for several months, the effect decreases slightly.

To restore the treatment effect, the use of Neomidantan can be temporarily discontinued.

Treatment should be discontinued gradually, as, regardless of the success of therapy, abrupt discontinuation of treatment may lead to a worsening of symptoms in patients with Parkinson's disease.

When starting Neomidantan, previously treated patients should continue taking their previously prescribed medications; in many cases, the dose of other antiparkinsonian drugs can be gradually reduced without affecting the success of the treatment. However, if undesirable side effects occur more frequently, the dose should be reduced more rapidly. Previously treated patients who have received high doses of anticholinergics or levodopa should receive a long-term, up to 15 days, initial treatment with low doses of Neomidantan.

Influenza A virus

Children aged 10 and over, adolescents and adults

under 65 years of age: 100 mg twice daily

Adults aged 65 years and over: see special dosage instructions.

Prevention.

Effective prevention and treatment of influenza A virus has been observed with a dose of 100 mg per day. This dose can be administered to patients who are intolerant to the drug at a dose of 200 mg per day.

For effective prevention, it is necessary to start taking the drug in this dosage regimen as soon as any contact with a sick person with influenza virus is inevitable; treatment should continue throughout the entire period of the influenza A virus epidemic, usually about 6 weeks. If Neomidantan was used together with an inactivated influenza A virus vaccine, treatment should be continued for 2 or 3 weeks after vaccination.

Treatment.

Treatment of influenza should be started as soon as possible and continued for 4–5 days. If Neomidantan is used within 48 hours of the onset of symptoms, fever and other symptoms of the disease are reduced.

Specific dosage instructions for all indications.

Dosage and administration for elderly patients (≥ 65 years).

The plasma concentration of amantadine depends on renal function. Elderly patients may have a tendency to have a longer half-life and a reduced renal clearance compared to young adults. Therefore, for elderly patients without renal impairment, the recommended maximum daily dose is 100 mg. In patients with renal impairment, the dosing interval should be adjusted (see “Method of administration and dosage”, “Special dosage instructions for all indications”, “Patients with renal impairment”).

Patients with renal impairment.

In patients with impaired renal function and in patients on hemodialysis, the half-life of amantadine is significantly prolonged, leading to increased plasma concentrations. In these patients, after taking the initial dose on the first day, the dose of Neomidantan should be carefully adjusted by increasing the interval between doses according to creatinine clearance (see table below).

Starting dose:

For patients with renal impairment for the treatment of influenza A virus, the initial dose of Neomidantan is 200 mg on the first day of therapy, after which the dose is adjusted according to creatinine clearance (table). For patients with renal impairment who have started antiparkinsonian therapy, the initial dose is 100 mg of Neomidantan on the first day of therapy, after which the dose is adjusted according to creatinine clearance (table). Patients with Parkinson's disease who have received maintenance therapy for treatment and in whom renal insufficiency is first established do not require an initial dose; these patients can immediately receive treatment at a dose according to creatinine clearance (table).

Dose according to creatinine clearance:

Patients on hemodialysis are usually prescribed 100 mg of the drug per week and, if necessary, with good tolerability of the drug, the dose is increased to 200 mg per week (see sections “Method of administration and dosage”, “Special dosage instructions for all indications”, “Dosage and method of administration for elderly patients” and “Special precautions for use”).

Plasma concentrations of amantadine should be monitored. Patients should be closely monitored (see Pharmacokinetics).

If you miss a dose, take it as soon as you remember, unless it is almost time for your next dose. Never take a double dose. If necessary, consult your doctor.

Children

The drug is prescribed to children from 10 years of age for the prevention and treatment of influenza A virus.

Overdose

Symptoms: Acute psychosis and disorientation, aggressive behavior, blurred vision, hyperventilation, hyperreflexia, restlessness, convulsions, extrapyramidal phenomena, torsion spasms, mydriasis, dysphagia, confusion, delirium, visual hallucinations, myoclonus, nausea, vomiting, dry mouth, pulmonary edema, respiratory failure, respiratory distress syndrome, hypertension, cardiac arrhythmia, sinus tachycardia, angina attacks. Coma, respiratory and cardiac arrest, sudden coronary death within a few hours after overdose are possible. Renal dysfunction is possible, including increased urea nitrogen, decreased creatinine clearance, urinary retention.

Taking Neomidantan in a dose of 1 g or more can be fatal.

Treatment. There is no specific antidote. To prevent absorption of the drug, it is necessary to induce vomiting or wash the stomach (if the patient is conscious), use activated charcoal; ensure the support of vital body functions, adequate hydration. For rapid excretion of the drug, ensure an acidic urine reaction. A small amount of the drug is excreted by hemodialysis. Careful monitoring of blood pressure, heart rate, ECG, respiratory function, body temperature is recommended for timely detection of the development of arterial hypotension and cardiac arrhythmia and, if necessary, their treatment. To reduce the severity of symptoms from the central nervous system, it is recommended to prescribe intravenous physostigmine to adults at a dose of 1–2 mg, if necessary - repeatedly, but not more than 2 mg per hour. In case of urinary retention, it is necessary to perform catheterization of the bladder. Chlorpromazine is used to relieve psychosis.

Adverse reactions

Adverse reactions usually occur within the first 2–4 days of treatment and disappear within 24–48 hours after discontinuation of the drug.

It is not possible to establish a direct relationship between dose and the incidence of adverse reactions. However, the incidence of adverse reactions increases with increasing dose. This is especially true for CNS adverse reactions.

Adverse reactions identified during clinical trials, obtained from spontaneous reports, as well as from literature sources, are listed according to the MedDRA system organ classification. Within each system organ class, adverse reactions are listed by frequency, starting with the most frequent. In turn, within each frequency group, adverse reactions are listed in order of decreasing seriousness.

Frequency definition:

very common (≥1/10), common (≥1/100 to 1/10), uncommon (≥1/1000 to 1/100), rare (≥1/10000 to 1/1000), very rare (1/10000).

Blood and lymphatic system disorders: rarely - leukopenia, frequency unknown - leukocytosis.

Metabolism and nutrition: lack of appetite.

On the part of the psyche: often - depression, anxiety, elevated mood, rarely - psychotic disorders.

Nervous system: often - agitation, nervousness, impaired concentration, vertigo, dizziness, headache, insomnia, lethargy, hallucinations, nightmares, ataxia, slurred speech, blurred vision, rarely - confusion, disorientation, tremor, dyskinesia, seizures, symptoms similar to neuroleptic malignant syndrome (even without discontinuation of treatment, see "Discontinuation of treatment"), frequency unknown - coma, stupor, hypokinesia, hypertension, mania, aggressive behavior, paranoid reactions, involuntary muscle contractions, gait disturbance, paresthesia, ECG changes and tremor.

Hallucinations, confusion, and nightmares occur more frequently if Neomidantan is used with anticholinergics or if the patient suffers from any psychiatric disorders.

Cases of hypomania and mania have been reported. The occurrence of these adverse reactions is not noted in the literature. Cases of delirium, catatonia, hallucinations, confusion and disorientation have also been reported on discontinuation of amantadine treatment in patients with Parkinson's disease.

Cardiovascular system: often - palpitations, orthostatic hypotension, rarely - arrhythmias, heart failure, including malignant arrhythmia, hypotension and tachycardia.

On the part of the organs of vision: rarely - corneal damage, for example, punctate subepithelial opacities, which may be associated with punctate keratitis, edema of the corneal epithelium and pronounced deterioration of visual acuity, mydriasis.

Vascular: often - swelling in the lower legs.

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

Skin and subcutaneous tissue disorders: often - Livedo reticularis ("marbled" skin), hyperhidrosis, rarely - skin rashes, photosensitivity reactions, itching.

On the part of the kidneys and urinary tract: rarely - urinary incontinence, urinary retention in patients with prostatic hyperplasia.

On the part of the immune system: hypersensitivity reactions in case of intolerance to any component of the drug.

Impulse control disorders: Patients treated with dopamine agonists, including Neomidantan, may experience symptoms such as excessive gambling, increased libido, hypersexuality, compulsive spending, and excessive or compulsive eating.

Abrupt discontinuation of the drug may cause delirium, agitation, mania, hallucinations, paranoid reactions, stupor, fear, depression, and slurred speech.

General disorders: peripheral edema of the lower extremities, hyperthermia, neuroleptic malignant syndrome (see section "Special warnings and precautions for use"), allergic reactions, including anaphylactic reactions, fever.

Investigations: increased levels of creatine phosphokinase, blood urea, serum creatinine, alkaline phosphatase, lactate dehydrogenase, bilirubin, gamma-glutamyl transpeptidase, serum glutamine-oxalate transaminase, and serum glutamine-pyruvate transaminase.

If during treatment you experience any side effects not listed in this instruction, or if any of the mentioned side effects is particularly severe, please consult a doctor.

Expiration date

5 years.

Storage conditions

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

Keep out of reach of children.

Packaging

10 capsules in a blister. 5 blisters in a cardboard pack.

Vacation category

According to the recipe.

Producer

JSC "Olainfarm"/JSC "Olainfarm".

Location of the manufacturer and its business address

5 Rupnicu street, Olaine, LV–2114, Latvia.