Noogeron-Teva - instructions for use, dose, side effects, contraindications

Composition:1 tablet contains: active substance memantine hydrochloride 10.00 mg / 20.00 mg; auxiliary substances (core): cellulose microcrystalline 144.00 mg / 288.00 mg, silicon colloidal dioxide 1.00 mg / 2.00 mg, croscarmellose sodium 3.40 mg / 6.80 mg, magnesium stearate 1.60 mg / 3.20 mg; auxiliary substances (film shell): for tablets 10 mg: Opadrai 03A28315 white 4.800 mg (hypromellose 6 cp 3.120 mg, titanium dioxide (E 171) 1.440 mg, talc 0.240 mg); for tablets 20 mg: opadine 02G34586 pink 9.600 mg (hypromellose 5 cc 6,000 mg, titanium dioxide (E 171) 1.800 mg, macrogol-6000 0.960 mg, macrogol-400 0.600 mg, iron dye red oxide (E 172) 0.170 mg, indigocarmine (E 132) 0.067 mg, ferric oxide black oxide (E 172) 0.003 mg).

Description:

Dosage of 10 mg: Oval biconvex tablets covered with a film shell of white or almost white color, on one side with a risk and engraved "M" on the right and left of the risks,on the other side with the risk and engraving "1" to the left of the risks and "0" to the right of the risks.

Dosage of 20 mg: Oval biconvex tablets covered with a filmy coating of light pink or pink with a brownish hue, with an engraved "M" on one side and "20" on the other side.

On the cross-section - the core is white or almost white.

Pharmacotherapeutic group:Treatment for dementia

ATX: & nbsp

N.06.D.X.01 Memantine

N.06.D.X Other drugs for the treatment of dementia

Pharmacodynamics:

The adamantane derivative. Is a non-competitive antagonist N-methyl-O-aspartate (NMDA) -receptors, has a modulating effect on the glutamatergic system. It regulates ion transport, blocks calcium channels, normalizes the membrane potential, improves the process of nerve impulse transmission. Improves cognitive processes, increases daily activity.

Pharmacokinetics:

Suction

Eating does not affect the absorption of memantine. After oral administration memantine quickly and completely absorbed. Maximum concentration in blood plasma (FROM_m_Oh) is between 3 and 8 hours after ingestion. In patients with normal renal function, cumulation of memantine was not observed.

Distribution

At a daily dose of 20 mg per day, the equilibrium concentrations of memantine in blood plasma are 70-150 ng / ml. The ratio of the average concentration of memantine in the cerebrospinal fluid to plasma concentration when administered at a daily dose of 5-30 mg is 0.52. The volume of distribution is about 10 l / kg. Approximately 45% of memantine binds to plasma proteins.

Metabolism

About 80% of the memantine taken internally is excreted unchanged. The main metabolites: M-3,5-dimethyl-glutananthane, isomer mixture of 4- and 6-hydroxymemanthine and 1-nitroso-3,5-dimethyladamantane do not possess their own pharmacological activity. In conditions in vitro metabolism, carried out by cytochrome P450 isoenzymes, was not revealed.

In the study with oral administration ¹⁴C-memantine averaged 84% of the ingested dose was withdrawn within 20 days, with more than 99% excreted by the kidneys.

Excretion

Memantine is excreted monoexponentially with a half-life (T1 / 2) of the terminal phase between 60 and 100 hours. It is excreted by the kidneys. In volunteers with normal renal function, the total clearance is 170 ml / min / 1.73 m², part of the total renal clearance is achieved through tubular secretion.Renal excretion also includes tubular reabsorption, mediated, possibly, by cationic transport proteins. The rate of renal elimination of memantine in conditions of alkaline urine reaction can decrease by 7-9 times. The alkalinization of urine can be caused by a sudden change in diet, for example, when switching from animal products

origin on a vegetarian diet or because of excessive use of alkaline gastric buffers.

Linearity

In the range of doses of 10-40 mg in volunteers revealed the linearity of pharmacokinetics. Pharmacokinetic / pharmacodynamic relationship

When taking memantine at a dose of 20 mg / day, the level of concentration in the cerebrospinal fluid is equal to the value k_i (inhibition constant), which in the region of the frontal cortex is 0.5 μmol / l.

Indications:

Dementia of the Alzheimer's type of moderate and severe degree.

Contraindications:

- Hypersensitivity to memantine and other components of the drug;

- Severe hepatic insufficiency (class C on the Child-Pugh scale);

- Pregnancy and lactation;

- Age to 18 years (effectiveness and safety not established).

Carefully:

Epilepsy, thyrotoxicosis, a predisposition to the development of seizures, the simultaneous use of antagonists NMDA-receptors (amantadine, ketamine, dextromethorphan), factors that increase the pH of urine (a sudden change in diet, for example, a switch to vegetarianism, a copious intake of alkaline gastric buffers), renal tubular acidosis, severe urinary tract infections caused by Proteus spp., myocardial infarction (in the anamnesis), heart failure III-IV functional class by classification NYHA, uncontrolled arterial hypertension, renal failure, hepatic insufficiency.

Pregnancy and lactation:

In connection with a possible delay in intrauterine development, the drug Noogeron-Teva is not used in pregnancy. Studies conducted on animals indicate the possibility of the drug to cause a delay in intrauterine development when used in doses similar to therapeutic in humans.

There is no information on the excretion of memantine in breast milk. However, given the lipophility of memantine, isolation is possible. Therefore, during the treatment with Noogeron-Teva, breastfeeding should be stopped.

Dosing and Administration:

Therapy should be carried out under the supervision of a physician experienced in the diagnosis and treatment of dementia in Alzheimer's disease. Therapy should be started only if the person who provides regular patient care will monitor the patient taking the medication. The diagnosis should be made in accordance with the current recommendations.

The tolerability and dosage of the drug Noogeron-Teva should be evaluated regularly, mainly within three months after initiation of therapy. Then, the clinical efficacy of the drug and the tolerability of therapy should be regularly assessed in accordance with current clinical guidelines. Supportive therapy can be continued indefinitely with the therapeutic effect and good tolerability of the drug Noogeron-Teva. It should stop using Noogeron-Teva if the therapeutic effect is no longer observed or if the patient does not tolerate treatment.

The drug Noogeron-Teva is administered orally once a day, the drug should be taken at the same time every day, regardless of food intake.

To reduce the risk of side effects, a gradual increase in dose is recommended: 5 mg per week for the first three weeks of therapy.

The maximum daily dose is 20 mg per day.

The recommended maintenance dose of Noogeron-Teva is 20 mg per day. The following dosing regimen is recommended:

1-st week (1-7 days): daily dose - 5 mg ½ tablets 10 mg).

The second week (8-14 days): daily dose - 10 mg (1 tablet 10 mg).

3rd week (15-21 days): daily dose - 15 mg (1 each ½ tablets 10 mg).

Starting with the 4th week: a daily dose of 20 mg (2 tablets 10 mg).

Elderly patients (older 65)

Correction of the dose is not required.

Impaired renal function

In patients with a creatinine clearance (CK) of 50-80 ml / min, no dose adjustment is required. Patients with moderate renal failure (CK 30-49 ml / min) are recommended 10 mg / day. If the drug is well tolerated within 7 days, the dose can be increased to 20 mg / day according to the standard scheme. In patients with severe renal failure (CK 5-29 ml / min) daily dose should not exceed 10 mg / day.

Impaired liver function

In patients with mild and moderate impairment of liver function (class A and B on the Child-Pugh scale), dose adjustment is not required.Patients with severe hepatic insufficiency (class C on the Child-Pugh scale) drug Noogeron-Teva is contraindicated.

Side effects:

Undesirable effects are classified according to the frequency of their development: very often (≥ 1/10), often (≥ 1/100, <1/10), infrequently (≥ 1/1000, <1/100), rarely (≥ 1 / 10000, <1/1000), very rarely (<1/10000), unknown frequency - the available data are insufficient to estimate the frequency of the side effect.

Infectious and parasitic diseases: infrequently - fungal infections.

Immune system disorders: often hypersensitivity to the components of the drug.

Disorders of the psyche: often - drowsiness; infrequent - confusion, hallucinations *, unknown frequency: psychotic reactions.

Impaired nervous system: often - dizziness, imbalance; infrequently - gait disturbance; very rarely - cramps.

Heart Disease: infrequently - heart failure.

Vascular disorders: often - increased blood pressure; infrequently, venous thrombosis and / or thromboembolism.

Disorders from the gastrointestinal tract: often constipation; infrequently - vomiting, nausea; unknown frequency - pancreatitis.

Disorders from the liver and bile ducts: often - increased indicators of "liver" enzymes; an unknown frequency is hepatitis.

Disturbances from the respiratory system, chest and mediastinal organs: often - shortness of breath.

General disorders and disorders at the site of administration: often - headache; infrequently - fatigue.

* Hallucinations were mainly observed in patients with Alzheimer's disease at the stage of severe dementia.

In the postmarketing period, the following adverse reactions were reported: agranulocytosis, leukopenia (including neutropenia), pancytopenia, thrombocytopenia, thrombocytopenic purpura, hepatitis, acute renal failure, Stevens-Johnson syndrome.

Overdose:

Symptoms

With relatively large overdoses (200 mg once and 105 mg / day for 3 days), the following symptoms were noted: fatigue, weakness and / or diarrhea or symptoms were absent.

In cases of an overdose of 140 mg once, or in the case of taking an unknown dose, patients experienced side effects from the central nervous system: confusion, hypersomnia, drowsiness, dizziness, agitation, aggression, hallucinations, gait disturbance and / or digestive system: vomiting, diarrhea.

In the worst case of overdose (2000 mg memantine), the patient survived, with adverse reactions from the nervous system (coma for 10 days, then diplopia and agitation). The patient received symptomatic treatment and plasmapheresis. The patient recovered without further complications. In another case of severe overdose (400 mg), the patient also survived and recovered. There are described side reactions from the central nervous system: anxiety, psychosis, visual hallucinations, convulsive alertness, drowsiness, stupor and loss of consciousness.

Treatment

In case of an overdose, symptomatic treatment is performed. There is no specific antidote. It is necessary to use standard medical measures for excretion of active substance from the stomach, for example, gastric lavage, reception of activated carbon, acidification of urine, it is possible to perform forced diuresis.

Interaction:

With simultaneous use with drugs levodopa, dopamine receptor antagonists and m-holinoblokatorami action of the latter can be strengthened.

With simultaneous use with barbiturates, neuroleptics, the effect of the latter may decrease.With simultaneous application, the effect of dantrolene or baclofen can be altered (enhanced or decreased), so the doses of the drugs should be selected individually. Simultaneous administration with amantadine, ketamine, phenytoin and dextromethorphan should be avoided because of the increased risk of developing psychosis. Possible an increase in plasma concentrations of cimetidine, ranitidine, procainamide, quinidine. quinine and nicotine with simultaneous administration with memantine.

It is possible to reduce the level of hydrochlorothiazide when taken concomitantly with memantine.

Possible an increase in INR (an international normalized ratio) in patients taking oral anticoagulants (warfarin).

Memantine can increase the excretion of hydrochlorothiazide.

Simultaneous use with antidepressants, selective serotonin reuptake inhibitors and monoamine oxidase inhibitors requires close monitoring of patients.

The pharmacokinetic interaction of memantine with glibenclamide, metformin, donepezil, galantamine is absent.

In conditions in vitro memantine does not inhibit isoenzymes CYP1A2, 2A6, 2C9, 2D6, 2E1, 3A, flavin-containing monoxidase, epoxyhydrolase, or sulfation.

Special instructions:

It is recommended to be used with caution in patients with epilepsy, history of seizures or in patients with a predisposition to epilepsy.

The simultaneous use of memantine and antagonists should be avoided NMDA- receptors, such as amantadine, ketamine or dextromethorphan. These compounds act on the same receptor system as memantine, therefore unwanted reactions (mainly associated with the central nervous system) can occur more often and be more pronounced.

The presence of factors influencing the pH of the urine (sudden changes in diet, for example, the transition from a diet that includes animal products to a vegetarian diet, or intensive consumption of alkaline gastric buffers), as well as renal tubular acidosis or severe urinary tract infections caused by Proteus spp., require careful monitoring of the patient's condition.

Of the majority of clinical studies, patients with a history of myocardial infarction decompensated by chronic heart failure (III-IV functional class by classification NYHA) or uncontrolled hypertension were excluded.Therefore, data on the use of memantine in these patients are limited, the drug should be taken under close medical supervision.

Effect on the ability to drive transp. cf. and fur:In patients with Alzheimer's disease, at the stage of moderate or severe dementia, the ability to drive vehicles and manage complex mechanisms is usually impaired. Besides, memantine can cause a change in the reaction rate, so patients need to refrain from managing motor vehicles or working with complex mechanisms.

Form release / dosage:

Tablets, film-coated 10 mg, 20 mg.

Packaging:

Dosage of 10 mg:

For 10 tablets in a blister of PVC / PE / PVDC / aluminum foil.

3, 6 or 9 blisters together with instructions for use in a cardboard box.

For 7 tablets in a blister of PVC / PE / PVDC / aluminum foil.

1 blister together with instructions for use in a cardboard box.

Dosage of 20 mg:

For 10 tablets in a blister of PVC / PE / PVDC / aluminum foil.

1, 6 or 9 blisters together with instructions for use in a cardboard box. For 7 tablets in a blister of PVC / PE / PVDC / aluminum foil.

1 blister together with instructions for use in a cardboard box.

Storage conditions:

Store at a temperature not exceeding 25 ° C.

Keep out of the reach of children.

Shelf life:

2 years. Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LP-004184

Date of registration:15.03.2017

Expiration Date:15.03.2022

The owner of the registration certificate:Teva Pharmaceutical Enterprises Co., Ltd.Teva Pharmaceutical Enterprises Co., Ltd. Israel

Manufacturer: & nbsp

TEVA Pharmaceutical Industries, Ltd. Israel

Representation: & nbspTeva Teva Israel

Information update date: & nbsp04.04.2017

Illustrated instructions

Instructions

Noogeron-Teva (Noojerone-Teva)