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

Excipients: microcrystalline cellulose 136,80 mg, calcium hydrophosphate 84,50 mg, croscarmellose sodium 4.80 mg, silicon dioxide colloid 1.50 mg, magnesium stearate 2.40 mg;

film sheath: Opadrai II gray 45F27505 8.00 mg (hypromellose-2910 / 15cP 2.5 mg, polydextrose 2.5 mg, titanium dioxide 2.48 mg, macrogol / macrogol-4000 0.5 mg, ferric oxide black oxide 0.02 mg ).

Description:

Oval, biconvex tablets of gray color, covered with a film shell, with engraving "10" and the risk between the figures on one side and engraving "MM" and the risk between the letters on the other side.

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

Pharmacotherapeutic group:dementia treatment

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-D-aspartite (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. The maximum concentration in the blood plasma (C_m_Oh) is from 3 to 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 in 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: N-3,5-dimethyl-gludananthane, the isomer mixture of 4- and 6-hydroxymemanthine and 1-nitroso-3,5-dimethyladamantane do not have intrinsic 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In the study with oral administration ¹⁴C-memantine averaged 84% of the ingested dose was withdrawn within 20 days, with more than 99% excreted by the kidneys.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 (T_1/2) of the terminal phase is from 60 to 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. Alkalinization of urine can be caused by a sudden change in diet, for example, when switching from animal products to 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 (efficacy 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, Noogerone 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, 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.

Tolerance and dose of Noogeron 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 for a therapeutic effect and good tolerability of the drug Noogeron. It should stop using Noogeron if the therapeutic effect is no longer observed or if the patient does not tolerate treatment.

The drug Noogeron is administered orally once a day, the drug should be taken at the same time each 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.

Recommended maintenance dose drug Noogerone: 20 mg per day.

The following is recommended dosing regimen:

1-st week (1-7 days): daily dose - 5 mg 1/2 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 ½ tablets 10 mg).

Starting with the 4th week: a daily dose of 20 mg (1 tablet 10 mg).

Elderly patients (over 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 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; infrequently - confusion, hallucinations *; unknown frequency: psychotic reactions.

Disturbances from the 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.

Disturbances 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.

AT postmarketing period the following adverse reactions have been 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. 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 the simultaneous use of levodopa, dopamine receptor antagonists, m-holinoblokatorami with the drugs, the effect of the latter can be enhanced.

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 increase in plasma concentrations of cimetidine, ranitidine, procainamide, quinidine, quinine and nicotine while taking 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 in the patient of factors that affect the increase in the pH of urine (sudden changes in diet, for example, a change from diet,including products of animal origin, 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 de- compensated for 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.

Packaging:

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

By 3, 6 or 9 blisters 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:

3 years.

Do not use after the expiration date stated on the package.

Terms of leave from pharmacies:On prescription

Registration number:LSR-000973/10

Date of registration:15.02.2010 / 14.01.2013

Expiration Date:Unlimited

The owner of the registration certificate:Pliva of Hrvatska dooPliva of Hrvatska doo Croatia

Manufacturer: & nbsp

PLIVA HRVATSKA, d.o.o. Croatia

TEVA Operations Poland, Sp. z o.o. Poland

Representation: & nbspTeva Teva Israel

Information update date: & nbsp06.12.2016

Illustrated instructions

Instructions

Noogeron (Noojerone)