Memantine-Alvogen - instructions for use, dose, side effects, contraindications

Component	amount, mg
Component	10 mg	20 mg
Active substance:
Memantine hydrochloride	10,0	20,0
Excipients:
Polakrilin	25,0	50,0
Microcrystalline cellulose	65,0	130,0
Lactose Monohydrate	12,5	25,0
Croscarmellose sodium	7,5	15,0
Mannitol	119,75	239,5
Aspartame	2,5	5,0
Silica colloidal dioxide	2,5	5,0
The iron dye red oxide (E 172)	0,25	0,5
A peppermint flavor (maltodextrin 71.0%, modified starch (E1450) 2.5%, peppermint oil 26.0%)	1,25	2,5
Magnesium stearate	3,75	7,5

Description:

Dosage of 10 mg:

Round, flat tablets with bevelled edges, light pink with interspersed more dark and light colors, engraved "10" on one side.

Dosage of 20 mg:

Round, flat pills with beveled edges, light pink with interspersed more dark and light colors, engraved "20" on one side.

Pharmacotherapeutic group:Dementia remedy

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-aspartate (NMDA)-pechainopoin, 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

After oral administration memantine quickly and completely absorbed. Memantine has an absolute bioavailability of about 100%. Average time to reach the maximum concentration in the blood plasma (t_max) is from 3 before 8 hours. There are no data on the effect of food on the absorption of memantine.

Distribution

A daily dose of 20 mg creates an equilibrium concentration of memantine in the blood plasma in the range of 70-150 ng / ml (0.5-1 μmol / l) with large individual variations.With the appointment of a daily dose of 5-30 mg, the ratio of the mean concentration in the cerebrospinal fluid (CSF) to the plasma concentration equal to 0.52 was calculated. The volume of distribution is about 10 l / kg. Approximately 45% of memantine binds to plasma proteins.

Metabolism

In the body, about 80% of circulating memantine-related compounds are present in the form of the ancestors of the class. The main metabolites: N-4-3,5-dimethylgludantan, isomer mixture of 4- and 6-hydroxymemanthine and 1-nitroso-3,5-dimethyladamantane. None of these metabolites is active against NMDAreceptors. In the laboratory (in vitro) a cytochrome P450 mediated metabolism was not detected.

Excretion

In the study with ingestion of a labeled ¹⁴C-memantine more than 84% of the dose was excreted for 20 days, more than 99% was excreted by the kidneys.

In patients with normal renal function, no cumulation of the drug was noted. Memantine is displayed monoexponentially with a half-life (t_1/2) 60-100 h. Memantine is excreted in the urine, with 57-82% is displayed unchanged. In healthy volunteers with normal renal function, the total clearance (Cl_total) is 170 ml / min / 1.73 m², part of which is due to tubular secretion.Renal excretion also includes tubular reabsorption, mediated, possibly, by cationic transport proteins. The rate of renal clearance of memantine may decrease with alkalinization of urine (pH 7-9). The alkalinization of urine can be caused by a dramatic change in the diet, for example, when switching from meat to vegetarian, or because of excessive intake of alkaline gastric buffers.

Linearity

In the range of doses of 10-40 mg in healthy volunteers, linearity of pharmacokinetics was revealed.

Pharmacokinetic / pharmacodynamic relationship

With daily intake of 20 mg memantine, its concentration in the CSF is equal to the value ki (inhibition constant), which in the frontal regions of the brain is 0.5 μmol / l.

Indications:

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

Contraindications:

- Hypersensitivity to memantine or other components of the drug;

- severe renal failure (creatinine clearance 5-29 ml / min);

- severe hepatic impairment;

- children and adolescents under 18 years of age (effectiveness and safety have not been established to date);

- pregnancy;

- breast-feeding;

- lactose intolerance, lactase deficiency, glucose-galactose malabsorption;

- phenylketonuria.

Carefully:

Carefully prescribe to patients with thyrotoxicosis, epilepsy (in the anamnesis); simultaneous use of antagonists NMDA-receptors (amantadine, ketamine, dextromethorphan), the presence of factors that increase the pH of urine (a sudden change in diet, for example, the transition to vegetarianism, a copious intake of alkaline buffer solutions), severe urinary tract infections (caused by Proteus bacteria), myocardial infarction (in the anamnesis), heart failure III-IV functional class (according to classification NYHA), uncontrolled arterial hypertension, renal failure, hepatic insufficiency, predisposition to the development of convulsions, renal tubular acidosis.

Pregnancy and lactation:

There is no data on the use of memantine in pregnant women. A drug Memantine-Alvogen contraindicated in pregnant women.

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 data whether the memantine in breast milk. Taking into account the lipophilic structure of memantine, it can be assumed that memantine can penetrate into breast milk. If you need to take the drug during lactation, breastfeeding should be discontinued.

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 should be evaluated on a regular basis, 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.

Discontinue use if the therapeutic effect is no longer observed or if the patient does not tolerate treatment.

For oral administration.The drug should be taken once a day at the same time, regardless of food intake.

Pills Memantina-Alvogen, dispersible in the oral cavity, easily break down, caution should be exercised when taking it. Do not take the tablets with wet hands, as they may break.

Take the blister by the edges and separate one cell of the blister from the rest of the strip, gently tearing it off the perforations around it.

Carefully remove the cover from the back.

Put the tablet on the tongue, the tablet will dissolve quickly, and you can swallow it without water.

To reduce the risk of adverse events, the dose is achieved by gradual titration at 5 mg per week as follows:

Week 1 (day 1-7)

At 5 mg per day for 7 days

Week 2 (day 8-14)

At 10 mg per day for 7 days

Week 3 and onwards

At 15 mg per day.

The maintenance dose (starting from the 4th week)

At 20 mg per day.

Considering the impossibility of dividing the pill, it is recommended to use the drug memantine in tablets of 5 mg and 15 mg at the stage of dose escalation.

The maximum daily dose is 20 mg per knock.

The recommended maintenance dose is 20 mg per day.

The duration of treatment is determined by the severity of the patient's response to therapy and the tolerability of the drug.

Special patient groups

Elderly patients

In patients older than 65 years, dose adjustment is not required.

Patients with impaired renal function

Patients with mild renal impairment (creatinine clearance 50-80 ml / min) do not need to change the dose. For patients with moderate renal insufficiency (creatinine clearance 30-49 ml / min) daily dose is 10 mg per day. In the future, with good tolerability of the drug for at least 7 days of treatment, the dose can be increased to 20 mg per day according to the standard scheme.

Patients with impaired hepatic function

Dose correction is not required in patients with a mild or moderate liver function disorder (class A and B according to Child-Pugh classification).

Side effects:

The frequency of side effects is classified according to clinical manifestations and frequency: very often (≥1 / 10), often (from ≥1 / 100 to <1/10), infrequently (from ≥1 / 1000 to <1/100), rarely (from ≥1 / 10000 to <1/1000), very rarely (<10000), the frequency is unknown (can not be estimated from the available data).

Infectious and parasitic diseases: infrequently - fungal infections.

Immune system disorders: often - hypersensitivity to the drug.

Disorders of the psyche: infrequent - confusion, hallucinations (mainly observed in patients with severe Alzheimer's disease); frequency unknown - psychotic reactions.

Disturbances from the nervous system: often - headache, dizziness, drowsiness, imbalance; infrequently - gait disturbance; very rarely - cramps.

Disorders from the cardiovascular system: often - increased blood pressure; infrequently - venous thrombosis / thromboembolism, heart failure.

Disturbances from the respiratory system: often - shortness of breath.

Disorders from the digestive system: often constipation; infrequently - vomiting; frequency unknown - pancreatitis.

Disorders from the liver and bile ducts: often - elevated indicators of liver tests.

Other: infrequently - fatigue.

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

In Alzheimer's disease, patients may experience depression, suicidal thoughts and suicide attempts.In clinical practice, these effects were reported in patients.

If any of these instructions side effects are compounded, or if you notice any side effects not listed in this manual, inform the doctor about it.

Overdose:

There are limited data on overdose obtained in the course of clinical trials and post-registration experience with the use of memantine.

Symptoms

With relatively large overdoses (200 mg once and 105 mg per day for 3 days), the following symptoms were noted: fatigue, weakness and / or diarrhea or symptoms were absent. In cases of an overdose at a dose of less than 140 mg once, or in the case of an unknown dose, there were side reactions 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, the patient survived after taking a dose of 2000 mg memantine, he had adverse reactions from the central 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, the patient survived and recovered after taking memantine at a dose of 400 mg once. The patient observed side effects in the central nervous system: anxiety, psychosis, visual hallucinations, decreased seizure threshold, drowsiness, stupor, unconsciousness.

Treatment

Gastric lavage, activated charcoal, symptomatic therapy, acidification of urine, forced diuresis. There is no specific antidote.

Interaction:

Levodopa, dopamine receptor agonists and m-cholinoblocking agents

With the simultaneous use of levodopa, dopamine receptor antagonists, m-holinoblokatorami with the drugs, the effect of the latter can be enhanced.

Barbiturates and antipsychotics

With the simultaneous use of memantine with barbiturates, neuroleptics, the effect of the latter may decrease.

Dantrolene and baclofen

When combined, the effect of dantrolene or baclofen can be altered (enhanced or decreased), so the doses of the drugs should be selected individually.

Amantadine, ketamine, phenytoin and dextromethorphan

Avoid simultaneous use with amantadine, ketamine, phenytoin and dextromethorphan because of the increased risk of developing psychosis.

Cimetidine, ranitidine, procainamide, quinidine, quinine and nicotine

Possible increase in plasma concentrations of cimetidine, ranitidine, procainamide, quinidine, quinine and nicotine while taking with memantine.

Hydrochlorothiazide

It is possible to reduce the concentration of hydrochlorothiazide when used simultaneously with memantine.

Memantine can increase the excretion of hydrochlorothiazide.

Indirect anticoagulants

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

Antidepressants, selective serotonin reuptake inhibitors and monoamine oxidase inhibitors

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

Glibenclamide, metformin and donepezil

The pharmacological interaction of memantine with glibenclamide, metformin or donepezil is absent.

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

Special instructions:

In patients with epilepsy, history of seizures, or in patients with a predisposition for epilepsy, caution should be taken with the drug Memantine-Alvogen.

The joint 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, so unwanted reactions (mainly associated with the central nervous system) can occur more often and be expressed. The presence of a number of factors that can increase urine pH in patients requires careful medical observation. These include: sudden changes in diet, for example, the transition from a meat diet to a vegetarian diet, or a large intake of alkaline gastric buffer solutions. Also, urine pH can be increased by renal tubular acidosis or severe urinary tract infections caused by Proteus spp.

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. Therefore, data on the use of memantine in these patients are limited, and the drug intake Memantine-Alvogen should be carried out under the close supervision of a physician.

Effect on the ability to drive transp. cf. and fur:

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

Form release / dosage:

Tablets dispersible in the oral cavity, 10 mg and 20 mg.

Packaging:

For 15 tablets, dispersible in the mouth, in a blister of Al / OBA / PVC and Al / paper / PET / hot-melt layer.

By 2, 4 or 6 blisters together with instructions for use in a pack of cardboard.

Storage conditions:

In the dark place at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

3 years.

Do not use after the expiry date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LP-004063

Date of registration:09.01.2017

Expiration Date:09.01.2022

The owner of the registration certificate:Alvogen IPKo S.A.L.Alvogen IPKo S.A.L. Luxembourg

Manufacturer: & nbsp

Genepharm, S.A. Greece

Representation: & nbspAlvogen Pharma Trading EuropeAlvogen Pharma Trading Europe

Information update date: & nbsp28.01.2017

Illustrated instructions

Instructions

Memantine-Alvogen (Memantin-Alvogen)