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

Excipients: lactose monohydrate - 174.75 mg, cellulose microcrystalline - 52,10 mg, talc - 11,15 mg, silicon dioxide colloid, anhydrous - 1,25 mg, magnesium stearate - 0,75 mg;

tablet shell: 33G28707 Opaprai II white (hypromellose (E 464) - 40,000%, lactose monohydrate 22,000%, macrogol 3000 8,000%, titanium dioxide (E 171) 24,000%, triacetin 6,000%) 2.00 mg, carnauba wax - q. s.

Description:

Tablets covered with a film coat of white or almost white color, biconvex, oblong, with rounded ends, narrowed in the middle, with a risk on each 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, by chemical structure and pharmacological properties, is close to amantadine. Being 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 membrane potential, improves the process of nerve impulse transmission. Improves cognitive processes, increases daily activity.

Pharmacokinetics:

Suction

Eating does not affect absorption. After oral administration memantine quickly and completely absorbed from the gastrointestinal tract. The maximum concentration in the blood plasma is reached within 3-8 hours after taking a single dose.

Distribution

Daily intake of a daily dose of 20 mg leads to an equilibrium plasma concentration of memantine 70-150 ng / ml. When a daily dose of 5-30 mg is used, the ratio of the average concentration in the cerebrospinal fluid to the concentration in the blood plasma is 0.52. The volume of distribution is about 10 l / kg. About 45% of memantine binds to blood plasma proteins.

Metabolism

80% of memantine circulating in the blood is unchanged substance. The main metabolites are N-3,5-dimethylgludantan, isomer mixture of 4- and 6-hydroxymemanthine and 1-nitroso-3,5-dimethyladamantane. None of the metabolites has antagonistic activity in relation to NMDAreceptors, i.e., does not have pharmacological activity. The involvement of cytochrome P450 in metabolism in vitro not found.

Excretion

Memantine is excreted mainly by the kidneys with urine. Excretion occurs single-phase, the half-life is 60-100 hours. 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. Kidney excretion also includes tubular reabsorption, possibly mediated cationic transport proteins. With an alkaline urine reaction, excretion slows down (an average of 80% with a pH of 8). The alkalinization of urine can be caused by a sudden change in diet, for example, when switching from a diet that includes animal products to a vegetarian diet, or due to the intensive use of alkaline gastric buffers.

With normal renal function, no cumulation of the drug was noted.

Linearity

Studies conducted with volunteers showed that pharmacokinetics is linear in the dose range of 10-40 mg.

Pharmacokinetic / pharmacodynamic dependence

When using memantine at a dose of 20 mg / day, the level of concentration in the cerebrospinal fluid corresponds to the value of the inhibition constant (Ki), that for memantine is 0.5 μmol in the region of the frontal cortex of the brain.

Indications:

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

Contraindications:

- Hypersensitivity to memantine and / or to any auxiliary substance of the drug;

- severe hepatic insufficiency (class C according to the Child-Pugh classification);

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

- Pregnancy;

- the period of breastfeeding;

- Children under 18 years of age (efficacy and safety not established).

If you have any of the listed conditions, always consult a doctor before taking the drug.

Carefully:

- thyrotoxicosis;

- Epilepsy, predisposition to epilepsy;

- convulsions (including in the anamnesis);

- simultaneous use of antagonists NMDA-receptors (amantadine, ketamine, dextromethorphan);

- the presence of factors that increase the pH of urine (a sharp change in diet, for example, the transition to a vegetarian diet, a copious intake of alkaline gastric buffers);

- renal tubular acidosis;

- severe urinary tract infections caused by bacteria of the genus Proteus;

- myocardial infarction (in history);

- heart failure (III-IV functional class by classification NYHA);

uncontrolled arterial hypertension;

- kidney failure;

- hepatic insufficiency (class A and B according to the Child-Pugh classification).

Pregnancy and lactation:

Pregnancy

The use in pregnancy is contraindicated, since there is no evidence of the effect of memantine on the course of pregnancy. Experimental studies conducted on animals indicate the possibility of slowing intrauterine growth at the level of exposure to identical or slightly higher concentrations of memantine compared to those in humans. A potential risk to a person is not known.

Breastfeeding period

It is not known whether excretion of memantine occurs in breast milk, therefore, women taking memantine, you should stop breastfeeding.

Dosing and Administration:

Therapy with memantine should be initiated and conducted under the supervision of a physician with experience in the diagnosis and treatment of Alzheimer's dementia. Before the start of treatment it is necessary to provide care for the patient with a view to regular monitoring of the patient's drug intake. The diagnosis is made in accordance with the current recommendations. The tolerability and dosage of memantine should be reviewed regularly, preferably within the first three months after initiation of treatment.

After that, the clinical effectiveness of memantine and the patient's tolerability of treatment should be reviewed according to current clinical guidelines. Supportive treatment can be continued indefinitely until a positive therapeutic effect is achieved, and until the patient normally tolerates treatment with memantine. Remission of memantine should be discontinued in the absence of a positive therapeutic effect or if the patient is intolerant of the drug.

For oral administration. Apply once a day at the same time, regardless of food intake. Begin treatment memantine recommended with the use of minimally effective doses.

Scheme of treatment: during the first week of therapy (days 1-7) - 5 mg / day; during the second week (days 8-14) - 10 mg / day; during the third week (days 15-21) - 15 mg / day; starting with the fourth week - 20 mg / day.

The recommended maintenance dose is 20 mg / day.

The maximum daily dose is 20 mg.

Special patient groups

In patients older than 65 years, as well as patients with creatinine clearance 50-80 ml / min correction of the dose is not required.

Patients with moderate renal insufficiency

When creatinine clearance is 30-49 ml / min, the recommended daily dose initially does not exceed 10 mg. In the future, with good tolerability of the drug for 7 days, the dose can be increased to 20 mg according to the standard scheme. In severe renal failure (creatinine clearance 5-29 ml / min) daily dose should not exceed 10 mg.

Patients with impaired hepatic function

Patients with mild to moderate liver impairment (class A and B according to the Child-Pugh classification) do not need to adjust the dosage regimen.

Patients with severe impairment of liver function (class C according to the Child-Pugh classification) use of memantine is contraindicated.

Side effects:

The following are side effects,classified by groups of systems and organs and frequency: very often (≥1 / 10); often (≥1 / 100 to <1/10); infrequently (≥1 / 1000 to <1/100); rarely (≥1 / 10,000 to <1/1000); very rarely (<1/10 000), including individual messages; the frequency is unknown (there is currently no data on the prevalence of adverse reactions).

From the central nervous system

Often: headache, dizziness, drowsiness, imbalance.

Infrequent: gait disturbance, confusion, hallucinations (hallucinations were observed, mainly, in patients with dementia of the Alzheimer's type of severe degree).

Very rarely: convulsions.

The frequency is unknown: psychotic reactions, impaired consciousness, increased excitability, depression, anxiety, suicidal thoughts, increased intracranial pressure, muscle hypertonia.

From the side of the cardiovascular system

Often: increased blood pressure.

Infrequent: venous thrombosis / thromboembolism, heart failure.

From the digestive system

Often: constipation.

Infrequent: nausea, vomiting.

The frequency is unknown: pancreatitis, hepatitis.

From the respiratory system

Often: shortness of breath.

From the genitourinary system

The frequency is unknown: acute renal failure, cystitis, increased libido. Allergic reactions

Often: hypersensitivity to the components of the drug.

The frequency is unknown: allergic reactions, Stevens-Johnson syndrome.

From the skin

Frequency unknown: thrombocytopenic purpura.

Laboratory indicators

Often: increased activity of "liver" enzymes.

Frequency unknown: agranulocytosis, leukopenia (including neutropenia), pancytopenia, thrombocytopenia.

Other

Infrequent: increased fatigue.

Rarely: fungal infections.

Frequency unknown: Candidiasis.

In the post-registration period, patients with Alzheimer's disease were registered with depression, suicidal thoughts and suicides.

There are separate reports of the occurrence of adverse reactions when the drug is used in clinical practice: dizziness, drowsiness, intracranial pressure, nausea, hallucinations, headache, impaired consciousness, hypertension of muscles, gait disturbance, depression, convulsions, psychotic reactions, suicidal thoughts, constipation, pancreatitis, candidamycosis, increased blood pressure,vomiting, cystitis, increased libido, venous thrombosis, thromboembolism, allergic reactions.

If any of the side effects listed in the manual are aggravated, or if you notice any other side effects not listed in the instructions, tell your doctor.

Overdose:

There are limited data on overdose, obtained during clinical trials and post-registration surveillance.

Symptoms

Overdosing with the use of relatively large doses of memantine (200 mg once, or 150 mg per day for 3 days) is expressed by symptoms of fatigue, weakness and / or diarrhea or the absence of symptoms. An overdose of a single or unknown amount of memantine when administered to a single dose of 140 mg of memantine is expressed by symptoms associated with the central nervous system (confusion, drowsiness, dizziness, vertigo, anxiety, agitation, hallucinations, gait disturbance) and / or gastrointestinal disturbances (vomiting, diarrhea ).

In the most serious cases of overdose, the patient survived after taking more than 2000 mg of memantine with adverse effects from the nervous system (coma for 10 days, later diplopia, agitation).The patient received symptomatic therapy and plasmapheresis and recovered without consequences.

Another described case of a serious overdose is 400 mg of memantine once. The patient recovered without consequences. There were undesirable phenomena from the nervous system: anxiety, psychosis, visual hallucinations, stupor, seizures, drowsiness, unconsciousness.

Treatment

Symptomatic therapy, gastric lavage, reception of activated charcoal, urine acidification, forced diuresis (if necessary). There is no specific antidote.

Interaction:

With the simultaneous use of memantine with preparations of levodopa, dopamine receptor agonists, m-holinoblokatorami their action may increase.

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

Simultaneous use of memantine with dantrolene or baclofen, as well as with spasmolytic drugs, can change (increase or decrease) their effect, so the doses of the drugs should be selected individually. The simultaneous use of memantine with amantadine, ketamine, phenytoin and dextromethorphan should be avoided because of the increased risk of developing psychosis.

With the simultaneous use of memantine with cimetidine, ranitidine, procainamide, quinidine, quinine and nicotine, the risk of increasing memantine concentration in the blood plasma increases.

With the simultaneous use of memantine with hydrochlorothiazide, a decrease in the concentration of hydrochlorothiazide in the blood plasma is possible due to an increase in its excretion from the body.

When used simultaneously with oral indirect anticoagulants (warfarin) it is possible to raise the international standardized ratio (INR). It is recommended to regularly monitor prothrombin time or INR in patients taking indirect anticoagulants simultaneously with memantine.

When used simultaneously with antidepressants, selective serotonin reuptake inhibitors and monoamine oxidase inhibitors, careful monitoring of patients is necessary.

According to the data of pharmacokinetic studies, in the young healthy volunteers, no single effects of memantine with glibenclamide / metformin or donepezil were observed.Clinical studies also did not reveal the effect of memantine on the pharmacokinetics of galantamine in young healthy volunteers.

In studies in vitro memantine did not inhibit isoenzymes CYP 1A2, 2A6, 2C9, 2D6, 2E1, 3A, monooxygenase containing flavin, epoxyhydrolase, and sulfation.

In case you are taking other medicines, Before using the drug, you should consult your doctor.

Special instructions:

An alkaline urine reaction requires a more careful observation of such patients because of the slower release of memantine. It is necessary to take into account some factors that cause an alkaline reaction of urine: abrupt changes in diet (replacement of meat ration for vegetarian or intensive use of antacid gastric agents), tubular renal acidosis or severe urinary tract infection caused by Proteus spp.

It should be carefully monitored for patients with a history of myocardial infarction, with chronic heart failure (III-IV functional class by classification NYHA) or uncontrolled hypertension, since data on the use of memantine in such patients are limited.

Use with caution in patients with thyrotoxicosis, epilepsy, convulsions (including anamnesis) and predisposition to epilepsy.

The simultaneous use of memantine and antagonists should be avoided NMDA- receptors (amantadine. ketamine, dextromethorphan), because adverse reactions can occur more often and with greater intensity, mainly at the level of the central nervous system.

The drug TINGREX® contains lactose monohydrate, therefore patients with hereditary intolerance to galactose, lactase deficiency or glucose-galactose malabsorption should not use it.

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

In patients with Alzheimer's dementia of moderate to severe severity, 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 7 tablets in a planar cell packaging made of polyvinylchloride film and aluminum foil.For 4 or 8 contour packagings together with the instructions for use are placed in a pack of cardboard.

For 10 tablets in a planar cell packaging made of polyvinylchloride film and aluminum foil. By 3, 6, 9 or 10 contour mesh packages together with the instruction for use are placed in a pack of cardboard.

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 expiry date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LP-003819

Date of registration:05.09.2016

Expiration Date:05.09.2021

The owner of the registration certificate:GRINDEX, JSC GRINDEX, JSC Latvia

Manufacturer: & nbsp

GRINDEX, AO Latvia

Representation: & nbspGrindeks Rus, Open CompanyGrindeks Rus, Open CompanyRussia

Information update date: & nbsp07.10.2016

Illustrated instructions

Instructions

Tingrex® (Tingrex®)