Maruksa, 20 mg 30 pcs

Moderate to severe dementia of the Alzheimer type.

Active ingredient

Composition

for 1 tablet

kernel:

Active substance:

Memantine hydrochloride 20.00 mg

Associates: lactose monohydrate, microcrystalline cellulose type 102, colloidal silicon dioxide, talc, magnesium stearate

Shell film: methacrylic acid and ethyl acrylate copolymer (1 : 1), 30% aqueous dispersion1, talc, triacetin, simethicone emulsion2

1 30% aqueous dispersion contains, in addition to methacrylic acid and ethyl acrylate copolymer, also sodium lauryl sulfate and polysorbate-80 as emulsifiers.

2 Simethicone emulsion contains: dimethicone, colloidal silicon dioxide hydrated, macrogoal stearyl ether, hydrogen peroxide, sorbic acid, water.

How to take, the dosage

The therapy should be supervised by a physician experienced in the diagnosis and treatment of dementia in Alzheimer’s disease. Therapy should only be initiated if the regular caregiver will monitor the patient’s medication intake. The diagnosis should be made according to current guidelines.

The tolerability and dose of Maruksa® should be evaluated regularly, preferably within three months of starting therapy. Thereafter, the clinical efficacy of the drug and tolerability of therapy should be regularly evaluated according to current clinical guidelines. Maintenance therapy can be continued indefinitely if there is therapeutic benefit and good tolerability of Maruksa®. The use of Maruksa® should be discontinued if the therapeutic effect is no longer observed or if the patient cannot tolerate the therapy.

Orally, once daily and always at the same time, regardless of meals.

Selection of therapy with Maruksa®, film-coated tablets, in a dose of 20 mg is not possible. For selection of therapy, memantine tablets in a lower dose of 10 mg can be used.

In order to reduce the risk of side effects, a gradual dose increase is recommended: 5 mg per week during the first 3 weeks of therapy. The recommended maintenance dose is 20 mg per day.

The following dosing regimen is recommended:

Week 1 (days 1-7): the daily dose is 5 mg.

2nd week (day 8-14): 10 mg daily dose.

Week 3 (days 15-21): daily dose – 15 mg.

Starting from the 4th week: daily dose – 20 mg.

Elderly patients (>65 years)

No dose adjustment is necessary.

Kidney function impairment

Dose adjustment is not required in patients with a creatinine clearance (CK) of 50-80 ml/min. Patients with moderate renal insufficiency (CK 30-49 ml/min) are recommended 10 mg/day. In case of good tolerability of the drug within 7 days, the dose can be increased to 20 mg/day according to the standard scheme. In patients with severe renal insufficiency (CKR 5-29 ml/min) the daily dose should be 10 mg/day.

Liver function disorders

In patients with mild to moderate impairment of liver function (Child-Pugh grades A and B), no dose adjustment is necessary. In patients with severe hepatic impairment (Child-Pugh class C) Maruksa® is contraindicated.

Interaction

Potentiate the effects of levodopa, dopamine receptor agonists and anticholinergic drugs.

The efficacy of barbiturates, antipsychotic (neuroleptics) drugs decreases with the simultaneous use of memantine.

Simultaneous use of memantine with dantrolene and baclofen, as well as with spasmolytics may be accompanied by the change of their effect that requires adjustment of the dose of these drugs.

Concurrent use of memantine and amantadine should be avoided due to the risk of psychosis. Memantine and amantadine belong to the group of NMDA-receptor antagonists. The risk of psychosis is also increased when memantine is used concomitantly with phenytoin, ketamine and dextromethorphan.

Concurrent use with cimetidine, ranitidine, procainamide, quinidine, quinine and nicotine increases the risk of increased plasma concentration of memantine.

Simultaneous use with hydrochlorothiazide may decrease the plasma concentration of hydrochlorothiazide due to its increased excretion from the body.

International normalized ratio (INR) increase is possible in patients who simultaneously take oral indirect anticoagulants (warfarin).It is recommended to monitor prothrombin time or INR regularly.

Concomitant use with antidepressants, selective serotonin reuptake inhibitors and monoamine oxidase inhibitors requires close patient monitoring.

No drug interactions have been reported with a single concomitant use of memantine with gibenclamide/metformin or donepizil in healthy volunteers.

No changes in the pharmacokinetics of galanthamine in healthy volunteers were noted when used concomitantly with memantine.

Under in vitro conditions Memantine does not inhibit the CYP 1A2, 2A6, 2C9, 2D6, 2E1, 3A, flavin-containing monooxygenase, epoxide hydrolase, or sulfation isoenzymes.

Special Instructions

Epilepsy, thyrotoxicosis, predisposition to seizures, simultaneous use of NMDA-receptor antagonists (amantadine, ketamine, dextromethorphan), factors that increase urinary pH (sudden change in diet, e.g. switch to vegetarianism, heavy intake of alkaline gastric buffers), renal tubular acidosis, severe urinary tract infections caused by Proteus spp., myocardial infarction (history), NYHA functional class III-IV heart failure, uncontrolled arterial hypertension, renal failure, liver failure.

It is contraindicated in children under 18 years old (effectiveness and safety is not established).

Patients of advanced age (over 65)

No dose adjustment is required.

Kidney function impairment

Dose adjustment is not required in patients with a creatinine clearance (CK) of 50-80 ml/min. Patients with moderate renal insufficiency (CK 30-49 ml/min) are recommended 10 mg/day. In case of good tolerability of the drug within 7 days, the dose can be increased to 20 mg/day according to the standard scheme. In patients with severe renal insufficiency (CKR 5-29 ml/min) the daily dose should be 10 mg/day.

Liver function disorders

In patients with mild to moderate impairment of liver function (Child-Pugh grades A and B), no dose adjustment is necessary. In patients with severe hepatic impairment (Child-Pugh class C) Maruksa® is contraindicated.

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

Concurrent use of memantine and NMDA receptor antagonists such as amantadine, ketamine, or dextromethorphan should be avoided. These compounds act on the same receptor system as memantine, therefore adverse reactions (mostly central nervous system related) may be more frequent and severe.

The presence in a patient of factors affecting elevated urinary pH (abrupt dietary changes, such as switching 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 close monitoring of the patient’s condition.

Patients with a history of myocardial infarction, decompensated chronic heart failure (NYHA functional class III-IV), or uncontrolled arterial hypertension were excluded from most clinical trials. Therefore, data on the use of memantine in such patients are limited and the drug should be administered under close medical supervision.

In patients with moderate to severe dementia with Alzheimer’s disease, the ability to drive vehicles and operate complex machinery is usually impaired. In addition, memantine may cause changes in reaction speed, so patients should refrain from driving or operating complex machinery.

Synopsis

Oval, biconvex, film-coated white tablets.

Contraindications

Side effects

World Health Organization (WHO) classification of side effect frequency:

very frequently ≥1/10

often ≥ 1/100 to < 1/10

infrequently from ≥ 1/1000 to < 1/100

rarely from ≥ 1/10000 to < 1/1000

very rarely < 1/10000

frequency is unknown cannot be estimated from available data.

In clinical trials, the overall incidence of adverse reactions did not differ when taking memantine and placebo. They were generally mild to moderate in severity. The most common adverse reactions in the memantine group compared to placebo were dizziness (6.3% vs. 5.6%, respectively), headache (5.2% vs. 3.9%), constipation (4.6% vs. 2.6%), drowsiness (3.4% vs. 2.2%, respectively) and hypertension (4.1% vs. 2.8%, respectively).

Side effects are presented as a MedDRA classification table:

Infectious and parasitic diseases

Infrequent

Fungal infections

Blood and lymphatic system disorders

Frequency unknown

Agranulocytosis, leukopenia (including neutropenia), pancytopenia, thrombocytopenia, thrombocytopenic purpura

Immune system disorders:

often

hypersensitivity to the drug components

Mental disorders

often

Sleepiness

Not often

Confusion

Hallucinations1

Frequency unknown

Psychotic reactions

Nervous system disorders

often

Dizziness, balance problems

Not often

Gait disturbance

Very rarely

Cramps

Heart disorders

Infrequently

Heart failure

Vascular disorders

often

Increased blood pressure

infrequent

Venous thrombosis/thromboembolism

disorders of the respiratory system, thorax and mediastinum organs

often

Shortness of breath

Gastrointestinal disorders

often

constipation

Not often

Nausea, vomiting

Frequency unknown

Pancreatitis

Liver and biliary tract disorders

often

Increased activity of “liver” enzymes

Frequency unknown

Hepatitis

Renal and urinary tract disorders

Frequency unknown

acute renal failure

Skin and subcutaneous tissue disorders

Frequency unknown

Stevens-Johnson syndrome

General disorders and disorders at the injection site

often

Headache

Infrequently

Fatigue

1Hallucinations were observed primarily in patients with Alzheimer’s disease in the severe dementia stage.

The following adverse reactions have been reported during post-registration use: Dizziness, somnolence, increased excitability, increased fatigue, restlessness, increased intracranial pressure, nausea, hallucinations, headache, impaired consciousness, muscle hypertonicity, gait disturbance, depression, seizures, psychotic reactions, suicidal thoughts, constipation, nausea, pancreatitis, candidiasis, increased blood pressure, vomiting, cystitis, increased libido, venous thrombosis, thromboembolism and allergic reactions.

Overdose

Symptoms:increased severity of side effects such as fatigue, weakness, diarrhea, confusion, drowsiness, dizziness, agitation, hallucinations, gait disturbance, nausea.

In the most severe case of overdose (2000 mg memantine), the patient survived, with adverse nervous system reactions (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. Central nervous system adverse reactions have been described: anxiety, psychosis, visual hallucinations, seizure readiness, somnolence, stupor, and loss of consciousness.

Treatment:in case of overdose, treatment is symptomatic. There is no specific antidote. Standard therapeutic measures aimed at elimination of the active substance from the stomach are necessary, such as gastric lavage, activated charcoal intake, urine acidification, forced diuresis is possible.

Pregnancy use

Due to a possible delay in intrauterine development, the drug Maruksa® is not used in pregnancy.

There is no data on memantine excretion with breast milk. However, due to lipophilicity of memantine, excretion is possible. Therefore, breast-feeding should be discontinued during the treatment with Maruksa®.

Similarities