Properties
What is it?
CARRIER MEMANTINE Composition Each film-coated tablet contains: Memantine hydrochloride - 10.00 mg Excipients: Celactose – 214.80 mg, Lactose – 12.20 mg, Croscarmellose sodium – 4.00 mg, Talc – 5.00 mg, Magnesium stearate – 1.60 mg, Hydroxypropyl methylcellulose – 2.30 mg, Povidone – 0.35 mg, Titanium dioxide – 3.10 mg, Sodium saccharin – 0.15 mg, Polyethylene glycol 6000 – 1.0 mg, Propylene glycol – 0.50 mg Therapeutic properties: Non-competitive inhibitor of NMDA (N-methyl-D-aspartate) receptors, thus reducing glutamatergic hyperactivity. Centrally acting muscle relaxant. Indication: Symptomatic treatment of cognitive disorders in patients with dementia, such as moderate to severe Alzheimer's disease. Treatment of muscle spasticity of central origin. See blog: Alzheimer's - What We Need to Know About the Disease Pharmacological action: Glutamate is the main excitatory neurotransmitter in the brain. Glutamatergic stimulation can lead to neuronal damage (excitotoxicity), which contributes to the pathogenic mechanisms of neurodegenerative diseases. Glutamate stimulates various postsynaptic receptors, including the N-methyl-D-aspartate (NMDA) receptor, which plays a significant role in memory processes and in the pathogenesis of Alzheimer's disease and dementia. As a non-competitive antagonist of NMDA, memantine reduces glutamatergic hyperactivity and thereby exerts its therapeutic effect. Clinical studies: To investigate the efficacy of memantine in Alzheimer's disease, 2 double-blind, placebo-controlled, randomized studies were conducted in the USA, evaluating both cognitive and daily functions. After examining many patients (n=252 and n=404), it was found that all indicators used to assess the above-mentioned functions significantly improved statistically in both studies. In the third study (n=166), improvement was observed in scales used to assess interpersonal relationships, daily functions, and global clinical effects. Pharmacokinetics: After oral administration, it is rapidly and completely absorbed. Its maximum concentration in plasma is reached 6-8 hours later. Its absorption is not dependent on food intake. The half-life of memantine is 60-100 hours. It does not change in the elderly, even in patients with moderate neurological damage. Only 45% of the drug binds to plasma proteins. A very small portion of memantine undergoes metabolism, while 57-82% of the administered dose is excreted unchanged in the urine. The remaining 20-40% is converted into 3 polar metabolites with weak pharmacological activity, which are also excreted in the urine. The main part of the drug is excreted through active tubular secretion. Dosage and administration The dosage of memantine should be selected individually for each patient. Recommended dosages are: Neurocognitive disorders: Week I: 1/2 tablet (5 mg) in the morning Week II: 1/2 tablet (5 mg) in the morning and at lunchtime Weeks III and subsequent: 1 tablet at breakfast and 1/2 or 1 tablet after lunch. Movement disorders of central origin: Week I: 1 tablet per day Week II: 2 tablets per day Week III: 2-3 tablets per day Week IV and subsequent: Dose equivalent to Week III, or depending on therapeutic effect, the dose can be increased up to 60 mg per day. Caution: The last daily dose should be administered by 5 PM. Memantine should be taken with or without food. Dosage in specific populations The dose should be reduced in cases of moderate renal impairment. The efficacy of memantine in patients with severe renal impairment has not been well studied, therefore its use is not recommended. The pharmacokinetics of memantine have not been studied in patients with liver failure. It is likely to have little effect on the drug, as memantine is mainly excreted by the kidneys. Dose titration is performed by a doctor. Contraindications Hypersensitivity to the active substance or any component of the preparation; acute confusional states, severe renal and hepatic impairment, pregnancy and lactation. Precautions This preparation may have a certain effect on driving and operating other machinery. Given that only 20-40% of the drug is metabolized in the liver, the pharmacokinetics of memantine do not significantly change in patients with impaired liver function. Dose reduction is recommended in patients with renal impairment. Any condition (diet, medications, clinical condition, etc.) that creates an alkaline environment in the urine will promote drug accumulation. In such conditions, memantine should be used with caution. Interactions with other medications: Memantine may increase the effect of anticholinergics, neuroleptics, barbiturates, dopaminergic agonists, L-DOPA (e.g., bromocriptine), and amantadine. Combined use with baclofen and dantrolene may have some effect on the drug's efficacy, therefore dose titration is required in such cases. Caution is advised when combining with MAOIs and SSRI antidepressants. Given that the excretion of memantine by the kidneys is reduced by 80% in alkaline urine (pH 8), combined use with acetazolamide or sodium bicarbonate may lead to drug accumulation and increase the risk of side effects. Since memantine is partially excreted via renal tubular secretion, combined use of drugs that also utilize the same cationic system in the kidneys, such as hydrochlorothiazide, triamterene, cimetidine, ranitidine, quinidine, and nicotine, may alter the levels of both drugs. However, in the combined use of memantine and hydrochlorothiazide/triamterene, the bioavailability of memantine and triamterene does not change, while the bioavailability of hydrochlorothiazide decreases by 20%. Side effects: In placebo-controlled clinical trials in patients with dementia, 2% of patients showed signs and symptoms of adverse events, which were more frequent in those treated with memantine than in placebo-treated patients. These adverse events are listed in the table. Other adverse events with a frequency of less than 2% in memantine-treated patients, and higher in placebo-treated patients, include: agitation, self-injury, urinary incontinence, diarrhea, bronchitis, insomnia, urinary tract infection, flu-like symptoms, gait disturbances, depression, upper respiratory tract infection, peripheral edema, nausea, anorexia, arthralgia. Organ or system | Adverse events | Placebo % | Placebo % ---|---|---|--- General | Fatigue | 1 | 2 | Pain | 1 | 3 Cardiovascular system | Hypertension | 2 | 4 Peripheral and central nervous system | Dizziness | 5 | 6 | Headache | 3 | 5 Gastrointestinal system | Constipation | 2 | 3 | Vomiting | 5 | 3 Musculoskeletal system | Lower back pain | 2 | 3 Psychiatric disorders | Confusion | 5 | 6 | Somnolence | 2 | 3 | Hallucinations | 2 | 3 Respiratory system | Cough | 3 | 4 | Dyspnea | 1 | 2 All adverse events that occurred in at least two patients during the conducted studies (excluding the side effects listed in the table) are listed below. These events are not necessarily related to memantine treatment, as similar events occurred with similar frequency in placebo-treated patients. General: Often: loss of consciousness. Rarely: hypothermia, allergic reaction. Cardiovascular system: Often: heart failure. Rarely: angina, bradycardia, myocardial infarction, thrombophlebitis, ventricular fibrillation, hypotension, cardiac arrest, orthostatic hypotension, pulmonary embolism, pulmonary edema. Peripheral and central nervous system: Often: transient ischemic attack, stroke, dizziness, ataxia, hypokinesia. Rarely: paresthesia, extrapyramidal disorders, hypertonia, tremor, aphasia, hyposthenia, coordination disorder, hemiplegia, hyperkinesia, involuntary muscle spasms, stupor, cerebral hemorrhage, neuralgia, ptosis, neuropathy. Gastrointestinal system: Rarely: gastroenteritis, diverticulitis, gastrointestinal hemorrhage, melena, esophageal ulcer. Lymphatic and blood disorders: Often: anemia. Rarely: leukopenia. Nutritional and metabolic disorders: Often: elevated alkaline phosphatase, weight loss. Rarely: dehydration, hyponatremia, worsening of diabetes mellitus. Psychiatric disorders: Often: aggressiveness. Less often: hallucinations, mood changes, emotional instability, neurosis, sleep disturbances, increased libido, psychosis, amnesia, apathy, paranoid reactions, thought disorder, abnormal crying, increased appetite, paranoia, delusion, depersonalization, neurosis, suicide attempt. Respiratory system: Often: pneumonia. Less often: apnea, asthma, hemoptysis. Skin and its appendages: Often: cataracts, conjunctivitis. Rarely: macular degeneration, decreased vision, decreased hearing, tinnitus, blepharitis, blurred vision, corneal opacity, glaucoma, conjunctival hemorrhage, eye pain, retinal hemorrhage, xerophthalmia, diplopia, tear secretion disorder, myopia, retinal detachment. Urinary system: Often: pollakiuria. Rarely: dysuria, hematuria, urinary retention. Overdose A case of overdose was reported where, after taking 400 mg of memantine, the patient developed restlessness, psychosis, visual hallucinations, somnolence, stupor, and clouded consciousness. The patient recovered without residual effects. As with other cases of overdose, symptomatic treatment is required. The excretion of memantine may be enhanced by increasing urine acidity. In case of overdose, contact the nearest hospital or toxicology center. Packaging 10, 30, and 60 film-coated tablets per pack. Shelf life 24 months Storage conditions Store in a cool, dry place, at a temperature of 15-30°C, out of reach of children. Dispensing from pharmacy: By prescription
