List of information required before use
Contraindications

• hypersensitivity to the active substance or to any of the excipients
• severe liver dysfunction
• pregnancy and lactation
• children and adolescents under 18 years of age

Necessary precautions for use
Caution should be exercised when prescribing the drug to patients with epilepsy, patients with episodes of seizures in the anamnesis, as well as patients with risk factors for the development of epilepsy.
Concomitant use of N-methyl-D-aspartate (NMDA) antagonists such as amantadine, ketamine, or dextromethorphan should be avoided. These compounds act on the same receptor system as memantine, so side effects (mostly related to the central nervous system) may be more frequent or more severe.
Some factors that cause an increase in urine pH may require close monitoring of the patient. These factors include abrupt changes in diet, such as replacing a meat-rich diet with a vegetarian diet or heavy use of antacid gastric antacids. In addition, urine pH may be elevated in renal tubular acidosis (RTA) or severe urinary tract infections caused by Proteus bacteria.
During most clinical trials, patients with recent myocardial infarction and patients with decompensated congestive heart failure (New York Heart Association class III-IV) and uncontrolled arterial hypertension were excluded. Accordingly, only limited data are available and patients with these conditions should be closely monitored by a physician.
Interactions with other medicinal products
Due to the pharmacological effects and mechanism of action of memantine, the following interactions may occur:
The mechanism of action suggests a possible enhancement of the effects of L-dopa, dopaminergic agonists and anticholinergic agents when NMDA-antagonists such as memantine are used concomitantly. The effects of barbiturates and neuroleptic agents may be attenuated. Concomitant use of memantine and antispasmodics, dantrolene or baclofen may change their effect and necessitate dose adjustment.
Concomitant use of memantine and amantadine should be avoided due to the risk of pharmacotoxic psychosis. Both compounds are chemically related NMDA (N-methyl-D-aspartate)-antagonists.
The same can be said for ketamine and dextromethorphan.
One published report noted a possible risk also with the combination of memantine and phenytoin.
Other medications such as cimetidine, ranitidine, procainamide, quinidine, quinine, and nicotine, which use the same renal cation transport system as amantadine, may also interact with memantine, leading to a potential risk of increased plasma levels of these drugs.
Concomitant use of memantine with hydrochlorothiazide or any combination drug that contains hydrochlorothiazide may result in decreased serum levels of the latter.
In postmarketing studies, isolated cases of increased international normalized ratio (INR) have been reported in patients taking warfarin and memantine concomitantly. Although a causal relationship has not been established, close monitoring of prothrombin time or INR is recommended in patients concomitantly taking oral anticoagulants.
In single-dose pharmacokinetics studies in young healthy subjects, no relevant interactions between memantine and the active ingredient glyburide/metformin or donepezil were observed.
In a clinical study involving young healthy subjects, no significant effect of memantine on the pharmacokinetics of galantamine was observed.
Under in vitro conditions, memantine is not an inhibitor of CYP 1A2, 2A6, 2C9, 2D6, 2E1, 3A, flavin-containing monooxygenase, epoxide hydrolase, or sulfathione.
Special Warnings
Pediatric Use
Memantine is not recommended for use in children and adolescents under 18 years of age due to lack of data on the safety and efficacy of the drug.
During pregnancy or lactation
There are no data on the effect of memantine when administered during pregnancy. Experimental studies in animals indicate a possible retardation of intrauterine growth when exposed to concentrations identical or slightly higher than those used in humans. The potential risk to humans is unknown. Memantine should not be used during pregnancy unless clearly and demonstrably necessary.
It is not known whether memantine is excreted into breast milk; however, this may occur, given the lipophilic nature of the substance. Women who use memantine should refrain from breastfeeding.
Fertility
No adverse effects of memantine on fertility in men and women have been observed.
Special indications concerning excipients
Lactose
Contraindicated in persons with hereditary galactose intolerance, Lapp (LAPP)-lactase enzyme deficiency, glucose-galactose malabsorption.
Peculiarities of the drug effect on the ability to drive a vehicle or potentially dangerous mechanisms
Alzheimer’s disease from moderate to severe forms usually causes impairment of the ability to drive a car and operate mechanisms. Moreover, memantine has an insignificant or moderate effect on human quick reaction time, therefore outpatients should be warned about the need to exercise special caution when driving motor transport or working with equipment.
Directions for use
Dosage regimen
Treatment should be initiated and conducted under the supervision of a physician. Therapy should be initiated only when a guardian or health care provider is present to supervise the patient's intake.
The diagnosis should be made in accordance with current recommendations. Tolerance and dose of memantine should be reassessed regularly, preferably within three months of treatment initiation. Thereafter, the clinical benefit of memantine and the patient’s response to treatment should be regularly evaluated according to current clinical guidelines. Maintenance treatment can be continued as long as the therapeutic benefit is favorable and the patient tolerates memantine treatment. Discontinuation of memantine should be considered when evidence of therapeutic benefit is no longer available or the patient does not tolerate treatment.
Adults
The maximum daily dose is 20 mg. To reduce the risk of adverse reactions, the maintenance dose is determined by gradually increasing the dose by 5 mg per week for the first 3 weeks as follows:
Week 1 (Day 1-7): take 5 mg (half of Memantine 10 mg tablet) per day for one week;
Week 2 (Day 8-14): take 10 mg (one Memantine 10 mg tablet or half of a Memantine 20 mg tablet) per day for one week;
Week 3 (day 15-21): take 15 mg (one and a half Memantine 10 mg tablets) per day for one week;
starting week 4: take 20 mg (2 Memantine 10 mg tablets or 1 Memantine 20 mg tablet) per day every day.
The recommended maintenance dose is 20 mg per day.
The duration of treatment is individually determined by a physician experienced in the diagnosis and treatment of Alzheimer’s disease.
Elderly patients
The recommended dose for patients over 65 years of age is 20 mg daily (2 tablets of Memantine 10 mg or 1 tablet of Memantine 20 mg once daily) as indicated.
Patients with impaired renal function
For patients with mild renal impairment (creatinine clearance 50-80 ml/min), no dose reduction is required. For patients with moderate renal impairment (creatinine clearance 30-49 ml/min), the daily dose should be reduced to 10 mg. The dose can be increased to 20 mg daily according to the standard regimen if there are no adverse reactions after at least 7 days of treatment. In patients with severe renal impairment (creatinine clearance 5-29 ml/min) the daily dose should be reduced to 10 mg.
Patients with impaired liver function
No dose adjustment is required for patients with mild to moderate hepatic impairment (Child-Pugh A, B). The use of memantine in patients with severe hepatic insufficiency is not recommended.
Method and route of administration
For oral administration.
The drug should be administered once a day, every day at the same time. Tablets can be administered independently of meals.
Measures to be taken in case of overdose
Symptoms: increased severity of side effects. Possible symptoms of overdose may include fatigue, weakness and/or diarrhea, confusion, drowsiness, dizziness, agitation, aggression, hallucinations and gait disturbance, or memantine overdose may occur without symptoms.
Treatment: In case of overdose treatment should be symptomatic.
There is no specific antidote for intoxication or overdose. Gastric lavage, activated charcoal to prevent potential recirculation in the intestine and liver, acidification of urine, forced diuresis.
If signs and symptoms of generalized central nervous system hyperstimulation occur, symptomatic therapy should be administered with caution.
Measures necessary in case of missing one or more doses of the medicinal product
A double dose should not be taken to make up for a missed dose of the drug. The next dose should be taken at the usual time.
Recommendations on how to consult a health care professional for clarification of how to use the medicinal product
If you have additional questions on the use of this drug, you should consult your attending physician.
Description of adverse reactions that occur during standard use of the drug and measures to be taken in this case
Frequently

• hypersensitivity to the active substance or to any of the medicine components
• drowsiness
• dizziness
• impaired balance
• hypertension
• dyspnea
• constipation
• Increased liver function
• headache

Infrequently

• fungal infections
• confusion
• hallucinations
• gait disturbances
• heart failure
• Venous thrombosis/thromboembolism
• vomiting
• increased fatigue

Very rare

• seizures

Frequency unknown

• psychotic reactions
• pancreatitis
• hepatitis

Alzheimer’s disease is associated with depression, suicidal tendencies, and suicide attempts. In the post-registration period, such cases have been reported in patients who used memantine.
If adverse drug reactions occur, contact your health care provider, pharmacist, or directly to the Adverse Drug Reactions (Actions) Information Database, including reports of drug ineffectiveness
Republican State enterprise on the Right of Economic Management National Center for Expertise of Medicines and Medical Devices of the Committee for Medical and Pharmaceutical Control of the Ministry of Healthcare of the Republic of Kazakhstan
http://www.ndda.kz
or
Kazakh Pharmaceutical Company MEDSERVICE PLUS RK, LLP
tel: +7 771 702 9595 (round the clock)
e-mail: qppvmsp@medservice.kz
Additional information
Composition of the medicinal product
One tablet contains:
active substance: memantine hydrochloride - 10 mg or 20 mg (equivalent to memantine - 8.31 mg or 16.62 mg, respectively)
excipients:
lactose monohydrate, microcrystalline cellulose, talc, silicon dioxide colloidal anhydrous, magnesium stearate;
film coating (Memantine tablets 10 mg):
lactose monohydrate, hypromellose (15 cP), titanium dioxide (E171), macrogol 4000, purified water;
film coating (Memantine tablets 20 mg):
lactose monohydrate, hypromellose (15 cP), titanium dioxide (E171), macrogol 4000, iron oxide yellow (E172), iron oxide red (E172), purified water.
Description of appearance, odor, taste
Round tablets, film-coated, white, biconvex, with a wide, pressure-sensitive score line on one side and the marking “M9MN” and “10” on the other (for a dosage of 10 mg).

Oval-shaped, film-coated tablets of pink color, biconvex, with a wide, pressure-sensitive score line on one side and the marking “M9MN” and “20” on the other (for a dosage of 20 mg).
Dosage form and packaging
10 tablets in a blister pack made of polyvinyl chloride film and aluminum foil.
3 blister packs together with instructions for medical use in Kazakh and Russian are placed in a cardboard pack.
Shelf life
3 years
Do not use after the expiration date.
Storage conditions
Store in the original packaging at a temperature not exceeding 25 °C.
Keep out of the reach of children!