Zemotine^® (Tablets) Instructions for Use

Marketing Authorization Holder

Sun Pharmaceutical Industries, Ltd. (India)

ATC Code

N06DX01 (Memantine)

Active Substance

Memantine (Rec.INN registered by WHO)

Dosage Forms

	Zemotine®	Film-coated tablets, 10 mg: 28, 30, or 90 pcs.
		Film-coated tablets, 20 mg: 28, 30, or 90 pcs.

Dosage Form, Packaging, and Composition

Film-coated tablets white or almost white, capsule-shaped, with an engraving “M” and “12” on either side of the score on one side and smooth on the other side.

Excipients: Prosolv HD90 – 179.0 [microcrystalline cellulose – 98%, colloidal silicon dioxide – 2%], croscarmellose sodium – 5 mg, talc – 4 mg, magnesium stearate – 2 mg.
Film coating composition: Opadry white (OY-S-58910) – 6 mg, including hypromellose 5 cP (65%) – 3.9 mg, titanium dioxide (20%) – 1.2 mg, macrogol 400 (10%) – 0.6 mg, talc (5%) – 0.3 mg.

7 pcs. – blisters (4) – cardboard packs.
15 pcs. – blisters (2) – cardboard packs.
15 pcs. – blisters (6) – cardboard packs.

Film-coated tablets from light red to grayish-red color, oval-shaped, with an engraving “M14” on one side and smooth on the other side.

Excipients: Prosolv HD90 – 358 mg [microcrystalline cellulose – 98%, colloidal silicon dioxide – 2%], croscarmellose sodium – 10 mg, talc – 8 mg, magnesium stearate – 4 mg.
Film coating composition Opadry pink (03B540015) – 12 mg, including hypromellose 6 cP (62.5%) – 7.5 mg, titanium dioxide (28.7%) – 3.44 mg; macrogol 400 (6.25%) – 0.75 mg, iron oxide red dye (2.05%) – 2.46 mg, iron oxide yellow dye (0.5%) – 0.06 mg.

7 pcs. – blisters (4) – cardboard packs.
15 pcs. – blisters (2) – cardboard packs.
15 pcs. – blisters (6) – cardboard packs.

Clinical-Pharmacological Group

Glutamate NMDA-receptor blocker. Drug for the treatment of dementia

Pharmacotherapeutic Group

Psychoanaleptics; agents for the treatment of dementia; other agents for the treatment of dementia

Pharmacological Action

An agent for the treatment of dementia. It is a non-competitive antagonist of glutamate NMDA receptors (including in the substantia nigra), thereby reducing the excessive stimulatory influence of cortical glutamate neurons on the neostriatum, which develops against the background of insufficient dopamine release. By reducing the entry of Ca²⁺ into neurons, it reduces the possibility of their destruction.

It has nootropic, cerebrovasodilating, antihypoxic, and psychostimulating effects.

It improves weakened memory, increases the ability to concentrate, reduces fatigue and symptoms of depression, and reduces spasticity of skeletal muscles caused by brain diseases or injuries.

Pharmacokinetics

After oral administration, it is rapidly and completely absorbed from the gastrointestinal tract. C_max is reached in 3-8 hours. Plasma protein binding is 45%. When taken at a dose of 20 mg/day, a C_ss of 70 to 150 ng/ml is achieved. V_d is 10 L/kg. Partially metabolized in the liver. Excreted by the kidneys. T_1/2 is 60-100 hours; clearance is 170 ml/min/1.73 m².

Indications

Moderate to severe dementia in Alzheimer’s disease.

ICD codes

Dosage Regimen

Administer orally. Initiate treatment at an initial dose of 5 mg once daily.

Increase the dose in 5 mg increments each week to improve tolerability. Follow this titration schedule: Week 1: 5 mg/day. Week 2: 10 mg/day (5 mg twice daily). Week 3: 15 mg/day (10 mg and 5 mg as separate doses). Week 4: 20 mg/day (10 mg twice daily).

The effective maintenance dose is 10 mg to 20 mg per day. Do not exceed the maximum recommended daily dose of 20 mg.

For patients with moderate renal impairment (creatinine clearance 30-49 mL/min), a maximum daily dose of 10 mg is recommended. The drug is contraindicated in severe renal impairment.

Administer tablets with water. They can be taken with or without food. The 20 mg tablet can be divided into equal halves.

Adverse Reactions

From the immune system common – hypersensitivity reactions.

From the psyche common – drowsiness; uncommon – confusion, hallucinations (mainly observed in patients with Alzheimer’s disease at the severe dementia stage); frequency unknown – psychotic reactions.

From the nervous system: common – dizziness, balance disorders; uncommon – gait disturbance; very rare – seizures.

From the cardiovascular system common – increased blood pressure; uncommon – heart failure, venous thrombosis and/or thromboembolism.

From the digestive system: common – constipation; uncommon – vomiting, nausea; frequency unknown – pancreatitis.

From the liver and biliary tract common – elevated liver enzyme levels; frequency unknown – hepatitis.

From the hematopoietic system frequency unknown – agranulocytosis, leukopenia (including neutropenia), pancytopenia, thrombocytopenia, thrombocytopenic purpura.

Other common – headache, shortness of breath; uncommon – fungal infections, fatigue; frequency unknown – acute renal failure, Stevens-Johnson syndrome.

Contraindications

Hypersensitivity to memantine; severe hepatic impairment; pregnancy; lactation period (breastfeeding); children and adolescents under 18 years of age (efficacy and safety of the drug have not been established).

With caution: epilepsy, thyrotoxicosis, predisposition to seizures, concurrent use of NMDA receptor antagonists (amantadine, ketamine, dextromethorphan), factors that increase urine pH (sudden change in diet, e.g., switching to a vegetarian diet, heavy intake of alkaline gastric buffers), renal tubular acidosis, severe urinary tract infections caused by Proteus spp., myocardial infarction (in history), heart failure, uncontrolled arterial hypertension, renal failure, mild or moderate hepatic impairment (Child-Pugh class A and B).

Use in Pregnancy and Lactation

Contraindicated for use during pregnancy and lactation (breastfeeding).

Use in Hepatic Impairment

Contraindicated for use in severe hepatic impairment (Child-Pugh class C). Use with caution in mild or moderate hepatic impairment (Child-Pugh class A and B).

Use in Renal Impairment

Contraindicated for use in renal failure. Use with caution in renal tubular acidosis, severe urinary tract infections caused by Proteus spp.

Pediatric Use

Contraindicated for use in children and adolescents under 18 years of age (efficacy and safety have not been established).

Special Precautions

It should be used with caution in patients with epilepsy, renal impairment, thyrotoxicosis, history of seizures, arterial hypertension, history of myocardial infarction, heart failure.

Concomitant 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 (mainly related to the CNS) may occur more frequently and be more pronounced.

The presence of factors in the patient that affect the increase in urine pH (sudden changes in diet, for example, switching from a diet including 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 careful monitoring of the patient’s condition.

Effect on ability to drive vehicles and machinery

Patients with Alzheimer’s disease at the stage of moderate or severe dementia usually have impaired ability to drive vehicles and operate complex machinery. In addition, Memantine may cause changes in reaction speed, so patients should refrain from driving vehicles or working with complex machinery.

Drug Interactions

When used concomitantly, Memantine may reduce the effects of barbiturates and neuroleptics.

The action of baclofen and dantrolene may be altered under the influence of memantine (dose adjustment may be required with this combination).

The effects of levodopa, dopamine receptor agonists, and anticholinergic agents are enhanced with the concomitant use of NMDA receptor antagonists.

Since Memantine and amantadine are NMDA receptor antagonists, concomitant use should be avoided due to the risk of toxic effects.

Combinations of memantine with ketamine, dextromethorphan, and phenytoin are also potentially toxic.

The same renal cationic transport system is used for the transport of amantadine, cimetidine, ranitidine, quinidine, quinine, and nicotine in the body, which may cause an interaction of these drugs with memantine, leading to an increase in its plasma concentration.

When used concomitantly, Memantine may cause a decrease in the serum concentration of hydrochlorothiazide.

When used concomitantly with warfarin and other indirect anticoagulants, careful monitoring of prothrombin time and INR is required.

Concomitant use with antidepressants, selective serotonin reuptake inhibitors, and MAO inhibitors requires careful monitoring of patients.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.