Memantine is indicated for the management of all forms of Alzheimer’s-type dementia. It may also be considered for use in other types of dementia.

Continuous activation of N-methyl-D-aspartate (NMDA) receptors in the central nervous system by the excitatory neurotransmitter glutamate is believed to play a role in the symptoms of Alzheimer’s disease. Memantine produces its therapeutic effect as a low to moderate affinity uncompetitive (open-channel) NMDA receptor antagonist, with preferential binding to NMDA receptor-operated cation channels.

Memantine is well absorbed following oral administration and demonstrates linear pharmacokinetics within the therapeutic dose range. It is mainly eliminated unchanged through urine, with a terminal elimination half-life of approximately 60–80 hours. Peak plasma concentrations are typically achieved within 3–7 hours after oral dosing, and food intake does not affect its absorption. The average volume of distribution ranges from 9–11 L/kg, and plasma protein binding is about 45%. Memantine undergoes partial metabolism in the liver. Around 48% of the administered dose is excreted unchanged in urine, while the remaining portion is converted mainly into three polar metabolites with minimal NMDA receptor antagonistic activity: N-glucuronide conjugate, 6-hydroxy memantine, and 1-nitroso-deaminated memantine. Approximately 74% of the administered dose is eliminated as the parent compound and N-glucuronide conjugate. The hepatic microsomal CYP450 enzyme system plays only a minor role in memantine metabolism.

The recommended maintenance dose of Memantine for adults and older patients is 20 mg every day. In order to lower the risk of side effects, the dose should be achieved by upward titration with 5 mg per week over 3 weeks, achieving the maintenance dose of 20 mg/day from the start of week 4 according to the following dosage guideline:

Week 1 (Everyday): Morning- 5 mg (1 tablet), Night- No dose
Week 2 (Everyday): Morning- 5 mg (1 tablet), Night- 5 mg (1 tablet)
Week 3 (Everyday): Morning- 10 mg (2 tablets), Night- 5 mg (1 tablet)
Week 4 and onwards (Everyday): Morning- 10 mg (2 tablets), Night- 10 mg (2 tablets)

Missed Dose: If any dose is missed, just wait and take the next dose at the usual time. Do not double the dose to compensate for the missed dose.

In case renal impairment: In patients with moderate renal impairment (creatinine clearance 30-49 ml/min) daily dose should be 10 mg (1 ml solution, equivalent to two downward strokes). If tolerated well after at least 7 days of treatment, the dose could be increased up to 20 mg/day according to standard titration scheme. In patients with severe renal impairment (creatinine clearance 5-29 ml/min) daily dose should be 10 mg (1 ml solution, equivalent to two downward strokes) per day.

In case of hepatic impairment: In patients with mild or moderate hepatic impaired function, no dosage adjustment is needed. Administration of memantine is not recommended in patients with severe hepatic impairment.

Children under 18 years: Memantine is not recommended for use in children below 18 years due to lack of data on safety and efficacy.

Due to the pharmacological effects and mechanism of action of memantine, concomitant use with L-dopa, dopaminergic agonists, and anticholinergic agents may enhance their effects when used with NMDA antagonists such as memantine. The effects of barbiturates and neuroleptics may be reduced. Concurrent use with antispasmodic agents such as dantrolene or baclofen may alter their effects and dose adjustment may be required. Memantine should not be used with amantadine, ketamine, dextromethorphan, phenytoin, cimetidine, ranitidine, procainamide, quinidine, quinine, or nicotine.

Memantine Hydrochloride is contraindicated in patients with known hypersensitivity to memantine hydrochloride or any excipients used in the formulation.

Most frequent side effects (≤2%) include hallucination, confusion, dizziness, headache, and fatigue. Occasional side effects include anxiety, increased muscle tone (hypertonus), vomiting, urinary tract infections, and increased sexual drive. In patients with a history of epilepsy, there may be a slight increased risk of seizures.

Pregnancy Category B. Adequate and well-controlled studies in pregnant women are not available. Memantine should be used during pregnancy only if the potential benefit outweighs the potential risk to the fetus. It is not known whether memantine is excreted in human breast milk. Caution should be exercised when administering memantine to nursing mothers.

Caregivers should be instructed on proper administration (twice daily for doses above 5 mg) and dose titration (minimum one-week interval between dose increases). In patients with renal impairment, renal function should be monitored regularly.

Seizures: Memantine has not been systematically studied in patients with seizure disorders. Clinical trials reported seizures in 0.2% of patients receiving memantine and 0.5% of placebo-treated patients.

Carcinogenesis, Mutagenesis and Impairment of Fertility: Studies show no evidence of carcinogenic, mutagenic, or fertility impairment risk with memantine use.

Operating Vehicles or Machinery: Memantine may impair reaction time; therefore, driving or operating machinery may be affected.

Drugs for Dementia.

Store in a cool and dry place, protected from light. Keep out of reach of children.