Generic
Memantine Hydrochloride
Pharmacology
Persistent activation of N-methyl-D-aspartate (NMDA) receptors in Central Nervous System by the excitatory amino acid glutamate has been hypothesized to contribute to the symptomatology of Alzheimer's disease. Memantine is postulated to exert its therapeutic effect through its action as a low to moderate affinity as an uncompetitive (open-channel) NMDA receptor antagonist which binds preferentially to the NMDA receptor-operated cation channels. Memantine is well absorbed after oral administration and has linear pharmacokinetics over the therapeutic dose range. It is excreted predominantly unchanged in the urine and has a terminal elimination half-life of about 60-80 hours. Following oral administration, Memantine is highly absorbed with peak concentrtions reached in about 3-7 hours. Food has no effect on the absorption of Memantine. The mean volume of distribution of Memantine is 9-11 L/kg and the plasma protein binding is low (45%). emantine undergoes partial hepatic metabolism. About 48% of administered drug is excreted unchanged in urine; the remainder is converted primarily to three polar metabolites which possess minimal NMDA receptor antagonistic activity: the N-glucuronide conjugate, 6-hydroxy Memantine and 1-nitroso-deaminated Memantine. A total of 74% of the administered dose is excreted as the sum of the parent drug and the N-glucuronide conjugate. The hepatic microsomal CYP-450 enzyme system does not play a significant role in the metabolism of Memantine.
Dosage Administration
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.
Contraindications
Most frequent side effects (frequency of 2% or less) include hallucination, confusion, dizziness, headache and fatigue. Occasional side effects include anxiety, hypertonus (heightened muscle tension), vomiting, bladder infections and increased sexual drive. If there is a history of epileptic seizures, there is a slight chance that Memantine may increase the probability of an attack.
Side Effects
Pregnancy Category B. Yet there are no adequate and well controlled studies of Memantine in pregnant women. Memantine should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. It is not known whether Memantine is excreted in human breast milk. Because many drugs are excreted in human milk, caution should be exercised when Memantine is administered to a nursing mother.
Pregnancy And Lactation
Caregivers should be instructed in the recommended administration (twice per day for doses above 5 mg) and dose escalation (minimum interval of one week between dose increases). If the patients suffer from kidney dysfunction, the kidney function should be monitored at regular basis. Seizures: Memantine has not been systematically evaluated in patients with a seizure disorder. One clinical trial shows that seizures occurred in 0.2% of patients treated with Memantine and 0.5% of patients treated with placebo. Carcinogenesis, Mutagenesis and Impairment of Fertility: Study shows that no risk of carcinogenesis, mutagenesis and impairment of fertility are caused after Memantine use. Operating Vehicles or Machinery: Taking Memantine may alter the reaction time significantly; therefore safe driving and safe operation of machinery may no longer be possible.
Therapeutic
Store in a cool and dry place, protected from light. Keep this medication out of reach of children.
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