Cara-tine

Uses

Memantine is used for the treatment of all froms of dementia of the Alzheimer's type. Memantine may also be used for other types of dementia.

Cara-tine is also used to associated treatment for these conditions: Alzheimer's Disease (AD), Moderate-to-severe Alzheimer's Disease, Mild Vascular dementia, Moderate Alzheimer's Type Dementia, Moderate Vascular dementia, Severe Alzheimer's Type Dementia

How Cara-tine works

Continuous activation of the N-methyl-D-aspartate (NMDA) receptors in the central nervous system caused by glutamate is thought to cause some of the Alzheimer's disease symptoms. This overactivation is thought to contribute to neurotoxicity due to the excitatory properties of glutamate . The pharmacological effect of memantine likely occurs via the drug's behavior as an uncompetitive (open-channel) NMDA receptor antagonist, preventing glutamate action on this receptor. Memantine has a preference for the NMDA receptor-operated cation channels. Despite these antagonist effects, memantine has not been proven to prevent or retard the neurodegeneration seen in patients diagnosed with Alzheimer’s disease .

Dosage

Cara-tine dosage

The recommended maintenance dose of Memantinefor 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.

Side Effects

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.

Toxicity

LD50

Oral LD50, mouse 437-498 mg/kg Oral LD50, rat 328-370 mg/kg

Carcinogenesis, Mutagenesis, Impairment of Fertility

No evidence of carcinogenicity was seen in mouse and rat models administered memantine at doses equivalent to supratherapeutic human doses . Additionally, no genotoxic potential was noted when a battery of assays was performed. No effects on fertility or reproductive performance were noted in rats given to 18 mg/kg/day (equivalent to 9 times the maximum recommended human dose) orally from 14 days preceding mating through gestation and lactation in females, or for 60 preceding mating activity in males animals .

Use in pregnancy

This drug is considered a pregnancy category B drug, meaning no sufficiently controlled and adequate studies of memantine in pregnant women have been performed. This drug should be taken during pregnancy only if the potential benefit justifies the possible fetal risk .

Use in nursing

It is unknown whether memantine is excreted in human milk. Due to that fact that many drugs are found excreted in human milk, caution should be observed when this drug is taken by a nursing mother .

Precaution

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.Neurological Conditions-

• 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.

Interaction

Amantadine, Anticholinergics, Anticonvulsives, Baclofen, Barbiturates, Cimetidine, Dantrolene, Dextromethorphan, Dopaminergic, Hydrochlorothiazide, Ketamine, Neuroleptics, Nicotine, Procainamide, Quinidine, Quinine, Ranitidine.

Volume of Distribution

The mean volume of distribution of memantine is 9-11 L/kg .

Elimination Route

After an oral dose, memantine is well absorbed. Its peak drug concentrations are attained in about 3-7 hours. Memantine shows linear pharmacokinetics when given at normal therapeutic doses. This drug can be taken without regard to food, as there is no effect of food on memantine absorption .

Half Life

Within the range of 60-100 hours .

The terminal elimination half-life was significantly increased in patients with moderate to severe renal impairment, in comparison with patients with normal renal function . Exercise caution when this drug is administered to patients with renal dysfunction.

Clearance

This drug is cleared by active tubular secretion in the kidneys. Tubular reabsorption of this drug is pH dependent .

Elimination Route

This drug is mainly excreted in the urine. Approximately 48% of administered memantine is excreted unchanged in urine .

The remainder of the drug is metabolized to three main metabolites. These metabolites are the N-glucuronide conjugate, 6-hydroxy memantine, and 1-nitroso-deaminated memantine, which show minimal NMDA receptor antagonist activity .

Pregnancy & Breastfeeding use

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.

Contraindication

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

Special Warning

In case of renal impairment: A target dose of 5 mg BID is recommended in patients with severe renal impairment (creatinine clearance: 5-29 ml/min).

In case of hepatic impairment: No dosage adjustment is needed in patients with mild or moderate hepatic impairment. Memantine should be administered with caution to patients with severe hepatic impairment.

Acute Overdose

Symptoms: Agitation, asthenia, bradycardia, vomiting, dizziness, vertigo, ECG changes, increased BP, visual hallucinations, confusion, lethargy, restlessness, slowed movement, somnolence, stupor, unsteady gait, weakness, loss of consciousness, psychosis, coma.

Management: Symptomatic and supportive treatment. May increase elimination by urinary acidification.

Storage Condition

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

Innovators Monograph

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