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 اطلاعات آلزانتين براي پزشكان

^®Alzantin

Easy to start, easy to take

ممانتين يك آنتاگونيست گيرنده  NMDA(ان-متيل دي-آسپارتات) مي‌باشد كه به صورت يك بلاك كننده نسبي براي اسيد آمينه تحريكي گلوتامات عمل مي‌كند. گلوتامات تنظيم كننده ورود كلسيم به داخل نورونها مي‌باشد كه لازمه يادگيري و حافظه است.

موارد مصرف⁽¹⁾

1- بيماري آلزايمر (متوسط تا شديد)

2- دمانس واسكولار(Vascular Dementia)

3- دمانس جسم لووي Lewy Body Dementia))

4- دمانس فرونتو‌تمپورال (Frontotemporal Dementia)

5- دمانس مختلط ((Mixed Dementia

6- ساير اختلالات حافظه

7- اسكيزو‌فرني كاتاتونيك  (Catatonic Schizophrenia)

8- . . . .

خلاصه اطلاعات براي تجويز دارو:^2و3 (براي اطلاعات بيشتر به كتب مرجع مراجعه فرماييد)

عوارض جانبي( شايعتر) شامل: سرف، سرگيجه، سردرد، گيجي، توهم، خستگي (شيوع در مطالعات زير ده درصد مي‌باشد)

كنتراانديكاسيون: فقط واكنش افزايش حساسيت(Hypersensitivity) به دارو

هشدارها و احتياطات :

1- در نارسايي كليوي شديد ماكزمم دوز مصرفي دارو به نصف كاهش مي‌يابد (10mg/day يا 5mg q 12 hr)

2- براي مصرف در مادران باردار گروه B مي‌باشد

3- در بعضي از بيماران صرعي سبب افزايش حملات مي‌شود كه نياز به تنظيم داروهاي مصرفي بيمار دارد.

4- مشكلات ادراري تناسلي كه سبب افزايش PH ادرار مي‌شوند ممكن است باعث افزايش سطح پلاسمايي ممانتين شوند (تنظيم دوز).

تداخل دارويي:

1- ساير مهار‌كننده‌هاي NMDA :كتامين، آمانتادين و دكسترومتورفان

2- داروهاي ايجاد‌كننده آلكالين در ادرار:  الف) مهار‌كننده‌‌هاي كربنيك‌آنهيدراز مانند استازولاميد و متازولاميد         ب) بي‌كربنات سديم

روش و مقدار تجويز ممانتين³ ( مورد تاييدFDA):

نكته مهم:  داروي ممانتين را در فاز متوسط تا شديد بيماري آلزايمر مي‌توان هم به صورت مونوتراپي و هم به صورت توام ‌درماني  ( combination therapy ) با ساير داروهاي مهار كننده كولين‌استراز  استفاده كرد.

منابع:

1- Micromedex 2007, Memantine

2- USP DI 2005, Memantine

3- PDR 2008

            Alzantin^®

Generic Name: Memantine hydrochloride

Category: Dementia symptoms treatment adjunct.

Composition:  Each Scored F.C. tablet   contains 10 mg Memantine hydrochloride.

Actions and Pharmacokinetics:

    Persistent activation of centralnervoussystem N-methyl-D-aspartate (NMDA) receptors by the excitatory amino acidglutamate has been hypothesized to contribute to the symptomatology of Alzheimer’s disease. Alzantin is postulated to exert its therapeuticeffect through its action as a low to moderate affinity uncompetitive (open-channel) NMDA receptorantagonist which binds preferentially to the NMDA receptor-operated cation channels. There is no evidence that Alzantin prevents or slows neurodegeneration in patients with Alzheimer’s disease.
Alzantin showed low to negligible affinity for GABA, benzodiazepine, dopamine, adrenergic, histamine and glycine receptors and for voltage-dependent Ca2+, Na+ or K+ channels. Alzantin also showed antagonistic effects at the 5HT3 receptor with a potency similar to that for the NMDA receptor and blocked nicotinicacetylcholine receptors with one-sixth to one-tenth the potency. In vitro studies have shown that Alzantin does not affect the reversibleinhibition of acetylcholinesterase by donepezil, galantamine, or tacrine. Alzantin is well absorbed after oraladministration and has linear pharmacokinetics over the therapeuticdose range. It is excreted predominantly in the urine, unchanged, and has a terminalelimination half life of about 60-80 hours.
Absorption and Distribution: Following oraladministration Alzantin is highly absorbed. Food has no effect on the absorption of Alzantin. The meanvolume of distribution of Alzantin is 9-11 L/kg and the plasma protein binding is low (45%). Metabolism and Elimination: Alzantin undergoes partial hepatic metabolism. About 57 TO 87% 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 Alzantin, and 1-nitroso-deaminated Alzantin.
 

Indications:

    Alzantin is indicated for the treatment of moderate to severe dementia of the Alzheimer’s type.

Contraindications:

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

Drug Interaction:

    N-methyl-D-aspartate (NMDA) antagonists: The combined use of Alzantin with other NMDA antagonists (amantadine, ketamine, and dextromethorphan) has not been systematically evaluated and such use should be approached with caution.

Drugs eliminated via renal mechanisms: Because Alzantin is eliminated in part by tubular secretion, coadministration of drugs that use the same renal cationic system, including hydrochlorothiazide (HCTZ), triamterene (TA), metformin, cimetidine, ranitidine, quinidine, and nicotine, could potentially result in altered plasma levels of both agents.

Drugs that make the urine alkaline: The clearance of Alzantin was reduced by about 80% under alkaline urine conditions at pH 8. Therefore, alterations of urine pH towards the alkaline condition may lead to an accumulation of the drug with a possible

Increase   in adverse effects. Urine pH is altered by diet, drugs (e.g. carbonic   anhydrase   inhibitors,  sodium   bicarbonate)   and clinical state of the patient (e.g. renal tubular acidosis or severe infections of the urinary tract). Hence, Alzantin should be used with caution under these conditions.

Precautions:

    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).

Neurological Conditions (Seizures): Alzantin has not been systematically evaluated in patients with a seizure disorder. In clinical trials of Alzantin seizures occurred in 0.2% of patients treated with Alzantin and 0.5% of patients treated with placebo.

Genitourinary Conditions: Conditions that raise urine pH may decrease the urinary elimination of Alzantin resulting in increased plasma levels of Alzantin.

Special Populations: No dosage adjustment is needed in patients with mild or moderate hepatic impairment. Alzantin should be administered with caution to patients with severe hepatic impairment. A dosage reduction is recommended in patients with severe renal impairment.

Pregnancy:

    Pregnancy Category B. There is no adequate and well-controlled studies of Alzantin in pregnant women. Alzantin should be used during pregnancy only if the potential benefit justifies the potentialrisk to the fetus.

Breast-Feeding:

    It is not known whether Alzantin is excreted in humanbreast milk. Because many drugs are excreted in human milk, caution should be exercised when Alzantin is administered to a nursing mother.

Adverse Effects:

    Most Frequent: Constipation, Cough, Dizziness, Headache Disorder, Hypertension

Less Frequent: Back Pain, Drowsiness, Dyspnea, Fatigue, Hallucinations, Impaired Cognition, Pain, Vomiting

Rare: Accidental Fall, Anorexia, Anxiety, Arthralgia, Bronchitis, Depression, Diarrhea, Feeling Agitated, Flu-Like Symptoms, Gait Abnormality, Insomnia, Nausea, Peripheral Edema, Trauma, Upper Respiratory Infection, Urinary Incontinence, Urinary Tract Infections.

Administration and Dosage:

    The dosage of Alzantin  shown to be effective in controlled clinical trials is 20 mg/day.

The recommended starting dose of Alzantin is 5 mg once daily. The recommended target dose is 20 mg/day. The dose should be increased in 5 mg increments to 10 mg/day (5 mg twice a day), 15 mg/day (5 mg and 10 mg as separate doses), and 20 mg/day (10 mg twice a day). The minimum recommended interval between dose increases is one week. Alzantin can be taken with or without food.

Storage: Store below 30ºC Protect from light and moisture. Keep out of reach of children.

How supplied: Box of 3 blisters of 10 tablets.