Donepezil

When ATH:
N06DA02

Pharmacological action

Piperidine derivatives. Donepezil hydrochloride - a white crystalline powder. Easily soluble in chloroform, soluble in water and glacial acetic acid, slightly soluble in ethanol and acetonitrile, practically insoluble in ethyl acetate and n-hexane.

Pharmacological action – anticholinesterase.

Inhibits cholinesterase and blocks the breakdown of acetylcholine, performing normal transmission in the CNS. Slows the progression of Alzheimer's disease, reduces the severity of cognitive symptoms (According to the test Folstein), in some cases, restore daily activity of patients and facilitates care of them. Corrects behavioral abnormalities: apathy, hallucinations and repetitive motion unthought.

Pharmacokinetics

After oral administration, Cmax in plasma is reached after about 3-4 hours, eating does not affect the absorption. T1 / 2 of plasma - about 70 no. The systematic use of single doses in the equilibrium concentration is reached, usually, 2-3 weeks after initiation of therapy. The distribution of donepezil in various body tissues understudied. Expected, that donepezil and / or its metabolites in the body can be kept more 10 days.

Donepezil is metabolized in the liver. The main products of the metabolism of the compounds of M1 and M2 (Products O-dealkylation and hydroxylation), M11 и М12 (Products glyukuronirovaniya M1 and M2, respectively,), M4 (hydrolysis product) and M6 (N-oxidation product). Information about the enterohepatic recirculation of donepezil and / or its metabolites is not. The binding of donepezil to plasma proteins - 95%. Information on the plasma protein binding of its active metabolite 6-O-no desmetildonepezila. Displayed donepezil, as well as its metabolites, primarily, urine: 79% dose found in urine and 21% - In the feces. The urine is found predominantly donepezil.

Pharmacokinetics in special clinical situations

Paul, race and smoking did not significantly affect the plasma concentrations of donepezil. Average levels of donepezil in plasma of patients correspond to those in healthy young volunteers. Abnormal liver function mild to moderate severity, and renal failure have no significant effect on clearance of donepezil.

Testimony

Alzheimer's disease and mild to moderate severity (symptomatic treatment of cognitive impairment).

Dosage regimen

Inside, once at night (before bedtime) 5-10 mg for 6 Sun. Receiving continue, if achieved improvement (According to relatives or persons, caring for the patient).

Contraindications

Hypersensitivity (incl. piperidine derivatives).

Restrictions apply

Heart rhythm disturbances, gastric ulcer and duodenal ulcer, bronchial asthma, chronic obstructive pulmonary disease, general anesthesia; concomitant use of NSAIDs, holinoblokatorov, other cholinesterase inhibitors; pregnancy, lactation, childhood.

Pregnancy and lactation

Category actions result in FDA - C.

Side effect

From the digestive tract: dyspepsia (nausea, vomiting, diarrhea).

From the nervous system and sensory organs: headache, dizziness, fatigue, insomnia, convulsions, fainting.

Cardio-vascular system and blood (hematopoiesis, hemostasis): bradycardia, violation of sinoatrial and AV conduction.

Other: increase in creatine phosphokinase.

Drug Interactions

The effect of increasing other anticholinesterase agents, Inhibitors of cytochrome P450 (slow biotransformation), weakening - holinoblokatory, inductors monooxygenase system (rifampicin, phenytoin, ethanol and the like.). When concomitant administration of narcosis, NSAIDs increases the likelihood of adverse events.

Overdose

Symptoms: cholinergic crisis (severe nausea, vomiting, excessive salivation, Sweating, bradycardia, decrease in blood pressure, respiratory depression, collapse and convulsions).

Treatment: simptomaticheskaya therapy. As an antidote can be used tertiary anticholinergics, in particular atropine in an initial dose of 1-2 mg / in, Thereafter, the dosage is adjusted depending on the effect of. Unknown, Whether donepezil removed and / or its metabolites by dialysis (hemodialysis, pyeritonyealinyi dialysis ili gyemofilitratsiya).

Precautions substance donepezil

Treatment is carried out under compulsory medical supervision. One of the conditions of effective therapy is appropriate patient care. For the period of the course should give up drinking alcohol.

Supportive therapy can be continued until, As long as the therapeutic effect. If the drug is no longer valid, it should be abolished. The effectiveness of donepezil hydrochloride in patients with severe dementia of Alzheimer's type, other types of dementia or other types of memory impairment (such as age-related deterioration of cognitive function) I have not been studied. Donepezil hydrochloride, It is a cholinesterase inhibitor, can enhance muscle relaxation suktsinilholinovogo type during anesthesia.

Cholinesterase inhibitors (incl. and donepezil hydrochloride) may have vagotonic effects on heart rate (in particular, cause bradycardia). The potential for this action may be important for patients with sick sinus syndrome or other supraventricular conduction disorders, such as sinoatrial or AV block.

With increased risk of developing ulcers, such as in patients with a history of ulcer disease or patients, receiving concomitant therapy with NSAIDs, during treatment is necessary to exercise increased caution, tk. holinomimetiki may increase the secretion of acid in the stomach.

Given the cholinomimetic effect of cholinesterase inhibitors, donepezil hydrochloride should be used with caution in patients with asthma or obstructive pulmonary disease in history.