A specific and reversible inhibitor of acetylcholinesterase, the main enzyme involved in the breakdown of acetylcholine in nerve endings at o.u.n. In clinical trials, patients with dementia in Alzheimer's disease have been shown to improve their cognitive ability and ability to adapt to function in society. The drug showed a dose-proportional positive clinical response. The effect of the drug on changing the course of neuropathology of the disease has not been studied, so it can not be attributed to any influence on the progression of the disease. After oral administration, peak blood levels are achieved after about 3-4 hours. Steady state is achieved within 3 weeks of starting treatment. The food does not affect the absorption of the drug. Donepezil is approximately 95% bound to plasma proteins. It is metabolised by cytochrome P450 to many metabolites. It is excreted mainly in the urine in the form of metabolites and in unchanged form. T0,5 in plasma is about 70 h.
Contraindications:
Hypersensitivity to donepezil hydrochloride, piperidine derivatives or other ingredients of the preparation. Pregnancy.
Precautions:
No studies on the use of donepezil have been performed in patients with severe dementia in Alzheimer's disease, other types of dementia or other types of memory impairment (eg related to aging). The drug may increase the effect of succinylcholine relaxants, used during general anesthesia. Use with caution in patients with a sick sinus syndrome or supraventricular dysfunction disorders (eg, sinoatrial or atrioventricular block). Caution should be exercised in patients with an increased risk of peptic ulcer disease (eg patients with a history of an ulcer or patients taking NSAIDs) and patients with a history of asthma or obstructive pulmonary disease. Cholinomimetics may contribute to generalized seizures and may exacerbate or induce extrapyramidal symptoms. There are no data on the use of the preparation in patients with severe hepatic impairment. Donepezil should not be used concomitantly with other acetylcholinesterase inhibitors, agonists or cholinergic antagonists. The product is not recommended for use in children. The preparation contains lactose - should not be used in patients with rare hereditary galactose intolerance, Lapp lactase deficiency or poor glucose-galactose absorption.
Pregnancy and lactation:
The drug should not be used during pregnancy and breast-feeding.
Side effects:
Common: diarrhea, nausea, vomiting, stomach upset, fainting, dizziness, insomnia; hallucinations, agitation, aggressive behavior (symptoms disappearing after dose reduction or discontinuation of the drug); anorexia, cold, skin rash, pruritus, muscle cramps, urinary incontinence, headache, fatigue, aches and pains. Uncommon: epileptic seizures, bradycardia, gastrointestinal bleeding, gastric and duodenal ulcer, slight increase in muscle creatine kinase activity. Rare: extrapyramidal symptoms, sinoatrial block, atrioventricular block, liver dysfunction including hepatitis (discontinuation of the drug should be considered if unexplained liver dysfunction occurs). In the event of fainting or seizure, the possibility of a heart block or sinus arrest should be considered.
Dosage:
Treatment should be initiated and supervised by a physician experienced in the diagnosis and treatment of Alzheimer's disease. Orally, in the evening, just before bedtime. Adults: The starting dose is 5 mg once a day. This dose should be used over a period of at least one month to assess the effectiveness of the preparation and to obtain steady-state drug concentrations in the serum. After assessing the effectiveness of treatment with a dose of 5 mg a day for one month, you can increase the dose to 10 mg once a day.The maximum recommended daily dose is 10 mg. No dosage adjustment is necessary for patients with renal insufficiency. In patients with mild or moderate hepatic impairment, the dose should be increased according to individual patient tolerability.
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