A specific and reversible inhibitor of acetylcholinesterase - the main enzyme involved in the breakdown of acetylcholine in nerve endings at o.u.n. In patients with Alzheimer's disease, the drug administered in therapeutic doses inhibits the enzyme activity in about 64-77%. The inhibition of acetylcholinesterase (AChE) in red blood cells by donepezil hydrochloride is correlated with changes in the ADAS-Cog scale, measuring selected elements of cognitive ability. The effect of donepezil on the course of basic neurological disease has not been studied, therefore, donepezil can not be considered to have any effect on the development of the disease. The maximum concentration of the drug in the blood occurs 3-4 hours after oral administration. Steady state is achieved within 3 weeks. Donepezil binds to plasma proteins in 95%. It is metabolised in the liver through the cytochrome P-450 system to numerous metabolites (one of the metabolites - 6-O-demethyldonepezil is pharmacologically active). It is excreted mainly in the form of metabolites - in the urine (57%) and partly in the faeces (14.5%). T0,5 is about 70 hours.
Contraindications:
Hypersensitivity to donepezil hydrochloride, piperidine derivatives or any of the excipients.
Precautions:
The drug is not recommended for use in children. The efficacy of donepezil has not been established in patients with advanced Alzheimer's disease, other types of dementia or other types of memory impairment (eg cognitive impairment related to age). Aggregate results of research on Alzheimer's disease and other studies on dementia, including studies on vasomotor dementia, indicate that the mortality rate in the placebo groups was numerically higher than the indicator in the groups receiving donepezil. Particularly cautiously use in patients with sinus node syndrome or other supraventricular conduction disorders, i.e. sinoatrial or atrioventricular block (the drug may exert a vagotonic effect on the heart rate); in patients with bronchial asthma or obstructive pulmonary disease; in patients with an increased risk of peptic ulcer disease (with a history of peptic ulcer disease or NSAIDs - these patients should be monitored for symptoms of peptic ulcer). The preparation of donepezil together with other acetylcholinesterase inhibitors, agonists or cholinergic antagonists should be avoided. Donepezil may increase muscle relaxation caused by succinylcholine derivatives during general anesthesia. Donepezil, as a cholinomimetic, may inhibit the outflow of urine from the bladder, exacerbate or cause extrapyramidal symptoms, cause convulsions. Consideration should be given to discontinuation of donepezil in the case of unexplained liver dysfunction. If you have symptoms of a neuroleptic malignant syndrome (NMS) or a high fever with an unexplained reason, without other clinical symptoms of RH, donepezil should be discontinued.
Pregnancy and lactation:
Do not use during pregnancy unless clearly necessary. Women receiving donepezil hydrochloride should not breast-feed.
Orally. Adults (including the elderly): initially 5 mg once a day for at least 1 month. After a clinical evaluation of the efficacy of the initial dose, the dose can be increased to 10 mg once a day. The maximum recommended daily dose is 10 mg.Treatment with donepezil can only be undertaken in cases where regular monitoring of the patient's intake is possible. Maintenance treatment should be continued for as long as the beneficial effect of the preparation is found; Regular clinical evaluation of the medicine's action is necessary. Discontinuation should be considered when there is no longer any clinical benefit.Special flu patients. No dosage adjustment is necessary for patients with renal insufficiency. Due to the possible increased drug exposure in patients with mild to moderate hepatic insufficiency, the dose should be adjusted to the patient's individual tolerability. There are no data on use in patients with severe hepatic impairment. The preparation should be taken in the evening, at bedtime.
(C)
