Universal reference book for medicines
Product name: YASNAL

Active substance: donepezil

Type: Selective inhibitor of brain acetylcholinesterase.
The drug for Alzheimer's disease
Manufacturer: KRKA (Slovenia)
Description of the active substance:
This information is a reference and it is not enough that the drug has been prescribed by a doctor ..

Selective and reversible inhibitor of acetylcholinesterase, which is the predominant type of cholinesterase in the brain.
Donepezil inhibits this enzyme more than 1000 times stronger than butyrylcholinesterase, contained mainly outside the central nervous system.
After a single dose of donepezil in doses of 5 mg or 10 mg, the inhibition of acetylcholinesterase activity, measured in erythrocyte membranes, was 63.6% and 77.3%, respectively.

Slows down the progression of Alzheimer's disease, reduces the severity of cognitive symptoms, in some cases restores the daytime activity of patients and facilitates the care of them.
Corrects behavioral disorders, reduces apathy, hallucinations and unreasonable repetitive motions.
After ingestion of C max, donepezil in blood plasma is reached after about 3-4 hours. Plasma concentrations and AUC increase in proportion to the dose.
T 1/2 from the plasma is approximately 70 hours, so when administered systemically in single doses, C ss is usually achieved within 2-3 weeks after the initiation of therapy. After reaching the equilibrium state, donepezil concentration in the plasma and the associated pharmacodynamic effects do not change significantly during the day. The intake of food does not affect the absorption of donepezil.
Binding to plasma proteins is about 95%.
It is assumed that donepezil and / or its metabolites can persist in the body for more than 10 days.
Donepezil is metabolized in the liver and is excreted, as well as its metabolites, which are formed with the participation of cytochrome P450 isoenzymes, mostly in kidneys in unchanged form: approximately 57% of the administered dose was detected in urine (17% unchanged) and 14.5% in feces masses.

After a single dose of 5 mg, the concentration of unmodified donepezil in plasma is 30% of the dose taken, 6-O-desmethyldonepezil - 11% (the only metabolite with similar activity with donepezil hydrochloride), donepezil-cis-N-oxide - 9% 5-O-desmethyldonepezil - 7% and glucuron conjugate 5-O-desmethyldonepezil - 3%.

T 1/2 of donepezil is about 70 hours.

In patients with mild or moderate impairment of liver function, elevated C ss of donepezil in blood plasma can be observed.

Symptomatic treatment of dementia of the Alzheimer's type of mild or moderate severity.

Adults (including elderly patients) are prescribed in an initial dose of 5 mg 1 time / day.
Admission in the initial dose is continued for at least 4-6 weeks to reach equilibrium concentrations of donepezil and determine the early clinical effect of therapy. After 1 month, the dose can be increased to 10 mg / day.
The maximum daily dose is 10 mg / day.

Supportive therapy can be continued as long as the therapeutic effect remains, which should be evaluated regularly.

From the side of the cardiovascular system: infrequently bradycardia;
rarely - sinoatrial blockade, AV blockade.
From the nervous system: often - fainting, fatigue, dizziness, headache, insomnia, hallucinations, agitation, aggressive behavior;
infrequently - convulsive seizures;rarely - extrapyramidal symptoms.
From the digestive system: very often - diarrhea, nausea;
often - vomiting, indigestion, anorexia, gastrointestinal disorders; infrequently - bleeding from the digestive tract, ulcers of the stomach and duodenum.
From the urinary system: often - urinary incontinence;
rarely - a violation of liver function, incl. hepatitis.
Dermatological reactions: often - a rash, itchy skin.

Laboratory tests: infrequent - a slight increase in the activity of the muscle fraction of CK in the blood serum.

Other: pain of different localization, flu-like syndrome, muscle cramps.

Pregnancy, lactation (breastfeeding), children and adolescents under 18, hypersensitivity to donepezil and piperidine derivatives.

Contraindicated in pregnancy and lactation (breastfeeding).

The safety and efficacy of donepezil in children has not been studied, so the drug is not recommended for this category of patients.

Use with caution in patients with obstructive pulmonary disease in history (including bronchial asthma), heart rhythm disorders, anesthesia, and patients with an increased risk of ulceration (eg, patients with a history of peptic ulcer disease or receiving concomitant therapy with NSAIDs), concomitantly with the administration of NSAIDs, cholinergic blockers or other cholinesterase inhibitors.

Treatment should be prescribed and conducted by a physician with experience in managing patients with Alzheimer's disease.

Supportive therapy can be continued as long as the therapeutic effect remains.
If the therapeutic effect disappears, then donepezil should be discarded. After discontinuation of treatment, there is a gradual decrease in donepezil, there is no information on withdrawal syndrome in the event of a sudden discontinuation. It is impossible to predict an individual reaction to donepezil therapy.
The efficacy of donepezil in patients with severe dementia of the Alzheimer's type, other types of dementia, or other types of memory impairment (eg, age-related deterioration of cognitive function) has not been studied.

Donepezil, being an inhibitor of cholinesterase, can enhance the muscle relaxancy of succinylcholine type during anesthesia.

Cholinesterase inhibitors (including donepezil) may have a vagotonic effect on heart rate (in particular, cause bradycardia).
The potential for this effect may be important for patients with SSSU or other supraventricular conduction disorders, such as sinoatrial or AV blockade.
It is believed that cholinomimetics are capable of causing generalized convulsions.
However, the appearance of seizures during treatment with donepezil can also be a manifestation of Alzheimer's disease.
Influence on the ability to manage motor vehicles and work with mechanisms

Dementia Alzheimer's type itself can be accompanied by a disruption in the ability to drive and use sophisticated technology.
In addition, donepezil, mainly at the beginning of treatment or with increasing doses, can cause fatigue, dizziness and muscle cramps. The question of the ability of a patient with Alzheimer's dementia during the use of donepezil to drive a car or use complicated equipment should be decided by the doctor after assessing the patient's individual response to treatment.
The clinical experience of using donepezil is limited, therefore, when taking into account the risk of unknown to the present moment, the manifestations of interaction with other drugs.

Donepezil metabolized with the participation of the isoenzyme CYP3A4 and to a lesser extent - CYP2D6.
Ketoconazole and quinidine, which are inhibitors of CYP3A4 and CYP2D6, respectively, suppress the metabolism of donepezil. Consequently, these and other CYP3A4 inhibitors, such as itraconazole and erythromycin, and CYP2D6 inhibitors, such as fluoxetine, can inhibit donepezil metabolism. In healthy volunteers, ketoconazole increased mean concentrations of donepezil by approximately 30%. However, this action was not comparable with the action of ketoconazole on other substances metabolized with the participation of CYP3A4, so it is unlikely to be of clinical significance.
Inducers of enzymes such as rifampicin, phenytoin, carbamazepine and ethanol can cause a decrease in donepezil.
However, the degree of such inhibitory or inducing action is unknown (caution is required when using simultaneously).
Donepezil can affect the effect of drugs that have anticholinergic activity.
In addition, with simultaneous use, donepezil can enhance the effects of succinylcholine, other muscle relaxants or cholinergic receptor agonists and beta-blockers that affect cardiac conduction, although in vitro studies have shown that donepezil has minimal effect on the hydrolysis of succinylcholine.
With simultaneous use of donepezil with other cholinomimetics and quaternary anticholinergic drugs, such as glycopyrrolate, cases of atypical changes in blood pressure and heart rate are described.

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