The use of donepezil in patients with severe Alzheimer’s disease or suffering from other types of dementia or other forms of memory disorders (eg, cognitive decline, Age) has not been studied

Anesthesia

Donepezil, like any cholinesterase inhibitor, may increase muscle relaxation induced by succinylcholine-type treatments during anesthesia

Cardiovascular disorders

Due to their pharmacological activity, cholinesterase inhibitors may have vagotonic effects on cardiac rhythm (eg, bradycardia). Their incidence may be particularly high in patients with sinus disease or other abnormalities of supraventricular conduction such as a sino-atrial or atrio-ventricular block.

Syncope and convulsions have been reported. When examining these patients, the possibility of heart block or prolonged sinus breaks should be considered.

Gastrointestinal disorders

Patients at risk for a particular ulcer, such as those with a history of ulcerative illness or receiving concomitant anti-inflammatory, non-steroidal (NSAID) Careful symptomatic monitoring. However, clinical studies conducted with donepezil have not shown increased incidence of ulcers or gastrointestinal bleeding compared to placebo.

Disorders, genitourinary

Although not observed in studies conducted with donepezil, cholinomimetics may induce urinary retention.
Neurological Disorders

Convulsions: cholinomimetics are described as potentially responsible for generalized convulsive seizures. However, convulsions can also be a manifestation of Alzheimer's disease.



NMS, a potentially fatal syndrome characterized by hyperthermia, stiffness, muscle, neurovegetative instability, altered consciousness and elevated serum creatine levels, phosphokinase, was very rarely reported, with donepezil, in particular , And in patients also receiving concomitant antipsychotics. Other signs may include myoglobinuria (rhabdomyolysis) and acute renal failure. If a patient develops signs or symptoms suggestive of a NMS, or has unexplained hyperthermia unaccompanied by other signs of NMS, treatment should be discontinued.
Broncho-pulmonary disorders
Because of their cholinomimetic activity, cholinesterase inhibitors should be prescribed with caution in patients with a history of asthma or bronchopulmonary disease, obstructive. >

Concomitant administration of donepezil and other acetylcholinesterase inhibitors, agonists or antagonists, of the cholinergic system should be avoided.

Hepatic impairment, severe

There are no data in patients with severe hepatic impairment

This drug contains lactose Patients with rare hereditary problems of galactose intolerance, lactase deficiency or glucose-galactose malabsorption syndrome should not take this drug

Mortality during studies in dementia, vascular

Three clinical studies with a duration of six months were conducted in patients with probable or possible NINDS-AIREN criteria for vascular dementia (DVa). The NINDS-AIREN criteria are designed to identify patients whose dementia is solely related to vascular causes and exclude patients suffering from Alzheimer's disease.

In the first study, the mortality rate was 2/198 (1.0%) with donepezil hydrochloride 5 mg, 5/206 (2.4%), donepezil hydrochloride 10 mg and 7/199 ( 3.5%) under placebo. In the second study, mortality rates were 4/208 (1.9%) under hydrochloride, donepezil 5 mg, 3/215 (1.4%) with donepezil hydrochloride 10 mg and 1/193 0.5%) on placebo. In the third study, mortality rates were 11/648 (1.7%) with donepezil hydrochloride 5 mg and 0/326 (0%) on placebo. The mortality rate in the three studies combined was higher in the group, donepezil (1.7%) than in the placebo group (1.1%), but this difference was not statistically significant. It appears that the majority of deaths in patients receiving either donepezil or placebo resulted from various vascular causes, which was predictable in this elderly population suffering from pre-existing vascular pathologies. An analysis of all serious vascular events with or without death did not show any difference in their rate of occurrence between the group donepezil and the placebo group

In studies conducted with donepezil hydrochloride in Alzheimer's disease on the one hand (n = 4146) and in all dementias, including vascular dementias, on the other hand, = 6888), the mortality rate in the placebo groups was higher than in the groups: donepezil.
The most frequently observed adverse effects were diarrhea, muscle cramps, fatigue, nausea, vomiting and insomnia.


System-organ

Very common

Frequent

Uncommon

Rare

Very rare

Infections

Cold.
Metabolism and nutrition

Anorexia.

Psychiatry

Hallucinations **. Agitation **. Aggressiveness **. Abnormal dreams and nightmares **.

Nervous system

Syncope *.

Dizziness.

Insomnia.
Convulsions *.

Extra-pyramidal symptoms.

Neuroleptic malignant syndrome.

Cardiac

Bradycardia.

Sino-auricular block.

Atrioventricular block.

Gastrointestinal

Diarrhea.

Nausea.
Vomiting. Abdominal Disorders

Gastrointestinal haemorrhage: Gastric and duodenal ulcer

Hepato-biliary

Hepatic impairment including hepatitis ***.

Skin and Appendages

Rash.

Pruritus

Musculoskeletal system

Muscular cramps.
Uro-genital
Urinary incontinence.

General

Headache.

Fatigue.
Pain.
Biological examination

Slight increase in serum concentrations of creatinine kinase, muscle

Trauma and poisoning

Accident.

* When considering patients with syncope or convulsion, the possibility of prolonged heart block or prolonged sinus pause should be considered (see Warnings and Precautions for Use).

** Reported cases of hallucinations, abnormal dreams, nightmares, agitation and aggression have decreased during dose reduction or discontinuation of treatment.
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*** In case of hepatitis, unknown etiology, ARICEPT should be discontinued.

Reporting of suspected adverse reactions

The reporting of suspected adverse reactions after authorization of the drug is important. It allows continuous monitoring of the ratio, benefit / risk of the drug. Health professionals report any suspected adverse effects via the national reporting system: National Agency for the Safety of Medicines and Health Products (ANSM) and network of Regional Centers of Pharmacovigilance. Www.ansm.sante.fr.