Alzepil, 5 mg 28 pcs.

A selective and reversible inhibitor of acetylcholinesterase, which is the main predominant type of cholinesterase in the brain. In vitro, donepezil inhibits this enzyme more than 1,000 times stronger than butyrylcholinesterase, an enzyme that is mainly outside the CNS.

A single dose of 5 mg or 10 mg in equilibrium is accompanied by a 63.6% and 77.3% inhibition of cholinesterase activity (assessed in the erythrocyte membrane model), respectively. The ability of donepezil hydrochloride to inhibit erythrocyte cholinesterase activity correlates with changes in ADAS-cog scores, which is a sensitive tool for assessing changes in cognitive function. The ability of donepezil hydrochloride to change the course of concomitant neurological changes has not been investigated. Thus, donepezil cannot be considered to affect disease progression.

The efficacy of donepezil has been investigated in four placebo-controlled studies, two six-month and two one-year studies.

The six-month clinical trial was analyzed using three efficacy criteria after donepezil was completed. They used the ADAS-Cog scale (a measure of cognitive function); the clinician’s impression of change scale based on interviews and data from caregivers (a measure of overall level of function); and the daily activity subscale of the clinical dementia assessment scale (a measure of the patient’s ability to participate in society, perform household chores, favorite activities, and self-care).

Patients who achieved the criteria below were considered to have responded to treatment.

Response = improvement of at least 4 points on the ADAS-Cog scale, no worsening on the CIBIC scale, no worsening on the Daily Activity subscale of the Clinical Dementia Rating Scale.

*p< 0.05, **p< 0.01

Donepezil hydrochloride caused a dose-dependent, statistically significant increase in the percentage of patients who were found to respond to treatment.

Indications

Attention Deficit and Memory Disorder, Alzheimer’s DiseaseSymptomatic treatment for mild to moderate Alzheimer’s disease

Active ingredient

Donepezil

Composition

1 tablet contains:

Active substance:

donepezil hydrochloride monohydrate – 5.21 mg (corresponds to donepezil hydrochloride – 5 mg)

Auxiliary substances:

Microcrystalline cellulose – 96 mg,

Hydroxypropylcellulose low substituted (L-HPC B1) – 24 mg,

Magnesium stearate – 1 mg.

Composition of the film coating:

Opadray Y-1-7000 white (hypromellose – 1.875 mg, titanium dioxide – 0.9375 mg, macrogol 400 – 0.1875 mg) – 3 mg.

How to take, the dosage

The drug is taken orally, preferably in the evening before bedtime.

The treatment should be started and carried out under the supervision of a physician experienced in the diagnosis and treatment of Alzheimer’s-type dementia. The diagnosis should be based on accepted guidelines, e.g., DSM-IV, ICD-10. Treatment with donepezil can only be started if there are caregivers who are able to monitor the patient’s intake regularly.

Adults, including elderly patients

Treatment begins with a dose of 5 mg once daily and continues for at least 4 weeks to reach C_ss donepezil and to evaluate the early clinical effect of therapy.

After 1 month, the dose of Alzepil^® can be increased to 10 mg once daily, which is the maximum recommended daily dose. Doses greater than 10 mg/day have not been studied in clinical trials.

The maintenance therapy can be continued as long as the therapeutic effect persists and should be evaluated regularly. If there is no therapeutic effect, treatment withdrawal should be considered.

After discontinuation of the drug, there may be a gradual decrease in the beneficial effect of treatment.

Patients with impaired renal function do not need to change the treatment regimen, since this condition does not affect donepezil clearance.

Due to possible increased exposure in mild to moderate hepatic impairment, the dose of the drug should be increased with regard to individual tolerance. There are no data about the use of the drug in patients with severe hepatic impairment.

Alzepil^® is not indicated for the treatment of children and adolescents.

Interaction

Alzepil and/or its metabolites do not inhibit the metabolism of theophylline, warfarin, cimetidine or digoxin.

Special Instructions

Treatment should be prescribed and administered by a specialist experienced in the management of patients with Alzheimer’s-type dementia. The diagnosis of the disease must be made in accordance with generally accepted criteria (e.g., DSM IV, ICD 10). Treatment can only be given if a person is able to control medication administration. Treatment is given as long as there is a therapeutic effect, which must be evaluated regularly. If there is no therapeutic effect, the drug must be discontinued. Individual response to therapy with Alzepil cannot be predicted. After withdrawal of the drug its effect gradually and slowly disappears. There is no information about withdrawal syndrome in case of abrupt discontinuation of the drug.

Contraindications

• hypersensitivity (including to piperidine derivatives);
• pregnancy (see “Administration during pregnancy and lactation”);
• lactation period (see “Administration during pregnancy and lactation”).
• pregnancy (see “Administration during pregnancy and lactation”);
• children under 18 years of age (due to lack of clinical data).

With caution: chronic obstructive pulmonary disease, bronchial asthma, cardiac arrhythmias, general anesthesia, peptic ulcer, concomitant use of NSAIDs, choline blockers or other cholinesterase inhibitors.

Side effects

Nausea, diarrhea, headache, fainting spells, dizziness, insomnia, fatigue, hallucinations, agitation, aggressive behavior (which ceases after dose reduction or drug withdrawal), vomiting, stomach upset, urinary incontinence, rash, skin itching, muscle cramps, anorexia, colds, pain of different localization, slight increase in serum concentration of muscle cretinine phosphokinase, bradycardia, seizures, gastrointestinal bleeding, gastric and duodenal ulcers, sinoatrial and atrioventricular block, extrapyramidal symptoms, liver function disorders, including hepatitis.

Overdose

Symptoms: cholinergic crisis (pronounced nausea, vomiting, salivation, sweating, bradycardia, arterial hypotension, respiratory depression, collapse and convulsions). Increased muscle weakness is possible, which may be fatal if respiratory muscles are affected.