Y.S.P. Industries


Y.S.P. Industries
Full Prescribing Info
Donepezil hydrochloride.
Donepezil Hydrochloride 5mg.
Donepezil Hydrochloride 10mg.
Pharmacology: Pharmacodynamics: Donepezil is a piperidine derivative, chemically distinct from the other agents in this class. Donepezil demonstrates relatively high selectivity for central nervous system acetylcholinesterase, with minimal peripheral activity. It reversibly and noncompetitively inhibits centrally-active acetylcholinesterase, the enzyme responsible for hydrolysis of acetylcholine. This is expected to result in increased concentrations of acetylcholine that are available for synaptic transmission. Alzheimer's disease is characterized by cholinergic deficiency in the cortex and basal forebrain, which contributes to cognitive deficits. Donepezil does not alter the course of the underlying dementing process.
Pharmacokinetics: Absorption: Donepezil hydrochloride is well absorbed from the gastrointestinal tract, maximum plasma concentrations being achieved within 3 to 4 hours after ingestion. Food did not affect the absorption of donepezil hydrochloride.
Distribution: It is about 95% bound to human plasma proteins, mainly albumin.
Metabolism: Donepezil is metabolized in the liver. Donepezil undergoes partial metabolism via the cytochrome P450 isoenzyme CYP3A4, and to lesser extent by CYP2D6, to 4 major metabolites. About 11% of a dose is present in plasma as 6-O-desmethyldonepezil, which has similar activity to the parent compound.
Excretion: Over 10 days, about 57% of a dose is recovered from the urine as unchanged drug and metabolites, and about 15% from the faeces; 28% remains unrecovered suggesting accumulation. The elimination half-life is about 70 hours. Steady-state concentrations are achieved within 3 weeks of the start of therapy.
*Sex, race and smoking history have no clinically significant influence on plasma concentrations of donepezil hydrochloride.
For the treatment of mild, moderate, and severe dementia in Alzheimer's disease.
Dosage/Direction for Use
Adult/Elderly: Mild to moderate Alzheimer's Disease: Treatment is initiated at 5mg/day (once-a-day-dosing). Donepezil should be taken orally, in the evening, just prior to retiring. The 5mg/day dose should be maintained for at least one month in order to allow the earliest clinical responses to treatment to be assessed and to allow steady-state concentrations of donepezil hydrochloride to be achieved. Following a 4 to 6 weeks of clinical assessment in patients who tolerated treatment at 5mg/day, the dose of Donepezil can be increased to 10mg/day (once-day-dosing). The maximum recommended daily dose is 10mg.
Severe Alzheimer's Disease: Donepezil is effective at a dose of 10mg administered once daily. However steady state is not achieved for 15 days and because the incidence of untoward effects may be influenced by the rate of dose escalation, a dose of 10mg should not be escalated until patients have been on a daily dose of 5mg for 4 to 6 weeks. Upon discontinuation of treatment, a gradual abatement of the beneficial effects of Donepezil is seen. There is no evidence of a rebound effect after abrupt discontinuation of therapy.
Treatment should be initiated and supervised by a physician experienced in the diagnosis and treatment of Alzheimer's dementia. Diagnosis should be made according to accepted guidelines (e.g. DSM IV, ICD 10). Therapy with donepezil should only be started if a caregiver is available who will regularly monitor drug intake for the patient. Maintenance treatment can be continued for as long as a therapeutic benefit for the patient exists. Therefore, the clinical benefit of donepezil should be reassessed on a regular basis. Discontinuation should be considered when evidence of a therapeutic effect is no longer present. Individual response to donepezil cannot be predicted.
Renal and hepatic impairment: A similar dose schedule can be followed for patients with renal impairment as clearance of donepezil hydrochloride is not affected by this condition.
Children: Donepezil is not recommended for use in children.
Mode of Administration(s): Oral: the orodispersible tablet should be placed on the tongue and allowed to disintegrate before swallowing with or without water, according to patient's preference.
Symptoms and Treatment of Overdose: Overdosage with cholinesterase inhibitors can result in cholinergic crisis characterized by severe nausea, vomiting, salivation, sweating, bradycardia, hypotension, respiratory depression, collapse and convulsions. Increasing muscle weakness is a possibility and may result in death if respiratory muscles are involved.
Treatment is symptomatic and supportive. Tertiary anticholinergics such as atropine may be used as an antidote for donepezil overdosage. Intravenous atropine sulphate titrated to effect is recommended: an initial dose of 1.0 to 2.0 mg IV with subsequent doses based upon clinical response. Atypical responses in blood pressure and heart rate have been reported with other cholinomimetics when co-administered with quaternary anti- cholinergics such as glycopyrrolate. It is not known whether donepezil hydrochloride and/or its metabolites can be removed by dialysis (hemodialysis, peritoneal dialysis, or hemofiltration).
Donepezil is contraindicated in patients with a known hypersensitivity to donepezil hydrochloride, piperidine derivatives, or to this product.
Special Precautions
Use of donepezil in patients with severe dementia, others types of dementia or other types of memory impairment (e.g: age-related cognitive decline) has not been investigated.
Anaesthesia: Donepezil as a cholinesterase inhibitor is likely to exaggerate succinylcholine-type muscle relaxation during anaesthesia.
Cardiovascular Conditions: Because of their pharmacological action, cholinesterase inhibitors may have vagotonic effects on heart rate (e.g. bradycardia). The potential for this action may be particularly important to patients with "sick sinus syndrome" or other supraventricular cardiac conduction conditions, such as sinoatrial or atrioventricular block.
There have been reports of syncope and seizures. In investigating such patients the possibility of heart block or long sinusal pauses should be considered.
Gastrointestinal Conditions: Patients at increased risk for developing ulcers, e.g., those with a history of ulcer disease or those receiving concurrent nonsteroidal anti-inflammatory drugs (NSAIDs), should be monitored for symptoms. However, the clinical studies with Donepezil showed no increase, relative to placebo, in the incidence of either peptic ulcer disease or gastrointestinal bleeding.
Genitourinary: Cholinomimetics may cause bladder outflow obstruction.
Neurological Conditions: Seizures: Cholinomimetics are believed to have some potential to cause generalised convulsions. However, seizure activity may also be a manifestation of Alzheimer's disease.
Cholinomimetics may have the potential to exacerbate or induce extrapyramidal symptoms.
Neuroleptic Malignant Syndrome (NMS): NMS, a potentially life-threatening condition characterised by hyperthermia, muscle rigidity, autonomic instability, altered consciousness and elevated serum creatine phosphokinases levels, has been reported to occur very rarely in association with donepezil, particularly in patients also receiving concomitant antipsychotics. Additional signs may include myoglobinuria (rhabdomyolysis) and acute renal failure. If a patient develops signs and symptoms indicative of NMS, or presents with unexplained high fever without additional clinical manifestations of NMS, treatment should be discontinued.
Pulmonary Conditions: Because of their cholinomimetic actions, cholinesterase inhibitors should be prescribed with care to patients with a history of asthma or obstructive pulmonary disease.
The administration of donepezil concomitantly with other inhibitors of acetylcholinesterase, agonists or antagonists of the cholinergic system should be avoided.
Severe Hepatic Impairment: There are no data for patients with severe hepatic impairment.
Effect on ability to drive and use machines: Donepezil has minor or moderate influence on the ability to drive and use machines. Dementia may cause impairment of driving performance or compromise the ability to use machinery. Furthermore, donepezil can induce fatigue, dizziness and muscle cramps, mainly when initiating or increasing the dose. The treating physician should routinely evaluate the ability of patients on donepezil to continue driving or operating complex machines.
Use In Pregnancy & Lactation
Neonates exposed to antipsychotic drugs during the third trimester of pregnancy are at risk for extrapyramidal and/or withdrawal symptoms following delivery. There have been reports of agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress, and feeding disorder in these neonates. These complications have varied in severity; while in some cases symptoms have been self-limited, in other cases neonates have required intensive care unit support and prolonged hospitalisation.
This product should be used during pregnancy only if the potential benefit justifies the potential risk to the foetus.
Side Effects
The most common adverse events are diarrhoea, muscle cramps, fatigue, nausea, vomiting and insomnia.
Adverse reactions are listed as follows: (see table).

Click on icon to see table/diagram/image
Drug Interactions
Donepezil hydrochloride and/or any of its metabolites do not inhibit the metabolism of theophylline, warfarin, cimetidine or digoxin in humans.
The metabolism of donepezil hydrochloride is not affected by concurrent administration of digoxin or cimetidine.
Donepezil hydrochloride has the potential to interfere with medications having anticholinergic activity.
There is potential for synergistic activity with concomitant treatment involving medications such as succinylcholine, other neuro-muscular blocking agents or cholinergic agonists or beta blocking agents that have effects on cardiac conduction. Concurrent use of donepezil and succinylcholine may result in prolonged neuromuscular blockade.
No adverse effects related to drug interactions were reported when patients were concomitantly administered donepezil and selective serotonin reuptake inhibitors, neuroleptics or (in a small number of cases) anti-Parkinsonian treatment.
Enzyme inducers, such as rifampicin, phenytoin, carbamazepine and alcohol may reduce the levels of donepezil. Since the magnitude of an inhibiting or inducing effect is unknown, such drug combinations should be used with care.
Concurrent use of donepezil and oxybutynin may result in decreased efficacy of the cholinesterase inhibitor.
Concurrent use of donepezil and tolterodine may result in decreased efficacy of the cholinesterase inhibitor.
Concurrent use of donepezil and ramelteon may result in increased ramelteon exposure.
Concurrent use of donepezil and bethanechol may result in cholinergic adverse effects (bradyarrhythmia, bronchospasm, hyperhidrosis, diarrhea, vomiting).
Concurrent use of donepezil and quinidine may result in increased donepezil bioavailability.
Concurrent use of donepezil and ketoconazole may result in increased donepezil bioavailability.
Other CYP3A4 inhibitors, such as itraconazole and erythromycin, and CYP2D6 inhibitors, such as fluoxetine could inhibit the metabolism of donepezil.
There is also the potential for synergistic activity with concomitant treatment involving beta blocking agents which have effects on cardiac conduction.
Store at temperature below 30°C.
Shelf-Life: 2 years.
MIMS Class
Neurodegenerative Disease Drugs
ATC Classification
N06DA02 - donepezil ; Belongs to the class of anticholinesterases. Used in the management of dementia.
Orodispersible tab 5 mg (a white color round, one side impressed with "Y" and the other sides impressed with a score) x 3 x 10's, 12 x 10's, 50 x 10's. 10 mg (a yellow color round, one side impressed with "Y" and the other sides impressed with a score) x 3 x 10's, 12 x 10's, 50 x 10's.
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