Donepezil

Registered South African indications:

• Dementia in Alzheimer's disease - Mild to moderate 

Contraindications

• Hypersensitivity to the active ingredient or any of its excipients
• Hypersensitivity to piperidine derivatives

Cautions

• Pregnancy
• Breastfeeding
• Hepatic impairment
• Porphyria
• Severe Alzheimer's dementia
• Other types of dementia or memory impairment
• Age-related cognitive decline
• Anaesthesia
• Sick sinus syndrome
• Supraventricular cardiac conduction conditions e.g. sinoatrial or atrioventricular block
• History of gastrointestinal ulcers or risk factors thereof
• Asthma
• Chronic obstructive pulmonary disease
• Galactose intolerance
• Total lactase deficiency
• Glucose-galactose malabsorption
• May impair ability to drive and operate machinery

Forms avail. in SA and covered in this monograph: tab 

Dosages below include:

• International manufacturer recommendations
• South African manufacturer recommendations

International manufacturer recommendations

Alzheimer's dementia - Mild to moderately severe

• Oral (tab): Initial: 5mg, dly, for at least 1 month; Then: Titrate to 10mg, dly if necessary according to patient response; Max: 10mg/24hrs

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Treatment should be initiated and supervised by a physician experienced in the diagnosis and treatment of Alzheimer's dementia

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Diagnosis should be made according to accepted guidelines

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Maintenance treatment can be continued for as long as therapeutic benefit for the patient exists

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Treatment should only be started if a caregiver is available who will regularly monitor drug intake for the patient

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Treatment should be reassessed on a regular basis

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Discontinuation should be considered when evidence of a therapeutic effect is no longer present

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Upon discontinuation of treatment, a gradual abatement of the beneficial effects is seen

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South African manufacturer recommendations

Dementia in Alzheimer's disease - Mild to moderate 

• Oral (tab): Initial: 5mg, dly for at least 4-6 weeks; Then: Titrate to 10mg, dly if necessary according to patient response; Max: 10mg/24hrs 

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The 5mg/day dose should be maintained for at least 4-6 weeks 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 one-month clinical assessment of treatment at 5mg/day, the dose can be increased to 10mg/day (once-a-day dosing). The maximum recommended daily dose is 10mg

Doses greater than 10mg/day have not been studied

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The established effective dosages is 5mg and 10mg administered once daily. Although there is no statistically significant evidence that a greater treatment effect is obtained from the use of the 10 mg dose, there is a suggestion, based on analysis of group data that some additional benefits may accrue to some patients from the use of the higher dose

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There is no evidence of a rebound effect after abrupt discontinuation of therapy

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Dosage for the dispersible tablet (ODT) is not yet available for inclusion in dosage section

Not indicated for use in children

Pregnancy

• Caution
• There is no adequate data from the use of donepezil in pregnant women.  Studies in animals have not shown teratogenic effect but have shown pre and post-natal toxicity. The potential risk for humans is unknown
• Donepezil should not be used during pregnancy unless clearly necessary

Breastfeeding

• Caution; not recommended
• Donepezil is excreted in the milk of rats. It is not known whether donepezil hydrochloride is excreted in human breast milk and there are no studies in breastfeeding women. Therefore, women on donepezil should not breastfeed

Fertility

• There is no relevant data to demonstrate the effect of donepezil on human fertility

Renal Impairment

• No dose adjustment recommended

Hepatic Impairment

• Mild to moderate: Caution; no dose adjustment recommended
  Dose escalation should be performed according to individual tolerability
• Severe: Caution; no information available 

Elderly

• No dose adjustment recommended

Porphyria Information

• Possibly porphyrinogenic (PSP)

Drugs in Sport

• Permitted - No warnings

Central Nervous System Disorders

• Syncope
• Dizziness
• Insomnia
• Seizure
• Extrapyramidal symptoms
• Neuroleptic malignant syndrome
• Hallucinations
• Agitation
• Aggressive behaviour
• Abnormal dreams and nightmares
• Headache
• Fatigue
• Pain

Cardiovascular Disorders

• Bradycardia
• Sino-atrial block
• Atrioventricular block 

Gastrointestinal Disorders

• Diarrhoea
• Nausea and vomiting
• Abdominal disturbance
• Gastrointestinal haemorrhage
• Gastric and duodenal ulcers
• Salivary hypersecretion

Hepatobiliary Disorders

• Liver dysfunction including hepatitis

Genitourinary Disorders

• Urinary incontinence

Endocrine and Metabolic Disorders

• Anorexia

Musculoskeletal Disorders

• Muscle cramps
• Rhabdomyolysis
• Increased muscle creatine kinase (minor)

Skin and Subcutaneous Tissue Disorders

• Rash
• Pruritis

Immune, Blood and Lymphatic System Disorders

• Common cold

• CYP3A4 inhibitors
• Ketoconazole
• Itraconazole
• Erythromycin
• CYP2D6 inhibitors
• Quinidine
• Fluoxetine
• Rifampicin
• Phenytoin
• Carbamazepine
• Succinylcholine
• Anticholinergic agents
• Cholinergic agents
• Neuromuscular blocking agents
• Beta-blockers
• Anaesthesia
• Antipsychotics
• Alcohol

• Mental status
• Weight

Donepezil hydrochloride is a specific and reversible inhibitor of acetylcholinesterase, the predominant cholinesterase in the brain. Donepezil hydrochloride is in vitro over 1000 times more potent an inhibitor of this enzyme than of butyrylcholinesterase, an enzyme that is present mainly outside the central nervous system.

Tablet 5mg

• Alizido (Zydus)
• Aricept (Pfizer) originator
• Arimentia (Pharmacare)
• Arimer (Ranbaxy)
• Curlovon (Dr Reddy)
• Donecept (Cipla Medpro)
• Donepezil Unicorn (Unicorn)
• Donerin 5 (Watson) 
• Jubezil (LeBasi)
• Macleods donepezil (Macleods)
• Nepizel (Unicorn)
• Ran-Donepezil (Ranbaxy)
• Zepanalz (Aurobindo)

Tablet 10mg

• Alizido (Zydus)
• Aricept (Pfizer) originator
• Arimentia (Pharmacare)
• Arimer (Ranbaxy)
• Curlovon (Dr Reddy)
• Donecept (Cipla Medpro)
• Donepezil Unicorn (Unicorn)
• Donerin 10 (Watson) 
• Jubezil (LeBasi)
• Macleods donepezil (Macleods)
• Nepizel (Unicorn)
• Ran-Donepezil (Ranbaxy)
• Zepanalz (Aurobindo)

Tablet dispersible 5mg

• Donecept ODT 5 (Cipla Medpro)

Tablet dispersible 10mg

• Donecept ODT 10 (Cipla Medpro)