Consumer medicine information

1. Why am I using APO-DONEPEZIL?

APO-DONEPEZIL contains the active ingredient donepezil hydrochloride. APO-DONEPEZIL is used to treat mild, moderate and severe Alzheimer's disease, also called dementia of the Alzheimer's type.
For more information, see Section 1. Why am I using APO-DONEPEZIL? in the full CMI.

2. What should I know before I use APO-DONEPEZIL?

Do not use if you have ever had an allergic reaction to APO-DONEPEZIL or any of the ingredients listed at the end of the CMI.
Talk to your doctor if you have any other medical conditions, take any other medicines, or are pregnant or plan to become pregnant or are breastfeeding.
For more information, see Section 2. What should I know before I use APO-DONEPEZIL? in the full CMI.

3. What if I am taking other medicines?

Some medicines may interfere with APO-DONEPEZIL and affect how it works.
A list of these medicines is in Section 3. What if I am taking other medicines? in the full CMI.

4. How do I use APO-DONEPEZIL?

• The usual starting dose is one APO-DONEPEZIL 5 mg tablet each day

• After one month, your doctor will assess your response and may increase your dose to one APO-DONEPEZIL 10 mg tablet each day.

5. What should I know while using APO-DONEPEZIL?

6. Are there any side effects?

Side effects include heartburn, indigestion, stomach pain, headache, dizziness, difficulty in sleeping, unusual tiredness, feeling sick, diarrhoea, vomiting, loss of appetite, weight loss, bruising, muscle cramps, joint pain, tingling or numbness of the hands or feet, depression, unusual dreams, agitation, aggressive behaviour, difficulty in urinating or passing urine more often.
For more information, including what to do if you have any side effects, see Section 6. Are there any side effects? in the full CMI.

1 Name of Medicine

Donepezil hydrochloride monohydrate.

2 Qualitative and Quantitative Composition

Each tablet contains 5 mg or 10 mg donepezil hydrochloride (as monohydrate) as the active ingredient, equivalent to 4.56 mg or 9.12 mg donepezil free base, respectively.
Excipients with known effect. APO-Donepezil tablets contain sugars as lactose.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

5 mg tablets. White to off-white, circular, biconvex, film coated tablets embossed with "C" on one side and "7" on the other side.
10 mg tablets. Yellow, circular, biconvex, film coated tablets embossed with "C" on one side and "6" on the other side.

4 Clinical Particulars

4.9 Overdose

Symptoms. Overdosage with cholinesterase inhibitors can result in cholinergic crisis characterised by severe nausea, vomiting, miosis, lacrimation, salivation, sweating, flushing, bradycardia, involuntary urination and/or defecation, bronchospasm, increased bronchial secretions, respiratory depression, collapse and convulsions/ seizures. Hypotension following overdose could be severe leading to cardiovascular collapse or shock. Abdominal pain, diarrhoea, increased micturition, diaphoresis, vertigo, fasciculations, tremors, agitation, lethargy, syncope and coma may occur. Various dysrhythmias, primarily heart block, may theoretically occur due to cholinergic effects. Increasing muscle weakness is a possibility and may result in death if respiratory muscles are involved. Due to its high degree of selectivity for AChE in the CNS and less peripheral selectivity, overdoses would be expected to exhibit more CNS related symptomatology, including extrapyramidal effects.
Overdoses of 45 mg and 50 mg in two elderly patients resulted in minimal effects, predominately gastrointestinal, and in one case persistent bradycardia (HR in the 40's) both with uneventful recoveries.
Treatment. As in any case of overdose, general supportive measures should be utilised. Cholinesterase activity may be depressed and should be monitored in plasma (pseudocholinesterase) and red blood cells. Monitor ECG following significant exposures. Monitor pulse oximetry and/or arterial blood gases and obtain a chest radiograph in patients with pulmonary symptoms. Tertiary anticholinergics such as atropine may be used as an antidote for donepezil hydrochloride 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 anticholinergics such as glycopyrrolate. Consider administration of activated charcoal in the event of a potentially toxic ingestion. Activated charcoal is most effective when administered within one hour of ingestion. In patients who are not fully conscious or have impaired gag reflex, consideration should be given to administering activated charcoal via nasogastric tube once the airway is protected. It is not known whether donepezil and/or its metabolites can be removed by dialysis (haemodialysis, peritoneal dialysis, or haemofiltration). Emesis is not recommended because of the potential for CNS depression and seizures.
For information on the management of overdose, contact the Poisons Information Centre on 131126 (Australia).

5 Pharmacological Properties

5.3 Preclinical Safety Data

Genotoxicity. Donepezil was not mutagenic in reverse mutation assays in bacteria or in the mouse lymphoma forward mutation assay in vitro. Donepezil did not induce unscheduled DNA synthesis in rat primary hepatocyte cultures following oral dosing of the animals. In the chromosome aberration test in cultures of Chinese hamster lung cells, some clastogenic effects were observed. Donepezil was not clastogenic in the in vivo mouse micronucleus test.
Carcinogenicity. No evidence of carcinogenicity was found in long-term studies in mice and rats with dietary dosing of donepezil hydrochloride resulting in peak plasma concentrations of up to 17 times and 6-19 times, respectively, that in humans at the recommended clinical dose of 10 mg/day.

6 Pharmaceutical Particulars

6.7 Physicochemical Properties

Donepezil hydrochloride is a white crystalline powder and is freely soluble in chloroform, soluble in water and in glacial acetic acid, slightly soluble in ethanol and in acetonitrile and practically insoluble in ethyl acetate and in n-hexane.
Chemical structure.
https://stagingapi.mims.com/au/public/v2/images/fullchemgif/CSDONMON.gif Chemical name: (RS)-2-[(1-benzyl-4-piperidyl) methyl]-5,6-dimethoxyindan-1-one hydrochloride monohydrate.
Molecular formula: C₂₄H₂₉NO₃.HCl.H₂O.
Molecular weight: 433.97.
CAS number. 884740-09-4.

7 Medicine Schedule (Poisons Standard)

S4 - Prescription Only Medicine.

Summary Table of Changes

https://stagingapi.mims.com/au/public/v2/images/fulltablegif/APODONST.gif