Donepezil Unicorn 5 and 10 mg Tablets

DONEPEZIL UNICORN is indicated for the symptomatic treatment of mild or moderate dementia in Alzheimeru2019s disease.

Adults/elderly: The initial dosage is 5 mg once daily. Although a higher dose of 10 mg did not provide a statistically significant greater clinical benefit than the 5 mg dose, a daily dose of 10 mg may provide additional benefit for some patients. After 4 u2013 6 weeks, when steady-state concentrations of donepezil hydrochloride are achieved, the clinical response of the patient should be assessed and the dosage can be increased if necessary to a maximum daily dosage of 10 mg once daily. DONEPEZIL UNICORN should be taken in the evening. Upon discontinuation of treatment, a gradual abatement of the beneficial effects of DONEPEZIL UNICORN is seen. There is no evidence of a rebound effect after abrupt discontinuation of therapy.

Renal and hepatic impairment: The clearance of DONEPEZIL UNICORN is not affected by renal or mild hepatic impairment. No dosage adjustments are required.

DONEPEZIL UNICORN is contraindicated in:

• Patients with known hypersensitivity to donepezil hydrochloride, piperidine derivatives, or to any of the inactive ingredients of DONEPEZIL UNICORN (see section 6.1).
• Pregnancy and lactation (see section 4.6).
• Children.
• Patients recovering from bladder or gastrointestinal surgery.

The supervision of an experienced doctor in the diagnosis and treatment of Alzheimeru2019s dementia is required when treatment is commenced. Maintenance treatment can be continued for as long as a therapeutic benefit for the patient exists. It is important to reassess the clinical benefit of DONEPEZIL UNICORN on a regular basis. If evidence of a therapeutic effect is no longer present, DONEPEZIL UNICORN should be discontinued. The individual response of patients to DONEPEZIL UNICORN cannot be predicted.

The use of DONEPEZIL UNICORN in patients with severe Alzheimeru2019s dementia, other types of dementia or other types of memory impairment (e.g. age related cognitive decline), has not been established.

Cardiovascular conditions: Cardiovascular conditions, such as sick sinus syndrome, supraventricular conduction problems e.g. sinoatrial or atrioventricular block and unexplained syncopal episodes: Cholinesterase inhibitors such as DONEPEZIL UNICORN may have vagotonic effects on heart rate (e.g. bradycardia). Syncopal episodes have been reported in association with the use of DONEPEZIL UNICORN. There have been post-marketing reports of QTc interval prolongation and torsades de pointes (see sections 4.5 and 4.8). Caution is advised in patients with pre-existing or family history of QTc prolongation, in patients treated with medicines affecting the QTc interval, or in patients with relevant pre-existing cardiac disease (e.g uncompensated heart failure, recent myocardial infarction, bradyarrhythmias), or electrolyte disturbances (hypokalaemia, hypomagnesaemia). Clinical monitoring (electrocardiogram [ECG]) may be required.

Surgery: DONEPEZIL UNICORN, as a cholinesterase inhibitor, it is likely to exaggerate succinylcholine-type muscle relaxation during anaesthesia.

Peptic ulcer disease or history thereof: DONEPEZIL UNICORN may be expected to increase gastric acid secretion due to increased cholinergic activity. Patients should thus be monitored closely for symptoms of gastrointestinal bleeding especially those receiving concurrent nonsteroidal anti-inflammatory drugs (NSAIDs).

Genitourinary: DONEPEZIL UNICORN may cause bladder outflow obstruction.

Seizures, history thereof and Parkinsonu2019s disease: DONEPEZIL UNICORN may cause generalised convulsions.

Asthma, history thereof or chronic obstructive pulmonary disease: DONEPEZIL UNICORN may aggravate these conditions due to the cholinomimetic actions. The administration of DONEPEZIL UNICORN concomitantly with other inhibitors of acetylcholinesterase, agonists or antagonists of the cholinergic system should be avoided (see section 4.5).

Neuroleptic malignant syndrome (NMS) NMS, a potentially life-threatening condition characterised by hyperthermia, muscle rigidity, autonomic instability, altered consciousness and elevated serum creatine phosphokinase levels have 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 with DONEPEZIL UNICORN should be discontinued.

Severe hepatic impairment: There is no known effect in patients with severe hepatic impairment.

Lactose warning: DONEPEZIL UNICORN contains lactose. Patients with rare hereditary conditions of galactose intolerance e.g galactosaemia, Lapp lactase deficiency, glucose-galactose malabsorption or fructose intolerance should not take DONEPEZIL UNICORN, which may have an effect on the glycaemic control of patients with diabetes mellitus.

Anticholinergics: Because of the mechanism of action of DONEPEZIL UNICORN, it has the potential to interfere with the activity of anticholinergic medicines.

Cholinergic agonists and other cholinesterase inhibitors: A synergistic effect may be expected when DONEPEZIL UNICORN is given concurrently with succinylcholine, similar neuromuscular blocking agents or cholinergic agonists such as bethanechol or beta-blocking agents which have an effect on cardiac conduction.

Nonsteroidal anti-inflammatory drugs (NSAIDs): DONEPEZIL UNICORN may increase gastric acid secretion due to the increased cholinergic activity, and patients should be monitored for symptoms of active or occult gastrointestinal bleeding. Cases of QTc interval prolongation and torsades de pointes have been reported for donepezil, as in DONEPEZIL UNICORN. Caution is advised when DONEPEZIL UNICORN is used in combination with other medicines known to prolong the QTc interval and clinical monitoring (electrocardiogram [ECG] may be required. Examples include:

• Class IA antiarrhythmics (e.g. quinidine)
• Class III antiarrhythmics (e.g. amiodarone, sotalol)
• Certain antidepressants (e.g citalopram, escitalopram, amitriptyline)
• Other antipsychotics (e.g. phenothiazine derivatives, sertindole, pimozide, ziprasidone)
• Certain antibiotics (e.g. clarithromycin, erythromycin, levofloxacin, moxifloxacin)

Medicines that induce the isoenzymes CYP2D6 and CYP3A4: Carbamazepine, dexamethasone, phenobarbitone, phenytoin, rifampicin and alcohol may increase the rate of elimination of DONEPEZIL UNICORN.

Medicines highly bound to plasma proteins: Although DONEPEZIL UNICORN is highly bound to plasma proteins (96 %), no displacement interactions were observed with furosemide, digoxin and warfarin. The metabolism of donepezil is not affected by concurrent administration of digoxin, cimetidine, thioridazine, risperidone or sertraline. In vitro studies have shown that the cytochrome P450 enzymes 3A4 and to a minor extent 2D6 are involved in the metabolism of donepezil. Ketoconazole and quinidine, inhibitors of CYP3A4 and 2D6 respectively may inhibit donepezil metabolism.

Pregnancy: The safe use of DONEPEZIL UNICORN in pregnancy and lactation has not been established. The potential risk for humans is unknown. DONEPEZIL UNICORN should not be used during pregnancy.

Breastfeeding: The safety of DONEPEZIL UNICORN in lactation has not been established. Donepezil is excreted in the milk of rats. It is not known whether donepezil is excreted in human breast milk and there are no studies in lactating women. Therefore, women on DONEPEZIL UNICORN should not breastfeed.

Fertility: There are no data on the effect of DONEPEZIL UNICORN.

DONEPEZIL UNICORN can affect the ability to drive a vehicle and to perform skilled tasks, such as operating machinery. Caution should be exercised.

Tabulated summary of adverse reactions The following adverse reactions have been identified according to the following categories, frequent, less frequent and frequency unknown.

MedDRA system organ class Frequency Side effects Infections and infestations Frequent Cold, influenza. Blood and lymphatic system disorders Less frequent Ecchymosis. Frequency unknown Haemolytic anaemia. Metabolism and nutrition disorders Frequent Anorexia. Less frequent Dehydration. Frequency unknown Hyponatraemia. Psychiatric disorders Frequent Agitation Less frequent Mental depression Frequency unknown Neuroleptic malignant syndrome, convulsions, hallucinations, confusion. Nervous system disorders Frequent Insomnia, fatigue, agitation. Less frequent Vertigo, dizziness, ataxia, abnormal dreams, headache, somnolence, syncope, aphasia, paraesthesia, tremor, mood or mental changes including abnormal crying, aggression, delusions, irritability, nervousness or restlessness. Eye disorders Less frequent Cataract, eye irritation, blurred vision. Cardiac disorders Less frequent Angina, bradycardia, atrial fibrillation. Frequency unknown Sino-atrial block, atrioventricular block, Polymorphic ventricular tachycardia including Torsades de Pointes: electrocardiogram QT interval prolonged. Vascular disorders Less frequent Vasodilation and hot flushes, hypertension or hypotension. Respiratory, thoracic and mediastinal disorders Less frequent Bronchitis, upper respiratory tract infections, influenza, dyspnoea, pharyngitis. Gastrointestinal disorders Frequent Nausea, diarrhoea, vomiting, dyspepsia. Less frequent Peptic ulcers, constipation, weight loss, bloating, epigastric pain, faecal incontinence, gastrointestinal bleeding. Frequency unknown Cholecystitis, abdominal pain. Hepato-biliary disorders Frequency unknown Pancreatitis, hepatitis.

Skin and subcutaneous tissue disorders Less frequent Pruritus, diaphoresis, urticaria, ecchymoses. Frequency unknown Rash. Musculoskeletal, connective tissue and bone disorders Frequent Muscle cramps. Less frequent Arthritis, bone fracture. Renal and urinary disorders Less frequent Frequent urination, urinary tract infections, urinary incontinence, nocturia. Reproductive system and breast disorders Less frequent: Increased libido. General disorders and administrative site conditions Less frequent: Pain including chest pain, toothache. Investigations Frequency unknown Minor changes in serum concentrations of creatine kinase.

Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicine is important. It allows continued monitoring of the benefit/risk balance of the medicine. Health care providers are asked to report any suspected adverse reactions to SAHPRA via the u201c6.04 Adverse Drug Reactions Reporting Formu201d, found online under SAHPRAu2019s publications: https://www.sahpra.org.za/Publications/Index/8 or directly to Unicorn Pharmaceuticals (Pty) Ltd. at [email protected].

Overdosage with DONEPEZIL UNICORN can result in cholinergic crisis characterised by bradycardia, hypotension, severe nausea, vomiting, salivation, sweating, 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 UNICORN overdosage. Intravenous atropine sulphate titrated to effect is recommended; initially, a dose of 1,0 to 2,0 mg IV, with subsequent doses based upon clinical response. It is not known whether donepezil hydrochloride and/or its metabolites can be removed by dialysis (haemodialysis, peritoneal dialysis or haemofiltration).