Curlovon 5 5 mg FC tablet

CURLOVON is indicated for the symptomatic treatment of mild or moderate dementia in Alzheimer's disease.

The established effective dosages of CURLOVON is 5 mg and 10 mg 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. Treatment is initiated at 5 mg/day (once-a-day dosing). The 5 mg/day dose should be maintained for at least 4 to 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 5 mg/day, the dose of CURLOVON can be increased to 10 mg/day (once-a-day dosing). The maximum recommended daily dose is 10 mg. Doses greater than 10 mg/day have not been studied. There is no evidence of a rebound effect after abrupt discontinuation of therapy. Renal and Hepatic Impairment: A similar dose schedule can be followed for patients with renal or mild to moderate hepatic impairment as clearance of donepezil hydrochloride is not affected by these conditions.

Hypersensitivity to donepezil hydrochloride, piperidine derivatives, or to any inactive ingredients used in the formulation. Safety and efficacy of donepezil hydrochloride have not been established in children; therefore it is not recommended for use in children.

Only a doctor, experienced in the treatment of Alzheimeru2019s dementia, should initiate treatment. Maintenance treatment can be continued for as long as a therapeutic benefit for the patient exists. Individual response to CURLOVON cannot be predicted. Therefore, the clinical benefit of CURLOVON should be reassessed on a regular basis. Discontinuation should be considered when evidence of a therapeutic effect is no longer present. The use of CURLOVON in patients with severe dementia, other types of dementia or other types of memory impairment (e.g. age related cognitive decline), has not been established. Anaesthesia: CURLOVON as a cholinesterase inhibitor, is likely to exaggerate succinylcholine-type muscle relaxation during anaesthesia. Cardiovascular Conditions: Due to their pharmacological action, cholinesterase inhibitors, such as CURLOVON, 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. Syncopal episodes have been reported in association with the use of CURLOVON. Gastrointestinal Conditions: CURLOVON may promote gastric acid production. Therefore patients should be monitored closely for symptoms of active or occult gastrointestinal bleeding, especially those at increased risk of developing ulcers e.g. those with a history of ulcer disease or those receiving concurrent non-steroidal anti-inflammatory medicines (NSAIDS). Clinical studies with donepezil hydrochloride have shown no increase, relative to placebo, in the incidence of either peptic ulcer disease or gastrointestinal bleeding. CURLOVON, as a predictable consequence of its pharmacological properties, has been shown to produce diarrhoea, nausea and vomiting. These effects, when they occur, appeared more frequently with the 10 mg/day dose than with the 5 mg/day dose. In most cases, these effects have been mild and transient, sometimes lasting one to three weeks, and have resolved during continued use of CURLOVON. Genitourinary: CURLOVON may cause bladder outflow obstruction. Neurological Conditions: CURLOVON is believed to have some potential to cause generalised convulsions. However, seizure activity may also be a manifestation of Alzheimer's Disease. Pulmonary Conditions: CURLOVON should be prescribed with care to patients with a history of asthma or obstructive pulmonary disease. The administration of CURLOVON concomitantly with other inhibitors of acetylcholinesterase, or with agonists or antagonists of the cholinergic system, should be avoided.

Medicines Highly Bound to Plasma Proteins: Medicine displacement studies have been performed in vitro between this highly bound medicine (96 %) and other medicines such as furosemide, digoxin and warfarin. CURLOVON, at concentrations of 0,3 to 10 u03bcg/ml, did not affect the binding of furosemide (5 u03bcg/ml), digoxin (2 u03bcg/ml), and warfarin (3 u03bcg/ml) to human albumin. Similarly, the binding of CURLOVON to human albumin was not affected by furosemide, digoxin and warfarin. Effect of CURLOVON on the Metabolism of Other Medicines: No in vivo clinical trials have investigated the effect of donepezil hydrochloride on the clearance of medicines metabolised by CYP3A4 (e.g. cisapride) or by CYP2D6 (e.g. imipramine). However, in vitro studies show a low rate of binding to these enzymes (mean Ki about 50-130 u03bcM). This indicates, given the therapeutic plasma concentrations of donepezil (164 u03bcM), little likelihood of interference. Whether donepezil hydrochloride has any potential for enzyme induction is not known. Donepezil hydrochloride and/or any of its metabolites do not inhibit the metabolism of theophylline, warfarin, cimetidine, digoxin, thioridazine, risperidone and sertraline in humans. In a study of Parkinsonu2019s disease patients on optimal treatment with levodopa/carbidopa, administration of donepezil hydrochloride for 21 days had no effects on levodopa or carbidopa blood levels. In this study no effects on motor activity were observed. Effect of Other Medicines on the Metabolism of CURLOVON: Ketoconazole and quinidine, inhibitors of CYP450, CYP3A4 and CYP2D6, respectively, inhibit donepezil metabolism in vitro. Therefore these and other CYP3A4 inhibitors, such as itraconazole and erythromycin, and CYP2D6 inhibitors such as fluoxetine could inhibit the metabolism of donepezil. In a study in healthy volunteers, ketoconazole increased mean donepezil concentrations by 30 %. These increases are smaller than those produced by ketoconazole for other agents sharing the CYP3A4 pathway and are not likely to be clinically relevant. Administration of donepezil had no effect on the pharmacokinetics of ketoconazole. Inducers of CYP2D6 and CYP3A4 (e.g. phenytoin, carbamazepine, alcohol, dexamethasone, rifampicin and phenobarbital) could increase the rate of elimination of donepezil hydrochloride. Formal pharmacokinetic studies demonstrated that the metabolism of donepezil hydrochloride is not significantly affected by concurrent administration of digoxin, cimetidine, risperidone or sertraline. Use with anticholinergics: Because of their mechanism of action, cholinesterase inhibitors have the potential to interfere with the activity of anticholinergic medications. Use with Cholinomimetics and other Cholinesterase Inhibitors: A synergistic effect may be expected when cholinesterase inhibitors are given concurrently with succinylcholine.

CURLOVON is not recommended in pregnancy and lactation as safety has not been established.

Dementia may cause impairment of driving performance or compromise the ability to use machinery. Furthermore, CURLOVON can induce fatigue, dizziness and muscle cramps, mainly when initiating or increasing the dose. The treating medical doctor should routinely evaluate the ability of patients on CURLOVON to continue driving or operating complex machines.

The side-effects reported with CURLOVON and their frequency, are listed below. Infections and Infestations: Frequent: Common cold, influenza. Metabolism and nutrition disorders: Less frequent: Dehydration. Psychiatric disorders: Frequent: Abnormal dreams, agitation, delusions, depression, hallucinations, insomnia. Less frequent: Abnormal crying, aggressive behaviour, irritability, nervousness, restlessness, confusion. Reproductive system and breast disorders: Less frequent: Increased libido. Nervous system disorders: Frequent: Dizziness, headache, somnolence. Less frequent: Aphasia, ataxia, paraesthesia, syncope, tremor, seizure, extrapyramidal symptoms. Eye disorders: Less frequent: Cataract, eye irritation, blurred vision. Ear and labyrinth disorders: Less frequent: Vertigo. Cardiac disorders: Less frequent: Atrioventricular block, bradycardia, sinoatrial block, angina pectoris. Vascular disorders: Less frequent: Hot flushes, hypertension, hypotension, vasodilation. Respiratory, thoracic and mediastinal disorders: Less frequent: Dyspnoea, sore throat. Gastrointestinal disorders: Frequent: Abdominal disturbance, anorexia, diarrhoea, faecal incontinence, nausea, vomiting, dyspepsia. Less frequent: Bloating, epigastric pain, gastrointestinal haemorrhage, toothache, duodenal ulcer, gastric ulcer. Hepato-biliary disorders: Less frequent: Hepatitis. Skin and subcutaneous tissue disorders: Less frequent: Diaphoresis, ecchymosis, pruritus, urticaria, rash. Musculoskeletal and connective tissue disorders: Frequent: Muscle cramps. Renal and urinary disorders: Frequent: Frequent urination. Less frequent: Nocturia, urinary incontinence. General disorders and administration site conditions: Frequent: Fatigue, pain, sweating. Less frequent: Chest pain. Investigations: Frequent: Weight decreases. Less frequent: Minor increases in serum concentrations of muscle creatine kinase. Injury, poisoning and procedural complications: Less frequent: Accidental falls, bone fractures. There is evidence to suggest that the frequency of these common adverse events may be affected by rate of dose titration.

Dose-related signs of cholinergic stimulation were observed in animals and included reduced spontaneous movement, prone position, staggering gait, lacrimation, clonic convulsions, depressed respiration, salivation, miosis, fasciculation and lower body surface temperature. Overdosage with CURLOVON can result in cholinergic crisis characterised 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. General supportive measures should be utilised. Tertiary anticholinergics such as atropine may be used as an antidote for CURLOVON 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. It is not known whether donepezil hydrochloride and/or its metabolites can be removed by dialysis (haemodialysis, peritoneal dialysis, or haemofiltration).