Sign Out
Treatment should be initiated by a physician experienced in the treatment of dementia. Diagnosis should be made according to accepted guidelines (e.g. DSM IV, ICD 10). Therapy with donepezil hydrochloride 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 hydrochloride 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 hydrochloride cannot be predicted. The use of ARICEPT in patients with other types of dementia or other types of memory impairment (e.g. age-related cognitive decline), has not been investigated.
Anaesthesia: ARICEPT, 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 the sinoatrial and atrioventricular nodes. This effect may manifest as bradycardia or heart block in patients both with and without known underlying cardiac conduction abnormalities. Syncopal episodes have been reported in association with the use of ARICEPT Film-coated Tablets 23 mg. There have been post marketing reports of QTc interval prolongation and Torsade de Pointes (see Interactions and Adverse Reactions). Caution is advised in patients with pre-existing or family history of QTc prolongation, in patients treated with drugs 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 (ECG) may be required.
Nausea and Vomiting: ARICEPT, as a predictable consequence of its pharmacological properties, has been shown to produce diarrhea, nausea, and vomiting. These effects, when they occur, appear more frequently with the 10 mg/day dose than with the 5 mg/day dose, and more frequently with the 23 mg/day dose than with the 10 mg/day dose. Specifically, in a controlled trial that compared a dose of 23 mg/day to 10 mg/day in patients who had been treated with donepezil hydrochloride 10 mg/day for at least three months, the incidence of nausea in the 23 mg/day dose group was markedly greater than in the patients who continued on 10 mg/day dose (11.8% vs 3.4%, respectively), and the incidence of vomiting in the 23 mg/day dose group was markedly greater than in the 10 mg/day dose group (9.2% vs 2.5%, respectively). The percentage of patients who discontinued treatment due to vomiting in the 23 mg/day dose group was markedly higher than in the 10 mg/day dose group (2.9% vs 0.4%, respectively). Although in most cases, these effects have been mild and transient, sometimes lasting one to three weeks, and have resolved during continued use of ARICEPT, patients should be observed closely at the initiation of treatment and after dose increases.
Peptic Ulcer Disease and GI Bleeding: Through their primary action, cholinesterase inhibitors may be expected to increase gastric acid secretion due to increased cholinergic activity. Therefore, patients should be monitored closely for symptoms of active or occult, gastrointestinal bleeding, especially those at increased risk for developing ulcers, e.g., those with a history of ulcer disease or those receiving concurrent non-steroidal anti-inflammatory drugs (NSAIDS). Results of a controlled clinical study of ARICEPT Film-coated Tablets 23 mg showed an increase relative to donepezil hydrochloride 10 mg/day, in the incidence of peptic ulcer disease (0.4% vs. 0.2%) and gastrointestinal bleeding from any site (1.1% vs. 0.6%).
Weight Loss: Weight loss was reported as an adverse event, in 4.7% of patients assigned to ARICEPT Film-coated Tablets 23 mg compared to 2.5% of patients assigned to 10 mg donepezil hydrochloride. Compared to their baseline weights, 8.4% of patients in the ARICEPT Film-coated Tablets 23 mg group were found to have a weight decrease of ≥ 7% by the end of the study, while 4.9% of the group taking 10 mg donepezil hydrochloride were found to have a weight loss of ≥ 7% at the end of the study.
Genitourinary: Although not observed in clinical trials of ARICEPT, 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.
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 ARICEPT 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.
Neurologic: Neuroleptic Malignant Syndrome (NMS): There have been very rare post-marketing reports of Neuroleptic Malignant Syndrome (NMS) in patients treated with ARICEPT with or without concomitant antipsychotic medication. NMS is a potentially life-threatening condition characterized by hyperthermia, muscle rigidity, autonomic instability (e.g. irregular pulse or blood pressure, tachycardia, diaphoresis, and cardiac dysrhythmia), altered consciousness and elevated serum creatine phosphokinase (CPK) levels. 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 in the absence of additional clinical manifestations of NMS, ARICEPT therapy should be discontinued.
Rhabdomyolysis (Muscle Effects): Rare cases of rhabdomyolysis (including acute renal failure) have been reported in patients treated with ARICEPT, particularly in the days following dose initiation and dose increase. Majority of these cases occurred independently of Neuroleptic Malignant Syndrome (NMS). Patients should be carefully monitored for muscle pain, tenderness or weakness and darkened urine, particularly if accompanied by malaise or fever. Blood creatine phosphokinase (CPK) levels should be assessed in patients experiencing these symptoms. ARICEPT therapy should be discontinued if markedly elevated CPK levels are measured and/or if the patient develops signs and symptoms indicative of rhabdomyolysis. Although the decision to discontinue ARICEPT should be made based on the clinical judgement of the treating physician, in most post-marketing cases, therapy was withdrawn when CPK levels were 5X upper limit of normal or higher. Caution should be particularly exercised in prescribing ARICEPT to patients with predisposing/risk factors such as prior history of muscular disorders, uncontrolled hypothyroidism, hepatic or renal impairment, and in patients who are receiving concomitant medications that can cause rhabdomyolysis (e.g., statins, antipsychotics, selective serotonin reuptake inhibitor/serotonin norepinephrine reuptake inhibitor).
Lower Weight Individuals: In the controlled clinical trial, among patients in the ARICEPT Film-coated Tablets 23 mg treatment group, those weighing < 55 kg reported more nausea, vomiting, and decreased weight than patients weighing 55 kg or more. There were more withdrawals due to adverse events as well. This finding may be related to higher plasma exposure associated with lower weight.
Effects on ability to drive and use machines: Dementia may cause impairment of driving performance or compromise the ability to use machinery. Furthermore, donepezil hydrochloride 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 hydrochloride to continue driving or operating complex machines.
Use in Children: The safety and effectiveness of ARICEPT in children have not been established.
Use in the Elderly: Alzheimer's disease is a disorder occurring primarily in individuals over 55 years of age. The mean age of patients enrolled in the clinical study with ARICEPT was 73 years; 80% of these patients were between 65 and 84 years old, and 49% of patients were at or above the age of 75. The efficacy and safety data presented in the clinical trials section were obtained from these patients. There were no clinically significant differences in most adverse events reported by patient groups ≥ 65 years old and < 65 years old.
