Alzer Special Precautions

Gastrointestinal Conditions: Donepezil hydrochloride, 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. Although in most cases, these effects have been mild and transient, sometimes lasting one to three weeks, and have resolved during continued use, patients should be observed closely at the initiation of treatment and after dose increases.
Neuroleptic Malignant Syndrome (NMS): There have been very rare post-marketing reports of Neuroleptic Malignant Syndrome (NMS) in patients treated with donepezil hydrochloride 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, donepezil hydrochloride therapy should be discontinued.
Rhabdomyolysis (Muscle Effects): Rare cases of rhabdomyolysis (including acute renal failure) have been reported in patients treated with donepezil hydrochloride, 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. Donepezil hydrochloride 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 donepezil hydrochloride should be made based on the clinical judgement of the treating physician, in most post-marketing cases, therapy was withdrawn when CPK levels were 5X upper limit of normal or higher.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 donepezil hydrochloride 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).
The use of Donepezil Hydrochloride in patients with other types of dementia or other types of memory impairment (e.g., age-related cognitive decline), has not been investigated.
Anaesthesia: Donepezil Hydrochloride, 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 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.
There have been reports of syncope and seizures. In investigating such patients the possibility of heart block or long sinusal pauses should be considered.
Gastrointestinal Conditions: Patients at increased risk for developing ulcers, e.g., those with a history of ulcer disease or those receiving concurrent nonsteroidal anti-inflammatory drugs (NSAIDs), should be monitored for symptoms. However, the clinical studies with Donepezil Hydrochloride showed no increase, relative to placebo, in the incidence of either peptic ulcer disease or gastrointestinal bleeding.
Genitourinary: Although not observed in clinical trials of Donepezil Hydrochloride, 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 Donepezil Hydrochloride 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.
This medicinal product contains lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
Effects on ability to drive and use machines: Donepezil has minor or moderate influence on the ability to drive and use machines.
Dementia may cause impairment of driving performance or compromise the ability to use machinery. Furthermore, donepezil 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 to continue driving or operating complex machines.