r inclusion because of a combination of seriousness, frequency of reporting, or potential causal connection to memantine and have not been listed elsewhere in labeling. However, because some of these adverse reactions were reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship between their occurrence and the administration of memantine. These events include:
Blood and Lymphatic System Disorders: agranulocytosis, leukopenia (including neutropenia), pancytopenia, thrombocytopenia. thrombotic thrombocytopenic purpura.
Cardiac Disorders: atrial fibrillation, atrioventricular block (including 2nd and 3rd degree block), cardiac failure, orthostatic hypotension, and torsades de pointes.
Endocrine Disorders: inappropriate antidiuretic hormone secretion.
Gastrointestinal disorders: colitis, pancreatitis.
General disorders and administration site conditions: malaise, sudden death.
Hepatobiliary Disorders: hepatitis (including abnormal hepatic function test, cytolytic and cholestatic hepatitis), hepatic failure.
Infections and infestations: sepsis.
Investigations: electrocardiogram QT prolonged, international normalized ratio increased.
Metabolism and Nutrition Disorders: hypoglycaemia, hyponatraemia.
Nervous System Disorders: convulsions (including grand mal), cerebrovascular accident, dyskinesia, extrapyramidal disorder, hypertonia, loss of consciousness, neuroleptic malignant syndrome, Parkinsonism, tardive dyskinesia, transient ischemic attack.
Psychiatric Disorders: hallucinations (both visual and auditory), restlessness, suicidal ideation.
Renal and Urinary Disorders: acute renal failure (including abnormal renal function test), urinary retention.
Skin Disorders: rash, Stevens Johnson syndrome.
Vascular Disorders: pulmonary embolism, thrombophlebitis, deep venous thrombosis.
The following adverse events have been reported to be temporally associated with memantine treatment and are not described elsewhere in the product labeling: aspiration pneumonia, bone fracture, carpal tunnel syndrome, cerebral infarction, chest pain, cholelithiasis, claudication, depressed level of consciousness (including rare reports of coma), dysphagia, encephalopathy, gastritis, gastroesophageal reflux, intracranial hemorrhage, hyperglycemia, hyperlipidemia, ileus, impotence, lethargy, myoclonus, supraventricular tachycardia, and tachycardia. However, there is again no evidence that any of these additional adverse events are caused by memantine.
7 DRUG INTERACTIONS
No drug-drug interaction studies have been conducted with NAMENDA XR, specifically.
7.1 Use with other N-methyl-D-aspartate (NMDA) Antagonists The combined use of NAMENDA XR with other NMDA antagonists (amantadine, ketamine, and dextromethorphan) has not been systematically eva luated and such use should be approached with caution.
7.2 Effect of Memantine on the Metabolism of Other Drugs In vitro studies conducted with marker substrates of CYP450 enzymes (CYP1A2, -2A6, -2C9, -2D6, -2E1, -3A4) showed minimal inhibition of these enzymes by memantine. In addition, in vitro studies indicate that at concentrations exceeding those associated with efficacy, memantine does not induce the cytochrome P450 isozymes CYP1A2, -2C9, -2E1 and -3A4/5. No pharmacokinetic int |
