Memantine

Cardiovascular effects including tachycardia and hypertension were documented in overdose. Bradyarrhythmia and myocardial infarction are rare post-marketing events. Caution is warranted in patients with pre-existing cardiovascular disease, particularly at supratherapeutic doses.

benzodiazepine use, opioid use, alcohol use, barbiturate use

Concurrent use of CNS depressants may produce additive sedation and respiratory depression. This is a class-level dissociative contraindication based on shared CNS-depressant pharmacodynamics.

ketamine use, dextromethorphan use, PCP use, nitrous oxide use, MXE use, amantadine use

Concurrent use of other NMDA receptor antagonists produces additive or synergistic channel blockade, increasing the risk of confusion, dissociation, psychosis, and other neuropsychiatric adverse effects. FDA labeling advises caution.

Seizures are documented in memantine overdose and listed as a rare post-marketing adverse event. Patients with a history of seizures or conditions lowering the seizure threshold should use memantine with caution, particularly at supratherapeutic doses.

Severe renal impairment dramatically increases memantine exposure (AUC +115%, t½ +95%). Dose reduction is required; use without adjustment risks toxicity. Not an absolute contraindication — memantine can be used with appropriate dose modification.

renal tubular acidosis, severe UTI with urea-splitting organisms, chronic antacid use, sodium bicarbonate use, carbonic anhydrase inhibitor use

Conditions or medications that alkalinize the urine reduce memantine renal clearance by ~80%, potentially converting a tolerable dose into a toxic one. This is the most clinically significant pharmacokinetic interaction for memantine.

Hypersensitivity to memantine hydrochloride or any component of the formulation is an absolute contraindication per FDA labeling. Post-marketing reports include Stevens-Johnson syndrome.