Memry Drug Interactions

Tablet: N-methyl-D-aspartate antagonists (amantadine, ketamine and dextromethorphan): Increased risk of CNS toxicity when memantine hydrochloride is given with NMDA antagonists. Avoid concomitant use. These compounds act at the same receptor system as memantine hydrochloride, and thus adverse drug reactions, mainly CNS-related, may be more frequent or more pronounced.
L-dopa, dopaminergic agonists (e.g., bromocriptine) and anticholinergics: The mode of action suggests that the effects of these drugs may be enhanced by concomitant treatment with NMDA-antagonists such as memantine hydrochloride.
Barbiturates and neuroleptics: The effects of these drugs may be reduced by memantine hydrochloride.
Antispasmodic agents (dantrolene or baclofen): Concomitant administration of memantine hydrochloride with the antispasmodic agents, dantrolene or baclofen, can modify their effects and a dosage adjustment may be necessary.
Oral anticoagulants (e.g., warfarin): Memantine hydrochloride possibly enhances the anticoagulant effect of warfarin. Close monitoring of prothrombin time or INR is advisable for patients concomitantly treated with oral anticoagulants.
Cimetidine, ranitidine, procainamide, quinidine, quinine, and nicotine: May also possibly interact with memantine hydrochloride leading to a potential risk of increased plasma levels of both agents.
Diuretics [e.g., hydrochlorothiazide (HCTZ), triamterene (TA)]: There may be a possibility of reduced HCTZ plasma level when memantine hydrochloride is used concomitantly. However, co-administration of memantine hydrochloride and HCTZ/TA did not affect the bioavailability of either memantine hydrochloride or TA; the bioavailability of HCTZ is decreased by 20%.
Primidone: Memantine hydrochloride possibly reduces the effects of primidone.
Selegiline: Memantine hydrochloride possibly enhances the effects of selegiline.
Glibenclamide/metformin, donepezil and galantamine: No relevant drug-drug interaction.
Effects of memantine on substrates of microsomal enzymes: In vitro studies done with marker substrates of CYP450 enzymes (CYP1A2, -2A6, -2C9, -2D6, -2E1, -3A4) showed minimal inhibition of these enzymes by memantine hydrochloride. Also, in vitro studies indicate that at concentrations exceeding those associated with efficacy, memantine hydrochloride does not induce the cytochrome P450 isoenzymes CYP1A2, CYP2C9, CYP2E1, and CYP3A4/5. No pharmacokinetic interactions with drugs metabolized by these enzymes are expected.
Oral soln: NMDA Antagonists (e.g., amantadine, ketamine, dextromethorphan): Concomitant use of NMDA antagonists should be avoided. These compounds act at the same receptor system as memantine, and therefore adverse drug reactions (e.g., CNS-related) may be more frequent or more pronounced. There is a risk of pharmacotoxic psychosis when memantine is given with amantadine, since these drugs are chemically related to NMDA antagonists.
Drugs affecting the CNS (e.g., L-dopa, dopaminergic agonists, anticholinergics, amantadine): The mode of action suggests that the effects of L-dopa, dopaminergic agonists (e.g., bromocriptine), and anticholinergics on the CNS may be potentiated with the coadministration of NMDA antagonists, including memantine.
The effects of barbiturates and neuroleptics may be diminished. The concurrent use of memantine with antispasmodic agents such as dantrolene or baclofen may modify their effects. Dose adjustments may be required if these drugs are to be coadministered with memantine. These recommendations are mainly based on theoretical information.
In vitro studies demonstrate that memantine does not affect the reversible acetylcholinesterase inhibition of donepezil, galantamine, or tacrine. The concomitant use of memantine with donepezil did not affect the pharmacokinetics of either drugs or alter substantially the acetylcholinesterase inhibition of donepezil.
Oral anticoagulants: Isolated cases of increased international normalized ratio (INR) have been reported in patients concomitantly treated with warfarin during postmarketing experience. Although causal relationship has not been established, close monitoring of prothrombin time or INR is recommended for patients receiving concomitant treatment with memantine and oral anticoagulants. Concurrent use of memantine and hydrochlorothiazide/triamterene did not affect bioavailability of either memantine or triamterene, and plasma concentrations and AUC of hydrochloride decreased by only 20%.
Alkalinizing agents (e.g., carbonic anhydrase inhibitors, sodium bicarbonate): Concomitant use of agents that increase urine pH may result to decreased clearance of memantine and lead to an accumulation of the drug and possible increase in adverse effects. At alkaline conditions (i.e., pH 8), the memantine clearance was decreased by approximately 80%. Caution must be observed when alkalinizing agents are coadministered with memantine. The pharmacokinetics of memantine is similar in smokers and non-smokers, suggesting that nicotine may not alter the pharmacokinetics of memantine.
Drugs using the same renal cationic transport system as amantadine (e.g., cimetidine, ranitidine, procainamide, quinidine, quinine, hydrochlorothiazide, triamterene, metformin, and nicotine): Altered plasma levels of both drugs is possible when memantine is coadministered with drugs secreted by the same renal cationic transport system as amantadine.
Highly protein bound drugs (e.g., warfarin, digoxin): As the protein binding of memantine is low (45%) interactions with highly protein bound drugs is unlikely.
Pregnancy: There are no adequate and well-controlled studies on the use of memantine in pregnant women. Memantine should not be given to pregnant women, unless clearly necessary and the expected benefits significantly outweighs the possible risks to the fetus. The serum level of hydrochlorothiazide may be reduced when memantine is concomitantly administered with hydrochlorothiazide or any combination with hydrochlorothiazide.
Immune system disorders: Bronchospasm, drug hypersensitivity, hypersensitivity, erythema multiforme.
Blood and lymphatic system disorders: Agranulocytosis, anemia, epistaxis, leukocytosis, leukopenia, neutropenia, pancytopenia, polycythemia, thrombocytopenia, thrombotic thrombocytopenic purpura.
Neoplasms benign, malignant and unspecified (including cysts and polyps): Basal cell carcinoma, benign gastrointestinal neoplasm, benign female breast neoplasm, carcinoma, cyst, malignant female breast neoplasm, lymphoma, malignant skin neoplasm, neoplasm, squamous cell carcinoma.
Infections and infestations: Abscess, bacterial infection, bronchitis, candida infection, eye infection, fungal infection, infections, onychomycosis, sepsis, upper respiratory tract infection, urinary tract infection, viral infection. The most common adverse events associated with memantine include dizziness, confusion, headache, constipation, cough, hypertension, back pain, hallucination, pain, somnolence, vomiting, dyspnea, and fatigue.
Acetylcholinesterase (AChE) inhibitors: In vitro studies demonstrated that memantine does not affect the reversible acetylcholinesterase inhibition by donepezil, tacrine, or galantamine. In young healthy adult subjects under steady-state conditions of donepezil, concurrent use with memantine did not alter the pharmacokinetics of either drug and did not affect donepezil-mediated AChE inhibition. A 24-week clinical study showed that in patients with moderate to severe Alzheimer's disease, the adverse event profiles were similar for patients treated with a combination of memantine and donepezil or placebo and donepezil.
The possibility of compromised renal function in elderly patients should be considered when memantine was concomitantly used with other drugs eliminated via renal mechanisms.
In single dose pharmacokinetic studies, no relevant interaction between memantine and glyburide/metformin was observed. The hypoglycemic effects of the glyburide/metformin combination were also not affected. The renal excretion of metformin and memantine should be considered when memantine and metformin will be used concomitantly.
Drugs metabolized by CYP enzymes: Due to its low extent of metabolism by CYP450 isoenzymes, metabolic drug interactions appear unlikely. In vitro studies revealed that memantine minimally inhibits CYP 1A2, 2A6, 2C9, 2D6, 2E1, and 3A4. No induction of CYP 1A2, 2C9, 2E1, or 3A4/5 were observed in vitro at concentrations greater than those associated with clinical efficacy. Pharmacokinetic interactions with drugs metabolized by these enzymes are not expected. In a pharmacokinetics study in healthy adult subjects, memantine did not significantly affect the steady state pharmacokinetics of galantamine.
CYP Inhibitors and/or Inducers: Drugs that are substrates and/or inhibitors of the CYP450 system are unlikely to interact with memantine.
Atropine: Although serious interactions between very high doses of memantine and atropine have been noted in a toxicity study in rats, this interaction occurred under conditions not relevant to human treated at therapeutic doses of memantine.