Namenda Xr (memantine HCl)

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There are no contraindication interactions for this drug.

Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

Memantine/N-Methyl-D-Aspartate (NMDA) Antagonists

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: N-methyl-D-aspartate (NMDA) antagonists act at the same receptor system as does memantine.(1,2)

CLINICAL EFFECTS: Concurrent use may result in more frequent and more pronounced side effects, especially CNS-related effects.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: The UK manufacturer of memantine states that the concurrent use of memantine with N-methyl-D-aspartate (NMDA) antagonists such as amantadine or ketamine should be avoided.(1) The US manufacturer of memantine states that concurrent use should be approached with caution.(2)

DISCUSSION: Because N-methyl-D-aspartate (NMDA) antagonists act at the same receptor system as does memantine, concurrent use may result in more frequent and more pronounced side effects, especially CNS-related effects. Therefore, the UK manufacturer of memantine states that the concurrent use of memantine with NMDA antagonists such as amantadine or ketamine should be avoided.(1) The US manufacturer of memantine states that concurrent use should be approached with caution.(2) In a study in 52 healthy subjects, concurrent memantine (20 mg daily) and dextromethorphan/quinidine (30/30 mg daily) resulted in no changes in dextromethorphan or memantine levels. There was a slight increase in dizziness as measured by the dizziness visual analog scale (VAS) when compared to memantine alone but not the combination of dextromethorphan/quinidine alone. For other pharmacodynamic assessments, there was either no effect or improvement on some subscales.(3)

Moderate Interaction: Assess the risk to the patient and take action as needed.

Memantine; Amantadine/Urinary Alkalinizers

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Memantine and amantadine elimination is impaired by urinary alkalinization.(1,2)

CLINICAL EFFECTS: Potentiation of memantine or amantadine effects may be observed.

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Monitor patient for adverse reactions such as dizziness, headache, or confusion if a urinary alkalinizer is required. The memantine or amantadine dose may need to be adjusted when a urinary alkalinizer is started or stopped.(1,2)

DISCUSSION: The clearance of memantine was reduced by about 80% under alkaline urine conditions at pH 8. Urine alkalinization may lead to an accumulation of memantine with a possible increase in adverse effects. Urine pH is also altered by diet and clinical state of the patient (e.g., renal tubular acidosis or severe infections of the urinary tract). Hence, memantine should be used with caution under these conditions.(1) A study in rats showed that concomitant administration of sodium bicarbonate with amantadine caused a decrease in amantadine renal clearance (1.16 vs. 0.76). Amantadine's area-under-the-curve (AUC) was increased approximately 78%.(3) A study in 12 healthy subjects showed that plasma concentrations of memantine are dependent on urine pH. Alkaline urine pH caused a 79% reduction in renal clearance.(4)

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• Congenital long QT syndrome

• Chronic kidney disease stage 4 (severe) GFR 15-29 ml/min
• Chronic kidney disease stage 5 (failure) GFr<15 ml/min

• Disease of liver
• Kidney disease with likely reduction in glomerular filtration rate (GFr)

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Less Frequent

• Hypertension
• Influenza

Rare or Very Rare

• Acute renal failure
• Agranulocytosis
• Chronic heart failure
• Hepatitis
• Leukopenia
• Pancreatitis
• Pancytopenia
• Stevens-johnson syndrome
• Suicidal ideation
• Thrombocytopenic disorder
• Thrombotic thrombocytopenic purpura

More Frequent

• Constipation
• Cough
• Diarrhea
• Dizziness
• Headache disorder

Less Frequent

• Acute abdominal pain
• Aggressive behavior
• Back pain
• Depression
• Drowsy
• Hypotension
• Symptoms of anxiety
• Urinary incontinence
• Vomiting
• Weight gain

Rare or Very Rare

• Pharyngitis

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