Memantine Hcl Er (memantine HCl)

Memantine is commercially available as memantine hydrochloride; dosage is expressed in terms of the hydrochloride salt.

Memantine hydrochloride is administered orally (as tablets, extended-release capsules, or oral solution) without regard to meals. Memantine hydrochloride tablets and oral solution are equivalent on a mg-per-mg basis.

The oral solution should be administered using the oral dosing syringe provided by the manufacturer, referring to the accompanying patient information for instructions. Memantine hydrochloride oral solution should not be mixed with any other liquid.

The extended-release capsules should be swallowed intact and not divided, chewed, or crushed; alternatively, the capsules may be opened, sprinkled on applesauce, and swallowed without chewing.

The fixed-combination preparation containing memantine hydrochloride and donepezil hydrochloride (Namzaric(R)) may be used in patients currently receiving a stable dosage of donepezil hydrochloride 10 mg daily. The fixed-combination capsules should be swallowed intact (and not divided, chewed, or crushed); alternatively, the capsules may be opened, sprinkled on applesauce, and swallowed without chewing. The entire contents of each capsule should be consumed; the dose should not be divided.

If a dose of memantine is missed, the next dose should be taken as scheduled; the dose should not be doubled to make up for a missed dose. If treatment is interrupted for several days, the drug may need to be restarted with a lower dosage and retitrated.

There is no enhanced messaging for this drug.

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)

Known hypersensitivity to memantine hydrochloride or any ingredient in the formulation.

• 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)

Common adverse effects reported with conventional preparations of memantine include dizziness, confusion, headache, and constipation.

Common adverse effects reported with the extended-release capsule formulation of the drug include headache, diarrhea, and dizziness.

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

No enhanced messaging available.

Safety and efficacy of memantine have not been established in pediatric patients.

Memantine has been evaluated in children 6-12 years of age with autism spectrum disorders (ASD)+; however, efficacy has not been demonstrated. (See Uses: Autism Spectrum Disorders.)

There are no adequate data to inform the developmental risks associated with the use of memantine in pregnant women. In animal reproduction studies, adverse developmental effects (e.g., decreased body weight, decreased skeletal ossification) were observed when the drug was administered to pregnant rats during the period of organogenesis or from late gestation throughout lactation to weaning at doses higher than those used clinically.

It is not known whether memantine is distributed into human milk or if the drug has any effects on the nursing infant or milk production. The known benefits of breast-feeding should be considered along with the mother's clinical need for memantine and any potential adverse effects on the breast-fed infant from the drug or underlying maternal condition.

Clinical studies have been conducted principally in older patients since dementia of the Alzheimer's type occurs mainly in patients 65 years of age or older. Memantine pharmacokinetics were similar in elderly patients and younger adults.