Memantine hydrochloride is an orally active NMDA receptor antagonist. The chemical name for memantine hydrochloride is 1-amino-3,5-dimethyladamantane hydrochloride with the following structural formula: The molecular formula is C 12 H 21 N•HCl and the molecular weight is 215.76. Memantine hydrochloride occurs as a white to off-white, colored powder and is slightly soluble in water, soluble in methanol and practically insoluble in acetone. Memantine hydrochloride extended-release capsules are supplied for oral administration as 7 mg, 14 mg, 21 mg, and 28 mg capsules. Each capsule contains extended-release pellets with the labeled amount of memantine hydrochloride USP and the following inactive ingredients: ethylcellulose, hypromellose, polyethylene glycol, sugar spheres [which contains starch (maize) and sucrose] and talc. The hard gelatin capsule shell contains gelatin, iron oxide yellow and titanium dioxide. In addition the 14 mg, 21 mg and 28 mg hard gelatin capsule shell contains FD&C blue 1 and FD&C yellow 6. The 7 mg, 14 mg and 21 mg capsules are imprinted with black ink containing black iron oxide, potassium hydroxide and shellac. The 28 mg capsules are imprinted with white ink containing potassium hydroxide, shellac and titanium dioxide. Chemical Structure

Memantine hydrochloride extended-release capsules are indicated for the treatment of moderate to severe dementia of the Alzheimer’s type. Memantine hydrochloride is a N-methyl-D-aspartate (NMDA) receptor antagonist indicated for the treatment of moderate to severe dementia of the Alzheimer’s type.

Each capsule contains 7 mg, 14 mg, 21 mg, or 28 mg of memantine hydrochloride USP. The 7 mg capsules are white to off-white coated pellets filled in the yellow opaque cap/yellow opaque body hard gelatin capsules imprinted with “M 7” on cap with black ink. The 14 mg capsules are white to off-white coated pellets filled in the yellow opaque cap/dark green opaque body hard gelatin capsules imprinted with “M 14” on cap with black ink. The 21 mg capsules are white to off-white coated pellets filled in the white to off-white cap/dark green opaque body hard gelatin capsules imprinted with “M 21” on cap with black ink. The 28 mg capsules are white to off-white coated pellets filled in the dark green opaque cap/dark green opaque body hard gelatin capsules imprinted with “M 28” on cap with white ink. Memantine hydrochloride is available as an extended-release capsule in the following strengths: 7 mg, 14 mg, 21 mg, 28 mg

The recommended starting dose of memantine hydrochloride extended-release capsules is 7 mg once daily; the dose should be increased in 7 mg increments to the recommended maintenance dose of 28 mg once daily; the minimum recommended interval between dose increases is one week. Patients with severe renal impairment: the recommended maintenance dose of memantine hydrochloride extended-release capsules is 14 mg once daily

Recommended Dosing The dosage of memantine hydrochloride extended-release capsules shown to be effective in a controlled clinical trial is 28 mg once daily. The recommended starting dose of memantine hydrochloride extended-release capsules is 7 mg once daily. The dose should be increased in 7 mg increments to the recommended maintenance dose of 28 mg once daily. The minimum recommended interval between dose increases is one week. The dose should only be increased if the previous dose has been well tolerated. The maximum recommended dose is 28 mg once daily. Memantine hydrochloride extended-release capsules can be taken with or without food. Memantine hydrochloride extended-release capsules can be taken intact or may be opened, sprinkled on applesauce, and thereby swallowed. The entire contents of each memantine hydrochloride extended-release capsules should be consumed; the dose should not be divided. Except when opened and sprinkled on applesauce, as described above, memantine hydrochloride extended-release capsules should be swallowed whole. Memantine hydrochloride extended-release capsules should not be divided, chewed, or crushed. If a patient misses a single dose of memantine hydrochloride extended-release capsules, that patient should not double up on the next dose. The next dose should be taken as scheduled. If a patient fails to take memantine hydrochloride extended-release capsules for several days, dosing may need to be resumed at lower doses and retitrated as described above

Switching from Memantine Hydrochloride Tablets to Memantine Hydrochloride Extended-Release Capsules Patients treated with memantine hydrochloride tablets may be switched to memantine hydrochloride extended-release capsules as follows: It is recommended that a patient who is on a regimen of 10 mg twice daily of memantine hydrochloride tablets be switched to memantine hydrochloride extended-release capsules 28 mg once daily capsules the day following the last dose of 10 mg memantine hydrochloride tablet. There is no study addressing the comparative efficacy of these 2 regimens. In a patient with severe renal impairment, it is recommended that a patient who is on a regimen of 5 mg twice daily of memantine hydrochloride tablets be switched to memantine hydrochloride extended-release capsules 14 mg once daily capsules the day following the last dose of 5 mg memantine hydrochloride tablet

Dosing in Patients with Renal Impairment In patients with severe renal impairment (creatinine clearance of 5 to 29 mL/min, based on the Cockcroft-Gault equation), the recommended maintenance dose (and maximum recommended dose) is 14 mg/day .

Conditions that raise urine pH may decrease the urinary elimination of memantine resulting in increased plasma levels of memantine. (5.1 , 7.1) 5.1 Genitourinary Conditions Conditions that raise urine pH may decrease the urinary elimination of memantine resulting in increased plasma levels of memantine .

7.1 Drugs That Make Urine Alkaline The clearance of memantine was reduced by about 80% under alkaline urine conditions at pH 8. Therefore, alterations of urine pH towards the alkaline condition may lead to an accumulation of the drug with a possible increase in adverse effects. Urine pH is altered by diet, drugs (e.g., carbonic anhydrase inhibitors, sodium bicarbonate) 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

Use with Other N-methyl-D-aspartate (NMDA) Antagonists The combined use of memantine hydrochloride extended-release capsules with other NMDA antagonists (amantadine, ketamine, and dextromethorphan) has not been systematically evaluated and such use should be approached with caution.