Memantine Hydrochloride

Memantine Hydrochloride Extended-Release Capsules are indicated for the treatment of moderate to severe dementia of the Alzheimer’s type.

• 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. (
  
  
  2.1

  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 capsule 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.
  )
  
• Patients with severe renal impairment: the recommended maintenance dose of memantine hydrochloride extended-release capsules is 14 mg once daily. (
  
  
  2.3

  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

  [see Clinical Pharmacology (

  12.3

  )]

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Each capsule contains 7 mg, 14 mg, 21 mg, or 28 mg of memantine hydrochloride, USP.

• The 7 mg capsules are an opaque buff capsule, with “YH” black imprint on the cap and “123” black imprint on the body.
• The 14 mg capsules are an opaque buff cap and opaque dark green body capsule, with “YH” black imprint on the cap and “124” black imprint on the body.
• The 21 mg capsules are an opaque white cap and opaque dark green body capsule, with “YH” black imprint on the cap and “125” black imprint on the body.
• The 28 mg capsules are a dark green opaque capsule, with “YH” white imprint on the cap and “126” white imprint on the body.

There are no adequate data on the development risk associated with the use of memantine hydrochloride extended-release capsules in pregnant women.

Adverse developmental effects (decreased body weight and skeletal ossification) were observed in the offspring of rats administered memantine during pregnancy at doses associated with minimal maternal toxicity. These doses are higher than those used in humans at the maximum recommended daily dose of memantine hydrochloride extended-release capsules

In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. The background risk of major birth defects and miscarriage for the indicated population is unknown.

Oral administration of memantine (0, 2, 6, or 18 mg/kg/day) to rats during the period of organogenesis resulted in decreased skeletal ossification in fetuses at the highest dose tested. The higher no-effect dose for adverse developmental effects (6 mg/kg) is 2 times the maximum recommended human daily dose (MRHD) of memantine hydrochloride extended-release capsules (28 mg) on a body surface area (mg/m
²) basis.

Oral administration of memantine to rabbits (0, 3, 10, or 30 mg/kg/day) during the period of organogenesis resulted in no adverse developmental effects. The highest dose tested is approximately 20 times the MRHD of memantine hydrochloride extended-release capsules on a mg/m
²basis.

In rats, memantine (0, 2, 6, or 18 mg/kg/day) was administered orally prior to and throughout mating and, in females, through the period of organogenesis or continuing throughout lactation to weaning. Decreased skeletal ossification in fetuses and decreased body weight in pups were observed at the highest dose tested. The higher no-effect dose for adverse developmental effects (6 mg/kg/day) is 2 times the MRHD of memantine hydrochloride extended-release capsules on a mg/m
²basis.

Oral administration of memantine (0, 2, 6, or 18 mg/kg/day) to rats from late gestation throughout lactation to weaning, resulted in decreased pup weights at the highest dose tested. The higher no-effect dose (6 mg/kg/day) is approximately 2 times the MRHD of memantine hydrochloride extended-release capsules on a mg/m
²basis.

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

  Genitourinary Conditions

  Conditions that raise urine pH may decrease the urinary elimination of memantine resulting in increased plasma levels of memantine

  [see Drug Interactions (

  7.1

  )]

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  ,
  
  
  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.
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