Patients with Alzheimer's disease and vascular dementia are treated for dementia with memantine (Namenda), an inhibitor of NMDA type glutamate receptors.

Memantine Uses:

• Alzheimer disease:

  • Used for treatment of moderate dementia associated with Alzheimer's

• Off Label Use of Memantine in Adults:

  • mild to moderate vascular dementia.

Memantine (Namenda) Dose in Adults:

Memantine (Namenda) Dose in the treatment of moderate to severe Alzheimer disease: Oral:

• Immediate-release:

  • Initial: 5 mg once a day, if tolerated for 1-week up titrate to 5 mg twice a day, if well-tolerated up titrate after at least 1 week has passed to a maximum target dose of 20mg/day.
  • Give in two divided doses when using more than 5mg/day.
  • In case treatment is held for a long period of time restart with a lower dose and up titrate again
  • Suggested titration:
    • 5 mg daily for ≥1 week;
    • 5 mg twice daily for ≥1 week;
    • 15 mg daily given in 5 mg and 10 mg separate doses for ≥1 week;
    • then 10 mg twice daily

• Extended-release:

  • Initial: 7 mg once daily, increase the dose by 7 mg daily, goal maximum dose is 28 mg/day; Let week or more pass between upgrading doses

Note: Start the transition from immediate release to extended release the day after the final dosage of immediate release. 28mg extended-release  formulation can be made from 10mg immediate-release.

• Missed dose:

  • If a dose is missed, take the subsequent dose as usual. If a dose is missed for a prolonged period of time, start over at the lower  dose and titrate up once more.

Memantine (Namenda) Dose for treating mild to moderate Vascular dementia (off-label): Oral:

• Immediate release:

  • Initial: 5 mg once per day; up titrate by 5 mg per day each week to the target dose of 10 mg twice per day.

Use in Children:

Not indicated.

Memantine Pregnancy Category: B

• Studies on animals have shown adverse effects.

Use of Memantine while breastfeeding

• It is not known whether breastmilk contains memantine or not.
• Before using lactating mothers, weigh the risk and benefits

Memantine (Namenda) Dose in Kidney Disease:

• Mild impairment:
  • No dose adjustment required.
• Moderate impairment:
  • US labeling:
    • No dose adjustment required.
  • Canadian labeling: (CrCl 30 to 49 mL/minute):
    • Initial: If tolerated for a week, increase the dose to 5 mg twice daily. If well tolerated, increase the dose after at least a week to a maximum goal dose of 20 mg/day.
• Severe impairment:
  • US labeling:
    • CrCl 5 to 29 mL/minute:
      • Immediate-release:  If tolerated for a week, increase the dose to 5 mg twice daily. If well tolerated,  increase the  dose after at least a week to a maximum goal dose of 14 mg/day.
  • Note: While switching from immediate to extended-release, patients on 5 mg twice daily should be switched to extended-release  14 mg once daily.
  • Canadian labeling:
    • CrCl 15 to 29 mL/minute:
      • Initial: 5 mg once daily for 1 week if tolerated may upgrade to 5mg twice a day.

Memantine Dose in Liver disease:

• Mild-to-moderate impairment:
  • Dose adjustment is not needed.
• Severe impairment:
  • Although there is no recommended dose adjustment by the manufacturer, it is not advised to use in cases of severe hepatic  impairment.

Except as mentioned, adverse effects are comparable between formulations for immediate and prolonged release.

Less Common Side Effects of Memantine:

• Cardiovascular:

  • Hypotension
  • Hypertension

• Central nervous system:

  • Aggressive behavior
  • Confusion
  • Hallucination
  • Anxiety
  • Drowsiness
  • Pain
  • Headache
  • Fatigue
  • Depression
  • Dizziness

• Endocrine & metabolic:

  • Weight gain

• Gastrointestinal:

  • Vomiting
  • Abdominal pain
  • Constipation
  • Diarrhea

• Genitourinary:

  • Urinary incontinence

• Infection:

  • Influenza

• Neuromuscular & skeletal:

  • Back pain

• Respiratory:

  • Dyspnea
  • Cough

Contraindications to Memantine (Namenda):

Hypersensitivity to memantine and any component of the formulation

Warnings and precautions

• Hypersensitivity

  • There have been reports of uncommon cutaneous hypersensitivity reactions such Stevens-Johnson syndrome and  erythema multifem.
  • You should be very careful for signs of skin rash.
  • If you experience a reaction to the skin, stop using immediately

• Cardiovascular disease

  • There is a low risk of developing cardiotoxicity. 
  • An increase in the incidence of angina, heart failure, hypertension, bradycardia and cardiac failure was observed (compared to placebo). 
  • Be aware of the potential for cardiovascular disease.

• Hepatic impairment

  • Patients with severe hepatic impairment should be cautious. 
  • Due to the lack of data, Canadian labeling suggests that severe impairment should be avoided.

• Ophthalmic disease

  • Use caution if you have any eye problems.

• Renal impairment

  • Nephrotoxic. Adjust the dose according to creatinine clearance

• Seizure disorder

  • In cases where seizure disorders have already manifested, use with caution.

Memantine: Drug Interaction

Monitoring parameters:

• Cognitive function
• Functional outcomes (eg, Activities of Daily Living [ADLs], Instrumental Activities of Daily Living [IADLs]) (eg, Activities of Daily Living [ADLs],  Instrumental Activities of Daily Living [IADLs])
• Periodic eye exam (Canadian labeling)

How to administer Memantine (Namenda)?

• Taking it with or without food is acceptable.
• You can take extended-release capsules whole or broken, but you shouldn't chew, crush, or divide them.
• Administer oral solution with provided dosing device; Do not mix with other liquids, Canadian labeling however suggests can be taken with water.

Mechanism of action of Memantine (Namenda):

• The major excitatory amino acid in the central nervous system, glutamate, overexcites glutamate receptors in Alzheimer's.
• This leads to excitotoxicity as well as neuronal death.
• N-methyl D-aspartate (NMDA) glutamate receptors are blocked by the antagonist memantine.
• Magnesium ions block the (unstimulated NMDA receptor ion canal) and are displaced by agonist-induced neuropolarization.
• This occurs in normal physiology as well as in Alzheimer's disease.
• According to the theory, in AD, pathologic or excessive receptor activation plugs the channel pore and prevents magnesium from entering,  leading to persistently open circumstances and an excessive calcium influx.
• Memantine acts as a receptor blocker by binding to the intrapore magnesium site under excessive stimulation conditions; normal functioning neurons are not affected.

Absorption:

• Well absorbed

Protein binding:

• 45%

Metabolism:

• Largely independent of the CYP enzyme system, partially hepatic, and produces 3 metabolites (minimal activity)

Half-life elimination:

• Terminal: ~60 to 80 hours

Time to peak, serum:

• Immediate-release: 3 to 7 hours;
• Extended-release: 9 to 12 hours

Excretion:

• Urine (74 percent; 48 percent of the whole dosage were unaltered drugs; active tubular secretion; reabsorption was increased in alkaline PH).

International Brands of Memantine:

• Namenda
• Namenda Titration Pak
• Namenda XR
• Namenda XR Titration Pack
• ACT Memantine
• APO-Memantine
• Ebixa
• MED-Memantine
• MYLAN-Memantine
• PMSMemantine
• RAN-Memantine
• RATIO-Memantine
• RIVA-Memantine
• SANDOZ Memantine FCT
• SANDOZ Memantine
• Abixa
• Admed
• Admenta
• Akatinol
• Albix
• Alzema
• Amint-10
• Axura
• Carrier
• Cerentia
• Cognitine
• Cordure
• Delmenda
• Dementa
• Denigma
• Ebix
• Ebixa
• Esmirtal
• Eutebrol
• Evy
• Exenta
• Foliant
• Limember
• Lindex
• Manotin
• Mantomed
• Marixino
• Mema
• Memadem-10
• Memanto
• Memanxa
• Memary
• Mementor
• Memogen
• Memora
• Memoria
• Memoril
• Memox
• Memry
• Memxa
• Mentin
• Mentra
• Nemdatine
• Neumantine
• Neuroplus
• Pentabixa
• Remem
• Remtin
• Tabixa
• Vilimen
• Witgen
• Ymana
• Zimerz

Memantine Brand Names in Pakistan: