Memantine Hydrochloride

Registered South African indications:

• Alzheimer's disease - Moderately severe to severe

Contraindications 

• Hypersensitivity to the active ingredient or any of its excipients 

Cautions 

• Pregnancy
• Breastfeeding
• Moderate to severe renal impairment (CrCl 5-49ml/min)
• Severe hepatic impairment (Child-Pugh Class C)
• Porphyria
• Epilepsy
• History of seizures
• Predisposing factors for epilepsy
• Factors that may raise urine pH
  - Drastic changes in diet, e.g. carnivore to vegetarian diet
  - Massive ingestion of alkalising gastric buffers
  - Renal tubulary acidosis
  - Severe urinary tract infections with Proteus bacteria
• Recent myocardial infarction
• Uncompensated congestive heart failure (NYHA III-IV)
• Uncontrolled hypertension
• Coadministration with other N-methyl-D-aspartate (NMDA)-antagonists
• May impair ability to drive and operate machinery

Forms avail. in SA and covered in this monograph: tab 

Dosages below include:

• International manufacturer recommendations
• South African manufacturer recommendations

International manufacturer recommendations

Alzheimer's disease - moderate to severe 

• Oral (tab): Initial: 5mg, dly for 7 days; Then: 10mg, dly for 7 days; Then: 15mg, dly for 7 days; Then: 10mg, 12hrly OR 20mg, dly for 7 days; Maintenance: 20mg, dly; Max: 20mg/24hrs

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Memantine should be administered orally once a day and should be taken at the same time every day. The film-coated tablets can be taken with or without food

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Therapy should only be started if a caregiver is available who will regularly monitor the intake of the medicinal product by the patient

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Diagnosis should be made according to current guidelines

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Tolerance and dosing should be reassessed on a regular basis, preferably within 3 months after initiation. Thereafter, clinical benefit and patient's tolerance should be reassessed according to current clinical guidelines

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Maintenance treatment can be continued for as long as therapeutic benefit is favourable and patient tolerates treatment with memantine. Continue discontinuation when therapeutic effect is no longer present or patient does not tolerate treatment

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South African manufacturer recommendations

Alzheimer's disease - Moderately severe to severe

• Oral (tab): Initial: 5mg, dly in the morning, for 7 days; Then: 10mg, dly (as 5mg, 12hrly) for 7 days; Then: 15mg, dly (as 10mg in the morning and 5mg in the afternoon), for 7 days; Then: 10mg, 12hrly; Maintenance: 20mg, dly (as 10mg, 12hrly); Max: 20mg/24hrs

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Treatment should be initiated and supervised by a medical practitioner experienced in the diagnosis and treatment of Alzheimer's dementia. Therapy should only be started if a caregiver is available who will regularly monitor medicine intake by the patient

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Diagnosis should be made according to current guidelines

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Efficacy has not been established beyond 6 months

International manufacturer recommendations

No information available

South African manufacturer recommendations

Not established for use in children below 18 years

Pregnancy

• Caution
• There is no or limited amount of data from the use of memantine in pregnant women
• Animal studies indicate a potential for reducing intrauterine growth at exposure levels, which are identical or slightly higher than at human exposure. The potential risk for humans is unknown. Memantine should not be used during pregnancy unless clearly necessary

Breastfeeding

• Caution; not recommended 
• It is not known whether memantine is excreted in human breast milk but, taking into consideration the lipophilicity of the substance, this probably occurs. Women taking memantine should not breastfeed

Fertility

• No adverse effects of memantine were noted on male and female fertility

Renal Impairment

• Mild (CrCl 50–80ml/min): No dose adjustment recommended
• Moderate (CrCl 30–49ml/min): Caution; dose adjustment recommended
  Daily dose should be 10mg, dly; If tolerated well after ≥7 days of treatment; The dose may be increased up to 20mg/day according to the standard titration scheme 
• Severe (CrCl 5-29ml/min): Caution; dose adjustment recommended
  Max: 10mg/24hrs 

Hepatic Impairment  

• Mild to moderate (Child-Pugh Classes A & B): No dose adjustment recommended
• Severe (Child-Pugh Class C): Caution; no information available
  No data on the use of memantine in severe hepatic impairment are available. The administration of memantine is not recommended in these patients 

Elderly 

• No dose adjustment recommended

Porphyria Information

• Probably not porphyrinogenic (PNP)

Drugs in Sport

• Permitted - No warnings

Central Nervous System Disorders 

• Headache
• Fatigue
• Somnolence
• Confusion
• Hallucinations
• Psychotic reactions
• Dizziness
• Balance disorders
• Abnormal gait
• Seizures

Cardiovascular Disorders 

• Cardiac failure
• Hypertension
• Venous thrombosis
• Thromboembolism

Respiratory Disorders

• Dyspnoea

Gastrointestinal Disorders 

• Constipation
• Vomiting
• Pancreatitis

Hepatobiliary Disorders

• Elevated hepatic function tests
• Hepatitis

Immune, Blood and Lymphatic System Disorders 

• Hypersensitivity
• Fungal infections

• L-dopa
• Dopaminergic agonists
• Anticholinergic agents
• Other N-methyl-D-aspartate antagonists
• Amantadine
• Ketamine
• Dextromethorphan
• Barbiturates
• Neuroleptics
• Antispasmodic agents
• Dantrolene
• Baclofen
• Phenytoin
• Oral anticoagulants
• Warfarin
• Hydrochlorothiazide
• Cimetidine
• Ranitidine
• Procainamide
• Quinidine
• Quinine
• Nicotine

• Cognitive function

None routine. Specific cases may require:

• Ophthalmic exam
• Functional outcomes

Isolated cases reported in post-marketing experience

• Alzheimer's disease has been associated with depression, suicidal ideation and suicide. In post-marketing experience these reactions have been reported in patients treated with memantine

Memantine is a voltage-dependent, moderate-affinity uncompetitive NMDA-receptor antagonist. It modulates the effects of pathologically elevated tonic levels of glutamate that may lead to neuronal dysfunction. There is increasing evidence that malfunctioning of glutamatergic neurotransmission, in particular at NMDA-receptors, contributes to both expression of symptoms and disease progression in neurodegenerative dementia.

Tablet 10mg

• Cognimet  (Dr Reddy) originator
• Ebitine (Adcock Ingram)
• Ebixa (H. Lundbeck)
• Memantine unicorn (Unichem) 
• Meminist (Unichem)
• Memor (Zydus)