Amantadine

Registered South African indications:

• Parkinson's syndrome
• Influenza A infection

Contraindications

• Hypersensitivity to the active ingredient or to any of its excipients
• Pregnancy
• Breastfeeding
• End-stage renal impairment (eGFR ≤10ml/min/1.73m²)
• History of seizures or epilepsy
• History of gastric ulceration

Cautions

• Moderate to severe renal impairment (eGFR ≥11-49ml/min/1.73m²)
• Hepatic impairment
• Elderly
• Children (for prophylaxis or treatment of influenza A)
• Underlying psychiatric disorders
• Cardiovascular disorders, or history thereof
• Congestive heart failure
• Abrupt withdrawal
• Untreated angle closure glaucoma
• Blurred vision or other visual problems
• Benzyl alcohol intolerance (particularly in children)
• May affect ability to drive and operate machinery

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

Parkinson's syndrome

• Oral (cap): Initial: 100mg, dly for 7 days; Titrate by 100mg at intervals of 1 week; Maintenance: 200-400mg/day, in divided doses; Max: 400mg/24hrs

Dose to be titrated according to signs and symptoms

Doses above 200mg may provide additional relief, but may be associated with increasing toxicity

Influenza A infection

- Prophylaxis

• Oral (cap): 100mg, 12-24hrly; Treatment duration: Duration of the outbreak

- Treatment

• Oral (cap): 100mg, 12-24hrly; Treatment duration: 4-5 days

Due to high resistance rates, amantadine is no longer recommended by the CDC for the treatment or prophylaxis of influenza A. All dosages above are based on the manufacturer's recommendations

Effective prevention and treatment of have been reported with 100 mg daily

Treat daily while the protection from infection is required. In most of the cases this is expected to be for 6 weeks

When used with inactivated influenza A vaccine, amantadine is continued for 2 to 3 weeks following inoculation

Paed. forms avail. in SA and covered in this monograph: cap

Influenza A infection

Younger than 10 years

• Not established for use

Between 10-15 years

• Oral (cap): 100mg, 24hrly, for the recommended period; Treatment duration: Generally 3-5 days

Older than 15 years

• See adult dose

Due to high resistance rates, amantadine is no longer recommended by the CDC for the treatment or prophylaxis of influenza A. All dosages above are based on the manufacturer's recommendations

Pregnancy

• Contraindicated
• Amantadine-related complications during pregnancy have been reported; thus amantadine is contraindicated during pregnancy and in women trying to become pregnant

Breastfeeding

• Contraindicated
• Amantadine is passed into breast milk. Undesirable effects have been reported in breastfed infants; thus amantadine should not be used in breastfeeding

Fertility

• There are insufficient data to adequately assess effects on the reproductive system

Renal Impairment

• eGFR 50-89ml/min/1.73m²: No dose adjustment recommended
• eGFR 11-49ml/min/1.73m²: Caution; dose adjustment recommended
• eGFR ≤10ml/min/1.73 m²: Contraindicated

Hepatic Impairment

• Caution; no dose adjustment recommended

Elderly

• Caution; no dose adjustment recommended
  Lowest effective dose should be used

Porphyria Information

• Not yet classified (NC)

Drugs in Sport

• Permitted - No warnings

Central Nervous System Disorders

• Anxiety
• Euphoric mood
• Dizziness
• Headache
• Lethargy
• Hallucinations  
• Nightmares
• Ataxia
• Dysarthria
• Attention disturbance
• Nervousness
• Depression
• Insomnia
• Myalgia
• Confusional states
• Disorientation
• Psychotic disorder
• Tremor
• Dyskinesia
• Convulsions  
• Neuroleptic malignant-like syndrome
• Delirium
• Hypomanic state
• Mania
• Impulse control disorders

Cardiovascular Disorders

• Livedo reticularis
• Palpitations
• Orthostatic hypotension
• Cardiac failure

Gastrointestinal Disorders

• Dry mouth
• Decreased appetite
• Nausea and vomiting
• Constipation
• Diarrhoea

Hepatobiliary Disorders

• Reversible elevation of hepatic enzymes

Genitourinary Disorders

• Urinary retention
• Urinary incontinence

Endocrine and Metabolic Disorders

• Anorexia

Skin and Subcutaneous Tissue Disorders

• Hyperhidrosis
• Rash
• Photosensitivity reaction

Immune, Blood and Lymphatic System Disorders

• Leucopenia

Sensory Disorders

• Corneal lesions
• Punctate subepithelial opacities (with superficial punctate keratitis)
• Corneal epithelial oedema
• Reduced visual acuity
• Blurred vision

Others

• Peripheral oedema

• Anticholinergic agents
• Levodopa
• Neuroleptic agents
• Central nervous depressants
• Alcohol
• Diuretic combination agents

None routine. Specific cases may require

• Renal function
• Mental health status
• Blood pressure
• Signs and symptoms of impulse control disorder

Abrupt withdrawal (Parkinson's syndrome)

• Abrupt discontinuation of amantadine may result in worsening of Parkinsonism or in symptoms resembling neuroleptic malignant syndrome or cognitive manifestations (e.g. catatonia, confusion, disorientation, worsening of mental status, delirium)
• Amantadine should not be stopped abruptly in patients who are treated concurrently with neuroleptics

Resistance (Influenza A infection)

• Resistance to amantadine occurs during serial passage of influenza virus strains in vitro or in vivo in the presence of the drug
• Due to high resistance rates, amantadine is no longer recommended by the CDC for the treatment or prophylaxis of influenza A

Amantadine has been shown to be a low affinity antagonist at the N-methyl-­D­aspartate (NMDA) subtype of glutamate receptors. Overactivity of glutamatergic neurotransmission has been implicated in the generation of Parkinsonian symptoms. In addition, amantadine may also exert some anticholinergic activity.

Amantadine specifically inhibits the replication of influenza A viruses at low concentrations by inhibiting an early stage in viral replication by blocking the proton pump of the M2 protein of the virus. It stops the virus uncoating and inactivates newly synthesised viral hemagglutinin.

Capsule 100mg

• Symmetrel (Novartis) originator
• Symadin (Alchemy)