Amantadine

Precautions: Do not use for Influenza management as of 2011 CDC Guidelines
1. Due to resistance, these agents are not now routinely used for Influenza treatment and prophylaxis (use Neuraminidase Inhibitors)
2. CDC no longer recommends Amantadine or Rimantadine for Influenza prophylaxis or treatment
  1. Use Neuraminidase Inhibitors instead
Prior indications for Influenza A management (no longer used)
1. Influenza Prophylaxis
  1. Given if Vaccine contraindicated
  2. Can be given concurrently with Influenza Vaccine
    1. Covers 2 week period until Immunity established
2. Influenza A Treatment
  1. Shortens course by 1 day and lessens symptoms
  2. Start within 48 hours to be effective
Influenza B is not covered by these Antiviral Agents
1. See Neraminidase Inhibitors: Oseltamivir (Tamiflu) or Zanamivir (Relenza)

Absolute Contraindications
1. Seizure Disorder
Relative Contraindications for Amantadine
1. Age over 65 years
2. Renal Insufficiency

Antiviral Agent derived from Adamantane (a diamond-like molecule originally discovered in petroleum)
Releases Dopamine from intact nerve terminals
Weak non-competitive NMDA receptor Antagonist

Renal Dosing adjustment needed for GFR <60 ml/min
Amantadine Immediate Release Tablets (for Parkinsonism, Extrapyramidal Side Effects)
1. Start 100 mg orally twice daily
2. Titrate to 300 to 400 mg/day orally divided three to four times daily
Amandatine Extended Release
1. Osmolex ER (for Parkinsonism with Extrapyramidal Side Effects)
  1. Start 129 mg orally daily in morning
  2. May increase dose on a weekly basis as needed to maximum dose 322 mg/day
2. Gocovri (for Levodopa-Associated Dyskinesia in Parkinsonism)
  1. Start 137 mg orally at bedtime
  2. May increase dose to 274 mg orally daily after one week

General
1. CDC no longer recommends Amantadine or Rimantadine for Influenza prophylaxis or treatment
2. Prophylaxis and Treatment dosages are the same
3. Dose: 4.4 - 8.8 mg/kg/day divided bid for 5 days
4. May dose daily, but causes greater Nausea and Vomiting
Age 1-9 years old or weight under 40 kg
1. Amantadine 5mg/kg/day orally divided twice daily (up to 75 mg twice daily )
Age 10 to 64 years old
1. Amantadine 100 mg orally twice daily
Age over 65 years old
1. Amantadine 100 mg orally daily (avoid if possible)
Renal Insufficiency (based on Creatinine Clearance)
1. Consider avoiding Amantadine
2. CrCl 30-50 ml/min: Amantadine 100 mg orally daily
3. CrCl 15-29 ml/min
  1. Load: Amantadine 200 mg on Day 1
  2. Next: Amantadine 100 mg every other day
4. CrCl <15 ml/min: Amantadine 200 mg every 7 days

Consider split dosing especially in elderly
Rimantadine causes less adverse effects than Amantadine
QTc Prolongation (risk of Torsades de Pointes) in the elderly
Amantadine and Rimantadine cross blood-brain barrier
1. Antihistamines may block drugs crossing barrier
2. Spector (1988) J Pharmacol Exp Ther 244:516-9 [PubMed]
Related Symptoms
1. Jitteriness
2. Anxiety
3. Insomnia
4. Anticholinergic effects (Dry Mouth)
5. Orthostatic Hypotension or Lightheadedness
6. Irritability
7. Difficulty concentrating (5-10%)
8. Suicidality
9. Hallucinations, Confusion or Nightmares at high dose (severe Psychosis may occur in the elderly)
10. Abrupt medication stoppage may precipitate withdrawal, Delirium and risk of Neuroleptic Malignant Syndrome

Anticholinergic Agents (increased Anticholinergic effects)
Prolonged QT Interval due to Medication
1. Avoid combining Amantadine with other agents that prolong QTc
Agents that alkalinize the urine (e.g. carbonic anhydrase inhibitors)
1. Increase Amantadine levels
Alcohol
1. May increase Amantadine related CNS effects