II. Indications: Neurologic

  1. Parkinsonism
    1. Second-line agent (less effective than Levodopa), but more effective than AnticholinergicParkinsonism agents
  2. Levodopa-Associated Dyskinesia in Parkinsonism
  3. Extrapyramidal Side Effect

III. Indications: Influenza (Listed for historical reasons only)

  1. 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
  2. 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
  3. Influenza B is not covered by these Antiviral Agents
    1. See Neraminidase Inhibitors: Oseltamivir (Tamiflu) or Zanamivir (Relenza)

IV. Contraindications

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

V. Mechanism

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

VI. Medications

  1. Tablets: 100 mg
  2. Syrup: 50 mg/5cc

VII. Dosing: Neurologic

  1. Renal Dosing adjustment needed for GFR <60 ml/min
  2. 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
  3. 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

VIII. Dosing: Influenza (Historical)

  1. 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
  2. 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 )
  3. Age 10 to 64 years old
    1. Amantadine 100 mg orally twice daily
  4. Age over 65 years old
    1. Amantadine 100 mg orally daily (avoid if possible)
  5. 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

IX. Adverse Effects: Central Nervous System

  1. Consider split dosing especially in elderly
  2. Rimantadine causes less adverse effects than Amantadine
  3. QTc Prolongation (risk of Torsades de Pointes) in the elderly
  4. 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]
  5. 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

X. Adverse Effects: Gastrointestinal

  1. Amantadine and Rimantadine result in similar GI upset
  2. Nausea or Vomiting
  3. Dyspepsia
  4. Constipation

XI. Safety

  1. Pregnancy Category C
  2. Unknown safety in Lactation

XII. Drug Interactions

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

XIII. Precautions

  1. Adjust dosing in Renal Insufficiency if GFR <60 ml/min
  2. Unknown safety in pregnancy and Lactation

XV. References

  1. (2021) Med Lett Drugs Ther 63(1618): 25-32
  2. Olson (2020) Clinical Pharmacology, Medmaster Miami, p. 46-7
  3. Hamilton (2020) Tarascon Pocket Pharmacopoeia

Images: Related links to external sites (from Bing)

Related Studies

Cost: Medications

amantadine (on 12/21/2022 at Medicaid.Gov Survey of pharmacy drug pricing)
AMANTADINE 100 MG CAPSULE Generic $0.24 each
AMANTADINE 100 MG TABLET Generic $0.64 each
AMANTADINE 50 MG/5 ML SOLUTION Generic $0.02 per ml

Ontology: Adamantane (C0001392)

Definition (MSH) A tricyclo bridged hydrocarbon.
Concepts Organic Chemical (T109)
MSH D000218
English Adamantane, Diamantane, Tricyclo(3.3.1.1(3,7))decane, adamantane, Adamantane [Chemical/Ingredient]
Swedish Adamantan
Czech adamantan
Finnish Adamantaani
Russian DIAMANTAN, ADAMANTAN, АДАМАНТАН, ДИАМАНТАН
Japanese アダマンタン, ジアマンタン
Croatian Not Translated[Adamantane]
Polish Adamantan
French Adamantane
German Adamantan
Italian Adamantano
Portuguese Adamantano
Spanish Adamantano

Ontology: Amantadine (C0002403)

Definition (NCI) A synthetic tricyclic amine with antiviral, antiparkinsonian, and antihyperalgesic activities. Amantadine appears to exert its antiviral effect against the influenza A virus by interfering with the function of the transmembrane domain of the viral M2 protein, thereby preventing the release of infectious viral nucleic acids into host cells. Furthermore, this agent prevents virus assembly during virus replication. Amantadine exerts its antiparkinsonian effects by stimulating the release of dopamine from striatal dopaminergic nerve terminals and inhibiting its pre-synaptic reuptake. This agent may also exert some anticholinergic effect through inhibition of N-methyl-D-aspartic acid (NMDA) receptor-mediated stimulation of acetylcholine, resulting in antihyperalgesia.
Definition (MSH) An antiviral that is used in the prophylactic or symptomatic treatment of influenza A. It is also used as an antiparkinsonian agent, to treat extrapyramidal reactions, and for postherpetic neuralgia. The mechanisms of its effects in movement disorders are not well understood but probably reflect an increase in synthesis and release of dopamine, with perhaps some inhibition of dopamine uptake.
Definition (CSP) antiviral that is used in the prophylactic or symptomatic treatment of influenza A; it is also used as an antiparkinsonian agent, to treat extrapyramidal reactions, and for postherpetic neuralgia.
Concepts Pharmacologic Substance (T121) , Organic Chemical (T109)
MSH D000547
SnomedCT 372763006, 51361008
LNC LP14353-4, MTHU006774
English 1-Aminoadamantane, Adamantylamine, Amantadine, 1 Aminoadamantane, Tricyclo(3.3.1.13,7)decan-1-amine, Amantadine [Chemical/Ingredient], amatadine, AMANTADINE, amantadine, Amantadine (product), Amantadine (substance), Amatadine
Swedish Amantadin
Czech amantadin
Finnish Amantadiini
Italian 1-Aminoadamantano, Adamantilamina, Amantadina
Russian AMANTADIN, АМАНТАДИН
Japanese アマンタジン
Croatian AMANTADIN
Polish Symmetrel, Amantadyna
Spanish amantadina (producto), amantadina (sustancia), amantadina, Amantadina
French Amantadine
German Amantadin
Portuguese Amantadina

Ontology: Symmetrel (C0026055)

Concepts Pharmacologic Substance (T121) , Organic Chemical (T109)
MSH D000547
English symmetrel, Ciba Geigy Brand of Amantadine Hydrochloride, Ciba-Geigy Brand of Amantadine Hydrochloride, Du Pont Brand of Amantadine Hydrochloride, Endantadine, Endo Brand of Amantadine Hydrochloride, Mantadix, Novartis Brand of Amantadine Hydrochloride, Alliance Brand of Amantadine Hydrochloride, Symmetrel