II. Indications

  1. Precaution: 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 management
      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)

III. Contraindications

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

IV. Supplied

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

V. Dosing

  1. General
    1. Prophylaxis and Treatment dosages are the same
    2. Rimantadine not indicated for treatment under age 14
    3. Dose: 4.4 - 8.8 mg/kg/day divided bid for 5 days
    4. May dose qd, but causes greater Nausea and Vomiting
  2. Age 1-9 years old or weight under 40 kg
    1. Amantadine 5mg/kg/day divided bid (up to 75 mg bid)
    2. Rimantadine 5mg/kg/day divided bid (up to 75 mg bid)
  3. Age 10 to 64 years old
    1. Amantadine 100 mg PO bid
    2. Rimantadine 100 mg PO bid
  4. Age over 65 years old
    1. Rimantadine 100 mg PO qd
    2. Amantadine 100 mg PO qd (avoid if possible)
  5. Renal Insufficiency (based on Creatinine Clearance)
    1. Consider avoiding Amantadine
    2. CrCl 30-50 ml/min: Amantadine 100 mg qd
    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 q7 days

VI. Adverse Effects: CNS Side effects

  1. Consider split dosing especially in elderly
  2. Rimantadine causes less adverse effects than Amantadine
  3. 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]
  4. Related Symptoms
    1. Jitteriness
    2. Anxiety
    3. Insomnia
    4. Lightheadedness
    5. Irritability
    6. Difficulty concentrating (5-10%)

VII. Adverse Effects: Gastrointestinal

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

VIII. Precautions

  1. Adjust dosing in Renal Insufficiency

IX. Resources

  1. CDC MMWR - ACIP Guidelines on antivirals in Influenza (2011)
    1. http://www.cdc.gov/mmwr/preview/mmwrhtml/rr6001a1.htm

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Cost: Medications

amantadine (on 5/17/2017 at Medicaid.Gov Survey of pharmacy drug pricing)
AMANTADINE 100 MG CAPSULE Generic $1.03 each
AMANTADINE 100 MG TABLET Generic $1.50 each
AMANTADINE 50 MG/5 ML SOLUTION Generic $0.02 per ml

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

Ontology: Rimantadine (C0035629)

Definition (NCI) A cyclic amine and alpha-methyl derivative of amantadine with antiviral activity. Although the exact mechanism of action of rimantadine is not understood, this agent appears to exert its antiviral effect against influenza A virus by interfering with the function of the transmembrane domain of the viral M2 protein, thereby preventing the uncoating of the virus and subsequent release of infectious viral nucleic acids into the cytoplasm of infected cells.
Definition (MSH) An RNA synthesis inhibitor that is used as an antiviral agent in the prophylaxis and treatment of influenza.
Concepts Pharmacologic Substance (T121) , Organic Chemical (T109)
MSH D012299
SnomedCT 108712009, 372532009
English Remantadine, Riamantadine, Rimantadine, Tricyclo(3.3.1.13,7)decane-1-methanamine, alpha-methyl-, Rimantadine [Chemical/Ingredient], remantadine, RIMANTADINE, 1-(1-Adamantyl)ethylamin, Tricyclo(3.3.1.1(sup 3,7))decane-1-methanamine, alpha-methyl-, HSDB 7438, alpha-Methyl-1-adamantanemethylamine, rimantadine, Rimantadine (product), Rimantadine (substance)
Swedish Rimantadin
Czech rimantadin
Finnish Rimantadiini
Russian REMANTADIN, RIMANTADIN, РЕМАНТАДИН, РИМАНТАДИН
Japanese リマンタジン, レマンタジン
Polish Rymantadyna
Spanish rimantadina (producto), rimantadina (sustancia), rimantadina, Remantadina, Rimantadina
French Rimantadine
German Remantadin, Rimantadin
Italian Rimantadina
Portuguese Remantadina, Rimantadina

Ontology: Flumadine (C0733408)

Concepts Pharmacologic Substance (T121) , Organic Chemical (T109)
MSH D012299
English Flumadine, Forest Brand of Rimantadine Hydrochloride