Amantadine

SPECIAL ALERTS Updated Influenza Guidelines - January 16, 2006
The Center for Disease Control (CDC) has made an interim recommendation to the 2005-2006 Influenza Guidelines. Due to increased resistance reported during the beginning of this season, the CDC is recommending that amantadine and rimantadine no longer be used for the treatment or prophylaxis of influenza A in the United States. If an antiviral medication is needed, oseltamivir or zanamivir should be used. Amantadine may still be used for its other approved indications, such as in the treatment of Parkinson's disease.
For additional information, refer to the following CDC website: http://www.cdc.gov/mmwr/preview/mmwrhtml/mm55d117a1.htm?s_cid=mm55d117a1_e
U.S. BRAND NAMES — Symmetrel®
PHARMACOLOGIC CATEGORY Anti-Parkinson's Agent, Dopamine AgonistAntiviral Agent, Adamantane
DOSING: ADULTS Influenza A treatment: Oral: 100 mg twice daily; initiate within 24-48 hours after onset of symptoms; discontinue as soon as possible based on clinical response (generally within 3-5 days or within 24-48 hours after symptoms disappear).
Influenza A prophylaxis: Oral: 100 mg twice daily; continue treatment throughout the peak influenza activity in the community or throughout the entire influenza season in patients who cannot be vaccinated. Development of immunity following vaccination takes ~2 weeks; amantadine therapy should be considered for high-risk patients from the time of vaccination until immunity has developed.
Drug-induced extrapyramidal symptoms: Oral: 100 mg twice daily; may increase to 300-400 mg/day, if needed
Parkinson's disease or Creutzfeldt-Jakob disease (unlabeled use): Oral: 100 mg twice daily as sole therapy; may increase to 400 mg/day if needed with close monitoring; initial dose: 100 mg/day if with other serious illness or with high doses of other anti-Parkinson drugs
DOSING: PEDIATRIC
(For additional information see "Amantadine: Pediatric drug information")Influenza A treatment: Oral: Note: Initiate within 24-48 hours after onset of symptoms; discontinue as soon as possible based on clinical response (generally within 3-5 days or within 24-48 hours after symptoms disappear) 1-9 years: 5 mg/kg/day in 2 divided doses (manufacturers range: 4.4-8.8 mg/kg/day); maximum dose: 150 mg/day 10 years and <40 kg: 5 mg/kg/day; maximum dose: 150 mg/day 10 years and 40 kg: Refer to adult dosing.
Influenza A prophylaxis: Oral: Refer to "Influenza A treatment" dosing. Continue treatment throughout the peak influenza activity in the community or throughout the entire influenza season in patients who cannot be vaccinated. Development of immunity following vaccination takes ~2 weeks; amantadine therapy should be considered for high-risk patients from the time of vaccination until immunity has developed. For children <9 years receiving influenza vaccine for the first time, amantadine prophylaxis should continue for 6 weeks (4 weeks after the first dose and 2 weeks after the second dose)
DOSING: ELDERLY — Adjust dose based on renal function; some patients tolerate the drug better when it is given in 2 divided daily doses (to avoid adverse neurologic reactions).
Influenza A prophylaxis or treatment: 100 mg/day in patients 65 years
DOSING: RENAL IMPAIRMENT Clcr 30-50 mL/minute: Administer 200 mg on day 1, then 100 mg/day
Clcr 15-29 mL/minute: Administer 200 mg on day 1, then 100 mg on alternate days
Clcr <15 mL/minute: Administer 200 mg every 7 days
Hemodialysis: Administer 200 mg every 7 days
Peritoneal dialysis: No supplemental dose is needed
Continuous arteriovenous or venous-venous hemofiltration: No supplemental dose is needed
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, as hydrochloride: 100 mg
Syrup, as hydrochloride: 50 mg/5 mL (480 mL)
Tablet, as hydrochloride: 100 mg Symmetrel®: 100 mg
DOSAGE FORMS: CONCISE Capsule: 100 mg
Syrup: 50 mg/5 mL
Tablet: 100 mg Symmetrel®: 100 mg
GENERIC EQUIVALENT AVAILABLE — Yes
USE — Prophylaxis and treatment of influenza A viral infection (per manufacturer labeling; also refer to current CDC guidelines for recommendations during current flu season); treatment of parkinsonism; treatment of drug-induced extrapyramidal symptoms
ADVERSE REACTIONS SIGNIFICANT 1% to 10%: Cardiovascular: Orthostatic hypotension, peripheral edema Central nervous system: Agitation, anxiety, ataxia, confusion, delirium, depression, dizziness, dream abnormality, fatigue, hallucinations, headache, insomnia, irritability, nervousness, somnolence Dermatologic: Livedo reticularis Gastrointestinal: Anorexia, constipation, diarrhea, nausea, xerostomia Respiratory: Dry nose
<1% (Limited to important or life-threatening): Aggressive behavior, agranulocytosis, allergic reaction, amnesia, anaphylaxis, arrhythmia, cardiac arrest, CHF, coma, delirium, delusions, diaphoresis, dysphagia, dyspnea, eczematoid dermatitis, euphoria, hyperkinesis, leukopenia, mania, neutropenia, neuroleptic malignant syndrome (NMS; associated with dosage reduction or abrupt withdrawal of amantadine), oculogyric episodes, paresthesia, photosensitivity, psychosis, pulmonary edema, rash, respiratory failure (acute), seizures, suicidal ideation, suicide, urinary retention, withdrawal reactions (may include delirium, hallucinations, and psychosis), visual disturbances
CONTRAINDICATIONS — Hypersensitivity to amantadine, rimantadine, or any component of the formulation
WARNINGS / PRECAUTIONS — Use with caution in patients with liver disease, history of recurrent and eczematoid dermatitis, uncontrolled psychosis or severe psychoneurosis, seizures, and in those receiving CNS-stimulant drugs; reduce dose in renal disease. When treating Parkinson's disease, do not discontinue abruptly. In many patients, the therapeutic benefits of amantadine are limited to a few months. Elderly patients may be more susceptible to CNS effects (using 2 divided daily doses may minimize this effect). Has been associated with neuroleptic malignant syndrome (associated with dose reduction or abrupt discontinuation). Has not been shown to prevent bacterial infection or complications when used as prophylaxis or treatment of influenza A. Use with caution in patients with CHF, peripheral edema, or orthostatic hypotension. Avoid in untreated angle closure glaucoma. Due to increased resistance, in June 2006, the CDC recommended that amantadine no longer be used for the treatment or prophylaxis of influenza A in the United States until susceptibility has been re-established.
DRUG INTERACTIONS Anticholinergics may potentiate CNS side effects of amantadine; monitor for altered response; includes benztropine and trihexyphenidyl, as well as agents with anticholinergic activity (eg, quinidine, tricyclics, and antihistamines).
Antipsychotics (typical): May reduce the anti-Parkinsonian effects of amantadine
Triamterene: Has been reported to increase the potential for toxicity with amantadine (limited documentation); monitor response.
Vaccine: Influenza (live, attenuated): The live, attenuated form of influenza vaccine (administered intranasally) should not be administered within 2 weeks before or 48 hours after amantadine (unless medically indicated). Inactivated vaccine (trivalent) may be administered without concern to patients receiving amantadine.
ETHANOL / NUTRITION / HERB INTERACTIONS — Ethanol: Avoid ethanol (may increase CNS adverse effects).
PREGNANCY RISK FACTOR — C (show table)
PREGNANCY IMPLICATIONS — Teratogenic effects were observed in animal studies; limited data in humans. Impaired fertility has also been reported during animal studies and during human in vitro fertilization.
LACTATION — Enters breast milk/not recommended
PRICING — (data from drugstore.com)Syrup (Amantadine HCl) 50 mg/5 mL (120): $15.99
Syrup (Symmetrel) 50 mg/5 mL (120): $36.23
Tablets (Symmetrel) 100 mg (60): $82.09
MONITORING PARAMETERS — Renal function, Parkinson's symptoms, mental status, influenza symptoms, blood pressure
TOXICOLOGY / OVERDOSE COMPREHENSIVE — Symptoms of overdose are generally consistent with excessive anticholinergic effects and include nausea, vomiting, slurred speech, blurred vision, lethargy, hallucinations, seizures, myoclonic jerking, and ventricular arrhythmias. Acute toxicity may be primarily due to anticholinergic effects. The minimum lethal dose may be as low as 1 g. Treatment should be supportive and directed at reducing CNS stimulation, controlling seizures, and maintaining cardiovascular function.
CANADIAN BRAND NAMES — Endantadine®; PMS-Amantadine; Symmetrel®
INTERNATIONAL BRAND NAMES — a.m.t. (DE); Amanda (TW); Amandin (TW); Amandine (UY); Amantadin (EE); Amantadin-ratiopharm (PL); Amantan (BE); Amantix (CO, PL); Amantrel (IN); Amazolon (JP); Atarin (FI); Boidan (JP); Endantadine (CA); Enzil (TW); Hofcomant (AT, FI); Infectoflu (DE); Influ-A (IL); Mantadan (IT); Mantidan (BR); Paritrel (IL); PK-Merz (AE, AT, BF, BG, BH, BJ, CH, CI, CL, CR, CY, CZ, DE, DO, EG, ET, GH, GM, GN, GT, HK, HU, IL, IQ, IR, JO, KE, KR, KW, LB, LR, LY, MA, ML, MR, MU, MW, MY, NE, NG, OM, PA, PK, PT, PY, QA, SA, SC, SD, SL, SN, SY, TW, TZ, UG, YE, ZM, ZW); PMS-Amantadine (CA); Prayanol (CL); Protexin (ES); Symmetrel (AE, AT, AU, BH, CA, CH, CY, DE, EG, GB, GR, HR, IE, IQ, IR, JO, KW, LB, LY, NL, NO, NZ, OM, QA, SA, SY, VE, YE, ZA); Tregor (DE); U.M.T. (DE); Viregyt-K (PL); Virofral (SE); Virosol (AR)
MECHANISM OF ACTION — As an antiviral, blocks the uncoating of influenza A virus preventing penetration of virus into host; antiparkinsonian activity may be due to its blocking the reuptake of dopamine into presynaptic neurons or by increasing dopamine release from presynaptic fibers
PHARMACODYNAMICS / KINETICS Onset of action: Antidyskinetic: Within 48 hours
Absorption: Well absorbed
Distribution: Vd: Normal: 1.5-6.1 L/kg; Renal failure: 5.1 +/- 0.2 L/kg; in saliva, tear film, and nasal secretions; in animals, tissue (especially lung) concentrations higher than serum concentrations; crosses blood-brain barrier
Protein binding: Normal renal function: ~67%; Hemodialysis: ~59%
Metabolism: Not appreciable; small amounts of an acetyl metabolite identified
Bioavailability: 86% to 90%
Half-life elimination: Normal renal function: 16 +/- 6 hours (9-31 hours); End-stage renal disease: 7-10 days
Excretion: Urine (80% to 90% unchanged) by glomerular filtration and tubular secretion Total clearance: 2.5-10.5 L/hour
PATIENT INFORMATION — Do not abruptly discontinue therapy; it may precipitate a parkinsonian crisis. May impair ability to perform activities requiring mental alertness or coordination. Take throughout flu season or for at least 10 days following vaccination for effective prophylaxis. Take second dose of the day in early afternoon to decrease incidence of insomnia.