|
This information has been developed and provided by an independent third-party source. Merck & Co., Inc. does not endorse and is not responsible for the accuracy of the content, or for practices or
standards of non-Merck sources.
Pronunciation
(a MAN ta deen)
Generic Available (U.S.)
Yes
Index Terms
Brand Names: Canada
Pharmacologic Category
Pharmacologic Category Synonyms
Use: Labeled Indications
Prophylaxis and treatment of influenza A viral infection (per manufacturer labeling; also refer to current ACIP guidelines for recommendations during current flu season); treatment of parkinsonism; treatment of drug-induced extrapyramidal symptoms
Pregnancy Risk Factor
C
Pregnancy Considerations
Teratogenic effects were observed in animal studies and in case reports in humans.Influenza infection may be more severe in pregnant women. Untreated influenza infection is associated with an increased risk of adverse events to the fetus and an increased risk of complications or death to the mother. Oseltamivir and zanamivir are currently recommended for the treatment or prophylaxis influenza in pregnant women and women up to 2 weeks postpartum. Antiviral agents are currently recommended as an adjunct to vaccination and should not be used as a substitute for vaccination in pregnant women (consult current CDC guidelines).Healthcare providers are encouraged to refer women exposed to influenza vaccine, or who have taken an antiviral medication during pregnancy to the Vaccines and Medications in Pregnancy Surveillance System (VAMPSS) by contacting The Organization of Teratology Information Specialists (OTIS) at (877) 311-8972
Lactation
Enters breast milk/not recommended
Breast-Feeding Considerations
The CDC recommends that women infected with the influenza virus follow general precautions (eg, frequent hand washing) to decrease viral transmission to the child. Mothers with influenza-like illnesses at delivery should consider avoiding close contact with the infant until they have received 48 hours of antiviral medication, fever has resolved, and cough and secretions can be controlled. These measures may help decrease (but not eliminate) the risk of transmitting influenza to the newborn during breast-feeding. During this time, breast milk can be expressed and bottle-fed to the infant by another person who is not infected. Protective measures, such as wearing a face mask, changing into a clean gown or clothing, and strict hand hygiene should be continued by the mother for ≥7 days after the onset of symptoms or until symptom-free for 24 hours. Infant care should be performed by a noninfected person when possible (consult current CDC guidelines).
Contraindications
Hypersensitivity to amantadine or any component of the formulation
Warnings/Precautions
Concerns related to adverse effects:
• CNS depression: May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving).
• Impulse control disorders: Dopamine agonists used for Parkinson's disease or restless legs syndrome have been associated with compulsive behaviors and/or loss of impulse control, which has manifested as pathological gambling, libido increases (hypersexuality), and/or binge eating. Causality has not been established, and controversy exists as to whether this phenomenon is related to the underlying disease, prior behaviors/addictions and/or drug therapy. Dose reduction or discontinuation of therapy has been reported to reverse these behaviors in some, but not all cases.
• Melanoma: Risk for melanoma development is increased in Parkinson's disease patients; drug causation or factors contributing to risk have not been established. Patients should be monitored closely and periodic skin examinations should be performed.
• Neuroleptic malignant syndrome: Has been associated with neuroleptic malignant syndrome (associated with dose reduction or abrupt discontinuation).
• Suicidal ideation: There have been reports of suicidal ideation/attempt in patients with and without a history of psychiatric illness. May exacerbate mental problems in patients with a history of mental illness.
Disease-related concerns:
• Cardiovascular disease: Use with caution in patients with heart failure, peripheral edema, or orthostatic hypotension; dosage reduction may be required.
• Eczema: Use with caution in patients with a history of recurrent and eczematoid dermatitis.
• Glaucoma: Avoid in untreated angle closure glaucoma.
• Hepatic impairment: Use with caution in patients with hepatic impairment; rarely, elevations in transaminases have been reported.
• Influenza A: Appropriate use: Consult current guidelines. Due to increased resistance, the ACIP has recommended that rimantadine and amantadine no longer be used for the treatment or prophylaxis of influenza A in the United States until susceptibility has been re-established.
• Parkinson's disease: Appropriate use: When treating Parkinson's disease, do not discontinue abruptly. In many patients, the therapeutic benefits of amantadine are limited to a few months.
• Psychosis: Use with caution in patients with uncontrolled psychosis or severe psychoneurosis.
• Renal impairment: Use with caution in patients with renal impairment; dosage reduction recommended.
• Seizure disorder: Use with caution in patients with a history of seizure disorder.
Concurrent drug therapy issues:
• CNS stimulants: Use with caution in patients receiving CNS stimulant drugs.
Special populations:
• Elderly: Use with caution in the elderly; may be more susceptible to CNS effects (using 2 divided daily doses may minimize this effect). These patients may require dosage reductions based on renal function.
• Pediatrics: Safety and efficacy have not been established in children <1 year of age.
Other warnings/precautions:
• Withdrawal syndrome: May cause agitation, anxiety, delirium, delusions, depression, hallucinations, paranoia, parkinsonian crisis, slurred speech, or stupor. Upon discontinuation of amantadine therapy, gradually taper dose.
Adverse Reactions
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, lightheadedness, nervousness, somnolence
Dermatologic: Livedo reticularis
Gastrointestinal: Anorexia, constipation, diarrhea, nausea, xerostomia
Respiratory: Dry nose
<1%: Amnesia, dyspnea, eczematoid dermatitis, euphoria, heart failure, hyperkinesis, hypertension, leukopenia, libido decreased, neutropenia, oculogyric episodes, photosensitivity, psychosis, rash, seizure, slurred speech, suicide attempt, suicide ideation, suicide, urinary retention, visual disturbances, vomiting, weakness
Postmarketing and/or case reports: Aggressive behavior, agranulocytosis, alkaline phosphatase increased, allergic reaction, ALT increased, AST increased, anaphylaxis, arrhythmia, bilirubin increased, BUN increased, cardiac arrest, coma, CPK increased, creatinine increased, delusions, diaphoresis, dysphagia, EEG changes, fever, gait abnormal, GGT increased, hypertonia, hypokinesia, hypotension, keratitis, LDH increased, leukocytosis, mania, muscle contractions (involuntary), mydriasis, neuroleptic malignant syndrome (NMS; associated with dosage reduction or abrupt withdrawal of amantadine), paranoia, paresthesia, pruritus, pulmonary edema, respiratory failure (acute), stupor, tachycardia, tachypnea, tremor
Reported with dopamine agonists: Impulsive/compulsive behaviors (eg, pathological gambling, hypersexuality, binge eating)
Metabolism/Transport Effects
None known.
Drug Interactions
Antipsychotics (Atypical): May diminish the therapeutic effect of Anti-Parkinson's Agents (Dopamine Agonist). Risk D: Consider therapy modification
Antipsychotics (Typical): May enhance the therapeutic effect of Anti-Parkinson's Agents (Dopamine Agonist). Anti-Parkinson's Agents (Dopamine Agonist) may diminish the therapeutic effect of Antipsychotics (Typical). Management: Avoid concomitant therapy if possible and monitor for decreased effects of both agents when these combinations cannot be avoided. Atypical antipsychotics such as clozapine and quetiapine may be less likely to reduce the effects of anti-Parkinson's agents. Risk D: Consider therapy modification
Glycopyrrolate: Amantadine may enhance the anticholinergic effect of Glycopyrrolate. Risk C: Monitor therapy
Influenza Virus Vaccine (Live/Attenuated): Antiviral Agents (Influenza A and B) may diminish the therapeutic effect of Influenza Virus Vaccine (Live/Attenuated). Management: Avoid anti-influenza antivirals during the period beginning 48 hours prior to and ending 2 weeks after vaccine administration. Persons receiving these agents within 2 weeks of the live intranasal spray vaccine should receive a repeat vaccine dose. Risk D: Consider therapy modification
MAO Inhibitors: May enhance the orthostatic hypotensive effect of Orthostatic Hypotension Producing Agents. Risk C: Monitor therapy
Methylphenidate: May enhance the adverse/toxic effect of Anti-Parkinson's Agents (Dopamine Agonist). Risk C: Monitor therapy
Metoclopramide: May diminish the therapeutic effect of Anti-Parkinson's Agents (Dopamine Agonist). Risk C: Monitor therapy
Trimethoprim: May enhance the adverse/toxic effect of Amantadine. Specifically, the risk of myoclonus and/or delirium may be increased. Amantadine may increase the serum concentration of Trimethoprim. Trimethoprim may increase the serum concentration of Amantadine. Risk C: Monitor therapy
Ethanol/Nutrition/Herb Interactions
Ethanol: Avoid ethanol (may increase CNS adverse effects).
Storage
Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F).
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); Healthy, older (≥60 years) males: 29 hours (range: 20-41 hours); End-stage renal disease: 7-10 days
Time to peak, plasma: 2-4 hours
Excretion: Urine (80% to 90% unchanged) by glomerular filtration and tubular secretion
Dosage
Oral:
Children: Influenza A treatment/prophylaxis: Note: Due to issues of resistance, amantadine is no longer recommended for the treatment or prophylaxis of influenza A. Please refer to the current ACIP recommendations.
Influenza A treatment:
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 in 2 divided doses (CDC, 2011)
≥10 years and ≥40 kg: 100 mg twice daily (CDC, 2011)
Note: Initiate within 24-48 hours after onset of symptoms; continue for 24-48 hours after symptom resolution (duration of therapy is generally 3-5 days)
Influenza A prophylaxis: Refer to “Influenza A treatment” dosing. Note: Continue prophylaxis 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).
Adults:
Drug-induced extrapyramidal symptoms: 100 mg twice daily; may increase to 300 mg/day in divided doses, if needed
Parkinson's disease: Usual dose: 100 mg twice daily as monotherapy; may increase to 400 mg/day in divided doses, if needed, with close monitoring. Note: Patients with a serious concomitant illness or those receiving high doses of other anti-parkinson drugs should be started at 100 mg/day; may increase to 100 mg twice daily, if needed, after one to several weeks.
Influenza A treatment/prophylaxis: Note: Due to issues of resistance, amantadine is no longer recommended for the treatment or prophylaxis of influenza A. Please refer to the current ACIP recommendations. The following is based on the manufacturer's labeling:
Influenza A treatment: 200 mg once daily or 100 mg twice daily (may be preferred to reduce CNS effects); Note: Initiate within 24-48 hours after onset of symptoms; continue for 24-48 hours after symptom resolution (duration of therapy is generally 3-5 days).
Influenza A prophylaxis: 200 mg once daily or 100 mg twice daily (may be preferred to reduce CNS effects). Note: Continue prophylaxis 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.
Elderly (≥65 years): 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 treatment/prophylaxis: 100 mg once daily
Dosing interval in 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
Monitoring Parameters
Renal function, Parkinson's symptoms, mental status, influenza symptoms, blood pressure
Test Interactions
May interfere with urine detection of amphetamines/methamphetamines (false-positive).
Patient Education
Maintain adequate hydration, unless instructed to restrict fluid intake, and void before taking medication. Take last dose of day in the afternoon to reduce incidence of insomnia. May cause dizziness or lightheadedness. Avoid alcohol. You may experience decreased mental alertness or coordination, loss of impulse control (possibly manifested as pathological gambling, libido increases, and/or binge eating), nausea, or dry mouth. Report unusual respiratory difficulty or shortness of breath, change in balance, or changes in mentation (eg, depression, anxiety, irritability, hallucination, slurred speech).
Geriatric Considerations
Amantadine is no longer recommended for the treatment or chemoprophylaxis of influenza A infection. Elderly patients may be more susceptible to the CNS effects of amantadine. Adjust dose based on renal function. Liquid forms may be used to administer doses <100 mg.
Dental Health: Effects on Dental Treatment
Key adverse event(s) related to dental treatment: Xerostomia (prolonged use may cause significant xerostomia; normal salivary flow resumes upon discontinuation) and orthostatic hypotension.
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Infectious Diseases Comment
Consult current guidelines for appropriate use. Due to increased resistance the ACIP recommends 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. In some areas, resistance is developing against oseltamivir. 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 ACIP guidelines on the following CDC website: http://www.cdc.gov/flu/professionals/antivirals/index.htm
Mental Health: Comment
This agent should not be used for an acute dystonic reaction. No injectable dosage form is available. Amantadine is generally considered to be less effective than anticholinergic antiparkinsonian agents and beta-blockers for the management of akathisia. It is effective for pseudoparkinsonism, but long-term efficacy has not been established. Given its high cost relative to anticholinergics, it is usually reserved for second-line therapy. Tolerance has also been reported to occur with long-term use (Zubenko, 1984). However, it does not impair cognition by adding anticholinergic load. Amantadine should not be abruptly discontinued; doing so may precipitate a parkinsonian crisis. Additionally, agitation, delirium, delusions, hallucinations, paranoia, stupor, anxiety, depression, and slurred speech may be seen if it is abruptly stopped.
Zubenko GS, Barreira P, and Lipinski JF Jr, “Development of Tolerance to the Therapeutic Effect of Amantadine on Akathisia,” J Clin Psychopharmacol, 1984, 4(4):218-20.
Nursing: Physical Assessment/Monitoring
Recommendations for antiviral susceptibility and effectiveness have changed; amantadine is not recommended for use for the 2011 flu season. Monitor renal function at beginning of therapy and periodically throughout. Assess blood pressure; monitor for signs of fluid retention. When treating Parkinson's disease, taper slowly when discontinuing.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, oral, as hydrochloride: 100 mg
Capsule, softgel, oral, as hydrochloride: 100 mg
Solution, oral, as hydrochloride: 50 mg/5 mL (473 mL)
Syrup, oral, as hydrochloride: 50 mg/5 mL (10 mL, 473 mL, 480 mL)
Tablet, oral, as hydrochloride: 100 mg
Pricing: U.S. (www.drugstore.com)
Capsules (Amantadine HCl)
100 mg (30): $21.99
Syrup (Amantadine HCl)
50 mg/5 mL (120): $15.99
Tablets (Amantadine HCl)
100 mg (30): $52.99
References
Allen RM, “Palliative Treatment of Tardive Dyskinesia With Combination of Amantadine-Neuroleptic Administration,” Biol Psychiatry, 1982, 17(6):719-27.
Alphs L and Davis JM, “Noncatecholaminergic Treatments of Tardive Dyskinesia,” J Clin Psychopharmacol, 1982, 2(6):380-5.
Aoki FY and Sitar DS, “Amantadine Kinetics in Healthy Elderly Men: Implications for Influenza Prevention,” Clin Pharmacol Ther, 1985, 37(2):137-44.
Aoki FY and Sitar DS, “Clinical Pharmacokinetics of Amantadine Hydrochloride,” Clin Pharmacokinet, 1988, 14(1):35-51.
Borison RL, “Amantadine in the Management of Extrapyramidal Side Effects,” Clin Neuropharmacol, 1983, 6(Suppl 1):57-63.
Bradley JS, Byington CL, Shah SS, et al. “The Management of Community-Acquired Pneumonia in Infants and Children Older Than 3 Months of Age: Clinical Practice Guidelines by the Pediatric Infectious Diseases Society and the Infectious Diseases Society of America”, Clin Infect Dis, 2011, 53(7):e25-76.
Centers for Disease Control and Prevention (CDC), "Influenza Division, National Center for Immunization and Respiratory Diseases. Antiviral Agents for the Treatment and Chemoprophylaxis of Influenza --- Recommendations of the Advisory Committee on Immunization Practices (ACIP)," MMWR Surveill Summ, 2011, 60(1):1-28.
Centers for Disease Control and Prevention, "Interim Guidance: Considerations Regarding 2009 Novel H1N1 Flu Virus in Intrapartum and Postpartum Hospital Settings," Available at http://www.cdc.gov/h1n1flu/guidance/obstetric.htm
“Drugs for Non-HIV Viral Infections,” Med Lett Drugs Ther, 2002, 44(1123):9-16.
Factor SA, “Current Status of Symptomatic Medical Therapy in Parkinson's Disease,” Neurotherapeutics, 2008, 5(2):164-80.
Koller WC, Silver DE, and Lieberman A, “An Algorithm for the Management of Parkinson's Disease,” Neurology, 1994, 44(12 Suppl 10):1-52.
Merigan KS, and Browning RG, “Despiramine and Amantadine Causing False-Positive Urine Test for Amphetamine,” Ann Emerg Med, 1993, 22(12):1927-28.
Miller KS and Miller JM, “Toxic Effects of Amantadine in Patients With Renal Failure,” Chest, 1994, 105(5):1630.
Molina JA, Sàinz-Artiga MJ, Fraile A, et al, “Pathologic Gambling in Parkinson's Disease: A Behavioral Manifestation of Pharmacologic Treatment,” Mov Disord, 2000, 15(5):869-72.
Poldinger W, “Therapy of Extrapyramidal Side Effects, With Particular Reference to Persistent Dyskinesia and Lithium Tremor,” International Pharmacopsychiatry, 1978, 13(4):230-3.
Somani SK, Degelau J, Cooper SL, et al, “Comparison of Pharmacokinetic and Safety Profiles of Amantadine 50- and 100-mg Daily Doses in Elderly Nursing Home Residents,” Pharmacotherapy, 1991, 11(6):460-6.
Stange KC, Little DW, and Blatnik B, “Adverse Reactions to Amantadine Prophylaxis of Influenza in a Retirement Home,” J Am Geriatr Soc, 1991, 33(7):700-5.
Strong DK, Eisenstat DD, Bryson SM, et al, “Amantadine Neurotoxicity in a Pediatric Patient With Renal Insufficiency,” DICP, 1991, 25(11):1175-7.
Weintraub D, Siderowf AD, Potenza MN, et al, “Association of Dopamine Agonist Use With Impulse Control Disorders in Parkinson Disease,” Arch Neurol, 2006, 63(7):969-73.
Zubenko GS, Barreira P, and Lipinski JF Jr, “Development of Tolerance to the Therapeutic Effect of Amantadine on Akathisia,” J Clin Psychopharmacol, 1984, 4(4):218-20.
International Brand Names
Lexi-Comp.com
Last full review/revision March 2012
Content last modified March 2012
| 
