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amantadine; adamantamine (Symmetrel, Gocovri)

Tradename: Symmetrel. Indications: 1) treatment of parkinsonism a) helps rigidity & akinesia more than tremor [8] b) reduces treatment-induced dyskinesias - Gocovri FDA-approved for treatment of Sinemet-induced dyskinesia [12] 2) parkinsonian symptoms of carbon monoxide poisoning 3) treatment of extrapyramidal symptoms 4) treatment of restless legs syndrome 5) treatment of Huntington's chorea 6) prophylaxis & treatment of influenza A [2,9] 7) treatment of hyperactivity & irritability in children with autism & other developmental disorders [4] 8) treatment of fatigue in multiple sclerosis [10] Contraindications: - acute angle-closure glaucoma (any acute glaucoma) Dosage: 1) adults: a) 100 mg PO BID-TID (consider 100 mg QD in elderly) [7,8] b) restless legs syndrome: 100 mg QD-TID c) influenza 1] treatment: 100 mg PO BID for 5 days 2] prophylaxis: 100 mg BID for 14 days 3] consider 100 mg QD in elderly [7] d) max dose: 400 mg/day [8] 2) children: a) 1-9 years: 4.4-4.8 mg/kg/day up to 150 mg/day divided BID b) 9-12 years: 100-200 mg/day divided QD-BID Tabs: 100 mg. Syrup: 50 mg/5 mL (480 mL). Dosage adjustment in renal failure: creatinine clearance dosage > 50-90 mL/min every 24-48 hour dosing 10-50 mL/min every 48-72 hours dosing < 10 mL/min* every 7 day dosing * No additional dosing for hemodialysis Pharmacokinetics: -> elimination 1/2life 10-30 hours (500 hours ESRD) Adverse effects: 1) CNS: (13%) - dizziness, orthostatic hypotension, insomnia, anxiety, confusion, attention deficit, depression, psychosis, hallucinations, ataxia, amnesia , agitation, delirium 2) GI: nausea, dry mouth, constipation, diarrhea 3) Vascular: - livedo reticularis, orthostatic hypotension peripheral edema 4) other: - congestive heart failure, urinary retention, decreased libido, dyspnea, rash, photosensitivity elevation of serum transaminases, weight loss, fatigue, headache 5) rarely: - leukopenia, visual disturbances, eczematoid dermatitis Drug interactions: 1) additive anticholinergic effects in patients taking other anticholinergic agents concurrently 2) additive CNS stimulant effect in combination with other CNS stimulants Mechanism of action: 1) poorly understood antiviral activity a) possibly via inhibition of viral uncoating b) active only against influenza A c) influenza virus M2 inhibitor [10] d) resistance emerges rapidly [9] 2) facilitates release or inhibits re-uptake of dopamine 3) may reduce hyperactivity by blocking excitatory amino acid neurotransmitter glutamate [4] 4) weak NMDA receptor antagonist activity implicated in beneficial effect on treatment-induced dyskinesias [8]

Interactions

drug interactions

General

adamantane antiviral agent NMDA receptor antagonist pharmacologic agents for treatment of Parkinson's disease

Properties

INHIBITS: NMDA receptor MISC-INFO: elimination route KIDNEY 1/2life 9-37 HOURS therapeutic-range >300 NG/ML protein-binding 67% elimination by hemodialysis - peritoneal dialysis - pregnancy-category C safety in lactation ?

Database Correlations

PUBCHEM correlations

References

  1. The Pharmacological Basis of Therapeutics, 9th ed. Gilman et al, eds. Permagon Press/McGraw Hill, 1996.
  2. AHFS 96 Drug Information, GK McEnvoy et al (ed), American Society of Health-System Pharmacists, Bethesda, MD 1996, pg 432, 2703
  3. Drug Information & Medication Formulary, Veterans Affairs, Central California Health Care System, 1st ed., Ravnan et al eds, 1998
  4. Prescriber's Letter 8(10):56 2001
  5. Sanford Guide to antimicrobial therapy 2001
  6. Prescriber's Letter 10(11) 2003; detail document 191102
  7. Prescriber's Letter 11(1):1 2004
  8. Bronstein J, In: Intensive Course in Geriatric Medicine & Board Review, Marina Del Ray, CA, Sept 29-Oct 2, 2004
  9. Bright RA, Medina MJ, Xu X, Perez-Oronoz G, Wallis TR, Davis XM, Povinelli L, Cox NJ, Klimov AI. Incidence of adamantane resistance among influenza A (H3N2) viruses isolated worldwide from 1994 to 2005: a cause for concern. Lancet. 2005 Oct 1;366(9492):1175-81. Epub 2005 Sep 22. PMID: 16198766 - Centers for Disease Control and Prevention (CDC). High levels of adamantane resistance among influenza A (H3N2) viruses and interim guidelines for use of antiviral agents: United States, 2005-06 influenza season. MMWR Morb Mortal Wkly Rep. 2006 Jan 20;55(2):44-6. PMID: 16424859 - Prescriber's Letter 13(2): 2006 Detail-Document#: 220202 (subscription needed) http://www.prescribersletter.com - Bright RA et al, Adamantane resistance among influenza A viruses isolated early during the 2005-2006 influenza season in the United States. JAMA 2006 PMID: 16456807 - Centers for Disease Control and Prevention (CDC). CDC recommends against use of amantadine and rimantadine for the treatment of prophylaxis of influenza during the 2005- 2006 flu season. CDC Health Alert Network 2006, Jan 14 http://www.cdc.gov/flu/han011406.htm
  10. Medical Knowledge Self Assessment Program (MKSAP) 15, 16. American College of Physicians, Philadelphia 2009, 2012
  11. Department of Veterans Affairs, VA National Formulary
  12. Brooks M FDA Clears First Drug for Parkinson's Dyskinesia Medscape - Aug 25, 2017. http://www.medscape.com/viewarticle/884697

Component-of

amantadine/baclofen/diclofenac/gabapentin/lidocaine