amantadine; adamantamine (Symmetrel, Gocovri)
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Introduction
Tradename: Symmetrel.
Indications
- treatment of parkinsonism
- helps rigidity & akinesia more than tremor[8]
- reduces treatment-induced dyskinesias
- Gocovri FDA-approved for treatment of Sinemet-induced dyskinesia[12]
- parkinsonian symptoms of carbon monoxide poisoning
- treatment of extrapyramidal symptoms
- treatment of restless legs syndrome
- treatment of Huntington's chorea
- prophylaxis & treatment of influenza A[2][9]
- treatment of hyperactivity & irritability in children with autism & other developmental disorders[4]
- treatment of fatigue in multiple sclerosis[10]
Contraindications
Dosage
- adults:
- children:
Tabs: 100 mg.
Dosage adjustment in renal failure
Table
| 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 via kidney
1/2life = 9-37 hours
protein binding = 67 %
elimination by hemodialysis = -
elimination by peritoneal dialysis = -
Adverse effects
- CNS: (13%)
- dizziness, orthostatic hypotension, insomnia, anxiety, confusion, attention deficit, depression, psychosis, hallucinations, ataxia, amnesia , agitation, delirium
- GI: nausea, dry mouth, constipation, diarrhea
- Vascular:
- other:
- congestive heart failure, urinary retention, decreased libido, dyspnea, rash, photosensitivity elevation of serum transaminases, weight loss, fatigue, headache
- rarely:
Drug interactions
- additive anticholinergic effects in patients taking other anticholinergic agents concurrently
- additive CNS stimulant effect in combination with other CNS stimulants
Mechanism of action
- poorly understood antiviral activity
- possibly via inhibition of viral uncoating
- active only against influenza A
- influenza virus M2 inhibitor[10]
- resistance emerges rapidly[9]
- facilitates release or inhibits re-uptake of dopamine
- may reduce hyperactivity by blocking excitatory amino acid neurotransmitter glutamate[4]
- weak NMDA receptor antagonist activity implicated in beneficial effect on treatment-induced dyskinesias[8]
More general terms
- adamantane
- pharmacologic agents for treatment of Parkinson's disease
- antiviral agent
- NMDA receptor antagonist
References
- ↑ The Pharmacological Basis of Therapeutics, 9th ed. Gilman et al, eds. Permagon Press/McGraw Hill, 1996.
- ↑ 2.0 2.1 AHFS 96 Drug Information, GK McEnvoy et al (ed), American Society of Health-System Pharmacists, Bethesda, MD 1996, pg 432, 2703
- ↑ Drug Information & Medication Formulary, Veterans Affairs, Central California Health Care System, 1st ed., Ravnan et al eds, 1998
- ↑ 4.0 4.1 4.2 Prescriber's Letter 8(10):56 2001
- ↑ Sanford Guide to antimicrobial therapy 2001
- ↑ Prescriber's Letter 10(11) 2003; detail document 191102
- ↑ 7.0 7.1 7.2 Prescriber's Letter 11(1):1 2004
- ↑ 8.0 8.1 8.2 8.3 8.4 Bronstein J, In: Intensive Course in Geriatric Medicine & Board Review, Marina Del Ray, CA, Sept 29-Oct 2, 2004
- ↑ 9.0 9.1 9.2 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: https://www.ncbi.nlm.nih.gov/pubmed/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: https://www.ncbi.nlm.nih.gov/pubmed/16424859
Prescriber's Letter 13(2): 2006 Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=220202&pb=PRL (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: https://www.ncbi.nlm.nih.gov/pubmed/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 - ↑ 10.0 10.1 10.2 Medical Knowledge Self Assessment Program (MKSAP) 15, 16. American College of Physicians, Philadelphia 2009, 2012
- ↑ Department of Veterans Affairs, VA National Formulary
- ↑ 12.0 12.1 Brooks M FDA Clears First Drug for Parkinson's Dyskinesia Medscape - Aug 25, 2017. http://www.medscape.com/viewarticle/884697