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| '''For patient information, please click [[Amantadine (patient information)|here]]'''
| | __NOTOC__ |
| | | {{Amantadine}} |
| {{drugbox | | |
| | IUPAC_name = adamantan-1-amine
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| | image = Adamantadine-3D-balls.png
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| | width = 150
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| | CAS_number = 768-94-5
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| | ATC_prefix = N04
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| | ATC_suffix = BB01
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| | PubChem = 2130
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| | DrugBank = APRD00787
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| | C=10 | H=17 | N=1
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| | molecular_weight = 151.249 g/mol
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| | bioavailability = well absorbed
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| | protein_bound = approx 67%
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| | metabolism = negligible
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| | elimination_half-life = 10-14 hours, in renal impairment up to 7-10 days
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| | excretion = [[renal]]
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| | pregnancy_category = C
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| | legal_status =
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| | routes_of_administration = oral
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| }}
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| {{SI}}
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| {{CMG}} | | {{CMG}} |
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| ==Overview== | | ==Overview== |
| '''Amantadine''' (1-[[amino]][[adamantane]], sold as '''Symmetrel''') is an [[antiviral drug]] used both as an [[antiviral]] and an antiparkinsonic. | | '''Amantadine''' (1-[[amino]][[adamantane]], sold as '''Symmetrel''') is an [[antiviral drug]] used both as an [[antiviral]] and an antiparkinsonic. |
| | ==Category== |
| | Antiviral |
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| ==Uses== | | ==US Brand Names== |
| ===Approved===
| | Symadine<sup>®</sup>, Symmetrel<sup>®</sup> |
| It was approved by the [[Food and Drug Administration]] in 1976 for the treatment of [[Influenzavirus A]] in adults. In 1969 the drug was also discovered by accident to help reduce symptoms of [[Parkinson's disease]] and drug-induced [[extrapyramidal system|extrapyramidal]] syndromes. It is a derivative of [[adamantane]], like [[rimantadine]], a similar drug.
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| As an antiparkinsonic it can be used as monotherapy; or together with [[L-DOPA]] to treat L-DOPA-related motor fluctuations (i.e., shortening of L-DOPA duration of clinical effect, probably related to progressive neuronal loss) and L-DOPA-related dyskinesias ([[Chorea (disease)|choreiform]] movements associated with long-term L-DOPA use, probably related to chronic pulsatile stimulation of [[dopamine]] receptors).
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| ===Off-label uses===
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| There have been anecdotal reports, based on research by Dr. William Singer of Harvard University, that low-dose amantadine has been successfully used to treat [[Attention-deficit hyperactivity disorder|ADHD]].<ref>Hallowell, Edward M. and John J. Ratey, ''Delivered from Distraction: Getting the Most out of Life with Attention Deficit Disorder'' (2005), pp. 253-5.</ref> Amantadine has been shown to relieve [[SSRI]]-induced [[anorgasmia]] in some people, though not in all people.
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| == Side Effects ==
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| Amantadine has been associated with several [[central nervous system]] side effects, including nervousness, anxiety, agitation, insomnia, difficulty in concentrating, and exacerbations of pre-existing seizure disorders and psychiatric symptoms in patients with schizophrenia or Parkinson's disease. These side effects are likely due to amantadine's [[dopaminergic]] and [[adrenergic]] activity, and to a lesser extent, its activity as an [[anticholinergic]].
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| Cases of [[suicidal ideation]] in patients treated with amantadine have been described,<ref name="EndoPharmRXInfo">{{cite paper
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| | author =[[Endo Pharmaceuticals]]
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| | title =Symmetrel (Amantadine) Prescribing Information
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| | publisher =
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| | date =May 2003
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| | url =http://www.symmetrel.com/PDF/symmetrel_pack_insert.pdf
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| | format =PDF
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| | accessdate =2007-08-02}}</ref> although this [[psychiatric]] adverse event is relatively rare. Nonetheless, clinical surveillance of suicidal ideation in patients on amantadine is warranted at the clinician's discretion, as amantadine has been implicated as the major fatal (biologically [[toxic]]) factor in completed patient [[suicides]].<ref>Cook et al, "Fatal overdose with amantadine". ''Can. J. Psychiatry'' (Nov 1986); 31(8), pp. 757-758.</ref>
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| Another potential side effect is [[livedo reticularis]], a [[dermatological]] reaction that results in skin mottling and purpurish mesh network of [[blood vessels]].
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| == Mechanism of its effects ==
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| The mechanism of its antiparkinsonic effect is not fully understood, but it appears to be releasing dopamine from the [[nerve]] endings of the [[brain]] cells, together with stimulation of [[norepinephrine]] response. Furthermore, it appears to be a weak [[NMDA receptor antagonist]] and an anticholinergic.
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| The antiviral mechanism seems to be unrelated. The drug interferes with a viral protein, [[M2 protein|M2]] (an [[ion channel]]), which is needed for the viral particle to become "uncoated" once it is taken inside the cell by [[endocytosis]].
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| == Misuse ==
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| Recently, amantadine is reported to have been used in China poultry farming in an effort to protect the birds against [[avian influenza]].<ref name="WashPostBirdFlu">{{cite news
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| | last =Sipress
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| | first =Alan
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| | title =Bird Flu Drug Rendered Useless
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| | pages =A01
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| | publisher =Washington Post
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| | date =2005-06-18
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| | url =http://www.washingtonpost.com/wp-dyn/content/article/2005/06/17/AR2005061701214.html
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| | accessdate =2007-08-02 }}</ref> In western countries and according to international livestock regulations, amantadine is approved only for use in humans. Chickens in China have received an estimated 2.6 billion doses of amantadine.<ref name="WashPostBirdFlu"/> Avian flu ([[H5N1]]) strains in China and southeast Asia are resistant to amantadine, but strains circulating elsewhere seem to be sensitive. If amantadine resistant strains of the virus spread, the drug of choice in an avian flu outbreak will likely be restricted to one of the scarcer and costlier [[oseltamivir]] or [[zanamivir]], which work by a different mechanism and are less likely to trigger resistance.
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| == Declining effectiveness ==
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| Early in the 2005/2006 flu season, the United States' Center for Disease Control [CDC] found rates of amantadine resistance to be much higher than in previous seasons. Looking at samples from 26 states yielded the following findings:
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| <blockquote style="padding:1em; border:1px solid #2f6fab; color:black; background-color:#f9f9f9;">A total of 193 (92.3%) of 209 influenza A(H3N2) and 2 (25%) of 8 influenza A(H1N1) viruses analyzed contained point mutations resulting in a serine-to-asparagine change at amino acid 31 (S31N) of the M2 protein that conferred adamantane resistance. [http://jama.ama-assn.org/cgi/content/full/295.8.joc60020v1]</blockquote>
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| A resistance rate of 92% for the major flu strain was called "alarmingly high". The CDC issued an alert to doctors not to prescribe amantadine any more for the season.[http://www.abqtrib.com/albq/nw_science/article/0,2668,ALBQ_21236_4465998,00.html] Among some Asian countries, A/H3N2 and A/H1N1 resistance has reached 100%.<ref name="JIDResistance">{{cite journal
| | ==FDA Package Insert== |
| | last =Deyde
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| | first =Varough M.
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| | authorlink =
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| | coauthors =Xu, Xiyan; Bright, Rick A.; Shaw, Michael; Smith, Catherine B.; Zhang, Ye; Shu, Yuelong; Gubareva, Larisa V.; Cox, Nancy J.; Klimov, Alexander I.
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| | title =Surveillance of Resistance to Adamantanes among Influenza A(H3N2) and A(H1N1) Viruses Isolated Worldwide
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| | journal =Journal of Infectious Diseases
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| | volume =196
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| | issue =2
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| | pages =249-257
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| | date =2007-07-15
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| | url =http://www.journals.uchicago.edu/JID/journal/issues/v196n2/37908/37908.html?erFrom=-9031892158448947546Guest
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| | accessdate =2007-08-02 }}</ref>
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| == References ==
| | ''' [[Amantadine description|Description]]''' |
| {{reflist|2}}
| | '''| [[Amantadine clinical pharmacology|Clinical Pharmacology]]''' |
| | '''| [[Amantadine microbiology|Microbiology]]''' |
| | '''| [[Amantadine indications and usage|Indications and Usage]]''' |
| | '''| [[Amantadine contraindications|Contraindications]]''' |
| | '''| [[Amantadine warnings and precautions|Warnings and Precautions]]''' |
| | '''| [[Amantadine adverse reactions|Adverse Reactions]]''' |
| | '''| [[Amantadine drug interactions|Drug Interactions]]''' |
| | '''| [[Amantadine overdosage|Overdosage]]''' |
| | '''| [[Amantadine clinical studies|Clinical Studies]]''' |
| | '''| [[Amantadine dosage and administration|Dosage and Administration]]''' |
| | '''| [[Amantadine how supplied|How Supplied]]''' |
| | '''| [[Amantadine labels and packages|Labels and Packages]]''' |
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| == See also == | | ==Mechanism of Action== |
| *[[Rimantadine]]
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| *[[Tromantadine]]
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| {{Dopaminergic agents}}
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| {{Antivirals}}
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| {{Influenza}}
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| <!--Categories-->
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| [[Category:Antiparkinsonian agents]]
| | ==References== |
| [[Category:Amines]]
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| [[Category:Anti-influenza agents]]
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| [[Category:Drugs]]
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| <!--Other languages-->
| | {{Reflist|2}} |
| [[es:Amantadina]]
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| [[fr:Amantadine]]
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| [[ja:アマンタジン]]
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| [[pl:Amantadyna]]
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| [[pt:Amantidina]]
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| [[ru:Амантадин]]
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