Terbinafine
 | This articleneeds additional citations forverification.(January 2023) |
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| Clinical data | |
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| Trade names | Lamisil, Terbin, others |
| AHFS/Drugs | Monograph |
| MedlinePlus | a699061 |
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| Routes of administration | By mouth,topical |
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| Pharmacokineticdata | |
| Bioavailability | Readily absorbed: 70–90% |
| Protein binding | >99% |
| Metabolism | Liver |
| Eliminationhalf-life | Highly variable |
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| CompTox Dashboard(EPA) | |
| ECHA InfoCard | 100.119.605 |
| Chemical and physical data | |
| Formula | C21H25N |
| Molar mass | 291.438g·mol−1 |
| 3D model (JSmol) | |
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  (what is this?)(verify) | |
Terbinafineis anantifungal medicationused to treatpityriasis versicolor,fungal nail infections,andringwormincludingjock itchandathlete's foot.[1][2][3]It is eithertaken by mouthor applied to the skin as a cream or ointment.[1][4]The cream and ointment should not be used for fungal nail infections.[5]
Common side effects when taken by mouth include nausea, diarrhea, headache, cough, rash, andelevated liver enzymes.[1]Severe side effects includeliver problemsandallergic reactions.[1]Liver injury is, however, unusual.[6]Oral use duringpregnancyis not typically recommended.[1]The cream and ointment may result in itchiness but are generally well tolerated.[2]Terbinafine is in theallylaminesfamily of medications.[1]It works by decreasing the ability of fungi to synthesizeergosterol.[1]It appears to result infungal cell death.[7]
Terbinafine was discovered in 1991.[8]It is on theWorld Health Organization's List of Essential Medicines.[4]In 2021, it was the 245th most commonly prescribed medication in the United States, with more than 1million prescriptions.[9][10]
Medical uses
[edit]Terbinafine is mainly effective onmoldsof the orderOnygenalesand some yeasts in the genusCandida.[citation needed]
As a cream or powder, it is usedtopicallyfor superficial skin infections such asjock itch(tinea cruris),athlete's foot(tinea pedis), and other types ofringworm(tinea corporis).[11]
Tabletsby mouth are often prescribed for the treatment ofonychomycosis,a fungal nail infection, typically by a dermatophyte orCandidaspecies. Fungal nail infections are located deep under the nail in thecuticleto which topically applied treatments are unable to penetrate in sufficient amounts. The tablets may, rarely, causehepatotoxicity,so patients are warned of this and may be monitored withliver function tests.Alternatives to oral administration have been studied.[citation needed]
Terbinafine may induce or exacerbatesubacute cutaneous lupus erythematosus.Persons withlupus erythematosusshould first discuss possible risks with their doctor before initiation of therapy.[12]
Side effects
[edit]Many side effects andadverse drug reactionshave been reported with oral terbinafine hydrochloride,[13][14]possibly due to its extensivebiodistributionand the often extended durations involved in antifungal treatment (longer than two months). A comprehensive list of adverse events associated with terbinafine use includes:
- Gastrointestinal problems:Diarrhea,constipation,nausea,fullness, abdominal pain,indigestion,dyspepsia,gastritis,cholestasis,flatulence,altered stool colour, abdominal muscular pain
- Central nervous system or neurological problems:Headaches,dizziness,vertigo,light-headedness, decreased concentration levels, paraesthesia (pins and needles)
- Hepatic problems: Raised liver enzyme levels, liverinflammation(hepatitis), liver damage, liver failure
- Immune system problems: Decreasedwhite blood cellcounts includingpancytopenia,leukopenia,lymphopenia,thrombocytopenia,agranulocytosis,andneutropenia,autoimmunereactions such aslupus erythematosus
- Psychological problems:Depression,anxiety,insomnia,increased or unusualdreamactivity,malaise
- Sensory problems: Complete loss of taste (ageusia), decreased taste (hypogeusia) and distorted taste (dysgeusia), often involving a metallic taste sensation and dry mouth, visual disturbances including blurred vision, green vision and double vision. In extremely rare cases, the loss or impairment of taste is permanent[15]
- Skin problems:Rashes,hives(urticaria), skin irritation, itching,jaundice,Stevens–Johnson syndrome
- Other side effects:Fatigue,increased heart rate (tachycardia), hair loss (alopecia), decreasedred blood cellcount (anemia), muscle pain (myalgia), joint pain (arthralgia)
In 2015, physicians reported[16]that a patient with anMTHFRenzyme mutation (specifically theC677Tvariant) had developed an adverse reaction to Lamisil (headache, fatigue, anddizziness).Genetic testingrevealed the MTHFR C677T mutation. It was noted that Lamisil interferes with the methylation cycle and that this can cause side effects in individuals with the MTHFR C677T mutation.
Pharmacology
[edit] | This sectionneeds additional citations forverification.(March 2024) |
Like other allylamines, terbinafine inhibitsergosterolsynthesis by inhibitingsqualene epoxidase,an enzyme that catalyzes the conversion ofsqualenetolanosterol.In fungi, lanosterol is then converted toergosterol;in humans, lanosterol becomescholesterol.However,as fungi and animals diverged around 1.1 billion years ago- there is enough difference in this enzyme that terbinafine preferentially binds fungal squalene epoxidase, making it selective for inhibiting ergosterol production in fungi without significantly affecting cholesterol production in mammals. This is thought to fatally disrupt the fungalcell membrane.[citation needed]
Terbinafine is highlylipophilicand tends to accumulate inhair,skin,nails,andfat cells.
This accumulation results in therapeutic levels of terbinafine even after 80 days following one week treatment of 250 mg/day. Different dosing schedules have been proposed such as 500 mg/day for one week or 250 mg/day for two weeks each followed by a drug-free period of three or two weeks, totaling 3 months of treatment including the drug-free periods. Such intermittent dosing schedules appear to be as effective as continuous regimens.[17]
Chemistry
[edit]Terbinafinehydrochlorideis a white crystalline powder that is freely soluble inmethanolanddichloromethane,soluble inethanol,and slightly soluble in water.[citation needed]
Terbinafine is produced fromolefin metathesisof1,3-dichloropropeneandneohexenefollowed by reaction withN-methyl-1-naphthalenemethanamine.[citation needed]
Despite its name it does not containterbium.
History
[edit]Terbinafine first became available in Europe in 1991 and in the United States in 1996. The U.S.Food and Drug Administrationhas approved the first generic versions of prescription Lamisil (terbinafine hydrochloride) tablets. The remaining patent or exclusivity for Lamisil expired on June 30, 2007.
On September 28, 2007, the FDA stated that terbinafine is now approved for use bychildrenage four and up. Theantifungalgranulescan be sprinkled on a child's food to treatscalp fungus.[18]
In the United States the price in 1999 was $547 for a 12-week course; this fell to $10 by 2015, after the patent had expired.[19]
Society and culture
[edit]Brand names
[edit]- Terbinafine is sold in India as Terboderm by Omega Pharma and Tyza (Abbott Healthcare).[20]
- Lamisil in Argentina, Australia, Bangladesh,[21]Belgium, Brazil, Canada, Chile, Colombia, Croatia, Egypt, the Czech Republic, Denmark, Estonia, Finland, France, Germany, Greece, Hungary, Iceland, Ireland, Israel, Mexico, the Netherlands, New Zealand, Norway, Pakistan, Peru, the Philippines,[22]Romania, Russia, Slovakia, Slovenia, South Africa, Sweden, Thailand, the United Kingdom, the United States, and Venezuela
- Corbinal and Terbisil in Turkey, Pakistan, Undofen in Poland. Another alternate is Terbistad (Stada Arzneimittel).
- As a generic oral medication, it is sold as Sebifin, Tinasil, Terbisil, Terbicor, and Tamsil in Australia, whilst the generic topical medication is sold there as SolvEasyTinea and Tamsil.[23][24]
- It is also available as a generic medication in the United States, the United Kingdom, Belgium, Switzerland, Brazil, Mexico, Canada and France.
- In India, terbinafine hydrochloride is available in topical form under the brand names Triabin by Medley Pharmaceuticals, Sebifin (Sun Pharma), Zimig (GSK Pharma) and mycoCeaze (Progreś Laboratories). MycoVa, developed byApricus Biosciences,is a topical nail solution of terbinafine andDDAIP,which has completed three phase-III studies for the treatment ofonychomycosis.
- Other names include Terbinaforce (Mankind Pharma) and Tafine (Deurali Janta Pharmaceuticals Pvt Ltd.) Turbo (Apex Pharmaceuticals Pvt Ltd) in Nepal.
- The topical form is sold as Lamisil AT in the United States.
References
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- ^ab"Lamisil 1% w/w Cream – Summary of Product Characteristics (SPC) – (eMC)".electronic Medicines Compendium (eMC).17 March 2016.Archivedfrom the original on 20 December 2016.Retrieved17 December2016.
- ^Crawford F (July 2009)."Athlete's foot".BMJ Clinical Evidence.2009.PMC2907807.PMID21696646.
- ^abWorld Health Organization(2019).World Health Organization model list of essential medicines: 21st list 2019.Geneva: World Health Organization.hdl:10665/325771.WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO.
- ^Rang & Dale's Pharmacology(9th ed.). Elsevier. 2018. p. 694.ISBN9780702074479.
- ^Yan J, Wang X, Chen S (August 2014). "Systematic review of severe acute liver injury caused by terbinafine".International Journal of Clinical Pharmacy.36(4): 679–683.doi:10.1007/s11096-014-9969-y.PMID24986266.S2CID12867807.
- ^"Terbinafine".drugbank.ca.Retrieved2017-11-14.
- ^Ravina E (2011).The Evolution of Drug Discovery: From Traditional Medicines to Modern Drugs.John Wiley & Sons. p. 90.ISBN978-3-527-32669-3.Archivedfrom the original on 2016-12-20.
- ^"The Top 300 of 2021".ClinCalc.Archivedfrom the original on 15 January 2024.Retrieved14 January2024.
- ^"Terbinafine - Drug Usage Statistics".ClinCalc.Retrieved14 January2024.
- ^Markova T (January 2002)."Clinical inquiries. What is the most effective treatment for tinea pedis (athlete's foot)?".The Journal of Family Practice.51(1). Frontline Medical Communications: 21.PMID11927056.Archivedfrom the original on 2012-04-06.
- ^Callen JP, Hughes AP, Kulp-Shorten C (September 2001)."Subacute cutaneous lupus erythematosus induced or exacerbated by terbinafine: a report of 5 cases".Archives of Dermatology.137(9): 1196–1198.doi:10.1001/archderm.137.9.1196.PMID11559217.
- ^"Lamisil (terbinafine): Side Effects".Doublecheckmd. 2010-06-16. Archived from the original on 2013-09-21.Retrieved2013-11-09.
{{cite web}}:CS1 maint: bot: original URL status unknown (link) - ^McGuire S (2008-02-05)."Australian regulators issue warning on Novartis' Lamisil".Medical Marketing and Media.Mmm-online.Archivedfrom the original on 2013-11-09.Retrieved2013-11-09.
- ^Duxbury AJ, Oliver RJ, Pemberton MN (March 2000)."Persistent impairment of taste associated with terbinafine".British Dental Journal.188(6): 295–296.doi:10.1038/sj.bdj.4800461.PMID10800234.
Persistent loss of taste associated with terbinafine would however appear to be extremely rare.
- ^Trachtman JN, Pagano V (December 2015). "Antifolates and MTHFR".Therapeutic Drug Monitoring.37(6): 697–698.doi:10.1097/FTD.0000000000000215.PMID25929315.S2CID205604356.
- ^Gupta AK, Stec N, Bamimore MA, Foley KA, Shear NH, Piguet V (March 2020)."The efficacy and safety of pulse vs. continuous therapy for dermatophyte toenail onychomycosis"(PDF).Journal of the European Academy of Dermatology and Venereology.34(3): 580–588.doi:10.1111/jdv.16101.PMID31746067.S2CID208185915.
- ^"US FDA approves oral granules for scalp ringworm".Reuters.2007-09-28.Archivedfrom the original on 2009-03-23.
- ^Mikailov A, Cohen J, Joyce C, Mostaghimi A (March 2016)."Cost-effectiveness of Confirmatory Testing Before Treatment of Onychomycosis".JAMA Dermatology.152(3): 276–281.doi:10.1001/jamadermatol.2015.4190.PMID26716567.
- ^"Terbinafine brands in India".Brand index.DrugsUpdate India.Archivedfrom the original on 2015-09-23.
- ^"Lamisil".Medex.bd.Archived fromthe originalon 2019-01-19.RetrievedJanuary 17,2019.
- ^"Mercury Drug – The Leading Drugstore in the Philippines".mercurydrug.Archivedfrom the original on 2016-11-18.Retrieved2016-11-18.
- ^"Terbinafine".Pharmaceutical Benefits Scheme: A-Z list.Australian Government.Archivedfrom the original on 2014-02-12.
- ^"PI and CMI Trade Names and Active Ingredients containing Terbinafine".Therapeutic Goods Administration.Australian Government.Archivedfrom the original on 2017-09-10.
