Terbinafine

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Terbinafine
Terbinafine.svg
Systematic (IUPAC) name
[(2E)-6,6-dimethylhept-2-en-4-yn-1-yl](methyl)(naphthalen-1-ylmethyl)amine
Clinical data
Trade names Lamisil
AHFS/Drugs.com monograph
MedlinePlus a699061
Pregnancy cat. B
Legal status ?
Routes Oral, topical
Pharmacokinetic data
Bioavailability Readily absorbed: 70–90%
Protein binding >99%
Metabolism Hepatic
Half-life Highly variable
Identifiers
CAS number 91161-71-6 YesY 78628-80-5
ATC code D01AE15 D01BA02
PubChem CID 1549008
DrugBank DB00857
ChemSpider 1266005 YesY
UNII G7RIW8S0XP YesY
KEGG D02375 YesY
ChEMBL CHEMBL822 YesY
Chemical data
Formula C21H25N 
Mol. mass 291.43 g/mol
 YesY (what is this?)  (verify)

Terbinafine hydrochloride is a synthetic allylamine antifungal developed by Novartis. It is highly hydrophobic in nature and tends to accumulate in skin, nails, and fatty tissues.

Pharmacology[edit]

Generic terbinafine hydrochloride pills

Terbinafine hydrochloride is a white fine crystalline powder that is freely soluble in methanol and dichloromethane, soluble in ethanol, and slightly soluble in water.

Like other allylamines, terbinafine inhibits ergosterol synthesis by inhibiting squalene epoxidase, an enzyme that is part of the fungal cell membrane synthesis pathway. Because terbinafine prevents conversion of squalene to lanosterol, ergosterol cannot be synthesized. This is thought to change cell membrane permeability, causing fungal cell lysis.

Indications[edit]

Terbinafine is mainly effective on the dermatophyte group of fungi.

As a 1% cream or powder it is used topically for superficial skin infections such as jock itch (tinea cruris), athlete's foot (tinea pedis) and other types of ringworm (tinea corporis). Terbinafine cream works in about half the time required by other antifungals.[1]

Oral 250-mg tablets are often prescribed for the treatment of onychomycosis, a fungal nail infection, typically by a dermatophyte or Candida species. Fungal nail infections are located deep under the nail in the cuticle to which topically applied treatments are unable to penetrate in sufficient amounts. The tablets may, rarely, cause hepatotoxicity, so patients are warned of this and may be monitored with liver function tests. Alternatives to oral administration have been studied. In 2009, results from a clinical study of a new formulation (terbinafine in transfersomes, referred to as TDT-067) for topical treatment of onychomycosis were reported by Celtic Pharma.[2]

Terbinafine hydrochloride may induce or exacerbate subacute cutaneous lupus erythematosus. Persons with lupus erythematosus should first discuss possible risks with their doctor before initiation of therapy.[3]

FDA approval[edit]

Terbinafine first became available in Europe in 1991 and in The United States in 1996. The U.S. Food and Drug Administration has 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 Lamisil (terbinafine hydrochloride, by Novartis AG) is a new treatment approved for use by children age four and up. The antifungal granules can be sprinkled on a child's food to treat ringworm of the scalp, tinea capitis.[4]

Side effects[edit]

Many side effects and adverse drug reactions have been reported with oral terbinafine hydrochloride[5][6][7] possibly due to its extensive biodistribution and the often extended durations involved in antifungal treatment (longer than two months). A comprehensive list of adverse events associated with terbinafine use imncludes:

Brand names[edit]

Terbinafine is sold as Lamisil in Argentina, Australia, Belgium, Brazil, Canada, Chile, Croatia, Egypt, Czech, Denmark, Estonia, Finland, France, Germany, Greece, Hungary, Iceland, Ireland, Israel, Mexico, New Zealand, Norway, Pakistan (لیمسل), Peru, Romania, Russia, Slovakia, Slovenia, South Africa, Sweden, the United Kingdom, the United States, and Venezuela; also it is sold under the name Corbinal and Terbisil in Turkey, and Undofen in Poland. 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.[8][9] It is also available as a generic medication in the United States, the United Kingdom, Belgium, Switzerland, and Brazil. In India, terbinafine hydrochloride is available in topical form under the brand names Sebifin (Ranbaxy Labs), Zimig (GSK Pharma), and mycoCeaze (Progreś Laboratories). MycoVa, developed by Apricus Biosciences, is a topical nail solution of terbinafine and DDAIP, which has completed three phase-III studies for the treatment of onychomycosis. Other names include Terbinaforce (Mankind Pharma) and Tafine (Deurali Janta Pharmaceuticals Pvt Ltd.) in Nepal.

References[edit]

  1. ^ doug@gcnmedia.com. "What is the most effective treatment for tinea pedis (athlete’s foot)? : The Journal of Family Practice". Jfponline.com. Retrieved 2013-11-09. 
  2. ^ Staff (2009). "Clinical Trials Update". Genetic Engineering & Biotechnology News 29 (8): 58 
  3. ^ Callen JP, Hughes AP, Kulp-Shorten C (September 2001). "Subacute cutaneous lupus erythematosus induced or exacerbated by terbinafine: a report of 5 cases". Arch Dermatol 137 (9): 1196–8. doi:10.1001/archderm.137.9.1196. PMID 11559217. 
  4. ^ Reuters, US FDA approves oral granules for scalp ringworm
  5. ^ "DoubleCheckMD Side Effects". Doublecheckmd.com. 2010-06-16. Retrieved 2013-11-09. 
  6. ^ Stephen McGuire (2008-02-05). "Australian regulators issue warning on Novartis' Lamisil — Medical Marketing and Media". Mmm-online.com. Retrieved 2013-11-09. 
  7. ^ "Terbinafine-1 (Terbinafine Hydrochloride,Lamisil) | Drug Dosage and Side Effects". Healthline.com. 2009-02-27. Retrieved 2013-11-09. 
  8. ^ http://www.pbs.gov.au/medicine/item/2285G-2804N-4011D
  9. ^ https://www.ebs.tga.gov.au/