Terbinafine

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Terbinafine
Terbinafine.svg
Terbinafine ball-and-stick model.png
Clinical data
Trade names Lamisil, Terboderm, others
AHFS/Drugs.com Monograph
MedlinePlus a699061
Pregnancy
category
  • B
Routes of
administration
by mouth and topical
ATC code D01AE15 (WHO) D01BA02 (WHO)
Legal status
Legal status
  • Low-strength topical preparations available without prescription
Pharmacokinetic data
Bioavailability Readily absorbed: 70–90%
Protein binding >99%
Metabolism liver
Biological half-life Highly variable
Identifiers
CAS Number 91161-71-6 YesY 78628-80-5
PubChem (CID) 1549008
DrugBank DB00857 YesY
ChemSpider 1266005 YesY
UNII G7RIW8S0XP YesY
KEGG D02375 YesY
ChEBI CHEBI:9448 N
ChEMBL CHEMBL822 YesY
ECHA InfoCard 100.119.605
Chemical and physical data
Formula C21H25N
Molar mass 291.43 g/mol
3D model (Jmol) Interactive image
 NYesY (what is this?)  (verify)

Terbinafine, sold under the brand name Lamisil among others, is an antifungal medication used to treat ringworm, pityriasis versicolor, and fungal nail infections.[1][2] It is either taken by mouth or applied to the skin as a cream or ointment.[1][3] The cream and ointment are not effective for nail infections.[4]

Common side effects when taken by mouth include nausea, diarrhea, headache, cough, rash, and elevated liver enzymes.[1] Severe side effects include liver problems and allergic reactions.[1] Use during pregnancy is not typically recommended.[1] The cream and ointment may result in itchiness but are generally well tolerated.[2] Terbinafine is in the allylamines family of medications.[1] It works by decreasing the ability of fungi to make sterols.[1]

Terbinafine was discovered in 1991.[5] It is on the World Health Organization's List of Essential Medicines, the most effective and safe medicines needed in a health system.[6] The wholesale cost in the developing world is about 2.20 USD for a 20 gm tube.[7] In the United States a course of treatment costs less than 25 USD and is available over the counter.[4]

Medical uses[edit]

Terbinafine is mainly effective on the dermatophyte group of fungi.

As a 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.[8]

Tablets by mouth 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 by mouth administration have been studied.

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.[9]

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 terbinafine 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.[10]

Side effects[edit]

Many side effects and adverse drug reactions have been reported with oral terbinafine hydrochloride[11][12][13] 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 includes:

In 2015 physicians reported[15] that a patient with an MTHFR enzyme mutation (specifically the C677T variant) had developed an adverse reaction to Lamisil (headache, fatigue, and dizziness). Genetic testing revealed 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]

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. It is highly hydrophobic and tends to accumulate in hair, skin, nails, and fatty tissue.

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.

Brand names[edit]

Terbinafine is sold in India as Terboderm by Omega Pharma and Tyza (Abbott Healthcare),[16] Lamisil in Argentina, Australia, Belgium, Brazil, Canada, Chile, Croatia, Egypt, Czech, Denmark, Estonia, Finland, France, Germany, Greece, Hungary, Iceland, Ireland, Israel, Mexico, the Netherlands, New Zealand, Norway, Pakistan (لیمسل), Peru, the Philippines,[17] Romania, Russia, Slovakia, Slovenia, South Africa, Sweden, Thailand, 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.[18][19] It is also available as a generic medication in the United States, the United Kingdom, Belgium, Switzerland, Brazil and Mexico. In India, terbinafine hydrochloride is available in topical form under the brand names Triabin by Medley Pharmaceuticals, 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.) Turbo (Apex Pharmaceuticals Pvt Ltd) in Nepal. The topical form is sold as LamisilAT in the United States.

References[edit]

  1. ^ a b c d e f g "Terbinafine Hydrochloride". The American Society of Health-System Pharmacists. Retrieved 8 December 2016. 
  2. ^ a b "Lamisil 1% w/w Cream - Summary of Product Characteristics (SPC) - (eMC)". www.medicines.org.uk. 17 March 2016. Retrieved 17 December 2016. 
  3. ^ "19th WHO Model List of Essential Medicines (April 2015)" (PDF). WHO. April 2015. Retrieved May 10, 2015. 
  4. ^ a b Hamilton, Richart (2015). Tarascon Pocket Pharmacopoeia 2015 Deluxe Lab-Coat Edition. Jones & Bartlett Learning. p. 180. ISBN 9781284057560. 
  5. ^ Ravina, Enrique (2011). The Evolution of Drug Discovery: From Traditional Medicines to Modern Drugs. John Wiley & Sons. p. 90. ISBN 9783527326693. 
  6. ^ "WHO Model List of Essential Medicines (19th List)" (PDF). World Health Organization. April 2015. Retrieved 8 December 2016. 
  7. ^ "Terbinafine". International Drug Price Indicator Guide. Retrieved 8 December 2016. 
  8. ^ Markova, T (2002). "Clinical inquiries. What is the most effective treatment for tinea pedis (athlete's foot)?". The Journal of family practice. 51 (1): 21. PMID 11927056. 
  9. ^ Callen, Jeffrey P.; Hughes, Amy P.; Kulp-Shorten, Carol (2001). "Subacute Cutaneous Lupus Erythematosus Induced or Exacerbated by Terbinafine". Archives of Dermatology. 137 (9). doi:10.1001/archderm.137.9.1196. 
  10. ^ "US FDA approves oral granules for scalp ringworm". Reuters. 2007-09-28. 
  11. ^ "Lamisil (terbinafine): Side Effects". Doublecheckmd.com. 2010-06-16. Retrieved 2013-11-09. 
  12. ^ McGuire, Stephen (2008-02-05). "Australian regulators issue warning on Novartis' Lamisil". Medical Marketing and Media. Mmm-online.com. Retrieved 2013-11-09. 
  13. ^ "Terbinafine-1 (Terbinafine Hydrochloride,Lamisil)". Drug Dosage and Side Effects. Healthline.com. 2009-02-27. Retrieved 2013-11-09. 
  14. ^ Duxbury, A J; Oliver, R J; Pemberton, M N (2000). "Case report: Persistent impairment of taste associated with terbinafine". British Dental Journal. 188 (6): 295. doi:10.1038/sj.bdj.4800461. PMID 10800234. 
  15. ^ Trachtman, J. N.; Pagano, V (2015). "Antifolates and MTHFR". Therapeutic Drug Monitoring. 37 (6): 697–8. doi:10.1097/FTD.0000000000000215. PMID 25929315. 
  16. ^ "Terbinafine brands in India". Brand index. DrugsUpdate India. 
  17. ^ "Mercury Drug - The Leading Drugstore in the Philippines". www.mercurydrug.com. Retrieved 2016-11-18. 
  18. ^ "Terbinafine". Pharmaceutical Benefits Scheme: A-Z list. Australian Government. 
  19. ^ "PI and CMI Trade Names and Active Ingredients containing Terbinafine". Therapeutic Goods Administration. Australian Government.