Terbinafine

Terbinafine

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 category	B
Legal status	Low-strength topical preparations available without prescription
Routes of administration	Oral and topical
Pharmacokinetic data
Bioavailability	Readily absorbed: 70–90%
Protein binding	>99%
Metabolism	Hepatic
Biological half-life	Highly variable
Identifiers
CAS Number	91161-71-6 Y 78628-80-5
ATC code	D01AE15 D01BA02
PubChem	CID 1549008
DrugBank	DB00857 Y
ChemSpider	1266005 Y
UNII	G7RIW8S0XP Y
KEGG	D02375 Y
ChEBI	CHEBI:9448 N
ChEMBL	CHEMBL822 Y
Chemical data
Formula	C21H25N
Molar mass	291.43 g/mol
SMILES C(#C\C=C\CN(C)Cc2cccc1ccccc12)C(C)(C)C
InChI InChI=1S/C21H25N/c1-21(2,3)15-8-5-9-16-22(4)17-19-13-10-12-18-11-6-7-14-20(18)19/h5-7,9-14H,16-17H2,1-4H3/b9-5+ Y Key:DOMXUEMWDBAQBQ-WEVVVXLNSA-N Y
NY (what is this?)  (verify)

Terbinafine hydrochloride, also known under the trade name Lamisil,^[1] is a antifungal developed by Novartis. It is highly hydrophobic and tends to accumulate in hair, skin, nails, and fatty tissue.

It is on the WHO Model List of Essential Medicines, the most important medications needed in a basic health system.^[2]

Medical uses

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.^[3]

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.^[4]

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.^[5]

FDA approval

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.^[6]

Side effects

Many side effects and adverse drug reactions have been reported with oral terbinafine hydrochloride^[7][8][9] 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:

• Gastrointestinal problems: Diarrhea, constipation, nausea, sickness, 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, liver inflammation (hepatitis), liver damage, liver failure (leading to transplant — or death)
• Immune system problems: Decreased white blood cell counts including pancytopenia, leukopenia, lymphopenia, thrombocytopenia, agranulocytosis, and neutropenia, autoimmune reactions such as lupus erythematosus
• Psychological problems: Depression, anxiety, insomnia, increased or unusual dream activity, malaise
• Sensory problems: Complete loss of taste (ageusia) (sometimes permanent after the treatment), decreased taste (hypogeusia) and distorted taste (dysgeusia) (sometimes permanent after the treatment) often involving a metallic taste sensation and dry mouth, visual disturbances including blurred vision, green vision and double vision
• Skin problems: Rashes, hives (urticaria), skin irritation, itching (pruritis), jaundice, Stevens–Johnson syndrome
• Other side effects: Fatigue, increased heart rate (tachycardia), hair loss (alopecia), decreased red blood cell count (anemia), muscle pain (myalgia), joint pain (arthralgia)

Pharmacology

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.

Brand names

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, 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.^[10][11] 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 Sebifin (Ranbaxy Labs), Zimig (GSK Pharma), Tyza (Abbott Healthcare)^[12] 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