Terbinafine

Last updated
Terbinafine
Terbinafine.svg
Terbinafine ball-and-stick model.png
Clinical data
Trade names Lamisil, Terbin, others
AHFS/Drugs.com Monograph
MedlinePlus a699061
License data
Routes of
administration
By mouth, topical
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability Readily absorbed: 70–90%
Protein binding >99%
Metabolism Liver
Elimination half-life Highly variable
Identifiers
  • [(2E)-6,6-dimethylhept-2-en-4-yn-1-yl](methyl)(naphthalen-1-ylmethyl)amine
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard 100.119.605 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C21H25N
Molar mass 291.438 g·mol−1
3D model (JSmol)
  • C(#C\C=C\CN(C)Cc2cccc1ccccc12)C(C)(C)C
  • 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+ Yes check.svgY
  • Key:DOMXUEMWDBAQBQ-WEVVVXLNSA-N Yes check.svgY
 X mark.svgNYes check.svgY  (what is this?)    (verify)

Terbinafine, sold under the brand name Lamisil among others, is an antifungal medication used to treat pityriasis versicolor, fungal nail infections, and ringworm including jock itch and athlete's foot. [1] [2] [3] It is either taken by mouth or applied to the skin as a cream or ointment. [1] [4] The cream and ointment are not effective for nail infections. [5]

Contents

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] Liver injury is, however, unusual. [6] Oral 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 synthesize sterols. [1] It appears to result in fungal cell death. [7]

Terbinafine was discovered in 1991. [8] It is on the World 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 1 million prescriptions. [9] [10]

Medical uses

Terbinafine is mainly effective on fungi of the group Onygenales and some yeasts in the genus Candida (e.g. Candida glabrata )[ citation needed ]

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). [11]

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 oral administration have been studied.[ citation needed ]

Terbinafine may induce or exacerbate subacute cutaneous lupus erythematosus. Persons with lupus erythematosus should first discuss possible risks with their doctor before initiation of therapy. [12]

Side effects

Many side effects and adverse drug reactions have been reported with oral terbinafine hydrochloride, [13] [14] 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 [16] 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

Generic terbinafine hydrochloride pills Terbinafine hydrochloride pills.jpg
Generic terbinafine hydrochloride pills

Like other allylamines, terbinafine inhibits ergosterol synthesis by inhibiting squalene epoxidase, an enzyme that catalyzes the conversion of squalene to lanosterol. In fungi, lanosterol is then converted to ergosterol; in humans, lanosterol becomes cholesterol. 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 fungal cell membrane.[ citation needed ]

Terbinafine is highly lipophilic and tends to accumulate in hair, skin, nails, and fat 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

Terbinafine hydrochloride is a white crystalline powder that is freely soluble in methanol and dichloromethane, soluble in ethanol, and slightly soluble in water. [ citation needed ]

Terbinafine is produced from olefin metathesis of 1,3-dichloropropene and neohexene followed by reaction with N-methyl-1-naphthalenemethanamine.[ citation needed ]

Despite its name it does not contain terbium.

History

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. [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

Brand names

Related Research Articles

<span class="mw-page-title-main">Tinea cruris</span> Fungal infection

Tinea cruris, also known as jock itch, is a common type of contagious, superficial fungal infection of the groin and buttocks region, which occurs predominantly but not exclusively in men and in hot-humid climates.

<span class="mw-page-title-main">Nail disease</span> Medical condition

A nail disease or onychosis is a disease or deformity of the nail. Although the nail is a structure produced by the skin and is a skin appendage, nail diseases have a distinct classification as they have their own signs and symptoms which may relate to other medical conditions. Some nail conditions that show signs of infection or inflammation may require medical assistance.

<span class="mw-page-title-main">Antifungal</span> Pharmaceutical fungicide or fungistatic used to treat and prevent mycosis

An antifungal medication, also known as an antimycotic medication, is a pharmaceutical fungicide or fungistatic used to treat and prevent mycosis such as athlete's foot, ringworm, candidiasis (thrush), serious systemic infections such as cryptococcal meningitis, and others. Such drugs are usually obtained by a doctor's prescription, but a few are available over the counter (OTC). The evolution of antifungal resistance is a growing threat to health globally.

<span class="mw-page-title-main">Ketoconazole</span> Antifungal chemical compound

Ketoconazole, sold under the brand name Nizoral among others, is an antiandrogen, antifungal, and antiglucocorticoid medication used to treat a number of fungal infections. Applied to the skin it is used for fungal skin infections such as tinea, cutaneous candidiasis, pityriasis versicolor, dandruff, and seborrheic dermatitis. Taken by mouth it is a less preferred option and only recommended for severe infections when other agents cannot be used. Other uses include treatment of excessive male-patterned hair growth in women and Cushing's syndrome.

<span class="mw-page-title-main">Athlete's foot</span> Skin infection caused by fungus

Athlete's foot, known medically as tinea pedis, is a common skin infection of the feet caused by a fungus. Signs and symptoms often include itching, scaling, cracking and redness. In rare cases the skin may blister. Athlete's foot fungus may infect any part of the foot, but most often grows between the toes. The next most common area is the bottom of the foot. The same fungus may also affect the nails or the hands. It is a member of the group of diseases known as tinea.

<span class="mw-page-title-main">Griseofulvin</span> Antifungal medication used for dermatophytoses

Griseofulvin is an antifungal medication used to treat a number of types of dermatophytoses (ringworm). This includes fungal infections of the nails and scalp, as well as the skin when antifungal creams have not worked. It is taken by mouth.

<span class="mw-page-title-main">Tolnaftate</span> Chemical compound

Tolnaftate (INN) is a synthetic thiocarbamate used as an anti-fungal agent that may be sold without medical prescription in most jurisdictions. It is supplied as a cream, powder, spray, liquid, and liquid aerosol. Tolnaftate is used to treat fungal conditions such as jock itch, athlete's foot and ringworm.

Dermatophyte is a common label for a group of fungus of Arthrodermataceae that commonly causes skin disease in animals and humans. Traditionally, these anamorphic mold genera are: Microsporum, Epidermophyton and Trichophyton. There are about 40 species in these three genera. Species capable of reproducing sexually belong in the teleomorphic genus Arthroderma, of the Ascomycota. As of 2019 a total of nine genera are identified and new phylogenetic taxonomy has been proposed.

<span class="mw-page-title-main">Tinea corporis</span> Medical condition

Tinea corporis is a fungal infection of the body, similar to other forms of tinea. Specifically, it is a type of dermatophytosis that appears on the arms and legs, especially on glabrous skin; however, it may occur on any superficial part of the body.

<span class="mw-page-title-main">Tinea capitis</span> Cutaneous fungal infection of the scalp

Tinea capitis is a cutaneous fungal infection (dermatophytosis) of the scalp. The disease is primarily caused by dermatophytes in the genera Trichophyton and Microsporum that invade the hair shaft. The clinical presentation is typically single or multiple patches of hair loss, sometimes with a 'black dot' pattern, that may be accompanied by inflammation, scaling, pustules, and itching. Uncommon in adults, tinea capitis is predominantly seen in pre-pubertal children, more often boys than girls.

<span class="mw-page-title-main">Ciclopirox</span> Antifungal medication

Ciclopirox is a synthetic antifungal agent for topical dermatologic treatment of superficial mycoses. It is most useful against tinea versicolor. It is often used clinically as ciclopirox olamine, the olamine salt of ciclopirox.

<span class="mw-page-title-main">Dermatophytosis</span> Fungal infection of the skin

Dermatophytosis, also known as ringworm, is a fungal infection of the skin (Dermatomycosis). Typically it results in a red, itchy, scaly, circular rash. Hair loss may occur in the area affected. Symptoms begin four to fourteen days after exposure. Multiple areas can be affected at a given time.

<span class="mw-page-title-main">Onychomycosis</span> Medical condition

Onychomycosis, also known as tinea unguium, is a fungal infection of the nail. Symptoms may include white or yellow nail discoloration, thickening of the nail, and separation of the nail from the nail bed. Fingernails may be affected, but it is more common for toenails. Complications may include cellulitis of the lower leg. A number of different types of fungus can cause onychomycosis, including dermatophytes and Fusarium. Risk factors include athlete's foot, other nail diseases, exposure to someone with the condition, peripheral vascular disease, and poor immune function. The diagnosis is generally suspected based on the appearance and confirmed by laboratory testing.

<span class="mw-page-title-main">Butenafine</span> Chemical compound

Butenafine, sold under the brand names Lotrimin Ultra, Mentax, and Butop (India), is a synthetic benzylamine antifungal. It is structurally related to synthetic allylamine antifungals such as terbinafine.

<i>Trichophyton rubrum</i> Species of fungus

Trichophyton rubrum is a dermatophytic fungus in the phylum Ascomycota. It is an exclusively clonal, anthropophilic saprotroph that colonizes the upper layers of dead skin, and is the most common cause of athlete's foot, fungal infection of nail, jock itch, and ringworm worldwide. Trichophyton rubrum was first described by Malmsten in 1845 and is currently considered to be a complex of species that comprises multiple, geographically patterned morphotypes, several of which have been formally described as distinct taxa, including T. raubitschekii, T. gourvilii, T. megninii and T. soudanense.

<span class="mw-page-title-main">Naftifine</span> Chemical compound

Naftifine hydrochloride is an allylamine antifungal drug for the topical treatment of tinea pedis, tinea cruris, and tinea corporis.

<span class="mw-page-title-main">Clotrimazole</span> Chemical compound

Clotrimazole, sold under the brand name Lotrimin, among others, is an antifungal medication. It is used to treat vaginal yeast infections, oral thrush, diaper rash, tinea versicolor, and types of ringworm including athlete's foot and jock itch. It can be taken by mouth or applied as a cream to the skin or in the vagina.

<i>Microsporum audouinii</i> Species of fungus

Microsporum audouinii is an anthropophilic fungus in the genus Microsporum. It is a type of dermatophyte that colonizes keratinized tissues causing infection. The fungus is characterized by its spindle-shaped macroconidia, clavate microconidia as well as its pitted or spiny external walls.

Topical antifungaldrugs are used to treat fungal infections on the skin, scalp, nails, vagina or inside the mouth. These medications come as creams, gels, lotions, ointments, powders, shampoos, tinctures and sprays. Most antifungal drugs induce fungal cell death by destroying the cell wall of the fungus. These drugs inhibit the production of ergosterol, which is a fundamental component of the fungal cell membrane and wall.

References

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