General description

Terbinafine Hydrochloride, 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. It is either taken by mouth or applied to the skin as a cream or ointment. The cream and ointment are not effective for nail infections. Terbinafine Hydrochloride was discovered in 1991. It is on the World Health Organization's List of Essential Medicines. In 2017, it was the 307th most commonly prescribed medication in the United States, with more than one million prescriptions. Its appearance is as follows:

Figure 1 Appearance of Terbinafine Hydrochloride.

Application

Terbinafine Hydrochloride 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).[1] 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.[2]

Side effects

Many side effects and adverse drug reactions have been reported with oral terbinafine hydrochloride possibly due to its extensive biodistribution and the often extended durations involved in antifungal treatment (longer than two months). Common side effects when taken by mouth include nausea, diarrhea, headache, cough, rash, and elevated liver enzymes.[3] Severe side effects include liver problems and allergic reactions.[3] Liver injury is, however, unusual.[4] Use during pregnancy is not typically recommended.[3] The cream and ointment may result in itchiness but are generally well tolerated. Terbinafine Hydrochloride is in the allylamines family of medications.[1] It works by decreasing the ability of fungi to make sterols.[3] It appears to result in fungal cell death.

For example, Gastrointestinal problems: Diarrhea, constipation, nausea, fullness, abdominal pain, indigestion, dyspepsia, gastritis, cholestasis, flatulence, altered stool colour, abdominal muscular pain. 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 [5]

Pharmacology

Like other allylamines, Terbinafine Hydrochloride 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, there is sufficient genetic divergence between fungal and human squalene epoxidases that Terbinafine Hydrochloride preferentially binds fungal squalene epoxidase, making it selective for inhibiting ergosterol production in fungi without significantly affecting cholesterol production in humans. This is thought to change cell membrane permeability, causing fungal cell lysis. Terbinafine Hydrochloride is highly lipophilic and tends to accumulate in hair, skin, nails, and fatty tissue.

This accumulation results in therapeutic levels of Terbinafine Hydrochloride even after 80 days following one week treatment of 250 mg/day. Different dosing schedules have been proposed like 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, totalling 3 months of treatment including the drug-free periods. For nail infection a treatment of one month followed by a three months drug-free period repeated three times, totalling four times, showed to be a very effective treatment. Minimising side effects.

References

[1]Markova T (January 2002). Clinical inquiries. What is the most effective treatment for tinea pedis (athlete's foot)?. The Journal of Family Practice. Frontline Medical Communications. 51 (1): 15–22.

[2]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): 1196–8.

[3]Terbinafine Hydrochloride. The American Society of Health-System Pharmacists. Archived from the original on 21 December 2016. Retrieved 8 December 2016.

[4]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): 679–83.