Drug information of Terbinafine
Mechanism of effect
Terbinafine , an allylamine antifungal , inhibits biosynthesis of ergosterol, an essential component of fungal cell membrane, via inhibition of squalene epoxidase enzyme.
This results in fungal cell death primarily due to the increased membrane permeability mediated by the accumulation of high concentrations of squalene but not due to ergosterol deficiency.
The pharmacodynamics of Terbinafine tablets is unknown.
Following oral administration, Terbinafine is well absorbed (greater than 70%) and the bioavailability of Terbinafine tablets as a result of first-pass metabolism is approximately 40%. Peak plasma concentrations of 1 mcg/mL appear within 2 hours after a single 250 mg dose; the AUC is approximately 4.56 mcg•h/mL. An increase in the AUC of Terbinafine of less than 20% is observed when Terbinafine tablets are administered with food .
In plasma, Terbinafine is greater than 99% bound to plasma proteins and there are no specific binding sites. At steady-state, in comparison to a single dose, the peak concentration of Terbinafine is 25% higher and plasma AUC increases by a factor of 2.5; the increase in plasma AUC is consistent with an effective half-life of ~36 hours.
Terbinafine is distributed to the sebum and skin. A terminal half-life of 200 to 400 hours may represent the slow elimination of Terbinafine from tissues such as skin and adipose. Prior to excretion, Terbinafine is extensively metabolized by at least 7 CYP isoenzymes with major contributions from CYP2C9, CYP1A2, CYP3A4, CYP2C8, and CYP2C19. No metabolites have been identified that have antifungal activity similar to Terbinafine. Approximately 70% of the administered dose is eliminated in the urine.
Dermal mycosis :
Adults and chidren above 12 years old: solution twice daily for 2 weeks
Onychomycosis due dermtophyte :
Adults: 250 mg daily oral for 6 weeks for fingernails and 12 weeks for toenails
Tinea capitis :
- Children less than 25 kg: 125 mg daily orally
- Children 25 to 35 kg: 187.5 mg daily orally
- Children greater than 35 kg: 250 mg daily orally
Cutaneous and lymphocutaneous sportrichosis :
Adults: 500 mg twice daily; continue for 2 to 4 weeks after alllesions have healed
- Before prescribing Terbinafine tablets , perform liver function tests because hepatotoxicity may occur in patients with and without preexisting liver disease.
- Taste disturbance, including taste loss, has been reported with the use of Terbinafine tablets . It can be severe enough to result in decreased food intake, weight loss, anxiety, and depressive symptoms. Taste disturbance may resolve within several weeks after discontinuation of treatment, but may be prolonged (greater than 1 year), or may be permanent. If symptoms of a taste disturbance occur, Terbinafine tablets should be discontinued.
- Smell disturbance, including loss of smell, has been reported with the use of Terbinafine tablets. Smell disturbance may resolve after discontinuation of treatment, but may be prolonged (greater than 1 year), or may be permanent. If symptoms of a smell disturbance occur, Terbinafine tablets should be discontinued.
Points of recommendation
- Warn patients prescribed Terbinafine tablets and/or their caregivers to report immediately to their healthcare providers any symptoms or signs of persistent nausea, anorexia, fatigue, vomiting, right upper abdominal pain or jaundice, dark urine, or pale stools .
- Prescribers should be alert to the development of depressive symptoms, and patients should be instructed to report depressive symptoms to their physician.