Class: Anti-infective, Antifungal
- Tablets 250 mg
- Granules, oral 125 mg/packet
- Granules, oral 187.5 mg/packet
- Cream 1%
CO Terbinafine (Canada)
Sandoz Terbinafine (Canada)
Inhibits squalene epoxidase, resulting in ergosterol deficiency and a corresponding accumulation of squalene within the fungal cell leading to fungal cell death.
Absorption from oral terbinafine is greater than 70%; bioavailability is about 40%. Terbinafine C max is 1 mcg/mL, T max occurs 2 h after a 250 mg dose. AUC is 4.56 mcg•h/mL and is increased less than 20% with food. At steady state in comparison to single dose, C max is 25% higher and AUC is increased 2.5 times.
Terbinafine is more than 99% protein bound and there are no specific binding sites. It is distributed to the sebum and skin.
Prior to excretion, terbinafine is extensively metabolized by at least 7 CYP isoenzymes. There are no major metabolites that have antifungal activity similar to terbinafine.
Terbinafine half-life is 200 to 400 h, and the drug is about 70% eliminated in the urine.
Special PopulationsRenal Function Impairment
In renal function impairment (CrCl approximately 50 mL/min), terbinafine Cl is decreased 50%.Hepatic Function Impairment
In hepatic cirrhosis, terbinafine Cl is decreased 50%.
Indications and UsageTablets
Treatment of onychomycosis of the toenail or fingernail caused by dermatophytes.Topical
Interdigital tinea pedis, tinea cruris, or tinea corporis caused by Epidermophyton floccosum , Trichophyton mentagrophytes , or Trichophyton rubrum .Oral granules
Treatment of tinea capitis in patients 4 yr of age and older.
Dosage and AdministrationTinea Capitis
Adults and Children 4 yr of age and older
Patients weighing less than 25 kg, administer 125 mg once daily for 6 wk. Patients weighing 25 to 35 kg, administer 187.5 mg once daily for 6 wk. Patients weighing more than 35 kg, administer 250 mg once daily for 6 wk.Onychomycosis of Toenail and Fingernail
250 mg once daily for 6 wk.Toenail onychomycosis
250 mg once daily for 12 wk.Tinea Corpis, Tinea Cruris, Tinea Pedis
Adults and Children 12 yr of age and older
TopicalTinea corpis, tinea cruris
Apply to affected areas and surrounding skin once daily for 1 wk.Tinea pedis
Apply twice daily for 1 to 2 wk.
- Oral granules
- Take once a day with food.
- Sprinkle contents of packet on a spoonful of pudding or other soft, non-acidic food such as mashed potatoes and instruct patient to swallow entire spoonful. Do not sprinkle on applesauce or fruit-based foods.
- Advise patient to swallow without chewing.
Store oral granules at 59° to 86°F. Store tablets below 77°F. Protect from light. Store topical cream at 68° to 77°F.
Terbinafine decreases the Cl of IV caffeine 19%.Cimetidine
Terbinafine Cl is decreased 33% by cimetidine.Cyclosporine
Terbinafine increases the Cl of cyclosporine 15%.CYP2C9 and CYP3A4 inhibitors (eg, amiodarone, ketoconazole)
Terbinafine plasma concentrations may be elevated, increasing the risk of adverse reactions.Dextromethorphan
Plasma dextromethorphan concentrations may be elevated, increasing the pharmacologic effects and adverse reactions. Terbinafine inhibits dextromethorphan metabolism via the CYP2D6 enzyme.Paroxetine, tricyclic antidepressants (eg, amitriptyline, desipramine, imipramine), venlafaxine
Plasma concentrations of these agents may be elevated, increasing the pharmacologic effects and risk of adverse reactions.Rifampin
Terbinafine Cl is increased 100% by rifampin.Warfarin
Spontaneous reports of increases and decreases in PT time have been reported.
Laboratory Test Interactions
None well documented.
Headache (7%); fatigue, malaise (postmarketing).
Rash (6%); pruritus (3%); urticaria (1%); acute generalized exanthematous pustulosis and precipitation and exacerbation of cutaneous systemic lupus erythematosus; hair loss; psoriasiform eruptions and exacerbation of psoriasis; serious skin reactions, including Stevens-Johnson syndrome and toxic epidermal necrolysis (postmarketing).
Nasopharyngitis (10%); yellow-blue color vision confusion (5%); taste disturbance (3%); nasal congestion, pharyngolaryngeal pain, rhinorrhea (2%); toothache (1%); reduced visual acuity, taste loss, visual field defects (postmarketing).
Diarrhea (6%); vomiting (5%); dyspepsia, upper abdominal pain (4%); nausea (3%); abdominal pain (2%); acute pancreatitis (postmarketing).
Liver abnormalities (3%); hepatic injury, liver failure (postmarketing).
Agranulocytosis, anemia, pancytopenia, severe neutropenia, thrombocytopenia (postmarketing).
Allergic reactions including anaphylaxis, angioedema (postmarketing).
Weight loss (postmarketing).
Arthralgia, myalgia, rhabdomyolysis (postmarketing).
Cough (6%); upper respiratory tract infection (5%).
Pyrexia (7%); influenza (2%).
Pretreatment serum transaminases (ALT and AST) are advised for all patients.
Category B .
Excreted in breast milk.
Safety and efficacy not established (tablets).Oral granules
Safety and efficacy not established in children younger than 4 yr of age.Topical cream
Safety and efficacy not established in children younger than 12 yr of age.
Use of oral granules have not been studied in elderly patients.
Use in patients with CrCl less than 50 mL/min has not been studied. Do not use in patients with renal function impairment (CrCl up to 50 mL/min).
Not recommended in patients with active or chronic liver disease.
Transient increases in absolute lymphocyte counts have been observed. Severe neutropenia has also been reported.
Liver failure, some fatal or leading to liver transplantation, have occurred during postmarketing experience.
Precipitation and exacerbation of cutaneous and systemic lupus erythematosus have been reported during postmarketing experience.
Serious skin reactions, including Stevens-Johnson syndrome and toxic epidermal necrolysis, have occurred during postmarketing experience.
Changes in the ocular lens and retina have been reported.
Abdominal pain, dizziness, frequent urination, headache, nausea, rash, vomiting.
- Emphasize importance of completing full course of therapy, even if signs and symptoms of infection have disappeared.
- Warn patient to report any of the following to health care provider immediately: anorexia, dark urine, fatigue, persistent nausea, right upper abdominal pain, skin rash, vomiting, yellowing of the skin or eyes.
- Review dosing schedule and prescribed length of therapy with patient: 1 tablet daily for 6 wk (fingernail onychomycosis) or 12 wk (toenail onychomycosis).
- Instruct patient to take 1 tablet daily without regard to meals.
- Advise patient that if a dose is missed, take it as soon as possible, but if close to the next dose, do not double up and take the next dose as scheduled.
- Oral granules
- Instruct patient to take once a day with food.
- Advise patients to sprinkle contents of packet on a spoonful of pudding or other soft, non-acidic food such as mashed potatoes and swallow entire spoonful. Advise patient not to sprinkle granules on applesauce or fruit-based foods.
- Instruct patient to swallow granules without chewing.
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