Lamisil Information
Lamisil (Terbinafine) indications And Usage
Lamisil (Terbinafine) (terbinafine hydrochloride) Oral Granules are indicated for the treatment of tinea capitis in patients 4 years of age and older.
Lamisil (Terbinafine) Dosage And Administration
Lamisil (Terbinafine) (terbinafine hydrochloride) Oral Granules should be taken once a day for 6 weeks based upon body weight (See Table 1). Sprinkle the contents of each packet on a spoonful of pudding or other soft, non-acidic food such as mashed potatoes and swallow the entire spoonful (without chewing); do not use applesauce or fruit-based foods. Take with food. If two packets (250 mg) are required with each dose, either the content of both packets may be sprinkled on one spoonful, or the contents of both packets may be sprinkled on two spoonfuls of non-acidic food as directed above.
Lamisil (Terbinafine) Dosage Forms And Strengths
Oral Granules, 125 mg or 187.5 mg (terbinafine base equivalent) per packet. The film-coated granules are off-white to yellowish, round, biconvex, each having a diameter of approximately 2.1 mm.
Lamisil (Terbinafine) Contraindications
Lamisil (Terbinafine) (terbinafine hydrochloride) Oral Granules are contraindicated in individuals with a history of allergic reaction to oral terbinafine because of the risk of anaphylaxis.
Lamisil (Terbinafine) Warnings And Precautions
Cases of liver failure, some leading to liver transplant or death, have occurred with the use of oral terbinafine during postmarketing experience in individuals with and without pre-existing liver disease. In the majority of liver cases reported, the patients had serious underlying systemic conditions. The severity of hepatic events and/or their outcome may be worse in patients with active or chronic liver disease. Treatment with Lamisil (Terbinafine) Oral Granules should be discontinued if biochemical or clinical evidence of liver injury develops.
Lamisil (Terbinafine) Oral Granules are not recommended for patients with chronic or active liver disease. Before prescribing Lamisil (Terbinafine) Oral Granules, pre-existing liver disease should be assessed. Hepatotoxicity may occur in patients with and without pre-existing liver disease. Pretreatment serum transaminase (ALT and AST) tests are advised for all patients before taking Lamisil (Terbinafine) Oral Granules. Patients prescribed Lamisil (Terbinafine) Oral Granules and/or their guardians should be warned to report immediately to their physician any symptoms of persistent nausea, anorexia, fatigue, vomiting, right upper abdominal pain or jaundice, dark urine or pale stools. Patients with these symptoms should discontinue taking Lamisil (Terbinafine) Oral Granules, and the patient’s liver function should be immediately evaluated.
Taste disturbance, including taste loss, has been reported with the use of terbinafine. It can be severe enough to result in decreased food intake, weight loss, and depressive symptoms. Taste disturbance may resolve within several weeks after discontinuation of treatment, but may be prolonged (greater than one year), or may be permanent. If symptoms of a taste disturbance occur, Lamisil (Terbinafine) Oral Granules should be discontinued.
Smell disturbance, including loss of smell, has been reported with the use of Lamisil (Terbinafine) Tablets. Smell disturbance may resolve after discontinuation of treatment, but may be prolonged (greater than one year), or may be permanent. If symptoms of a smell disturbance occur, Lamisil (Terbinafine) Oral Granules should be discontinued.
Depressive symptoms have occurred during post-marketing use of terbinafine. Prescribers should be alert to depressive symptoms, and patients should be instructed to report depressive symptoms to their physician.
Lamisil (Terbinafine)
Lamisil (Terbinafine) . Drug Interactions
In vivo
max
In vitro
In vivo
The influence of terbinafine on the pharmacokinetics of fluconazole, cotrimoxazole (trimethoprim and sulfamethoxazole), zidovudine or theophylline was not considered to be clinically significant.
Co-administration of a single dose of fluconazole (100 mg) with a single dose of terbinafine resulted in a 52% and 69% increase in terbinafine C and AUC, respectively. Fluconazole is an inhibitor of CYP2C9 and CYP3A enzymes. Based on this finding, it is likely that other inhibitors of both CYP2C9 and CYP3A4 (e.g., ketoconazole, amiodarone) may also lead to a substantial increase in the systemic exposure (C and AUC) of terbinafine when concomitantly administered.
There have been spontaneous reports of increase or decrease in prothrombin times in patients concomitantly taking oral terbinafine and warfarin, however, a causal relationship between terbinafineand these changes has not been established.
Terbinafine clearance is increased 100% by rifampin, a CYP450 enzyme inducer, and decreased 33% by cimetidine, a CYP450 enzyme inhibitor. Terbinafine clearance is unaffected by cyclosporine. There is no information available from adequate drug-drug interaction studies with the following classes of drugs: oral contraceptives, hormone replacement therapies, hypoglycemics, phenytoins, thiazide diuretics, and calcium channel blockers.
Lamisil (Terbinafine) Use In Specific Populations
Pregnancy Category B.
There are no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, and because treatment of tinea capitis can be postponed until after pregnancy is completed, it is recommended that Lamisil (Terbinafine) (terbinafine hydrochloride) Oral Granules not be initiated during pregnancy.
Oral reproduction studies have been performed in rabbits and rats at doses up to 300 mg/kg/day [12x to 23x the Maximum Recommended Human Dose (MRHD), in rabbits and rats, respectively, based on body surface area (BSA) comparisons] and have revealed no evidence of impaired fertility or harm to the fetus due to terbinafine.
Lamisil (Terbinafine) overdosage
Clinical experience regarding overdose with oral terbinafine is limited. Doses up to 5 grams in adults (20 times the therapeutic daily adult dose) have been reported without inducing serious adverse reactions. The symptoms of overdose included nausea, vomiting, abdominal pain, dizziness, rash, frequent urination, and headache.
Lamisil (Terbinafine) description
Lamisil (Terbinafine) (terbinafine hydrochloride) Oral Granules 125 mg and 187.5 mg contain the synthetic allylamine antifungal compound, terbinafine hydrochloride.
Chemically, terbinafine hydrochloride is (E)--(6,6-dimethyl-2-hepten-4-ynyl)--methyl-1-naphthalenemethanamine hydrochloride. It has the empirical formula CHClN with a molecular weight of 327.90, and the following structural formula:
Terbinafine hydrochloride is a white to off-white fine crystalline powder. It is freely soluble in methanol and methylene chloride, soluble in ethanol, and slightly soluble in water.
Each packet of Lamisil (Terbinafine) Oral Granules contains:
Lamisil (Terbinafine) clinical Pharmacology
The pharmacokinetics in children 4 to 8 years of age with tinea capitis was investigated in a pharmacokinetic study after single and repeated (for 42 days) oral administration of Lamisil (Terbinafine) Oral Granules (N=16), once daily, using the body weight groups and doses described in section 2.2. The systemic exposure (C and AUC) of terbinafine in children had a relatively high inter-individual variability (ranging from 36% to 64%). At steady state the AUC increased by a mean factor of 1.9 to 2.1 across doses. The mean (SD) effective half-life obtained from the observed accumulation was 26.7 (13.8) hrs and 30.5 (9.3) hrs for the 125 mg and 187.5 mg doses, respectively.
Systemic exposure to terbinafine in the children did not exceed the highest values of the systemic exposure in adults receiving repeated once daily doses of 250 mg Lamisil (Terbinafine) (terbinafine hydrochloride) Tablets. A population pharmacokinetic evaluation of oral terbinafine that included children 4-12 years of age and adults 18-45 years of age (N=113) found that clearance (CL/F) of terbinafine is dependent on body weight in a nonlinear manner. For a typical child of 25 kg CL/F was predicted to be 19 L/h and for a typical adult of 70 kg body weight it was predicted to be 27 L/h. Over the weight range for pediatric patients included in the analysis (14.1 kg-68 kg), the predicted CL/F ranged between 15.6-26.7 L/hr. In plasma, terbinafine is >99% bound to plasma proteins. Prior to excretion, terbinafine is rapidly and extensively metabolized by at least seven 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. In adult patients with renal impairment (creatinine clearance ≤50 mL/min) or hepatic cirrhosis, the clearance of terbinafine is decreased by approximately 50% compared to normal volunteers
Terbinafine, an allylamine antifungal, inhibits biosysnthesis 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. Depending on the concentration of the drug and the fungal species tested , terbinafine may be fungicidal. However, the clinical significance of data is unknown.
Lamisil (Terbinafine) Oral Granules has been studied in tinea capitis [see ]
Lamisil (Terbinafine) Nonclinical Toxicology
In a 28-month oral carcinogenicity study in rats, an increase in the incidence of liver tumors was observed in males at the highest dose tested, 69 mg/kg/day (2x the MRHD based on AUC comparisons of the parent terbinafine); however, even though dose-limiting toxicity was not achieved at the highest tested dose, higher doses were not tested.
The results of a variety of (mutations in and , DNA repair in rat hepatocytes, mutagenicity in Chinese hamster fibroblasts, chromosome aberration and sister chromatid exchanges in Chinese hamster lung cells), and (chromosome aberration in Chinese hamsters, micronucleus test in mice) genotoxicity tests gave no evidence of a mutagenic or clastogenic potential.
Oral reproduction studies in rats at doses up to 300 mg/kg/day (approximately 12x the MRHD based on BSA comparisons) did not reveal any specific effects on fertility or other reproductive parameters. Intravaginal application of terbinafine hydrochloride at 150 mg/day in pregnant rabbits did not increase the incidence of abortions or premature deliveries nor affect fetal parameters.
A wide range of studies in mice, rats, dogs, and monkeys, and studies using rat, monkey, and human hepatocytes suggest that peroxisome proliferation in the liver is a rat-specific finding. However, other effects, including increased liver weights and APTT, occurred in dogs and monkeys at doses giving C trough levels of the parent terbinafine 2-3x those seen in humans at the MRHD. Higher doses were not tested.
In a 52-week oral toxicology study conducted in juvenile maturing dogs, increased heart and liver weights were noted in males and signs of CNS disturbance including 3 cases of single episodes of seizures were noted in females at the highest dose tested, 100 mg/kg/day [19x (males) and 10x (females) the MRHD based on AUC comparisons of the parent terbinafine]. No treatment related findings were noted at 30 mg/kg/day [1.6x (males) and 1.9x (females) the MRHD based on AUC comparisons of the parent terbinafine] in this study.
Lamisil (Terbinafine) Clinical Studies
Two randomized, multinational trials were conducted to investigate the safety and efficacy of Lamisil (Terbinafine) (terbinafine hydrochloride) Oral Granules in the treatment of subjects 4 to 12 years old with tinea capitis. Lamisil (Terbinafine) Oral Granules was dosed based on body weight. Griseofulvin dosed at 10-20 mg/kg was used as a comparator. Subjects were dosed for 6 weeks and followed for an additional 4 weeks.
The two trials enrolled 50% of subjects from the U.S. Additionally, among those with positive cultures, 65% and 54% of infections were due to , and 19% and 17% due to inStudies 1 and 2, respectively.
The primary efficacy endpoint was the proportion of subjects with complete cure (negative KOH, negative culture and absence of clinical signs of infection) at week 10. Table 3 below lists the efficacy results for Studies 1 and 2 overall and according to the dermatophyte species ( or Other).
Lamisil (Terbinafine) How Supplied/storage And Handling
Lamisil (Terbinafine) Oral Granules are supplied in cartons containing 14 laminated aluminum packets. Each packet contains approximately either 30 or 45 off-white to yellowish, round, biconvex, film-coated granules, corresponding to a single total dose of 125 mg or 187.5 mg (terbinafine base equivalent) per packet.
Pack of 3 cartons each containing 14 packets (42 packets).........NDC 0078-0499-59
Pack of 3 cartons each containing 14 packets (42 packets)..........NDC 0078-0500-59
Storage conditions of Lamisil (Terbinafine) Oral Granules 125 mg and 187.5 mg: Store at 25°C (77°F); excursions permitted to 15–30°C (59–86°F) [see USP Controlled Room Temperature].
Lamisil (Terbinafine) Patient Counseling Information
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Patients taking Lamisil (Terbinafine) (terbinafine hydrochloride) Oral Granules should receive the following information and instructions:
• Patients should be informed that Lamisil (Terbinafine) Oral Granules should be taken once a day with food. Patients should sprinkle the contents of each packet on a spoonful of pudding or other soft, non-acidic food such as mashed potatoes and swallow the entire spoonful; applesauce or fruit-based foods should not be used. The combination of food and granules should be swallowed without chewing. If two packets are required with each dose, the patient may either sprinkle the content of both packets on one spoonful of non-acidic food, or sprinkle the contents of both packets on two spoonfuls of non-acidic food as directed above.
•Patients prescribed Lamisil (Terbinafine) Oral Granules and/or their guardian should be warned to report immediately to their physician any symptoms of persistent nausea, anorexia, fatigue, vomiting, right upper abdominal pain, jaundice, dark urine or pale stools. Lamisil (Terbinafine) Oral Granules treatment should be discontinued.
• Patients and/or their guardian should be advised to report to their physician any signs of taste disturbance, smell disturbance and/or depressive symptoms. Lamisil (Terbinafine) Oral Granules treatment should be discontinued.
• Patients should be advised to immediately report to their physician or get emergency help if they experience any of the following symptoms: hives, mouth sores, blistering and peeling of skin, swelling of face, lips, tongue, or throat, difficulty swallowing or breathing. Lamisil (Terbinafine) Oral Granules treatment should be discontinued.
• Patients should be advised to report to their physician any symptoms of new onset or worsening lupus erythematosus. Symptoms can include erythema, scaling, loss of pigment, and unusual photosensitivity that can result in a rash. Lamisil (Terbinafine) Oral Granules treatment should be discontinued.
• Patients should be informed that if a progressive skin rash occurs, treatment with Lamisil (Terbinafine) Oral Granules should be discontinued.
• Photosensitivity reactions have been reported with the use of Lamisil (Terbinafine) . Patients should be advised to minimize exposure to natural and artificial sunlight (tanning beds or UVA/B treatment) while using Lamisil (Terbinafine) .
• Measurement of serum transaminases (ALT and AST) is advised for all patients before taking Lamisil (Terbinafine) Oral Granules.
• Patients should be advised that if they take too many Lamisil (Terbinafine) Oral Granules they should call their physician.
T2011-130
Lamisil (Terbinafine)
Lamisil (Terbinafine)
Lamisil (Terbinafine)
