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| Medication |
Strength |
Quantity |
| Lamisil (terbinafine - generic) |
250 mg |
30 |
Lamisil
Terbinafine HCl
Lamisil - Lamisil Side Effects - Lamisil Information
Pharmacology: Terbinafine is an allylamine which has a broad spectrum of antifungal activity. At low concentrations terbinafine is fungicidal against dermatophytes, molds and certain dimorphic fungi. Its activity against yeasts is fungicidal or fungistatic, depending on the species.
Terbinafine interferes specifically with fungal sterol biosynthesis by inhibition of squalene epoxidase in the fungal cell membrane. Its inhibition leads to a deficiency in ergosterol and to an intracellular accumulation of squalene, resulting in fungal cell death. When given orally, the drug concentrates rapidly in skin, hair and nails at levels associated with fungicidal activity.
The cream and spray have rapid onsets of action, concentrate in skin, and can be effective with short durations of treatment.
Pharmacokinetics: Oral: A single 250 mg oral dose of terbinafine tablets results in a peak plasma concentration of 0.97 µg/mL within 2 hours after administration. Seventy percent of the dose is absorbed by the gastrointestinal tract. The absorption half-life is 0.8 hours and the distribution half-life is 4.6 hours. The peak plasma concentration and bioavailability (AUC) roughly double when steady state is reached at 10 to 14 days. The bioavailability of terbinafine is moderately increased (20%) by food, but not sufficiently to require dosing adjustments.
Terbinafine binds strongly to plasma proteins (99%) and is lipophilic. Terbinafine is widely distributed in the body including adipose tissue. It rapidly diffuses through the dermis and concentrates in lipophilic stratum corneum. It is also secreted in sebum, thus achieving high concentrations in hair follicles, hair and sebum-rich skin. There is evidence that terbinafine is distributed in the nail plate within the first few weeks of commencing therapy.
Oral terbinafine is excreted mainly in urine (80%) and in feces (20%). Following absorption terbinafine is metabolised rapidly and extensively by the liver. At least 7 cytochrome P450 isoenzymes are involved in its metabolism with major contributions from CYP2C9, CYP1A2, CYP3A4, CYP2C8 and CYP2C19. Terbinafine inhibits, but is not metabolized by CYP2D6. Biotransformation is nearly complete and results in at least 15 identified metabolites all of which are excreted in the urine and lack antifungal activity. The plasma elimination half-life is 17 hours and the terminal half-life in stratum corneum, nail, hair, dermis and epidermis ranges from 22 to 28 days. Higher plasma concentrations were noted in older adults and in hypertensives and lower concentrations were noted in smokers.
Following a single 250 mg dose in 12 hepatically impaired cirrhotic (alcoholic) patients, total clearance of terbinafine was reduced by about 40%. In a sample of 12 renally impaired patients (median creatinine clearance of 17.6 mL/min), terbinafine clearance following a single 250 mg dose was halved resulting in the doubling or more of peak plasma concentrations or AUC. Patients at the highest and lowest ends of the renal impairment spectrum were not represented. There was no direct correlation between creatinine clearance and terbinafine clearance in renally impaired patients, the metabolism of the drug having been impaired in these patients due to competition between metabolite and parent drug.
Topical: Less than 5% of the dose is absorbed after topical application to humans; systemic exposure is thus very slight.
Indications: The treatment of fungal infections of the skin and nails caused by dermatophytes such as Trichophyton (e.g., T. rubrum, T. mentagrophytes, T. verrucosum, T. violaceum), M. canis, E. floccosum , and yeasts of the genus Candida (e.g., C. albicans ), as well as M. furfur.
Oral: Prior to initiating treatment with terbinafine tablets, appropriate nail or skin specimens should be obtained for laboratory testing (KOH preparation, fungal culture, or nail biopsy) in order to confirm the diagnosis of onychomycosis or dermatomycosis.
Oral terbinafine is indicated in the treatment of onychomycosis (fungal infection of the nail) caused by dermatophyte fungi.
Where oral therapy is considered appropriate owing to the site, severity or extent of the infection, terbinafine tablets may also be indicated in the treatment of tineal skin infections (tinea corporis, tinea cruris and tinea pedis).
Note: Oral terbinafine is not effective in pityriasis versicolor.
Topical: Cream: Terbinafine cream is indicated in the treatment of fungal infections of the skin caused by dermatophytes such as trichophyton, as well as yeast infections of the skin, principally those caused by the genus Candida (e.g., C. albicans ).
The cream is also indicated in the treatment of pityriasis (tinea) versicolor due to M. furfur .
Spray: The spray is indicated in the treatment of fungal infections of the skin caused by dermatophytes such as trichophyton.
The spray is also indicated in the treatment of pityriasis (tinea) versicolor due to M. furfur .
Note: Topical terbinafine is not effective in onychomycosis.
Contraindications: In patients with a hypersensitivity to terbinafine or any of the excipients (see Supplied).
Warnings: Rare cases of liver failure, some leading to death or liver transplant, have occurred with the use of terbinafine tablets for the treatment of onychomycosis and dermatomycosis in individuals with and without pre-existing liver disease.
In the majority of liver cases reported in association with terbinafine use, the patients had serious underlying systemic conditions and an uncertain causal association with terbinafine. The severity of hepatic events and/or their outcome may be worse in patients with active or chronic liver disease (see Precautions). Treatment with terbinafine tablets should be discontinued if biochemical or clinical evidence of liver injury develops (see Precautions).
There have been isolated reports of serious skin reactions (e.g., Stevens-Johnson syndrome and toxic epidermal necrolysis). If progressive skin rash occurs, treatment with terbinafine should be discontinued.
Isolated cases of blood dyscrasias have been reported in patients treated with terbinafine.
Precautions: General: Terbinafine tablets are not recommended for patients with chronic or active liver disease. Before prescribing terbinafine tablets, 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 terbinafine tablets. Patients prescribed terbinafine tablets 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 (see Warnings). Patients with these symptoms should discontinue taking oral terbinafine, and the patient's liver function should be immediately evaluated.
In patients with renal impairment (creatinine clearance £50 mL/min), the use of terbinafine has not been adequately studied, and therefore, is not recommended (see Pharmacology, Pharmacokinetics).
Changes in the ocular lens and retina have been reported following the use of terbinafine tablets in controlled trials. The clinical significance of these changes is unknown.
Transient decreases in absolute lymphocyte counts (ALC) have been observed in controlled clinical trials. The clinical significance of this observation is unknown. However, in patients with known or suspected immunodeficiency, physicians should consider monitoring complete blood counts in individuals using terbinafine therapy for greater than 6 weeks.
Isolated cases of severe neutropenia have been reported. These were reversible upon discontinuation of terbinafine, with or without supportive therapy. If clinical signs and symptoms suggestive of secondary infection occur, a complete blood count should be obtained. If the neutrophil count is £1000 cells/mm 3, terbinafine should be discontinued and supportive management started.
Terbinafine should be kept out of the reach of children.
Terbinafine cream and spray are for external use only. Contact with the eyes should be avoided. Terbinafine spray should not be used on the face.
In the case of accidental ocular contact, the eyes should be rinsed thoroughly with running water and patients should consult a physician if any symptoms persist. In case of accidental inhalation, patients should be advised to consult a physician if any symptoms develop and persist. Terbinafine spray should be used with caution in patients with lesions where alcohol could be irritating.
Pregnancy and Lactation: Though fetal toxicity and fertility studies have shown no adverse effects in animals, there is only very limited clinical experience with terbinafine in pregnant women; therefore, unless the potential benefits outweigh any potential risks, oral terbinafine should not be used during pregnancy.
Terbinafine is excreted in breast milk; therefore mothers receiving oral treatment with terbinafine should not breast-feed. However, with the cream and spray treatment, the small amounts absorbed through the skin are unlikely to affect the infant. Nursing mothers should avoid application of terbinafine topical formulations to the breast.
Geriatrics: Plasma concentrations and drug half-life appear to be slightly higher in elderly patients than in the general population. In addition, the incidence of all adverse events in a postmarketing surveillance study appeared to be slightly higher at normal adult doses; however, the overall rate of adverse events possibly or probably related to terbinafine did not appear to be different compared to the general population. When prescribing tablets for patients in this age group, the possibility of pre-existing impairment of liver or kidney function should be considered (see Pharmacology, Pharmacokinetics: Oral).
Children: The safety and efficacy of terbinafine have not been established in pediatric patients.
Drug Interactions : Tablets: Many categories of drugs are known to inhibit or induce drug metabolism by cytochrome P450 (CYP) enzymes located in the liver and intestine. Coadministration of such drugs may impact metabolic elimination of drugs and, in some cases, bioavailability may be either increased or decreased and possibly necessitate dosage adjustments.
Results from in vitro experiments and in vivo studies in healthy volunteers suggest that, in general, there is a low potential for terbinafine inhibition or induction of the elimination of drugs metabolised by various CYP isoenzymes (e.g., coumarin [warfarin], ethinyl estradiol, cyclosporine, terfenadine, triazolam, and tolbutamide). Some cases of menstrual irregularities and pregnancies have been reported in patients taking terbinafine concomitantly with oral contraceptives; however, the rate of occurrence appears to be within the background incidence for patients taking oral contraceptives alone.
In vitro and clinical studies, however, have shown that terbinafine is a potent inhibitor of the ethnically polymorphic CYP2D6 isoenzyme, which is responsible for the metabolism of a wide variety of drugs. Caution should be exercised in patients receiving concomitant therapy with drugs metabolized by CYP2D6, especially those with a narrow therapeutic window. This includes, but is not limited to, tricyclic and serotonin-reuptake inhibitor antidepressants (e.g., desipramine, fluvoxamine), antihypertensives such as b 1-adrenergic blocking agents (e.g. metoprolol, propranolol), certain antiarrhythmic agents (e.g., flecainide, propafenone), MAOI type B (e.g., selegiline) and antipsychotics (e.g. chlopromazine, haloperidol). For such drugs, which are metabolized by CYP2D6, and where therapeutic activity is dependent upon the parent compound, an increased effect (or toxicity) may be produced. In contrast, for compounds such as codeine, where a metabolite is primarily responsible for drug action, a decrease in therapeutic effect may be realized.
Because multiple CYP enzyme pathways are involved in the metabolism of terbinafine, alternate pathways are available if one is inhibited by a competing substrate. Therefore, it is expected that few interactions will occur that result in significant increases in terbinafine plasma concentrations. However, the plasma clearance of oral terbinafine has been shown to be increased by inducers of CYP enzyme metabolism (CL increased 100% by rifampin) and decreased by inhibitors (CL decreased 33% by cimetidine; and 42% by fluconazole). Where coadministration of such drugs is necessary terbinafine dosage may need to be adjusted accordingly.
Terbinafine coadministration has been reported to reduce plasma clearance of caffeine by 19% and of theophylline by 14%.
Cream and Spray: No drug interactions are known to date.
Carcinogenesis: An increase in liver tumors was observed in male rats at the highest dose level (69 mg/kg) during a life-time (123 weeks) carcinogenicity study. The changes included increased enzyme activity, peroxisome proliferation and altered triglyceride metabolism. The changes have been shown to be species specific since they were not seen in mice or monkeys.
Adverse Effects: Frequency estimate: very common ³10%, common ³1% to <10%, uncommon ³0.1% to <1%, rare ³0.01% to <0.1%, very rare <0.01%.
Tablets: In general terbinafine is well tolerated. Side effects are usually mild to moderate in severity and transient.
In clinical trials submitted for purposes of marketing approval in Canada adverse events occurred in 10.4% of patients receiving the recommended oral dose. Of these, 5% were mild to moderate gastrointestinal events (feeling of fullness, loss of appetite, dyspepsia, nausea, mild abdominal pain, diarrhea), 3% were nonserious forms of skin reactions (rash, urticaria) and the remainder were for musculoskeletal reactions (arthralgia, myalgia) and miscellaneous nonspecific events such as malaise or tiredness.
Adverse events not frequently observed include the following: Uncommon: Taste disturbances, including taste loss, which usually recover within several weeks after discontinuation of the drug were reported.
Rare: Idiosyncratic and symptomatic hepatobiliary reactions (2/3 primarily cholestatic in nature and the remainder involving hepatocytic damage or both) have been reported in association with terbinafine treatment, including very rare cases of liver failure (some leading to liver transplant or death). Unspecific prodromal symptoms (nausea, anorexia, fatigue, general malaise) have been reported. Liver enzyme increases have been noted in asymptomatic patients as well as in patients with more specific symptoms of hepatic dysfunction (jaundice, upper abdominal right quadrant pain, pruritus, pale stools, dark urine) (see Warnings and Precautions).
The frequency of reported apparent hepatic dysfunctions has varied. An analysis of 7 key placebo-controlled trials (262 placebo vs 1624 terbinafine patients) suggested increases of 1.4% vs 3.4% in liver function test indicators (APase, AST, ALT, g-GT, bilirubin >2x above upper normal). In a European postmarketing study in 25 884 patients, asymptomatic liver enzyme increases were reported in 0.17% of patients treated. The reporting frequency for symptomatic liver disorder possibly related to terbinafine was 1:13 000. The relative risk of acute liver injury in this group was considered to be 4.2 times the background incidence. In the less controlled circumstances of spontaneous worldwide reporting, the development of clinically significant signs and symptoms of hepatobiliary dysfunction for which no other cause was apparent, and in which terbinafine was considered the possible causative agent was calculated to be approximately 1:37 000 treated patients. The reporting frequency overall for hepatobiliary events including elevations in liver enzymes was 1:15 000. Very rare cases of liver failure, some fatal, have been associated with terbinafine treatment and the incidence rate is about 1:1 000 000 exposed patients.
Oral terbinafine has been rarely associated with systemic allergic reactions including urticaria, angioedema, arthralgia, arthritis and serum-sickness like reactions.
Very rare: Serious skin reactions (e.g., Stevens-Johnson syndrome, toxic epidermal necrolysis and erythema multiforme) and anaphylactic reactions have been reported.
Hair loss has been reported, however, a causal relationship has not been established.
Hematological disorders such as neutropenia, agranulocytosis, pancytopenia and thrombocytopenia have been reported. Very rare cases of thrombotic thrombocytopenic purpura (TTP) have been reported. The mechanism of TTP induction and the role of terbinafine have not been elucidated.
Isolated cases of photosensitivity have been reported in association with terbinafine.
Cream and Spray: Redness, itching, stinging may occur at the site of application; however, treatment rarely has to be discontinued for this reason. These minor symptoms must be distinguished from allergic reactions (e.g., widespread rash and/or redness, urticaria, angioedema, or positive rechallenge) which are rare but require discontinuation of the drug. In clinical trials, adverse reactions were recorded in 33 of the 1757 (1.8%) patients who received terbinafine cream, and in 39 of the 898 (4.3%) patients who received the terbinafine spray.
Overdose: Symptoms and Treatment: A few cases of overdosage with Lamisil tablets (up to 5 g) have been reported giving rise to headache, nausea, epigastric pain and dizziness. The recommended treatment of overdosage consists of eliminating the drug, primarily by the administration of activated charcoal and giving symptomatic supportive therapy, if needed.
No case of overdosage has been reported with terbinafine cream or spray. Should, however, terbinafine cream or spray be inadvertently ingested, adverse effects similar to those observed with an overdosage of terbinafine tablets are to be expected. The alcohol content of the spray (28.8% v/v) has to be taken into account.
Dosage: Oral: Tablets: Adults: 250 mg once daily.
Relief of clinical symptoms usually occurs within a few days. Irregular use or premature discontinuation of treatment increases the risk of recurrence. If there are no signs of improvement after 2 weeks the diagnosis should be verified.
Information for the Patient: See Blue Section--Information for the Patient Lamisil Tablets.
Supplied: Cream: Each g of white, smooth, glossy cream contains: terbinafine HCl 10 mg. Nonmedicinal ingredients: benzyl alcohol, cetyl alcohol, cetyl palmitate, isopropyl myristate, polysorbate 60, purified water, sodium hydroxide, sorbitan monostearate and stearyl alcohol. Tubes of 30 g. Store at temperatures between 15 and 30°C.
Spray: Each g of clear solution contains: terbinafine HCl 10 mg. Nonmedicinal ingredients: cetomacrogol 1000, ethanol, propylene glycol and water. Alcohol: 28.8% v/v. Bottles of 30 mL. Store at temperatures between 15 and 30°C.
Tablets: Each round, whitish/yellow uncoated tablet, scored on one side and embossed Lamisil 250, contains: terbinafine 250 mg, present as the hydrochloride salt. Nonmedicinal ingredients: cellulose microcrystalline, magnesium stearate, methylhydroxypropylcellulose, silica, colloidal anhydrous and sodium carboxymethyl starch. Blister strips of 14, cartons of 14 and 28. Store at temperatures between 15 and 30°C. Protect from light.
IMPORTANT NOTE: THE FOLLOWING INFORMATION IS INTENDED TO SUPPLEMENT, NOT SUBSTITUTE FOR, THE EXPERTISE AND JUDGMENT OF YOUR PHYSICIAN, PHARMACIST OR OTHER HEALTHCARE PROFESSIONAL. IT SHOULD NOT BE CONSTRUED TO INDICATE THAT USE OF THE DRUG IS SAFE, APPROPRIATE, OR EFFECTIVE FOR YOU. CONSULT YOUR HEALTHCARE PROFESSIONAL BEFORE USING THIS DRUG.
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