Lamisil Side Effects, and Drug Interactions - Terbinafine Hcl

Lamisil Side Effects, and Drug Interactions - Terbinafine Hcl

SIDE EFFECTS

The most frequently reported adverse events observed in the three US/Canadian placebo-controlled trials are listed in the table below. The adverse events reported encompass gastrointestinal symptoms (including diarrhea, dyspepsia, and abdominal pain), liver test abnormalities, rashes, urticaria, pruritus, and taste disturbances. In general, the adverse events were mild, transient, and did not lead to discontinuation from study participation.

Rare adverse events, based on worldwide experience with LAMISIL^® (terbinafine hydrochloride tablets) Tablets use, include: idiosyncratic and symptomatic hepatic injury and more rarely, cases of liver failure, some leading to death or liver transplant, (see WARNINGS and PRECAUTIONS), serious skin reactions (see WARNINGS), severe neutropenia (see PRECAUTIONS), thrombocytopenia and allergic reactions (including anaphylaxis). Uncommonly, LAMISIL^® may cause taste disturbance (including taste loss) which usually recovers within several weeks after discontinuation of the drug. There have been isolated reports of prolonged (greater than one year) taste disturbance. Rarely, taste disturbances associated with oral terbinafine have been reported to be severe enough to result in decreased food intake leading to significant and unwanted weight loss.

Other adverse reactions which have been reported include malaise, fatigue, vomiting, arthralgia, myalgia, and hair loss.

Clinical adverse effects reported spontaneously since the drug was marketed include altered prothrombin time (prolongation and reduction) in patients concomitantly treated with warfarin and LAMISIL^® (terbinafine hydrochloride tablets) Tablets and agranulocytosis (rare).

In vitro studies with human liver microsomes showed that terbinafine does not inhibit the metabolism of tolbutamide, ethinylestradiol, ethoxycoumarin, and cyclosporine. In vitro studies have also shown that terbinafine inhibits CYP2D6-mediated metabolism. This may be of clinical relevance for compounds predominantly metabolized by this enzyme, such as tricyclic antidepressants, ß-blockers, selective serotonin reuptake inhibitors (SSRIs), and monoamine oxidase inhibitors (MAO-Is) Type B, if they have a narrow therapeutic window.

In vivo drug-drug interaction studies conducted in normal volunteer subjects showed that terbinafine does not affect the clearance of antipyrine or digoxin. Terbinafine decreases the clearance of caffeine by 19%. Terbinafine increases the clearance of cyclosporine by 15%.

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 LAMISIL^® Tablets and 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, theophyllines, phenytoins, thiazide diuretics, beta blockers, and calcium channel blockers.