Included as part of the PRECAUTIONS section.
Cases of liver failure, some leading to liver transplant
or death, have occurred with the use of Lamisil Tablets in individuals with and
without preexisting liver disease.
In the majority of liver cases reported in association
with use of Lamisil Tablets, 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 Tablets
should be discontinued if biochemical or clinical evidence of liver injury
Lamisil Tablets are not recommended for patients with
chronic or active liver disease. Before prescribing Lamisil Tablets, liver
function tests should be performed since hepatotoxicity may occur in patients
with and without pre-existing liver disease. Periodic monitoring of liver
function tests is recommended. Lamisil should be immediately discontinued in
case of elevation of liver function tests. Patients prescribed Lamisil 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. Patients with these symptoms should
discontinue taking oral terbinafine, and the patientÃ¢â¬™s liver function should be
Taste Disturbance Including Loss of Taste
Taste disturbance, including taste loss, has been
reported with the use of Lamisil 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, Lamisil Tablets should be discontinued.
Smell Disturbance Including Loss Of Smell
Smell disturbance, including loss of smell, has been
reported with the use of Lamisil 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, Lamisil Tablets
should be discontinued.
Depressive symptoms have occurred during postmarketing
use of Lamisil Tablets. Prescribers should be alert to the development of
depressive symptoms, and patients should be instructed to report depressive
symptoms to their physician.
Transient decreases in absolute lymphocyte counts (ALCs)
have been observed in controlled clinical trials. In placebo-controlled trials, 8/465 subjects
receiving Lamisil Tablets (1.7%) and 3/137 subjects receiving placebo (2.2%)
had decreases in ALC to below 1000/mm³ on 2 or more occasions. In patients with
known or suspected immunodeficiency, physicians should consider monitoring
complete blood counts if treatment continues for more than 6 weeks. Cases of
severe neutropenia have been reported. These were reversible upon
discontinuation of Lamisil Tablets, 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/mm³,
Lamisil Tablets should be discontinued and supportive management started.
Serious Skin/Hypersensitivity Reactions
There have been postmarketing reports of serious
skin/hypersensitivity reactions [e.g., Stevens-Johnson Syndrome, toxic
epidermal necrolysis, erythema multiforme, exfoliative dermatitis, bullous
dermatitis, and drug reaction with eosinophilia and systemic symptoms (DRESS)
syndrome]. Manifestations of DRESS syndrome may include cutaneous reaction
(such as rash or exfoliative dermatitis), eosinophilia, and one or more organ
complications such as hepatitis, pneumonitis, nephritis, myocarditis, and pericarditis.
If progressive skin rash or signs/symptoms of the above drug reactions occur,
treatment with Lamisil Tablets should be discontinued.
During postmarketing experience, precipitation and
exacerbation of cutaneous and systemic lupus erythematosus have been reported
in patients taking Lamisil Tablets. Lamisil Tablets should be discontinued in
patients with clinical signs and symptoms suggestive of lupus erythematosus.
Measurement of serum transaminases (ALT and AST) is
advised for all patients before taking Lamisil Tablets.
Patient Counseling Information
See FDA-Approved Patient Labeling (PATIENT INFORMATION)
Patients taking Lamisil Tablets should receive the
following information and instructions:
- Advise patients 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 Tablets treatment should be
- Advise patients to immediately report to their physician any
symptoms of persistent nausea, anorexia, fatigue, vomiting, right upper
abdominal pain, jaundice, dark urine, or pale stools. Lamisil Tablets treatment
should be discontinued.
- Advise patients to report to their physician any signs of
taste disturbance, smell disturbance and/or depressive symptoms, fever, skin
eruption, lymph node enlargement, erythema, scaling, loss of pigment, and
unusual photosensitivity that can result in a rash. Lamisil Tablets treatment
should be discontinued.
- Advise patients to minimize exposure to natural and
artificial sunlight (tanning beds or UVA/B treatment) while using Lamisil
- Advise patients that if they forget to take Lamisil
Tablets, to take their tablets as soon as they remember, unless it is less than
4 hours before the next dose is due. Advise patients to call their physician if
they take too many Lamisil Tablets.
Carcinogenesis, Mutagenesis, Impairment Of Fertility
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 in vitro (mutations in E.
coli and S. typhimurium, DNA repair in rat hepatocytes, mutagenicity
in Chinese hamster fibroblasts, chromosome aberration, and sister chromatid exchanges
in Chinese hamster lung cells), and in vivo (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
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 onychomycosis can be postponed
until after pregnancy is completed, it is recommended that Lamisil Tablets 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.
After oral administration, terbinafine is present in
breast milk of nursing mothers. The ratio of terbinafine in milk to plasma is
7:1. Treatment with Lamisil Tablets is not recommended in women who are
The safety and efficacy of Lamisil Tablets have not been
established in pediatric patients with onychomycosis.
Clinical studies of Lamisil Tablets did not include
sufficient numbers of subjects aged 65 years and over to determine whether they
respond differently from younger subjects. Other reported clinical experience
has not identified differences in responses between the elderly and younger
patients. In general, dose selection for an elderly patient should be cautious,
usually starting at the low end of the dosing range, reflecting the greater
frequency of decreased hepatic, renal, or cardiac function, and of concomitant
disease or other drug therapy.
In patients with renal impairment (creatinine clearance
less than or equal to 50 mL/min) the use of Lamisil Tablets has not been