A1,
A2,
B,
C1,
C2,
D,
E,
F,
G-H,
I-K,
L,
M,
N,
O,
P1,
P2,
Q-R,
S,
T,
U-V,
W-Z
Thalomid Warnings, Precautions, Pregnancy, Nursing, Abuse - Thalidomide
Thalomid Warnings, Precautions, Pregnancy, Nursing, Abuse - Thalidomide
WARNINGS
(See BOXED WARNINGS.)
Birth defects : Thalidomide can cause severe birth defects in humans. (See BOXED WARNINGS and CONTRAINDICATIONS.) Patients should be instructed to take thalidomide only as prescribed and not to share their thalidomide with anyone else. Because thalidomide is present in the semen of patients receiving the drug, males receiving thalidomide must always use a latex condom during any sexual contact with women of childbearing potential. The risk to the fetus from the semen of male patients taking thalidomide is unknown.
Drowsiness and Somnolence : Thalidomide frequently causes drowsiness and somnolence. Patients should be instructed to avoid situations where drowsiness may be a problem and not to take other medications that may cause drowsiness without adequate medical advice. Patients should be advised as to the possible impairment of mental and/or physical abilities required for the performance of hazardous tasks, such as driving a car or operating other complex or dangerous machinery.
Peripheral Neuropathy : Thalidomide is known to cause nerve damage that may be permanent. Peripheral neuropathy is a common, potentially severe, side effect of treatment with thalidomide that may be irreversible. Peripheral neuropathy generally occurs following chronic use over a period of months; however, reports following relatively short-term use also exist. The correlation with cumulative dose is unclear. Symptoms may occur some time after thalidomide treatment has been stopped and may resolve slowly or not at all. Few reports of neuropathy have arisen in the treatment of ENL despite long-term thalidomide treatment. However, the inability clinically to differentiate thalidomide neuropathy from the neuropathy often seen in Hansen’s disease makes it difficult to determine accurately the incidence of thalidomide-related neuropathy in ENL patients treated with thalidomide.
Patients should be examined at monthly intervals for the first 3 months of thalidomide therapy to enable the clinician to detect early signs of neuropathy, which include numbness, tingling or pain in the hands and feet. Patients should be evaluated periodically thereafter during treatment. Patients should be regularly counseled, questioned, and evaluated for signs or symptoms of peripheral neuropathy. Consideration should be given to electrophysiological testing, consisting of measurement of sensory nerve action potential (SNAP) amplitudes at baseline and thereafter every 6 months in an effort to detect asymptomatic neuropathy. If symptoms of drug-induced neuropathy develop, thalidomide should be discontinued immediately to limit further damage, if clinically appropriate. Usually, treatment with thalidomide should only be reinitiated if the neuropathy returns to baseline status. Medications known to be associated with neuropathy should be used with caution in patients receiving thalidomide.
Thrombotic Events : Thrombotic events have been reported in patients treated with THALOMIDÒ (thalidomide). Patients with neoplastic and various inflammatory conditions being treated with THALOMIDÒ (thalidomide) may have an increased incidence of pulmonary embolism, deep vein thrombophlebitis, thrombophlebitis, or thrombosis. It is not known if concomitant therapy with other medications, including anticancer agents, are a contributing factor.
Dizziness and Orthostatic Hypotension : Patients should also be advised that thalidomide may cause dizziness and orthostatic hypotension and that, therefore, they should sit upright for a few minutes prior to standing up from a recumbent position.
Neutropenia : Decreased white blood cell counts, including neutropenia, have been reported in association with the clinical use of thalidomide. Treatment should not be initiated with an absolute neutrophil count (ANC) of <750/mm3. White blood cell count and differential should be monitored on an ongoing basis, especially in patients who may be more prone to neutropenia, such as patients who are HIV-seropositive. If ANC decreases to below 750/mm3 while on treatment, the patient’s medication regimen should be re-evaluated and, if the neutropenia persists, consideration should be given to withholding thalidomide if clinically appropriate.
Increased HIV Viral Load : In a randomized, placebo-controlled trial of thalidomide in an HIV-seropositive patient population, plasma HIV RNA levels were found to increase (median change = 0.42 log10 copies HIV RNA/mL, p = 0.04 compared to placebo).7 A similar trend was observed in a second, unpublished study conducted in patients who were HIV-seropositive.13 The clinical significance of this increase is unknown. Both studies were conducted prior to availability of highly active anti-retroviral therapy. Until the clinical significance of this finding is further understood, in HIV-seropositive patients, viral load should be measured after the first and third months of treatment and every 3 months thereafter.
PRECAUTIONS
General
The only type of thalidomide exposure known to result in drug-associated birth defects is as a result of direct oral ingestion of thalidomide. Currently no specific data are available regarding the cutaneous absorption or inhalation of thalidomide in women of childbearing potential and whether these exposures may result in any birth defects. Patients should be instructed to not extensively handle or open THALOMIDÒ (thalidomide) Capsules and to maintain storage of capsules in blister packs until ingestion. If there is contact with non-intact thalidomide capsules or the powder contents, the exposed area should be washed with soap and water.
Thalidomide has been shown to be present in the serum and semen of patients receiving thalidomide. If healthcare providers or other caregivers are exposed to body fluids from patients receiving THALOMIDÒ (thalidomide), appropriate precautions should be utilized, such as wearing gloves to prevent the potential cutaneous exposure to THALOMIDÒ (thalidomide) or washing the exposed area with soap and water.
Hypersensitivity : Hypersensitivity to THALOMIDÒ (thalidomide) has been reported. Signs and symptoms have included the occurrence of erythematous macular rash, possibly associated with fever, tachycardia, and hypotension, and if severe, may necessitate interruption of therapy. If the reaction recurs when dosing is resumed, THALOMIDÒ (thalidomide) should be discontinued.
Bradycardia : Bradycardia in association with thalidomide use has been reported. Cases of bradycardia have been reported, some required medical interventions. The clinical significance and underlying etiology of the bradycardia noted in some thalidomide-treated patients are presently unknown.
Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis : Serious dermatologic reactions including Stevens-Johnson syndrome and toxic epidermal necrolysis, which may be fatal, have been reported. THALOMIDÒ (thalidomide) should be discontinued if a skin rash occurs and only resumed following appropriate clinical evaluation. If the rash is exfoliative, purpuric, or bullous or if Stevens-Johnson syndrome or toxic epidermal necrolysis is suspected, use of THALOMIDÒ (thalidomide) should not be resumed.
Seizures : Although not reported from pre-marketing controlled clinical trials, seizures, including grand mal convulsions, have been reported during post-approval use of THALOMIDÒ (thalidomide) in clinical practice. Because these events are reported voluntarily from a population of unknown size, estimates of frequency cannot be made. Most patients had disorders that may have predisposed them to seizure activity, and it is not currently known whether thalidomide has any epileptogenic influence. During therapy with thalidomide, patients with a history of seizures or with other risk factors for the development of seizures should be monitored closely for clinical changes that could precipitate acute seizure activity.
Information for Patients
(See BOXED WARNINGS.)
Patients should be instructed about the potential teratogenicity of thalidomide and the precautions that must be taken to preclude fetal exposure as per the S.T.E.P.S.Ò program and boxed warnings in this package insert. Patients should be instructed to take thalidomide only as prescribed in compliance with all of the provisions of the S.T.E.P.S.Ò Restricted Distribution Program.
Patients should be instructed to not extensively handle or open THALOMIDÒ (thalidomide) Capsules and to maintain storage of capsules in blister packs until ingestion.
Patients should be instructed not to share medication with anyone else.
Patients should be instructed that thalidomide frequently causes drowsiness and somnolence. Patients should be instructed to avoid situations where drowsiness may be a problem and not to take other medications that may cause drowsiness without adequate medical advice. Patients should be advised as to the possible impairment of mental and/or physical abilities required for the performance of hazardous tasks, such as driving a car or operating other complex machinery. Patients should be instructed that thalidomide may potentiate the somnolence caused by alcohol.
Patients should be instructed that thalidomide can cause peripheral neuropathies that may be initially signaled by numbness, tingling, or pain or a burning sensation in the feet or hands. Patients should be instructed to report such occurrences to their prescriber immediately.
Patients should also be instructed that thalidomide may cause dizziness and orthostatic hypotension and that, therefore, they should sit upright for a few minutes prior to standing up from a recumbent position.
Patients should be instructed that they are not permitted to donate blood while taking thalidomide. In addition, male patients should be instructed that they are not permitted to donate sperm while taking thalidomide.
Laboratory Tests
Pregnancy Testing: (See BOXED WARNINGS.) Women of childbearing potential should have a pregnancy test performed (sensitivity of at least 50 mIU/mL). The test should be performed within the 24 hours prior to beginning thalidomide therapy and then weekly during the first 4 weeks of use, then at 4 week intervals in women with regular menstrual cycles or every 2 weeks in women with irregular menstrual cycles. Pregnancy testing and counseling should be performed if a patient misses her period or if there is any abnormality in menstrual bleeding.
Neutropenia: (See WARNINGS.)
Increased HIV Viral Load: (See WARNINGS.)
Carcinogenesis, Mutagenesis, Impairment of Fertility
Long-term carcinogenicity tests have not been conducted using thalidomide. Thalidomide gave no evidence of mutagenic effects when assayed in in vitro bacterial (Salmonella typhimurium and Escherichia coli; Ames mutagenicity test), in vitro mammalian (AS52 Chinese hamster ovary cells; AS52/XPRT mammalian cell forward gene mutation assay) and in vivo mammalian (CD-1 mice; in vivo micronucleus test) test systems.
Animal studies to characterize the effects of thalidomide on fertility have not been conducted.
Pregnancy
Pregnancy Category X (See BOXED WARNING and CONTRAINDICATIONS.)
Because of the known human teratogenicity of thalidomide, thalidomide is contraindicated in women who are or may become pregnant and who are not using the two required types of birth control or who are not continually abstaining from heterosexual sexual contact. If thalidomide is taken during pregnancy, it can cause severe birth defects or death to an unborn baby. Thalidomide should never be used by women who are pregnant or who could become pregnant while taking the drug. Even a single dose [1 capsule (50 mg, 100 mg, or a 200 mg)] taken by a pregnant woman can cause birth defects. If pregnancy does occur during treatment, the drug should be immediately discontinued. Under these conditions, the patient should be referred to an obstetrician/gynecologist experienced in reproductive toxicity for further evaluation and counseling. Any suspected fetal exposure to THALOMIDÒ (thalidomide) must be reported to the FDA via the MedWatch program at 1-800-FDA-1088 and also to Celgene Corporation.
Because thalidomide is present in the semen of patients receiving the drug, males receiving thalidomide must always use a latex condom during any sexual contact with women of childbearing potential. The risk to the fetus from the semen of male patients taking thalidomide is unknown.
Animal studies to characterize the effects of thalidomide on late-stage pregnancy have not been conducted.
Use in Nursing Mothers
It is not known whether thalidomide is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from thalidomide, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.
Pediatric Use
Safety and effectiveness in pediatric patients below the age of 12 years have not been established.
Geriatric Use
No systematic studies in geriatric patients have been conducted. Thalidomide has been used in clinical trials in patients up to 90 years of age. Adverse events in patients over the age of 65 years did not appear to differ in kind from those reported for younger individuals.
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