Thalidomide - Warnings and Precautions

5 WARNINGS AND PRECAUTIONS • Ischemic heart disease (including myocardial infarction) and stroke have been observed in patients treated with THALOMID in combination with dexamethasone. • Increased Mortality: Observed in patients with MM when pembrolizumab was added to dexamethasone and a thalidomide analogue. • Drowsiness and Somnolence: Instruct patients to avoid situations where drowsiness may be a problem and not to take other medications that may cause drowsiness. • Peripheral Neuropathy: Monitor patients for signs or symptoms of peripheral neuropathy during treatment.

Discontinue THALOMID if symptoms of drug-induced peripheral neuropathy occur, if clinically appropriate. • Dizziness and Orthostatic Hypotension: Advise patients to sit upright for a few minutes prior to standing up from a recumbent position. • Neutropenia and Thrombocytopenia: Patients may require dose interruption and/or dose reduction. ( 5.8 , 5.9 ) • Increased HIV Viral Load: Measure viral load during treatment. • Bradycardia: Monitor patients for bradycardia and possible syncope.

Dose reduction or discontinuation may be required. • Severe Cutaneous Reactions: Discontinue THALOMID for severe reactions. • Seizures: Monitor patients with a history of seizures or other risk factors for acute seizure activity. • Tumor Lysis Syndrome: Monitor patients at risk (e.g., those with high tumor burden prior to treatment) and take appropriate precautions. • Hypersensitivity: Monitor patients for potential hypersensitivity.

Discontinue THALOMID for angioedema and anaphylaxis.

5.1 Embryo-Fetal Toxicity THALOMID is a powerful human teratogen that induces a high frequency of severe and life-threatening birth defects, even after a single dose.

Mortality at or shortly after birth has been reported in about 40% of infants.

When there is no satisfactory alternative treatment, females of reproductive potential may be treated with THALOMID provided adequate precautions are taken to avoid pregnancy.

THALOMID is only available through the THALOMID REMS program [see Warnings and Precautions ] .

Oral ingestion is the only type of maternal THALOMID exposure known to result in drug-associated birth defects.

There are no specific data available regarding the reproductive risks of cutaneous absorption or inhalation of THALOMID; however, females of reproductive potential should avoid contact with THALOMID Capsules.

THALOMID Capsules should be stored in blister packs until ingestion.

If there is contact with non-intact THALOMID capsules or the powder contents, the exposed area should be washed with soap and water.

If healthcare providers or other care givers are exposed to body fluids from patients receiving THALOMID, the exposed area should be washed with soap and water.

Appropriate precautions should be utilized, such as wearing gloves to prevent the potential cutaneous exposure to THALOMID.

Females of Reproductive Potential Females of reproductive potential must avoid pregnancy for at least 4 weeks before beginning THALOMID therapy, during therapy, during dose interruptions and for at least 4 weeks after completing therapy.

Females must commit either to abstain continuously from heterosexual sexual intercourse or to use two methods of reliable birth control, beginning 4 weeks prior to initiating treatment with THALOMID, during therapy, during dose interruptions and continuing for 4 weeks following discontinuation of THALOMID therapy.

Two negative pregnancy tests must be obtained prior to initiating therapy.

The first test should be performed within 10-14 days and the second test within 24 hours prior to prescribing THALOMID therapy and then weekly during the first month, then monthly thereafter in females with regular menstrual cycles or every 2 weeks in females with irregular menstrual cycles [see Use in Specific Populations ].

Males Thalidomide is present in the semen of patients receiving THALOMID.

Therefore, males must always use a latex or synthetic condom during any sexual contact with females of reproductive potential while taking THALOMID and for up to 4 weeks after discontinuing THALOMID, even if they have undergone a successful vasectomy.

Male patients taking THALOMID must not donate sperm [see Use in Specific Populations ] .

Blood Donation Patients must not donate blood during treatment with THALOMID and for 4 weeks following discontinuation of the drug because the blood might be given to a pregnant female patient whose fetus must not be exposed to THALOMID.

5.2 THALOMID REMS Program Because of the embryo-fetal risk [see Warnings and Precautions ], THALOMID is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS), the THALOMID REMS program.

Required components of the THALOMID REMS program include the following: • Prescribers must be certified with the THALOMID REMS program by enrolling and complying with the REMS requirements. • Patients must sign a Patient-Physician Agreement Form and comply with the REMS requirements.

In particular, female patients of reproductive potential who are not pregnant must comply with the pregnancy testing and contraception requirements [see Use in Specific Populations ] and males must comply with contraception requirements [see Use in Specific Populations ]. • Pharmacies must be certified with the THALOMID REMS program, must only dispense to patients who are authorized to receive THALOMID and comply with REMS requirements.