INDICATIONS AND IMPORTANT SAFETY INFORMATION

INDICATIONS

Pomalidomide capsules are a thalidomide analogue indicated for the treatment of adult patients:

• in combination with dexamethasone, for patients with multiple myeloma (MM) who have received at least two prior therapies including lenalidomide and a proteasome inhibitor and have demonstrated disease progression on or within 60 days of completion of the last therapy.
• with AIDS-related Kaposi sarcoma (KS) after failure of highly active antiretroviral therapy (HAART) or in patients with KS who are HIV-negative.

CONTRAINDICATIONS

Pregnancy: Pomalidomide capsules can cause fetal harm when administered to a pregnant female and are contraindicated in females who are pregnant [see Boxed Warning]. If this drug is used during pregnancy or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential risk to a fetus.

Severe Hypersensitivity Reactions: Pomalidomide is contraindicated in patients who have demonstrated severe hypersensitivity (e.g., angioedema, anaphylaxis) to pomalidomide or any of the excipients.

WARNINGS AND PRECAUTIONS

Embryo-Fetal Toxicity: See BOXED WARNINGS.

• Females of Reproductive Potential: See Boxed WARNINGS.
• Males: Pomalidomide is present in the semen of patients receiving the drug. Males must always use a latex or synthetic condom during any sexual contact with females of reproductive potential while taking pomalidomide and for up to 4 weeks after discontinuing pomalidomide, even if they have undergone a successful vasectomy. Male patients taking lenalidomide must not donate sperm while taking pomalidomide and for up to 4 weeks after discontinuing lenalidomide.
• Blood Donation: Patients must not donate blood during treatment with pomalidomide 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 pomalidomide.

PS-Pomalidomide REMS Program: See Boxed WARNINGS. Because of the embryo-fetal risk, pomalidomide is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS), the PS-Pomalidomide REMS program. Prescribers and pharmacies must be certified with the PS-Pomalidomide REMS program by enrolling and complying with the REMS requirements; pharmacies must only dispense to patients who are authorized to receive Pomalidomide Capsules. Patients must sign a Patient-Physician Agreement Form and comply with REMS requirements; female patients of reproductive potential who are not pregnant must comply with the pregnancy testing and contraception requirements and males must comply with contraception requirements.

Venous and Arterial Thromboembolism: Venous thromboembolic events (deep venous thrombosis (DVT) and pulmonary embolism (PE)) and arterial thromboembolic events (myocardial infarction and stroke) have been observed in patients treated with pomalidomide. Patients with known risk factors, including prior thrombosis, may be at greater risk. Thromboprophylaxis is recommended, and the choice of regimen should be based on assessment of the patient's underlying risk factors.

Increased Mortality in Patients with MM with Pembrolizumab: In two randomized clinical trials in patients with MM, the addition of pembrolizumab to a thalidomide analogue plus dexamethasone resulted in increased mortality.

Hematologic Toxicity:

• MM: In patients receiving pomalidomide + low-dose Dex, neutropenia was the most frequently reported Grade 3 or 4 adverse reaction, followed by anemia and thrombocytopenia. Neutropenia of any grade was reported in 51% of patients, and Grade 3 or 4 neutropenia in 46%. The rate of febrile neutropenia was 8%. Monitor patients for hematologic toxicities, especially neutropenia. Monitor CBC weekly for the first 8 weeks and monthly thereafter. Patients may require dose interruption and/or modification
• KS: Hematologic toxicities were the most common (all grades and Grade 3 or 4) adverse reactions. 50% of patients had Grade 3 or 4 neutropenia. Monitor patients for hematologic toxicities, especially decreased neutrophils. Monitor CBC every 2 weeks for the first 12 weeks and monthly thereafter. Withhold, reduce the dose, or permanently discontinue pomalidomide based on the severity of the reaction.

Hepatotoxicity: Hepatic failure, including fatal cases, has occurred in patients treated with pomalidomide, as well as elevated levels of alanine aminotransferase and bilirubin. Monitor liver function tests monthly. Stop pomalidomide upon elevation of liver enzymes and evaluate. After return to baseline values, consider restarting treatment at a lower dose.

Severe Cutaneous Reactions: Severe cutaneous reactions including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug reaction with eosinophilia and systemic symptoms (DRESS) have been reported. These events can be fatal. Patients with a prior history of Grade 4 rash associated with thalidomide treatment should not receive pomalidomide. Consider pomalidomide interruption or discontinuation for Grade 2-3 skin rash. Permanently discontinue pomalidomide for Grade 4 rash, exfoliative or bullous rash, or for other severe cutaneous reactions such as SJS, TEN, or DRESS.

Tumor Lysis Syndrome (TLS): TLS may occur in patients treated with pomalidomide. At-risk patients include those with high tumor burden prior to treatment. These patients should be monitored closely and appropriate precautions taken.

Dizziness and Confusional State: 14% of patients who received pomalidomide + low-dose dex experienced dizziness and 7% experienced a confusional state; 1% experienced Grade 3 or 4 dizziness, and 3% experienced Grade 3 or 4 confusional state.

Neuropathy: In patients who received pomalidomide + low-dose dex, 18% experienced neuropathy, with approximately 12% experiencing peripheral neuropathy. 2% experienced Grade 3 neuropathy in one trial.

Risk of Secondary Primary Malignancies: Cases of acute myelogenous leukemia have been reported in patients receiving pomalidomide as an investigational therapy outside MM.

Hypersensitivity: Hypersensitivity, including angioedema, anaphylaxis, and anaphylactic reactions to pomalidomide have been reported. Permanently discontinue for angioedema or anaphylaxis.

ADVERSE REACTIONS

Multiple Myeloma

• In MM: Most common adverse reactions (≥30%) included fatigue and asthenia, neutropenia, anemia, constipation, nausea, diarrhea, dyspnea, upper-respiratory tract infections, back pain, and pyrexia.
• In KS: Serious adverse reactions occurred in 18% (5/28) of patients who received pomalidomide. Most common adverse reactions including laboratory abnormalities (≥30%) are decreased absolute neutrophil count or white blood cells, elevated creatinine or glucose, rash, constipation, fatigue, decreased hemoglobin, platelets, phosphate, albumin, or calcium, increased ALT, nausea, and diarrhea.

DRUG INTERACTIONS

Co-administration of fluvoxamine, a strong CYP1A2 inhibitor, increased Cmax and AUC of pomalidomide by 24% and 125% respectively. Avoid co-administration of strong CYP1A2 inhibitors (e.g. ciprofloxacin and fluvoxamine). If co-administration is unavoidable, reduce the pomalidomide dose. Smoking tobacco reduces pomalidomide AUC due to CYP1A2 induction. Smoking may reduce the efficacy of pomalidomide.

USE IN SPECIFIC POPULATIONS

• Pregnancy - See Boxed WARNINGS: If pregnancy does occur during treatment, immediately discontinue the drug. Under these conditions, refer patient to an obstetrician/gynecologist experienced in reproductive toxicity for further evaluation and counseling. Report any suspected fetal exposure to pomalidomide to the FDA via the MedWatch program at 1-800-FDA-1088 and also to Apotex Corp. at 1-800-706-5575.
• Lactation: There is no information regarding the presence of pomalidomide in human milk, the effects of pomalidomide on the breastfed infant, or the effects of pomalidomide on milk production. Because many drugs are excreted in human milk and because of the potential for adverse reactions in breastfed infants from pomalidomide, advise women not to breastfeed during treatment with pomalidomide.
• Renal Impairment: Starting dose adjustment is recommended for patients with severe renal impairment requiring dialysis. Hepatic Impairment: Dose adjustment is recommended in patients with hepatic impairment.
• Hepatic Impairment: Dose adjustment is recommended in patients with hepatic impairment.

To report SUSPECTED ADVERSE REACTIONS, contact Apotex, Inc. at 1-800-706-5575 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
Please see full Prescribing Information, including BOXED WARNINGS.