ASH Clinical News December 2014 | Page 88

Clinical Innovators Continued from page 81 partisan warfare and are obscured by the fog of political combat. In this kind of environment, it is impossible to correct the flaws that inevitably occur with a legislation of this complexity with the technical corrections that would normally occur. If the Affordable Care Act succeeds, it will do so under the most adverse political circumstances imaginable. The Commonwealth Fund frequently considers American health-care policy in a global context, providing important international comparisons. What do you see as special about the United States health-care context? Cross-national comparisons conducted by the Fund highlight the many ways in which our system lags behind other countries in the developed world. In one report, we compared the health systems in 11 industrialized countries, and we have repeatedly found that the U.S. system ranks last on composite measures of quality, efficiency, and ac cess to services. These reports have exploded the myth that we have “the best health system in the world.” We spend at least double the amount on health-care per person of any other developed nation, and we perform less well on measures of health and longevity – a finding also documented by the Institute of Medicine. We are unlikely to ever import wholesale the systemic approaches of other countries, but their examples serve as concrete, real proof that we can T:7” This brief summary does not include all the information needed to use POMALYST® (pomalidomide) safely and effectively. See full Prescribing Information for POMALYST. WARNING: EMBRYO-FETAL TOXICITY and VENOUS THROMBOEMBOLISM Embryo-Fetal Toxicity • POMALYST is contraindicated in pregnancy. POMALYST is a thalidomide analogue. Thalidomide is a known human teratogen that causes severe birth defects or embryo-fetal death. In females of reproductive potential, obtain 2 negative pregnancy tests before starting POMALYST treatment. • Females of reproductive potential must use 2 forms of contraception or continuously abstain from heterosexual sex during and for 4 weeks after stopping POMALYST treatment [see Contraindications (4), Warnings and Precautions (5.1), and Use in Specific Populations (8.1, 8.6)]. POMALYST is only available through a restricted distribution program called POMALYST REMS™ [see Warnings and Precautions (5.2)]. Venous Thromboembolism • Deep venous thrombosis (DVT) and pulmonary embolism (PE) occur in patients with multiple myeloma treated with POMALYST. Prophylactic anti-thrombotic measures were employed in the clinical trial. Consider prophylactic measures after assessing an individual patient’s underlying risk factors [see Warnings and Precautions (5.3)]. 2 DOSAGE AND ADMINISTRATION 2.1 Multiple Myeloma Females of reproductive potential must have negative pregnancy testing and use contraception methods before initiating POMALYST [see Warnings and Precautions (5.1) and Use in Specific Populations (8.6)]. The recommended starting dose of POMALYST is 4 mg once daily orally on Days 1-21 of repeated 28-day cycles until disease progression. POMALYST may be given in combination with dexamethasone [see Clinical Studies (14.1)]. POMALYST may be taken with water. Inform patients not to break, chew, or open the capsules. POMALYST should be taken without food (at least 2 hours before or 2 hours after a meal). Table 1: Dose Modification Instructions for POMALYST for Hematologic Toxicities Toxicity Neutropenia • ANC <500 per mcL or febrile neutropenia (fever more than or equal to 38.5°C and ANC <1,000 per mcL) • ANC return to more than or equal to 500 per mcL Dose Modification • For each subsequent drop <500 per mcL • Return to more than or equal to 500 per mcL Interrupt POMALYST treatment Resume POMALYST treatment at 1 mg less than the previous dose Thrombocytopenia • Platelets <25,000 per mcL Interrupt POMALYST treatment, follow CBC weekly Resume POMALYST treatment at 3 mg daily • Platelets return to >50,000 per mcL Interrupt POMALYST treatment, follow CBC weekly Resume POMALYST treatment at 3 mg daily • For each subsequent drop <25,000 per mcL • Return to more than or equal to 50,000 per mcL Interrupt POMALYST treatment Resume POMALYST treatment at 1 mg less than previous dose ANC, absolute neutrophil count. For other Grade 3 or 4 toxicities, hold treatment and restart treatment at 1 mg less than the previous dose when toxicity has resolved to less than or equal to Grade 2 at the physician’s discretion. To initiate a new cycle of POMALYST, the neutrophil count must bePrint-only content at least 500 per mcL and the platelet count must be at least 50,000 per mcL. If toxicities occur after dose reductions to 1 mg, then discontinue POMALYST. 2.3 Dose Adjustment for Strong CYP1A2 Inhibitors in the Presence of Strong CYP3A4 and P-gp Inhibitors Avoid co-administration of strong inhibitors of CYP1A2. If necessary to co-administer strong inhibitors of CYP1A2 in the presence of strong inhibitors of CYP3A4 and P-gp, reduce POMALYST dose by 50%. No clinical efficacy or safety data exist [see Drug Interactions (7.1) and Clinical Pharmacology (12.3)]. 4 CONTRAINDICATIONS Pregnancy POMALYST can cause fetal harm when administered to a pregnant female [see Warnings and Precautions (5.1) and Use in Specific Populations (8.1)]. POMALYST is contraindicated in females who are pregnant. Pomalidomide is a thalidomide analogue and is teratogenic in both rats and rabbits when administered during the period of organogenesis. 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 hazard to a fetus. 5 WARNINGS AND PRECAUTIONS 5.1 Embryo-Fetal Toxicity POMALYST is a thalidomide analogue and is contraindicated for use during pregnancy. Thalidomide is a known human teratogen that causes severe birth defects or embryo-fetal death [see Use in Specific Populations (8.1)]. POMALYST is only available through the POMALYST REMS program [see Warnings and Precautions (5.2)]. Females of Reproductive Potential Females of reproductive potential must avoid pregnancy while taking POMALYST and for at least 4 weeks after completing therapy. Females must commit either to abstain continuously from heterosexual sexual intercourse or to use 2 methods of reliable birth control, beginning 4 weeks prior to initiating treatment with POMALYST, during therapy, during dose interruptions, and continuing for 4 weeks following discontinuation of POMALYST 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 POMALYST therapy, and then weekly during the first month, then monthly thereafter in women with regular menstrual cycles, or every 2 weeks in women with irregular menstrual cycles [see Use in Specific Populations (8.6)]. Males Pomalidomide is present in the semen of patients receiving the drug. Therefore, males must always use a latex or synthe tic condom during any sexual contact with females of reproductive potential while taking POMALYST and for up to 28 days after discontinuing POMALYST, even if they have undergone a successful vasectomy. Male patients taking POMALYST must not donate sperm [see Use in Specific Populations (8.6)]. Blood Donation Patients must not donate blood during treatment with POMALYST and for 1 month following discontinuation of the drug because the blood might be given to a pregnant female patient whose fetus must not be exposed to POMALYST. 5.2 POMALYST REMS™ Program Because of the embryo-fetal risk [see Warnings and Precautions (5.1)], POMALYST is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called “POMALYST REMS.” Required components of the POMALYST REMS program include the following: • Prescribers must be certified with the POMALYST REMS program by enrolling and complying with the REMS requirements. • Patients must sign a Patient-Prescriber 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 (8.6)] and males must comply with contraception requirements [see Use in Specific Populations (8.6)]. • Pharmacies must be certified with the POMALYST REMS program, must only dispense to patients who are authorized to receive POMALYST, and comply with REMS requirements. Further information about the POMALYST REMS program is available www.CelgeneRiskManagement.com or by telephone at 1-888-423-5436. 5.3 Venous Thromboembolism Patients receiving POMALYST have developed venous thromboembolic events (VTEs) (venous thromboembolism) reported as serious adverse reactions. In the trial, all patients were required to receive prophylaxis or anti-thrombotic treatment; 81% used aspirin, 16% warfarin, 21% heparin, and 3% clopidogrel. The rate of deep vein thrombosis or pulmonary embolism was 3%. Consider anticoagulation prophylaxis after an assessment of each patient’s underlying risk factors. Cosmos Communications 1 K 28562a_pi 08.1.14 133 js 9 Q1 Q2 T:10” 1 INDICATIONS AND USAGE 1.1 Multiple Myeloma POMALYST is indicated for patients with multiple myeloma who have received at least two prior therapies including lenalidomide and bortezomib and have demonstrated disease progression on or within 60 days of completion of the last therapy. Approval is based on response rate [see Clinical Studies (14.1)]. Clinical benefit, such as improvement in survival or symptoms, has not been verified. 2.2 Dose Adjustments for Toxicities