WARNINGS WARNINGS ANDAND PRECAUTIONS PRECAUTIONS (continued) (continued) Dizziness Dizziness and and Confusional Confusional State: State: 18%18% of patients of patients experienced experienced dizziness dizziness and 12% and 12% of patients of patients experienced experienced a confusional a confusional state; state;
1% of1%patients of patients experienced experienced gradegrade 3/4 dizziness, 3/4 dizziness, and 3% andof3%patients of patients experienced experienced gradegrade 3/4 confusional 3/4 confusional state. state. Instruct Instruct patients patients to avoid to avoid situations situations where where dizziness dizziness or confusion or confusion may may be a be problem a problem and not andto nottake to take otherother medications medications that that may may causecause dizziness dizziness or confusion or confusion without without adequate adequate medical medical advice. advice. Neuropathy: Neuropathy: 18%18% of patients of patients experienced experienced neuropathy neuropathy (approximately (approximately 9% peripheral 9% peripheral neuropathy). neuropathy). ThereThere werewere no cases no cases of grade of grade 3 or higher 3 or higher neuropathy neuropathy adverse adverse reactions reactions reported. reported. RiskRisk of Second of Second Primary Primary Malignancies: Malignancies: CasesCases of acute of acute myelogenous myelogenous leukemia leukemia havehave beenbeen reported reported in patients in patients receiving receiving POMALYST POMALYST as anasinvestigational an investigational therapy therapy outside outside of multiple of multiple myeloma. myeloma.
ADVERSE ADVERSE REACTIONS REACTIONS In the Inclinical the clinical trial trial of 219 of patients 219 patients who who received received POMALYST POMALYST alonealone (n=107) (n=107) or POMALYST or POMALYST + low-dose + low-dose dexamethasone dexamethasone (low-dose (low-dose dex)dex) (n=112), (n=112), all patients all patients had at hadleast at least one treatment-emergent one treatment-emergent adverse adverse reaction. reaction. • In •the InPOMALYST the POMALYST alonealone versus versus POMALYST POMALYST + low+ dose low dose dexamethasone dexamethasone arms,arms, respectively, respectively, mostmost common common adverse adverse reactions reactions (≥30%) (≥30%) included included fatigue fatigue and asthenia and asthenia (55%, (55%, 63%), 63%), neutropenia neutropenia (52%, (52%, 47%),47%), anemia anemia (38%, (38%, 39%), 39%), constipation constipation (36%, (36%, 35%),35%), nausea nausea (36%, (36%, 22%), 22%), diarrhea diarrhea (34%, (34%, 33%), 33%), dyspnea dyspnea (34%, (34%, 45%),45%), upperupper respiratory respiratory tracttract infection infection (32%, (32%, 25%), 25%), backback painpain (32%, (32%, 30%), 30%), and pyrexia and pyrexia (19%, (19%, 30%)30%) • 90% • 90% of patients of patients treated treated withwith POMALYST POMALYST alonealone and 88% and 88% of patients of patients treated treated withwith POMALYST POMALYST + low-dose + low-dose dex had dex at hadleast at least one one treatment-emergent treatment-emergent NCI CTC NCI Grade CTC Grade 3 or 43 adverse or 4 adverse reaction reaction • In •the InPOMALYST the POMALYST alonealone versus versus POMALYST POMALYST + low+ dose low dose dexamethasone dexamethasone arms,arms, respectively, respectively, mostmost common common GradeGrade 3/4 adverse 3/4 adverse reactions reactions (≥15%) (≥15%) included included neutropenia neutropenia (47%, (47%, 38%), 38%), anemia anemia (22%, (22%, 21%),21%), thrombocytopenia thrombocytopenia (22%, (22%, 19%), 19%), and pneumonia and pneumonia (16%,(16%, 23%).23%). For other For other GradeGrade 3 or 43 toxicities or 4 toxicities besides besides neutropenia neutropenia and thrombocytopenia, and thrombocytopenia, holdhold treatment treatment and restart and restart treatment treatment at at 1 mg1less mg than less than the previous the previous dosedose whenwhen toxicity toxicity has resolved has resolved to less to than less than or equal or equal to Grade to Grade 2 at the 2 atphysician’s the physician’s discretion discretion • 67% • 67% of patients of patients treated treated withwith POMALYST POMALYST and 62% and 62% of patients of patients treated treated withwith POMALYST POMALYST + low-dose + low-dose dex had dex at hadleast at least one one treatment-emergent treatment-emergent serious serious adverse adverse reaction reaction • In •the InPOMALYST the POMALYST alonealone versus versus POMALYST POMALYST + low+ dose low dose dexamethasone dexamethasone arms,arms, respectively, respectively, mostmost common common serious serious adverse adverse reactions reactions (≥5%) (≥5%) werewere pneumonia pneumonia (14%, (14%, 19%), 19%), renalrenal failure failure (8%,(8%, 6%),6%), dyspnea dyspnea (5%,(5%, 6%),6%), sepsis sepsis (6%,(6%, 3%),3%), pyrexia pyrexia (3%,(3%, 5%) 5%) dehydration dehydration (5%,(5%, 3%),3%), hypercalcemia hypercalcemia (5%,(5%, 2%),2%), urinary urinary tracttract infection infection (0%,(0%, 5%),5%), and febrile and febrile neutropenia neutropenia (5%,(5%, 1%) 1%)
DRUG DRUG INTERACTIONS INTERACTIONS No formal No formal drugdrug interaction interaction studies studies havehave beenbeen conducted conducted withwith POMALYST. POMALYST. Pomalidomide Pomalidomide is primarily is primarily metabolized metabolized by CYP1A2 by CYP1A2 and and CYP3A. CYP3A. Pomalidomide Pomalidomide is also is also a substrate a substrate for P-glycoprotein for P-glycoprotein (P-gp). (P-gp). Coadministration Coadministration of POMALYST of POMALYST withwith drugsdrugs that that are strong are strong inhibitors inhibitors or inducers or inducers of CYP1A2, of CYP1A2, CYP3A, CYP3A, or P-gp or P-gp should should be avoided. be avoided. Cigarette Cigarette smoking smoking may may reduce reduce pomalidomide pomalidomide exposure exposure due due to CYP1A2 to CYP1A2 induction. induction. Patients Patients should should be advised be advised that that smoking smoking may may reduce reduce the effi thecacy efficacy of pomalidomide. of pomalidomide.
USEUSE IN SPECIFIC IN SPECIFIC POPULATIONS POPULATIONS Pregnancy: Pregnancy: If pregnancy If pregnancy doesdoes occuroccur during during treatment, treatment, immediately immediately discontinue discontinue the drug the drug and refer and refer patient patient to antoobstetrician/ an obstetrician/
gynecologist gynecologist experienced experienced in reproductive in reproductive toxicity toxicity for further for further evaluation evaluation and counseling. and counseling. Report Report any suspected any suspected fetalfetal exposure exposure to POMALYST to POMALYST to the toFDA the via FDAthe viaMedWatch the MedWatch program program at 1-800-332-1088 at 1-800-332-1088 and also and also to Celgene to Celgene Corporation Corporation at 1-888-423-5436. at 1-888-423-5436. Nursing Nursing Mothers: Mothers: It is not It isknown not known if pomalidomide if pomalidomide is excreted is excreted in human in human milk.milk. Pomalidomide Pomalidomide was excreted was excreted in the inmilk the milk of of lactating lactating rats.rats. Because Because manymany drugsdrugs are excreted are excreted in human in human milk milk and because and because of the ofpotential the potential for adverse for adverse reactions reactions in nursing in nursing infants infants fromfrom POMALYST, POMALYST, a decision a decision should should be made be made whether whether to discontinue to discontinue nursing nursing or toordiscontinue to discontinue the drug, the drug, taking taking into into account account the importance the importance of the ofdrug the drug to the tomother. the mother. Pediatric Pediatric Use:Use: Safety Safety and effectiveness and effectiveness of POMALYST of POMALYST in patients in patients under under the age the of age18ofhave 18 have not been not been established. established. Geriatric Geriatric Use:Use: No dosage No dosage adjustment adjustment is required is required for POMALYST for POMALYST based based on age. on age. Patients Patients greater greater thanthan or equal or equal to 65toyears 65 years of age of age werewere moremore likelylikely thanthan patients patients less than less than or equal or equal to 65toyears 65 years of age of to ageexperience to experience pneumonia. pneumonia. Renal Renal and and Hepatic Hepatic Impairment: Impairment: Pomalidomide Pomalidomide is metabolized is metabolized in the inliver. the liver. Pomalidomide Pomalidomide and its andmetabolites its metabolites are primarily are primarily excreted excreted by the bykidneys. the kidneys. The infl Theuence influence of renal of renal and hepatic and hepatic impairment impairment on the onsafety, the safety, efficacy, efficacy, and pharmacokinetics and pharmacokinetics of of pomalidomide pomalidomide has not hasbeen not been evaluated. evaluated. AvoidAvoid POMALYST POMALYST in patients in patients withwith a serum a serum creatinine creatinine >3.0>3.0 mg/dL. mg/dL. AvoidAvoid POMALYST POMALYST in in patients patients withwith serum serum bilirubin bilirubin >2.0>2.0 mg/dL mg/dL and AST/ALT and AST/ALT >3.0>3.0 x ULN. x ULN. Please Please see full see Prescribing full Prescribing Information, Information, including including Boxed Boxed WARNINGS, WARNINGS, CONTRAINDICATIONS, CONTRAINDICATIONS, WARNINGS WARNINGS ANDAND PRECAUTIONS, PRECAUTIONS, and and ADVERSE ADVERSE REACTIONS. REACTIONS. POMALYST® POMALYST® is a registered is a registered trademark trademark of Celgene of Celgene Corporation. Corporation. POMALYST POMALYST REMS™ REMS™ is a trademark is a trademark of Celgene of Celgene Corporation. Corporation. ©2013 ©2013 Celgene Celgene Corporation Corporation 02/1302/13 US-POM120044 US-POM120044