ASH Clinical News ACN_4.1_FULL_ISSUE_DIGITAL | Page 57

CLINICAL NEWS
The researchers reviewed claims from patients ( aged ≥9 months ) with SCD who were covered by either Medicaid or commercial insurance . Participants in the study were required to have either one inpatient or two outpatient claims per year between 2009 and 2014 , and the population was divided into cohorts according to year of diagnosis .
For each of the annual cohorts , there were between 2,619 and 3,285 patients
in the commercial insurance group and between 4,807 and 7,007 in the Medicaid group . About half of each cohort were women , but patients covered by Medicaid appeared to be younger than those covered by commercial insurance ( mean age = 27 years and 18 years , respectively [ ranges not provided ]).
The proportion of patients with SCD who were prescribed opioids remained stable each year across the study period ,
and consistently more Medicaid patients used an opioid ( 65 % -70 %), compared with patients covered by commercial insurance ( 54 % -57 %; p values not reported ). Medicaid patients also had higher numbers of vaso-occlusive crises and days on which opioids were supplied :
• average number of claims : 8.8-9.3 per year ( Medicaid ) and 6.1-6.5 per year ( commercial )
• average days supplied : 106.1-122.5 per year ( Medicaid ) and 93.4-102.1 per year ( commercial ; p values not provided )
Among both payers , opioid claims and days supplied were stable over time , Dr . Ballas noted , but opioid use increased markedly as pediatric patients aged into the adult health-care system . Between 23 and 64 percent of patients younger
Data Animal Data Following a single oral administration of pomalidomide to lactating rats approximately 14 days postpartum , pomalidomide was transferred into milk , with milk to plasma ratios of 0.63 to 1.46 .
8.3 Females and Males of Reproductive Potential Pregnancy Testing POMALYST can cause fetal harm when administered during pregnancy [ see Use in Specific Populations ( 8.1 )]. Verify the pregnancy status of females of reproductive potential prior to initiating POMALYST therapy and for at least 4 weeks after completing therapy . Advise females of reproductive potential that they must avoid pregnancy while taking POMALYST .
Females of reproductive potential must have 2 negative pregnancy tests before initiating POMALYST . The first test should be performed within 10-14 days , and the second test within 24 hours prior to prescribing POMALYST . Once treatment has started and during dose interruptions , pregnancy testing for females of reproductive potential should occur weekly during the first 4 weeks of use , then pregnancy testing should be repeated every 4 weeks in females with regular menstrual cycles . If menstrual cycles are irregular , the pregnancy testing should occur every 2 weeks . Pregnancy testing and counseling should be performed if a patient misses her period or if there is any abnormality in her menstrual bleeding . POMALYST treatment must be discontinued during this evaluation .
Contraception Females Females of reproductive potential must commit either to abstain continuously from heterosexual sexual intercourse or to use 2 methods of reliable birth control simultaneously : one highly effective form of contraception – tubal ligation , IUD , hormonal ( birth control pills , injections , hormonal patches , vaginal rings , or implants ), or partner ’ s vasectomy , and 1 additional effective contraceptive method – male latex or synthetic condom , diaphragm , or cervical cap . Contraception must begin 4 weeks prior to initiating treatment with POMALYST , during therapy , during dose interruptions , and continuing for 4 weeks following discontinuation of POMALYST therapy . Reliable contraception is indicated even where there has been a history of infertility , unless due to hysterectomy . Females of reproductive potential should be referred to a qualified provider of contraceptive methods , if needed .
Males Pomalidomide is present in the semen of males who take POMALYST . Therefore , males must always use a latex or synthetic condom during any sexual contact with females of reproductive potential while taking POMALYST and for up to 4 weeks after discontinuing POMALYST , even if they have undergone a successful vasectomy . Male patients taking POMALYST must not donate sperm .
Infertility Based on findings in animals , female fertility may be compromised by treatment with POMALYST [ see Nonclinical Toxicology ( 13.1 )].
8.4 Pediatric Use Safety and effectiveness have not been established in pediatric patients .
8.5 Geriatric Use No dosage adjustment is required for POMALYST based on age .
Of the total number of patients in clinical studies of POMALYST , 44 % were aged older than 65 years , while 10 % were aged older than 75 years . No overall differences in effectiveness were observed between these patients and younger patients . In these studies , patients older than 65 years were more likely than patients less than or equal to 65 years of age to experience pneumonia .
8.6 Renal Impairment In patients with severe renal impairment requiring dialysis , the AUC of pomalidomide increased by 38 % and the rate of SAE increased by 64 % relative to patients with normal renal function ; therefore ,
starting dose adjustment is recommended . For patients with severe renal impairment requiring dialysis , POMALYST should be administered after the completion of hemodialysis on dialysis days because exposure of pomalidomide could be significantly decreased during dialysis [ see Dosage and Administration ( 2.4 )].
8.7 Hepatic Impairment Pomalidomide is metabolized primarily by the liver . Following single dose administration , the AUC of pomalidomide increased 51 %, 58 %, and 72 % in subjects with mild ( Child-Pugh class A ), moderate ( Child-Pugh class B ), and severe ( Child-Pugh class C ) hepatic impairment compared to subjects with normal liver function . Dose adjustment is recommended in patients with hepatic impairment
[ see Dosage and Administration ( 2.5 ) and Clinical Pharmacology ( 12.3 )].
8.8 Smoking Tobacco Cigarette smoking reduces pomalidomide AUC by 32 % due to CYP1A2 induction . Advise patients that smoking may reduce the efficacy of pomalidomide .
10 OVERDOSAGE No specific information is available on the treatment of overdose with pomalidomide . Hemodialysis can remove pomalidomide from circulation .
13 NONCLINICAL TOXICOLOGY 13.1 Carcinogenesis , Mutagenesis , Impairment of Fertility Studies examining the carcinogenic potential of pomalidomide have not been conducted . One of 12 monkeys dosed with 1 mg / kg of pomalidomide ( an exposure approximately 15-fold of the exposure in patients at the recommended dose of 4 mg / day ) developed acute myeloid leukemia in a 9-month repeat-dose toxicology study .
Pomalidomide was not mutagenic or clastogenic in a battery of tests , including the bacteria reverse mutation assay ( Ames test ), the in vitro assay using human peripheral blood lymphocytes , and the micronucleus test in orally treated rats administered doses up to 2000 mg / kg / day .
In a fertility and early embryonic development study in rats , drug-treated males were mated with untreated or treated females . Pomalidomide was administered to males and females at doses of 25 to 1000 mg / kg / day . When treated males were mated with treated females , there was an increase in post-implantation loss and a decrease in mean number of viable embryos at all dose levels . There were no other effects on reproductive functions or the number of pregnancies . The lowest dose tested in animals resulted in an exposure ( AUC ) approximately 100-fold of the exposure in patients at the recommended dose of 4 mg / day . When treated males in this study were mated with untreated females , all uterine parameters were comparable to the controls . Based on these results , the observed effects were attributed to the treatment of females .
17 PATIENT COUNSELING INFORMATION See FDA-approved Patient Labeling ( Medication Guide )
Embryo-Fetal Toxicity Advise patients that POMALYST is contraindicated in pregnancy [ see Boxed Warning and Contraindications ( 4 )]. POMALYST is a thalidomide analogue and may cause serious birth defects or death to a developing baby [ see Warnings and Precautions ( 5.1 ) and Use in Specific Populations ( 8.1 )].
• Advise females of reproductive potential that they must avoid pregnancy while taking POMALYST and for at least 4 weeks after completing therapy .
• Initiate POMALYST treatment in females of reproductive potential only following a negative pregnancy test .
• Advise females of reproductive potential of the importance of monthly pregnancy tests and the need to use 2 different forms of contraception , including at least 1 highly effective form , simultaneously during POMALYST therapy , during therapy interruption , and for 4 weeks after she has completely finished taking POMALYST . Highly
effective forms of contraception other than tubal ligation include IUD and hormonal ( birth control pills , injections , patch , or implants ) and a partner ’ s vasectomy . Additional effective contraceptive methods include latex or synthetic condom , diaphragm , and cervical cap .
• Instruct patient to immediately stop taking POMALYST and contact her healthcare provider if she becomes pregnant while taking this drug , if she misses her menstrual period or experiences unusual menstrual bleeding , if she stops taking birth control , or if she thinks FOR ANY REASON that she may be pregnant .
• Advise patient that if her healthcare provider is not available , she should call Celgene Customer Care Center at 1-888-423-5436 [ see Warnings and Precautions ( 5.1 ) and Use in Specific Populations ( 8.3 )].
• Advise males to always use a latex or synthetic condom during any sexual contact with females of reproductive potential while taking POMALYST and for up to 4 weeks after discontinuing POMALYST , even if they have undergone a successful vasectomy .
• Advise male patients taking POMALYST that they must not donate sperm [ see Warnings and Precautions ( 5.1 ) and Use in Specific Populations ( 8.3 )].
• All patients must be instructed to not donate blood while taking POMALYST and for 1 month following discontinuation of POMALYST [ see Warnings and Precautions ( 5.1 )].
POMALYST REMS Program Because of the risk of embryo-fetal toxicity , POMALYST is only available through a restricted program called POMALYST REMS [ see Warnings and Precautions ( 5.2 )].
• Patients must sign a Patient-Physician Agreement Form and comply with the requirements to receive POMALYST . In particular , females of reproductive potential must comply with the pregnancy testing , contraception requirements , and participate in monthly telephone surveys . Males must comply with the contraception requirements [ see Use in Specific Populations ( 8.3 )].
• POMALYST is available only from pharmacies that are certified in POMALYST REMS . Provide patients with the telephone number and Web site for information on how to obtain the product .
Pregnancy Exposure Registry Inform females that there is a Pregnancy Exposure Registry that monitors pregnancy outcomes in females exposed to POMALYST during pregnancy and that they can contact the Pregnancy Exposure Registry by calling 1-888-423-5436 [ see Use in Specific Populations ( 8.1 )].
Venous and Arterial Thromboembolism Inform patients of the risk of developing DVT , PE , MI , and stroke and to report immediately any signs and symptoms suggestive of these events for evaluation
[ see Boxed Warnings and Warnings and Precautions ( 5.3 )].
Hematologic Toxicities Inform patients on the risks of developing neutropenia , thrombocytopenia , and anemia and the need to report signs and symptoms associated with these events to their healthcare provider for further evaluation [ see Warnings and Precautions ( 5.4 )].
Hepatotoxicity Inform patients on the risks of developing hepatotoxicity , including hepatic failure and death , and to report signs and symptoms associated with these events to their healthcare provider for evaluation [ see Warnings and Precautions ( 5.5 )].
Hypersensitivity Inform patients of the risk for angioedema and severe skin reactions and to report any signs and symptoms associated with these events to their healthcare provider for evaluation [ see Warnings and Precautions ( 5.6 )].
Dizziness and Confusional State Inform patients of the potential risk of dizziness and confusional state with the drug , to avoid situations where dizziness or confusional state may be a problem , and not to take other medications that