Label Changes for:
Changes have been made to the PRECAUTIONS and ADVERSE REACTIONS sections of the safety label.
Detailed View: Safety Labeling Changes Approved By FDA Center for Drug Evaluation and Research (CDER)
Postmarketing Experience (paragraph reformatted and bolded additions)
- The following adverse reactions have been identified during post approval use of POMALYST. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure: Pancytopenia, tumor lysis syndrome, allergic reactions (e.g., angioedema, urticaria), elevated liver enzymes, hepatic failure (including fatal cases), hepatitis B virus reactivation, herpes zoster, gastrointestinal hemorrhage, basal cell carcinoma and squamous cell carcinoma of the skin.
Drugs That Affect Pomalidomide Plasma Concentrations
- Pomalidomide is primarily metabolized by CYP1A2 and CYP3A4. Pomalidomide is also a substrate for Pglycoprotein (P-gp).
- In healthy volunteers, co-administration of fluvoxamine, a strong CYP1A2 inhibitor, increased Cmax and AUC of pomalidomide by 24% and 125% respectively. Increased pomalidomide exposure increases the risk of exposure related toxicities.
- Avoid co-administration of strong CYP1A2 inhibitors (e.g. ciprofloxacin and fluvoxamine). If co-administration is unavoidable, reduce the POMALYST dose.
USE IN SPECIFIC POPULATIONS
- PLLR Conversion; please refer to label.
- Safety and effectiveness have not been established in pediatric patients. (updated)
Renal Impairment (updated)
- 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.
Hepatic Impairment (updated)
- 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.
- Cigarette smoking reduces pomalidomide AUC by 32% due to CYP1A2 induction. Advise patients that smoking may reduce the efficacy of pomalidomide.
PATIENT COUNSELING INFORMATION
Pregnancy Exposure Registry (addition)
- 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.
Smoking Tobacco (new section)
- Advise patients that smoking tobacco may reduce the efficacy of POMALYST.
What is the most important information I should know about POMALYST?
- Before prescribing POMALYST, your healthcare provider will explain the POMALYST REMS program to you and have you sign the Patient-Physician Agreement Form.
Females who can become pregnant:
- Will have pregnancy tests weekly for 4 weeks, then every 4 weeks if your menstrual cycle is regular, or every 2 weeks if your menstrual cycle is irregular. If you miss your period or have unusual bleeding, you will need to have a pregnancy test and receive counseling.
- Must agree to use two acceptable forms of birth control at the same time, for at least 4 weeks before, while taking, during any breaks (interruptions) in your treatment, and for at least 4 weeks after stopping POMALYST.
- Talk with your healthcare provider to find out about options for acceptable forms of birth control that you may use to prevent pregnancy before, during, and after treatment with POMALYST.
- If you become pregnant while taking POMALYST, stop taking it right away and call your healthcare provider.
- If your healthcare provider is not available, you can call Celgene Customer Care Center at 1-888-423-5436.
Healthcare providers and patients should report all cases of pregnancy to:
- FDA MedWatch at 1-800-FDA-1088, and
- Celgene Corporation at 1-888-423-5436
There is a pregnancy exposure registry that monitors the outcomes of females who take POMALYST during pregnancy, or if their male partner takes POMALYST and they are exposed during pregnancy. You can enroll in this registry by calling Celgene Corporation at the phone number listed above.
What are the possible side effects of POMALYST?
POMALYST can cause serious side effects, including: (additions)
- Dizziness and confusion. See “What should I avoid while taking POMALYST?”
- Risk of new cancers (malignancies). New cancers, including certain blood cancers (acute myelogenous leukemia or AML) have been seen in people who received POMALYST. Talk with your healthcare provider about your risk of developing new cancers if you take POMALYST.
The most common side effects of POMALYST include:
- upper respiratory tract infection (addition)
VENOUS AND ARTERIAL THROMBOEMBOLISM
- Deep venous thrombosis (DVT), pulmonary embolism (PE), myocardial infarction, and stroke occur in patients with multiple myeloma treated with POMALYST. Antithrombotic prophylaxis is recommended
WARNINGS AND PRECAUTIONS
Venous and Arterial Thromboembolism
- Venous thromboembolic events (deep venous thrombosis and pulmonary embolism) and arterial thromboembolic events (myocardial infarction and stroke) have been observed in patients treated with POMALYST. In Trial 2, where anticoagulant therapies were mandated, thromboembolic events occurred in 8.0% of patients treated with POMALYST and low dose-dexamethasone (Low-dose Dex), and 3.3% of patients treated with high-dose dexamethasone. Venous thromboembolic events (VTE) occurred in 4.7% of patients treated with POMALYST and Lowdose Dex, and 1.3% of patients treated with high-dose dexamethasone. Arterial thromboembolic events include terms for arterial thromboembolic events, ischemic cerebrovascular conditions, and ischemic heart disease. Arterial thromboembolic events occurred in 3.0% of patients treated with POMALYST and Low-dose Dex, and 1.3% of patients treated with high-dose dexamethasone.
- Patients with known risk factors, including prior thrombosis, may be at greater risk, and actions should be taken to try to minimize all modifiable factors (e.g., hyperlipidemia, hypertension, smoking). Thromboprophylaxis is recommended, and the choice of regimen should be based on assessment of the patient's underlying risk factors.
- In trials 1 and 2 in patients who received POMALYST + Low-dose Dex, neutropenia was the most frequently reported Grade 3/4 adverse reaction, followed by anemia and thrombocytopenia. Neutropenia of any grade was reported in 51% of patients in both trials. The rate of Grade 3/4 neutropenia was 46%. The rate of febrile neutropenia was 8%.
- Hepatic failure, including fatal cases, has occurred in patients treated with POMALYST. Elevated levels of alanine aminotransferase and bilirubin have also been observed in patients treated with POMALYST. Monitor liver function tests monthly. Stop POMALYST upon elevation of liver enzymes and evaluate. After return to baseline values, treatment at a lower dose may be considered.
- Angioedema and severe dermatologic reactions have been reported. Discontinue POMALYST for angioedema, skin exfoliation, bullae, or any other severe dermatologic reactions, and do not resume therapy [see Dosage and Administration (2.2)].
Dizziness and Confusional State
- In trials 1 and 2 in patients who received POMALYST + Low-dose Dex, 14% of patients experienced dizziness and 7% of patients experienced a confusional state; 1% of patients experienced Grade 3 or 4 dizziness, and 3% of patients experienced Grade 3 or 4 confusional state. Instruct patients to avoid situations where dizziness or confusional state may be a problem and not to take other medications that may cause dizziness or confusional state without adequate medical advice.
- In trials 1 and 2 in patients who received POMALYST + Low-dose Dex, 18% of patients experienced neuropathy, with approximately 12% of the patients experiencing peripheral neuropathy. Two percent of patients experienced Grade 3 neuropathy in trial 2. There were no cases of Grade 4 neuropathy adverse reactions reported in either trial.
Tumor Lysis Syndrome
- Tumor lysis syndrome (TLS) may occur in patients treated with pomalidomide. Patients at risk for TLS are those with high tumor burden prior to treatment. These patients should be monitored closely and appropriate precautions taken.
- Tumor lysis syndrome