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The following adverse reactions have been identified during postapproval 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.

Blood and Lymphatic System Disorders: Pancytopenia

Endocrine Disorders: Hypothyroidism, hyperthyroidism

Gastrointestinal Disorders: Gastrointestinal hemorrhage

Hepatobiliary Disorders: Hepatic failure (including fatal cases), elevated liver enzymes

Immune system Disorders: Allergic reactions (e.g., angioedema, anaphylaxis, urticaria), solid organ transplant rejection

Infections and Infestations: Hepatitis B virus reactivation, Herpes zoster, progressive multifocal leukoencephalopathy (PML)

Subsection revised, additions underlined

The safety and effectiveness of POMALYST have not been established in pediatric patients. The safety and effectiveness were assessed but not established in two open-label studies: a dose escalation study in 25 pediatric patients aged 5 to <17 with recurrent, progressive or refractory CNS tumors [NCT02415153] and a parallel- group study conducted in 47 pediatric patients aged 4 to <17 years with recurrent or progressive high-grade glioma, medulloblastoma, ependymoma, or diffuse intrinsic pontine glioma (DIPG) [NCT03257631]. No new safety signals were observed in pediatric patients across these studies.

At the same dose by body surface area, pomalidomide exposure in 55 pediatric patients aged 4 to < 17 years old was within the range observed in adult patients with MM but higher than the exposure observed in adult patients with KS [see Clinical Pharmacology (12.3)].

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

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

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… These reactions can be fatal. Consider POMALYST interruption or discontinuation for Grade 2-3 skin rash.

Permanently discontinue POMALYST for Grade 4 rash, exfoliative or bullous rash, or for other severe cutaneous reactions such as SJS, TEN or DRESS.

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Endocrine disorders: Hypothyroidism, hyperthyroidism

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Immune system disorders: Allergic reactions (e.g., angioedema, anaphylaxis, urticaria), solid organ transplant rejection

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Who should not take POMALYST?

Do not take POMALYST if you:

• are pregnant, plan to become pregnant, or become pregnant during treatment with POMALYST. See “What is the most important information I should know about POMALYST?”

• are allergic to pomalidomide or any of the ingredients in POMALYST. See the end of this Medication Guide for a complete list of ingredients in POMALYST.

  
  

What should I tell my healthcare provider before taking POMALYST?

Before you take POMALYST, tell your healthcare provider if you:

…

• have liver problems

• have kidney problems and are receiving hemodialysis treatment

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What are the possible side effects of POMALYST?

POMALYST can cause serious side effects, including:

…

• Severe allergic reactions and severe skin reactions can happen with POMALYST and may cause death.

  Call your healthcare provider if you develop any of the following signs or symptoms during treatment with POMALYST:

• a red, itchy, skin                     

• peeling of your skin or blisters                       

• severe itching rash                        

• fever

Get emergency medical help right away if you develop any of the following signs or symptoms during treatment with POMALYST:

• swelling of your lips, mouth, tongue, or throat          

• a very fast heartbeat

• trouble breathing or swallowing       

• you feel dizzy or faint

• raised red areas on your skin (hives)

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Hypersensitivity

Inform patients of the potential for severe hypersensitivity reactions such as angioedema and anaphylaxis to POMALYST. Instruct patients to contact their healthcare provider right away for any signs and symptoms of these reactions. Advise patients to seek emergency medical attention for signs or symptoms of severe hypersensitivity reactions.

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Females of Reproductive Potential

Females of reproductive potential must avoid pregnancy for at least 4 weeks before beginning POMALYST therapy, during therapy, during dose interruptions and for at least 4 weeks after completing therapy.

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Angioedema and severe cutaneous reactions including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) and drug reaction with eosinophilia and systemic symptoms (DRESS) have been reported. DRESS may present with a cutaneous reaction (such as rash or exfoliative dermatitis), eosinophilia, fever, and/or lymphadenopathy with systemic complications such as hepatitis, nephritis, pneumonitis, myocarditis, and/or pericarditis. Discontinue POMALYST for angioedema, skin exfoliation, bullae, or any other severe cutaneous reactions such as SJS, TEN or DRESS, and do not resume therapy

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• Severe Cutaneous Reactions Including Hypersensitivity Reactions

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(additions underlined)

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

Blood and lymphatic system disorders: Pancytopenia

Gastrointestinal disorders: Gastrointestinal hemorrhage

Hepatobiliary disorders: Hepatic failure (including fatal cases), elevated liver enzymes

Immune system disorders: Allergic reactions (e.g., angioedema, urticaria)

Infections and infestations: Hepatitis B virus reactivation, Herpes zoster

Neoplasms benign, malignant and unspecified (incl cysts and polyps): Tumor lysis syndrome, basal cell carcinoma, and squamous cell carcinoma of the skin

Skin and Subcutaneous Tissue Disorders: Stevens-Johnson Syndrome, toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms (DRESS)

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Pregnancy Testing

OMALYST 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 during . Advise females of reproductive potential that they must avoid pregnancy 4 weeks before therapy, while taking POMALYST, during dose interruptions and for at least 4 weeks after completing therapy.

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Severe Cutaneous Reactions Including Hypersensitivity Reactions

Inform patients of the risk for angioedema and severe skin reactions such as SJS, TEN and DRESS and to report any signs and symptoms associated with these events to their healthcare provider for evaluation.

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In two randomized clinical trials in patients with multiple myeloma, the addition of pembrolizumab to a thalidomide analogue plus dexamethasone, a use for which no PD-1 or PD-L1 blocking antibody is indicated, resulted in increased mortality. Treatment of patients with multiple myeloma with a PD-1 or PD-L1 blocking antibody in combination with a thalidomide analogue plus dexamethasone is not recommended outside of controlled clinical trials.

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The following adverse reactions are described in detail in other labeling sections:

• Increased Mortality in Patients with Multiple Myeloma When Pembrolizumab Is Added to a Thalidomide Analogue and Dexamethasone

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No PD-1 or PD-L1 blocking antibodies are approved for the treatment of multiple myeloma. In two randomized clinical trials in patients with multiple myeloma, the addition of pembrolizumab to a thalidomide analogue plus dexamethasone resulted in increased mortality. In Study KN183 (NCT02576977), patients with relapsed or refractory multiple myeloma were randomized to receive pomalidomide and dexamethasone with (n=125) or without (n=124) pembrolizumab. The hazard ratio for overall survival (OS) was 1.61 (95% CI: 0.91, 2.85), increasing the relative risk of death by more than 50% in the experimental arm containing pembrolizumab.

Causes of death in the experimental arm, excluding disease progression, included: myocarditis, Stevens-Johnson syndrome, myocardial infarction, pericardial hemorrhage, cardiac failure, respiratory tract infection, neutropenic sepsis, sepsis, multiple organ dysfunction, and respiratory failure. In Study KN185 (NCT02579863), patients with newly-diagnosed multiple myeloma were randomized to receive lenalidomide and dexamethasone with (n=151) or without (n=150) pembrolizumab. The hazard ratio for OS was 2.06 (95% CI: 0.93, 4.55), increasing the relative risk of death by more than 100% in the experimental arm containing pembrolizumab. Causes of death in the experimental arm, excluding disease progression, included: intestinal ischemia, cardio-respiratory arrest, suicide, pulmonary embolism, cardiac arrest, pneumonia, sudden death, myocarditis, large intestine perforation, and cardiac failure.

The addition of a PD-1 or PD-L1 blocking antibody to a thalidomide analogue is not recommended for the treatment of patients with multiple myeloma outside of controlled clinical trials.

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The following adverse reactions are described in detail in other labeling sections:

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• Increased Mortality in Multiple Myeloma when Pembrolizumab Is Added to Dexamethasone and a Thalidomide Analogue

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Increased Mortality in Multiple Myeloma Patients When Pembrolizumab Was Added to Dexamethasone and a Thalidomide Analogue Regimen

Inform patients of potential for increased risk of death in people with multiple myeloma when a PD-1 blocking antibody was added to a dexamethasone and thalidomide analogue treatment regimen.

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What are the possible side effects of POMALYST?

POMALYST can cause serious side effects, including:

…

• Increased risk of death in people with multiple myeloma when used with pembrozilumab. An increased risk of death has been observed in people with multiple myeloma when pembrolizumab was added to dexamethasone and POMALYST. The use of these drugs together for treating multiple myeloma is not recommended outside of controlled clinical trials.

• 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.

• Pomalidomide is primarily metabolized by CYP1A2 and CYP3A4. Pomalidomide is also a substrate for Pglycoprotein (P-gp).

PLLR Conversion; please refer to label.

• 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.

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)

• 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.

• 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.

• Safety and effectiveness have not been established in pediatric patients. (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.

• Cigarette smoking reduces pomalidomide AUC by 32% due to CYP1A2 induction. Advise patients that smoking may reduce the efficacy of pomalidomide.

• Advise patients that smoking tobacco may reduce the efficacy of POMALYST.