Pomalyst

Pomalyst is a prescription medicine used to treat adults with:

• Multiple myeloma. Pomalyst is taken along with the medicine dexamethasone, in people who:
  • have received at least 2 prior medicines to treat multiple myeloma, including a type of medicine known as a proteasome inhibitor and lenalidomide, and
  • their disease has become worse during treatment or within 60 days of finishing the last treatment
• AIDS-related Kaposi sarcoma (KS). Pomalyst is taken when highly active antiretroviral therapy (HAART) has not worked well enough or stopped working (failed)
• KS who do not have HIV infection (HIV negative).

It is not known if Pomalyst is safe and effective in children.

Who should not take Pomalyst?

Do not take Pomalyst if you:

• are pregnant, plan to become pregnant, or become pregnant during treatment with Pomalyst.
• are allergic to pomalidomide or any of the ingredients in Pomalyst.

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.

Pomalyst is only available through a restricted distribution program called Pomalyst REMS.

Venous and Arterial Thromboembolism

• Deep venous thrombosis (DVT), pulmonary embolism (PE), myocardial infarction, and stroke occur in patients with multiple myeloma treated with Pomalyst. Prophylactic antithrombotic measures were employed in clinical trials. Thromboprophylaxis is recommended, and the choice of regimen should be based on assessment of the patient's underlying risk factors.

Pomalyst can cause serious side effects, including:

• Low white blood cells (neutropenia), low platelets (thrombocytopenia), and low red blood cells (anemia) are common with Pomalyst, but can also be serious. You may need a blood transfusion or certain medicines if your blood counts drop too low. Your blood counts should be checked weekly for the first 8 weeks of treatment and monthly after that.
• Severe liver problems, including liver failure and death. Your healthcare provider should do blood tests to check your liver function during your treatment with Pomalyst. Tell your healthcare provider right away if you develop any of the following symptoms of liver problems:
  • Yellowing of your skin or the white part of your eyes (jaundice)
  • Dark or brown (tea-colored) urine
  • Pain on the upper right side of your stomach area (abdomen)
  • Bleeding or bruising more easily than normal
  • Feeling very tired
• 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 rash
  • peeling of your skin or blisters
  • severe itching
  • 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
  • trouble breathing or swallowing
  • raised red areas on your skin (hives)
  • a very fast heartbeat
  • you feel dizzy or faint
• Dizziness and confusion. 
• Nerve damage. Stop taking Pomalyst and call your healthcare provider if you develop symptoms of nerve damage including: numbness, tingling, pain, burning sensation in your hands, legs, or feet.
• 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.
• Tumor lysis syndrome (TLS). TLS is caused by the fast breakdown of cancer cells. TLS can cause kidney failure and the need for dialysis treatment, abnormal heart rhythm, seizure, and sometimes death. Your healthcare provider may do blood tests to check you for TLS.

Your healthcare provider may tell you to stop taking Pomalyst if you develop certain serious side effects during treatment.

The most common side effects of Pomalyst in people with Multiple Myeloma include:

• tiredness and weakness
• constipation
• nausea
• diarrhea
• shortness of breath
• upper respiratory tract infection
• back pain
• fever

The most common side effects of Pomalyst in people with KS include:

• tiredness
• diarrhea
• abnormal kidney function tests
• decreased phosphate and calcium in the blood
• rash. See “Severe allergic reactions and severe skin reactions” above.
• nausea
• constipation
• increased blood sugar
• decreased albumin in the blood

These are not all the possible side effects of Pomalyst.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Pregnancy Testing Prior to Administration

• Females of reproductive potential must have negative pregnancy testing and use contraception methods before initiating Pomalyst.

Recommended Dosage for Multiple Myeloma

• The recommended dosage of Pomalyst is 4 mg once daily orally with or without food on Days 1 through 21 of each 28-day cycle until disease progression. Give Pomalyst in combination with dexamethasone.

Recommended Dosage for Kaposi Sarcoma

• The recommended dosage of Pomalyst is 5 mg once daily taken orally with or without food on Days 1 through 21 of each 28-day cycle until disease progression or unacceptable toxicity. Continue HAART as HIV treatment in patients with AIDS-related Kaposi sarcoma (KS).

Dosage Modifications for Hematologic Adverse Reactions

Multiple Myeloma: Dosage Modifications For Hematologic Adverse Reactions

• Initiate a new cycle of Pomalyst in patients with multiple myeloma (MM) when the neutrophil count is at least 500 per mcL and the platelet count is at least 50,000 per mcL.
• Dosage modification for Pomalyst for hematologic adverse reactions in patients with MM are summarized in Table 1.

Table 1: Dosage Modifications for Pomalyst for Hematologic in MM

Kaposi Sarcoma: Dosage Modifications for Hematologic Adverse Reactions

• Initiate a new cycle of Pomalyst in patients with KS when the neutrophil count is at least 1000 per mcL and the platelet count is at least 75,000 per mcL.
• Dose modifications for Pomalyst for hematologic adverse reactions in patients with KS are summarized in Table 2.

Table 2: Dosage Modifications for Pomalyst for Hematologic Adverse Reactions in KS

Dosage Modifications for Non-Hematologic Adverse Reactions

• Permanently discontinue Pomalyst for angioedema, anaphylaxis, Grade 4 rash, skin exfoliation, bullae, or any other severe dermatologic reaction.
• 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.

Dosage Modifications for Strong CYP1A2 Inhibitors

• Avoid concomitant use of Pomalyst with strong CYP1A2 inhibitors. If concomitant use of a strong CYP1A2 inhibitor is unavoidable, reduce Pomalyst dose to 2 mg.

Dosage Modification for Severe Renal Impairment on Hemodialysis

Take Pomalyst after completion of dialysis procedure on hemodialysis days.

• For patients with MM with severe renal impairment requiring dialysis, reduce the recommended dosage to 3 mg orally daily.
• For patients with KS with severe renal impairment requiring dialysis, reduce the recommended dosage to 4 mg orally daily.

Dosage Modification for Hepatic Impairment

Multiple Myeloma

• For patients with MM with mild or moderate hepatic impairment (Child-Pugh A or B), reduce the recommended dosage to 3 mg orally daily.
• For patients with MM with severe hepatic impairment (Child-Pugh C), reduce the recommended dosage to 2 mg.

Kaposi Sarcoma

• For patients with KS with mild, moderate, or severe hepatic impairment (Child-Pugh A, B, or C), reduce the recommended dosage to 3 mg orally daily.

Administration

• Swallow capsules whole with water. Do not break, chew, or open the capsules. Pomalyst may be taken with or without food.

Drugs That Affect Pomalidomide Plasma Concentrations

CYP1A2 Inhibitors

• In healthy subjects, co-administration of fluvoxamine, a strong CYP1A2 inhibitor, increased Cmax and AUC of pomalidomide by 24% and 125% respectively.
• Increased pomalidomide exposure may increase 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.

• Based on the mechanism of action and findings from animal studies, Pomalyst can cause embryo-fetal harm when administered to a pregnant female and is contraindicated during pregnancy.
• There is a pregnancy exposure registry that monitors pregnancy outcomes in females exposed to Pomalyst during pregnancy as well as female partners of male patients who are exposed to Pomalyst. This registry is also used to understand the root cause for the pregnancy. Report any suspected fetal exposure to Pomalyst to the FDA via the MedWatch program at 1-800-FDA-1088 and also to Celgene Corporation at 1-888-423­5436.
• There is no information regarding the presence of pomalidomide in human milk, the effects of Pomalyst on the breastfed child, or the effects of Pomalyst on milk production.
• Because many drugs are excreted in human milk and because of the potential for adverse reactions in a breastfed child from Pomalyst, women should not breastfeed during treatment with Pomalyst.