Usual Adult Dose for Multiple Myeloma

4 mg orally once a day on Days 1 through 21 of repeated 28-day cycles in combination with dexamethasone until disease progression or unacceptable toxicity

Comments:

• Consult the manufacturer product information for dexamethasone dosing.

Use: In combination with dexamethasone for patients with multiple myeloma who have received at least 2 prior therapies including lenalidomide and a proteasome inhibitor and have demonstrated disease progression on or within 60 days of completion of the last therapy

Usual Adult Dose for Kaposi's Sarcoma

5 mg orally once a day on Days 1 through 21 of repeated 28-day cycles until disease progression or unacceptable toxicity.

Comments:

• Continue HAART as HIV treatment in patients with AIDS-related Kaposi sarcoma while taking this drug.

Uses:

• For adult patients with AIDS-related Kaposi sarcoma (KS) after failure of highly active antiretroviral therapy (HAART)
• Kaposi sarcoma (KS) in adult patients who are HIV-negative

Renal Dose Adjustments

Multiple myeloma (MM) patients with severe renal impairment requiring dialysis: Reduce the dose to 3 mg orally daily.

Kaposi Sarcoma (KS) patients with severe renal impairment requiring dialysis: Reduce the dose to 4 mg orally daily.

Liver Dose Adjustments

DOSE MODIFICATIONS FOR HEPATIC IMPAIRMENT IN PATIENTS WITH MULTIPLE MYELOMA (MM):

• Mild (Child-Pugh A) or moderate (Child-Pugh B) hepatic impairment: Reduce the dose to 3 mg orally daily.
• Severe (Child-Pugh C) hepatic impairment: Reduce the dose to 2 mg orally daily.

DOSE MODIFICATIONS FOR HEPATIC IMPAIRMENT IN PATIENTS WITH KAPOSI SARCOMA (KS):

• Mild (Child-Pugh A), moderate (Child-Pugh B), and severe (Child-Pugh C): Reduce the dose to 3 mg orally daily.

Dose Adjustments

HEMATOLOGIC DOSE MODIFICATIONS FOR MULTIPLE MYELOMA (MM):
Hematologic adverse reactions: Initiate a new cycle of this drug in patients with multiple myeloma (MM) when the neutrophil count is at least 500/mcL and the platelet count is at least 50,000/mcL.
NEUTROPENIA:

• Absolute neutrophil count (ANC) less than 500/mcL or febrile neutropenia (fever 38.5 degrees Celsius or more and ANC less than 1000/mcL): Withhold therapy until ANC is greater than or equal to 500/mcL; follow complete blood count (CBC) weekly; resume therapy at 1 mg less than the previous dose; permanently discontinue therapy if unable to tolerate 1 mg once daily
• For each subsequent drop of ANC less than 500/mcL: Withhold therapy until ANC is greater than or equal to 500/mcL; resume therapy at 1 mg less than the previous dose; permanently discontinue therapy if unable to tolerate 1 mg once daily

THROMBOCYTOPENIA:

• Platelets less than 25,000/mcL: Withhold therapy until platelets are greater than or equal to 50,000/mcL; follow CBC weekly; resume therapy at 1 mg less than the previous dose; permanently discontinue therapy if unable to tolerate 1 mg once daily
• For each subsequent drop below 25,000/mcL: Withhold therapy until platelets are greater than 50,000/mcL; resume therapy at 1 mg less than the previous dose; permanently discontinue therapy if unable to tolerate 1 mg once daily

HEMATOLOGIC DOSE MODIFICATIONS FOR KAPOSI SARCOMA (KS):
Hematologic adverse reactions: Initiate a new cycle of this drug in patients with KS when the neutrophil count is at least 1000/mcL and the platelet count is at least 75,000/mcL.
NEUTROPENIA:

• Absolute neutrophil count (ANC) less than 500 to less than 1000/mcL:
• Day 1 of cycle: Withhold therapy until ANC is greater than or equal to 1000/mcL; resume therapy at the same dose.
• During cycle: Continue therapy at the current dose.
• ANC less than 500/mcL: Withhold therapy until ANC is greater than or equal to 1000/mcL; resume therapy at the same dose.

FEBRILE NEUTROPENIA:

• ANC less than 1000/mcL and single temperature greater than or equal to 38.3C OR ANC less than 1000/mcL and sustained temperature greater than or equal to 38C for more than 1 hour: Withhold therapy until ANC is greater than 1000/mcL; resume therapy at 1 mg less than the previous dose; permanently discontinue therapy if unable to tolerate 1 mg once daily

THROMBOCYTOPENIA:

• Platelet count 25,000 to less than 50,000/mcL:
• Day 1 of cycle: Withhold therapy until platelet count is greater than or equal to 50,000/mcL; resume therapy at the same dose
• During cycle: Continue therapy at the current dose.
• Platelet count less than 25,000/mcL: Permanently discontinue therapy.

DOSE MODIFICATIONS FOR NON-HEMATOLOGIC ADVERSE REACTIONS:

• Permanently discontinue therapy for angioedema, anaphylaxis, Grade 4 rash, skin exfoliation, bullae, or any other severe dermatologic reaction.
• For other Grade 3 or 4 toxicities, withhold therapy and restart 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.

DOSE MODIFICATIONS FOR STRONG CYP450 1A2 INHIBITORS:

• Avoid concomitant use of this drug with strong CYP450 1A2 inhibitors.
• If concomitant use of a strong CYP450 1A2 inhibitor is unavoidable, reduce the dose of this drug to 2 mg.

Precautions

The US FDA requires a Risk Evaluation and Mitigation Strategy (REMS) for this drug. DRUG and/or SHARED SYSTEM. It includes elements to assure safe use and an implementation system. For additional information: http://www.accessdata.fda.gov/scripts/cder/rems/index.cfm

US BOXED WARNING:

• EMBRYOFETAL TOXICITY: This drug is contradicted in pregnancy. It is an analog of thalidomide, a known human teratogen that causes severe birth defects or embryo-fetal death. Females of reproductive potential must have 2 negative pregnancy tests before starting therapy, and they must use 2 forms of contraception or continuously abstain from heterosexual sex during and for 4 weeks after stopping therapy. This drug 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 multiple myeloma patients treated with this drug. Thromboprophylaxis is recommended; the choice of regimen should be based on assessment of a patient's underlying risk factors.

CONTRAINDICATIONS:

• Hypersensitivity to the active component or any of the ingredients
• Pregnancy

Safety and efficacy have not been established in patients younger than 18 years.

Consult WARNINGS section for additional precautions.

Dialysis

This drug should be taken after completion of dialysis procedure on hemodialysis days.

Other Comments

Administration Advice:

• This drug should be taken without food, at least 2 hours before or 2 hours after a meal.
• This drug should be taken at the same time each day.
• This drug should be swallowed whole with water.
• Capsules should not be broken, chewed, opened, or crushed.
• A missed dose may still be taken up to 12 hours after the normally scheduled time; the dose should be skipped if more than 12 hours have elapsed. Two doses should not be taken at the same time to make up for a missed dose.
• Females of reproductive potential should have negative pregnancy testing and use contraception methods before initiating therapy with this drug.

General:

• Handling and disposal of this drug should be performed in a manner consistent with safe procedures for cytotoxic agents.

Monitoring:

• Embryofetal Toxicity: Pregnancy testing (1st test within 10 to 14 days and 2nd test within 24 hours prior to therapy initiation, then weekly during first 4 weeks of therapy, and every 4 weeks in women with regular menstrual cycles or every 2 weeks in women with irregular menstrual cycles thereafter)
• Hematologic: Toxicities (e.g., neutropenia, anemia, thrombocytopenia), CBC (baseline, then weekly for first 8 weeks of therapy, and monthly thereafter), signs of bleeding
• Hepatic: Liver function tests (monthly)
• Hypersensitivity: Serious allergic reactions (e.g., angioedema, skin exfoliation, bullae)
• Oncologic: Second primary malignancies

Patient Advice:

• Do not smoke during therapy as it may affect how well this drug works.
• Do not donate blood, semen, or sperm during therapy (including during dose interruptions) and for at least one month following the end of therapy.
• Avoid driving and other activities that require alertness (such as operating machinery) until you know how this drug affects you.
• Wash your skin immediately with soap and water and flush mucous membranes thoroughly with water if contact with the powder inside the drug capsule occurs.
• Do not give this drug to another person.