pomalidomide

General

High Alert Medication: This medication bears a heightened risk of causing significant patient harm when it is used in error.

**REMS Drug**

Pronunciation:
pom-a-lid-oh-mide


Trade Name(s)

  • Pomalyst

Ther. Class.

antineoplastics

Pharm. Class.

immunomodulatory agents

Indications

  • Multiple myeloma in patients who have received ≥2 prior therapies including lenalidomide and a proteasome inhibitor and have progressed on or within 60 days of completion of previous treatment (with prednisone).
  • AIDS-related Kaposi sarcoma after failure of highly active antiretroviral therapy.
  • Kaposi sarcoma in patients who are HIV-negative.

Action

Inhibits proliferation and induced apoptosis of hematopoietic tumor cells. Proliferation of resistant multiple myeloma cell lines and may act synergistically with dexamethasone. Enhances T cell and natural killer cell-mediated immunity and inhibits production of proinflammatory cytokines.

Therapeutic Effect(s):

Decreased progression of multiple myeloma and Kaposi sarcoma.

Pharmacokinetics

Absorption: Well absorbed following oral administration.

Distribution: Enters semen.

Metabolism and Excretion: Primarily metabolized in the liver by CYP1A2 and CYP3A4 with some metabolism by CYP2C19 and CYP2D6. Metabolites excreted in urine and feces. Minimal amounts excreted unchanged in urine.

Half-life: Normal subjects: 9.5 hr;  Patients with myeloma: 7.5 hr.

TIME/ACTION PROFILE

ROUTEONSETPEAKDURATION
POunknownunknownunknown

Contraindication/Precautions

Contraindicated in:

  • Severe hypersensitivity;
  • Blood should not be donated;
  • Serum creatinine >3 mg/dL;
  • Serum bilirubin >2 mg/dL and AST/ALT >3 times upper limit of normal;
  • Concurrent use of pembrolizumab (↑ risk of mortality);
  • OB:  Black Box:   Pregnancy;
  • Lactation: Lactation.

Use Cautiously in:

  • Rep:  Black Box:   Women of reproductive potential and men with female partners of reproductive potential;
  • Pedi:  Safety and effectiveness not established in children.

Adverse Reactions/Side Effects

CV: peripheral edema, DEEP VEIN THROMBOSIS (DVT), MI

Derm: dry skin, hyperhidrosis, night sweats, pruritus, rash, DRUG REACTION WITH EOSINOPHILIA AND SYSTEMIC SYMPTOMS (DRESS), skin exfoliation, STEVENS-JOHNSON SYNDROME (SJS), TOXIC EPIDERMAL NECROLYSIS (TEN)

Endo: hyperglycemia

F and E: hypercalcemia, hypocalcemia, hypokalemia, hyponatremia

GI: ↓ appetite, constipation, diarrhea, nausea, vomiting, HEPATOTOXICITY

GU: renal failure

Hemat: ANEMIA, leukopenia, lymphopenia, NEUTROPENIA, THROMBOCYTOPENIA

MS: arthralgia, back pain, bone pain, muscle spasms, muscle weakness, musculoskeletal pain, pain in extremity

Neuro: confusion, dizziness, insomnia, neuropathy, fatigue, STROKE, tremor, weakness

Resp: dyspnea, PULMONARY EMBOLISM (PE)

Misc: fever, INFECTION, MALIGNANCY, chills, HYPERSENSITIVITY REACTIONS (including anaphylaxis and angioedema)

* CAPITALS indicate life-threatening.
Underline indicate most frequent.

Interactions

Drug-Drug

  •  CYP3A inhibitors,  CYP1A2 inhibitors, or  P-glycoprotein (P-gp) inhibitors, including  ketoconazole, may ↑ levels and risk of toxicity; avoid concurrent use.
  •  CYP3A inducers,  CYP1A2 inducers, or  P-gp inducers, including  rifampin, may ↓ levels and effectiveness; avoid concurrent use.

Route/Dosage

Multiple Myeloma

PO (Adults): 4 mg once daily on Days 1–21 of each 28-day cycle; continue until disease progression;  Concurrent use of strong CYP1A2 inhibitor: 2 mg once daily on Days 1–21 of each 28-day cycle; continue until disease progression.

Renal Impairment 
PO (Adults): Hemodialysis: 3 mg once daily (give dose after dialysis on hemodialysis days); continue until disease progression.

Hepatic Impairment 
PO (Adults): Mild or moderate hepatic impairment: 3 mg once daily; continue until disease progression;  Severe hepatic impairment: 2 mg once daily; continue until disease progression.

Kaposi Sarcoma

PO (Adults): 5 mg once daily on Days 1–21 of each 28-day cycle; continue until disease progression or unacceptable toxicity;  Concurrent use of strong CYP1A2 inhibitor: 2 mg once daily on Days 1–21 of each 28-day cycle; continue until disease progression or unacceptable toxicity.

Renal Impairment 
PO (Adults): Hemodialysis: 4 mg once daily on Days 1–21 of each 28-day cycle (give dose after dialysis on hemodialysis days); continue until disease progression or unacceptable toxicity.

Hepatic Impairment 
PO (Adults): Mild, moderate, or severe hepatic impairment: 3 mg once daily on Days 1–21 of each 28-day cycle; continue until disease progression or unacceptable toxicity.

Availability (generic available)

Capsules: 1 mg, 2 mg, 3 mg, 4 mg

Assessment

  • Assess for signs of DVT and PE (dyspnea, chest pain, arm or leg swelling) periodically during therapy. Prophylactic anticoagulation is recommended.
  • Monitor for signs and symptoms of SJS, TEN, and DRESS (rash, exfoliative dermatitis, eosinophilia, fever, lymphadenopathy, hepatitis, nephritis, pneumonitis, myocarditis, pericarditis) during therapy. May be fatal.  If Grade 2 or 3 skin rash occurs,  hold or discontinue pomalidomide.  If Grade 4 rash; exfoliative or bullous rash; or SJS, TEN, or DRESS occurs,  permanently discontinue pomalidomide.
  • Monitor for hypersensitivity reactions (angioedema, skin exfoliation, bullae, severe dermatologic reactions) during therapy.  If symptoms occur,  permanently discontinue pomalidomide.

Lab Test Considerations:

Verify two negative pregnancy tests before starting therapy. Pregnancy tests must be done within 10–14 days and within 24 hr of starting therapy. Once treatment has started, pregnancy tests should occur weekly during first 4 wk of use and then every 4 wk in women with a regular menstrual cycle and every 2 wk in women with an irregular cycle. Discontinue therapy if pregnancy is suspected or confirmed.

  • Monitor liver function tests monthly.  If ↑ liver enzymes occurs , hold pomalidomide. After return to baseline values, may consider resuming pomalidomide at ↓ dose.
  •  Multiple Myeloma: Monitor CBC with differential weekly for 1st 8 wk of therapy and at least monthly thereafter. May cause neutropenia.  If ANC <500 cells/mcL or febrile neutropenia (fever ≥38.5°C and ANC <1000 cells/mcL),  hold pomalidomide until ANC ≥500 cells/mcL and follow CBC weekly. If ANC returns to ≥500 cells/mcL, resume pomalidomide at 1 mg/day less than previous dose.  For each subsequent drop of ANC <500 cells/mcL,  hold pomalidomide and resume at 1 mg/day less than previous dose when ANC returns to ≥500 cells/mcL.
  • May cause thrombocytopenia.  If platelets fall to <25,000 cells/mcL, hold pomalidomide until platelets ≥50,000 cells/mcL and follow CBC weekly. When platelets return to >50,000 cells/mcL, resume pomalidomide at 1 mg/day less than previous dose.  For each subsequent drop of platelets <25,000 cells/mcL,  hold pomalidomide and resume at 1 mg/day less than previous dose when platelet count returns to ≥50,000 cells/mcL.
  • Monitor liver function tests (AST, ALT, serum bilirubin) monthly during therapy. Hold pomalidomide if liver enzymes ↑. May restart therapy at a ↓ dose when levels return to normal. Permanently discontinue pomalidomide if unable to tolerate 1 mg once daily.
  •  Kaposi sarcoma: Monitor CBC every 2 wk for 1st 12 wk and monthly thereafter. May cause neutropenia.  If ANC 500–< 1000 cells/mcL,  for Day 1 of cycle, hold pomalidomide until ANC ≥1000 cells/mcL. Resume at same dose. During cycle, continue pomalidomide at same dose.  If ANC <500 cells/mcL,  hold pomalidomide until ANC ≥1000 cells/mcL. Resume at same dose.
  • May cause febrile neutropenia.  If ANC <1000 cells/mcL and single temperature ≥38.3° C or ANC <1000 cells/mcL and sustained temperature ≥38° C for >1 hr,  hold pomalidomide until ANC ≥1000 cells/mcL. Resume at 1 mg/day less than previous dose.
  • May cause thrombocytopenia.  If platelets 25,000–<50,000 cells/mcL,  for Day 1 of cycle, hold pomalidomide until platelets ≥50,000 cells/mcL. Resume at same dose. During cycle, continue at current dose.  If platelets <25,000 cells/mcL,  permanently discontinue pomalidomide. Permanently discontinue pomalidomide if unable to tolerate 1 mg once daily.
  • May cause hyperglycemia, hyponatremia, hypokalemia, hypocalcamia, and hypercalcemia.

Implementation

  •  REMS: Black Box:  Pomalidomide is only available through PS-Pomalidomide REMS program. Prescribers and pharmacies must be certified. Patients must sign a patient-prescriber form and comply with REMS requirements. Women of reproductive potential who are not pregnant must comply with pregnancy testing and contraception requirements, and men must comply with contraception requirements.
  • Thromboprophylaxis should be based on assessment of patient's underlying risk factors.
  • PO Administer with water on an empty stomach, without regard to food.  DNC: Swallow capsule whole with water; do not open, break, or chew. 

Patient/Family Teaching

  • Black Box:   REMS: Instruct patient to comply with all aspects of the  PS-Pomalidomide REMS program. Details available at www.PS-PomalidomideREMS.com.
  • Explain purpose and side effects of medication to patient. Advise patient to read  Patient Information  before starting therapy. Instruct patient to take as directed daily at the same time each day. Missed doses may be taken up to 12 hr after the time it would be normally be taken. If >12 hr, skip dose and take regularly scheduled dose the next day; do not double doses.
  • Advise patient to notify health care provider of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care provider before taking other medications.
  • Caution patient not to share pomalidomide with anyone, even someone who has similar symptoms.
  • Instruct patient to avoid smoking during therapy; may ↓ efficacy of pomalidomide.
  • Advise patient to notify health care provider if signs and symptoms of a blood clot (shortness of breath, chest pain, arm or leg swelling), heart attack (chest pain that may spread to arms, neck, jaw, back, or abdomen; feeling sweaty; shortness of breath; feeling sick or vomiting), or stroke (sudden numbness or weakness, especially on one side of body; severe headache or confusion; problems with vision, speech, or balance) occur.
  • Advise patient to notify health care provider if signs and symptoms of liver problems (yellowing of skin or white part of eyes, dark or brown urine, pain on upper right side of abdomen, unusual bleeding or bruising, feeling tired), skin reactions (red, itchy skin rash; peeling of skin; blisters; severe itching; fever), or allergic reaction (swelling of lips, mouth, tongue, or throat; trouble breathing or swallowing; very fast heartbeat; feeling dizzy or faint; hives) occur.
  • May cause dizziness and confusion. Caution patient to avoid driving and other activities requiring alertness until response to medication is known.
  • Advise patient to avoid donating blood while taking pomalidomide and for 1 mo following therapy.
  • Rep:  Black Box:   May cause fetal harm. Inform women of reproductive potential that they must use one highly effective method (IUD, hormonal contraceptive, tubal ligation, partner's vasectomy) and one additional method (latex or synthetic condom, diaphragm, cervical cap) for 4 wk before, during therapy and interruptions of therapy, and for 4 wk after last dose and to avoid breastfeeding during therapy. May impair female fertility. Encourage pregnant women and pregnant female partners of men exposed to pomalidomide during pregnancy to enroll in the registry to monitor outcomes of pregnancy by calling 1-888-423-5436. Pomalidomide is present in semen. Male patients receiving pomalidomide must always use a latex or synthetic condom during any contact with women of reproductive potential and for 4 wk after last dose, even if they have undergone a successful vasectomy. Instruct men to avoid donating sperm while taking pomalidomide and for 1 mo after last dose.

Evaluation/Desired Outcomes

Decrease progression of multiple myeloma and Kaposi sarcoma.