pomalidomide

General

**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 at least 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 (KS) after failure of highly active antiretroviral therapy.
  • KS 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 pro-inflammatory cytokines.

Therapeutic Effect(s):

Decreased progression of multiple myeloma and KS.

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;  myeloma patients– 7.5 hr.

TIME/ACTION PROFILE

ROUTEONSETPEAKDURATION
POunknownunknownunknown

Contraindication/Precautions

Contraindicated in:

  • Severe hypersensitivity
  • Blood should not be donated
  • Serum creatinine >3.0 mg/dL
  • Serum bilirubin >2.0 mg/dL and AST/ALT >3x ULN
  • Concurrent use of pembrolizumab (↑ risk of mortality)
  • OB:   Pregnancy
  • Lactation: Lactation.

Use Cautiously in:

  • Rep:   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: STROKE, peripheral edema, DEEP VEIN THROMBOSIS/PULMONARY EMBOLISM, 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: neuropathy, tremor, confusion, dizziness, insomnia, fatigue, weakness

Resp: dyspnea

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

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

Interactions

Drug-Drug

  • Blood levels and toxicity may be ↑  drugs that inhibit CYP3A, CYP1A2 or P-gp  inhibitors including  ketoconazole ; avoid concurrent use.
  • Blood levels and effectiveness may be ↓ by  drugs that are strong inducers of CYP1A2, CYP3A or P-gp, including  rifampin ; avoid concurrent use.
  •  Cigarette smoking  may ↓ blood levels and effectiveness.

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 (Child-Pugh Class A or B)– 3 mg once daily; continue until disease progression;  Severe hepatic impairment (Child-Pugh Class C)– 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 (Child-Pugh Class A, B, or C)– 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 deep venous thrombosis and pulmonary edema (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. Interrupt or discontinue therapy for Grade 2 or 3 skin rash. Permanently discontinue pomalidomide for Grade 4 rash, exfoliative or bullous rash, or for SJS, TEN or DRESS.

  • Monitor for hypersensitivity reactions (angioedema, skin exfoliation, bullae, severe dermatologic reactions) during therapy. If symptoms occur discontinue therapy and do not resume.

Lab Test Considerations:

Verify negative pregnancy test prior to therapy. Pregnancy tests must be done within 10–14 days and within 24 hrs of starting therapy. Once treatment has started pregnancy tests should occur weekly during first 4 wks of use, then every 4 wks in females with a regular menstrual cycle and every 2 wks in females with an irregular cycle. Pomalidomide must be discontinued if pregnancy is suspected or confirmed.

  • Monitor liver function tests monthly. Stop pomalidomide upon elevation of liver enzymes and evaluate. After return to baseline values, may consider resuming at a lower dose.
  •  Multiple Myeloma: Monitor CBC with differential, platelet count, hemoglobin and hematocrit weekly for first 8 wks of therapy and at least monthly thereafter. May cause neutropenia.  If absolute neutrophil count (ANC) <500/mcL or febrile neutropenia (fever ≥38.5° and ANC <1000/mcL),  hold pomalidomide until ANC ≥500/mcL and follow CBC weekly. If ANC returns to ≥500/mcL resume pomalidomide at 1 mg < previous dose.  For each subsequent drop <500/mcL,  hold therapy and resume at 1 mg/day < previous dose when ANC returns to ≥500/mcL.
  • May cause thrombocytopenia.  If platelets fall to <25,000/mcL, hold pomalidomide until platelets ≥50,000/mcL and follow CBC weekly. When platelets return to >50,000/mcL, resume at 1 mg < previous dose.  For each subsequent drop <25,000/mcL,  hold therapy and resume at 1 mg/day < previous dose when platelet count returns to ≥50,000/mcL.
  • Monitor liver function tests (AST, ALT, serum bilirubin) monthly during therapy. Interrupt therapy if liver enzymes ↑ and evaluate. May restart therapy at a lower dose when levels return to normal. Permanently discontinue pomalidomide if unable to tolerate 1 mg once daily.
  •  KS: Monitor CBC every 2 wks for first 12 wks and monthly thereafter. May cause neutropenia.  If ANC 500 to < 1,000/mcL,  For Day 1 of cycle: hold pomalidomide until ANC ≥1,000/mcL. Resume at same dose. During cycle: Continue pomalidomide at same dose.  If ANC <500/mcL,  hold pomalidomide until ANC ≥1,000/mcL. Resume at same dose.
  • May cause febrile neutropenia.  If ANC <1,000/mcL and single temperature ≥38.3° C or ANC <1,000/mcL and sustained temperature ≥38° C for >1 hour,  hold pomalidomide until ANC ≥1,000 per mcL. Resume at dose 1 mg < previous dose.
  • May cause thrombocytopenia.  If platelet count 25,000 to <50,000/mcL, For Day 1 of cycle: hold pomalidomide until platelet count ≥50,000/mcL. Resume at same dose. For During cycle: continue at current dose.  If platelet count less than 25,000/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: Pomalidomide is only available through POMALYST REMS program. Prescribers and pharmacies must be certified. Patients must sign a Patient-Prescriber form and comply with REMS requirements. Female patients of reproductive potential who are not pregnant must comply with pregnancy testing and contraception requirements and males must comply with contraception requirements.
  • Consider thromboprophylaxis 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

  • Instruct patient to take pomalidomide as directed daily at the same time each day. Missed doses may be taken up to 12 hrs after the time it would be normally be taken. If more than 12 hrs, skip dose and take regularly scheduled dose the next day; do not double doses.
  • Caution patient not to share pomalidomide with anyone, even someone who has similar symptoms.
  • Instruct patient to avoid smoking during therapy, may reduce efficacy of pomalidomide.

  • Advise patient to notify health care professional if signs and symptoms of a blood clot (shortness of breath, chest pain, arm or leg swelling) or heart attack (chest pain that may spread to arms, neck, jaw, back, or abdomen, feeling sweaty, shortness of breath, feeling sick or vomiting), stroke (sudden numbness or weakness, especially on one side of body, severe headache or confusion, problems with vision, speech, or balance), 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 notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care professional before taking other medications.
  • Advise patient to avoid donating blood while taking pomalidomide and for 1 mo following therapy.
  • Rep:  Pomalidomide may cause fetal harm. Inform females 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 at least 4 wks before, during therapy and interruptions of therapy, and for 4 wks following discontinuation of therapy and to avoid breastfeeding during therapy. May impair female fertility. Encourage females and female partners of male patients exposed to pomalidomide during pregnancy to enroll in the pregnancy exposure registry to monitor outcomes of pregnancy by calling 1-888-423-5436.
  • Rep:  Pomalidomide is present in semen. Male patients receiving pomalidomide must always use a latex or synthetic condom during any contact with females of reproductive potential and for 4 wks after discontinuation of therapy, even if they have undergone a successful vasectomy. Instruct male patients to avoid donating sperm while taking pomalidomide and for 1 mo following therapy.

Evaluation/Desired Outcomes

  • Reduction in clinical and laboratory symptoms of multiple myeloma.
  • Decrease in progression of KS.