pomalidomide

pom-a-LID-oh-mide

Therapeutic Classification: antineoplastics

Pharmacologic Classification: immunomodulatory agents

High Alert

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.

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 effects:

Decreased progression of multiple myeloma and Kaposi sarcoma.

Absorption: Well absorbed following oral administration.

Distribution: Enters semen.

Metabolism/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.

ROUTE	ONSET	PEAK	DURATION
PO	unknown	unknown	unknown

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: 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.

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)

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.

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.

(Generic available)

Capsules: 1 mg; 2 mg; 3 mg; 4 mg

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, interrupt or discontinue therapy. 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, discontinue therapy and do not resume.

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, then every 4 wk in females with a regular menstrual cycle and every 2 wk in females with an irregular cycle. Discontinue therapy if pregnancy is suspected or confirmed.
- Monitor liver function tests monthly. Discontinue if elevation of liver enzymes occurs. After return to baseline values, may consider resuming therapy at a ↓ dose.
- Multiple Myeloma: Monitor CBC with differential weekly for first 8 wk of therapy and at least monthly thereafter. May cause neutropenia. If ANC <500/mcL or febrile neutropenia (fever ≥38.5°C 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/day less than previous dose. For each subsequent drop of ANC <500/mcL, hold pomalidomide and resume at 1 mg/day less than 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 pomalidomide at 1 mg/day less than previous dose. For each subsequent drop of platelets <25,000/mcL, hold pomalidomide and resume at 1 mg/day less than 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 ↑. 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 first 12 wk and monthly thereafter. May cause neutropenia. If ANC 500 to < 1000/mcL, For Day 1 of cycle: hold pomalidomide until ANC ≥1000/mcL. Resume at same dose. During cycle: Continue pomalidomide at same dose. If ANC <500/mcL, hold pomalidomide until ANC ≥1000/mcL. Resume at same dose.
- May cause febrile neutropenia. If ANC <1000/mcL and single temperature ≥38.3° C or ANC <1000/mcL and sustained temperature ≥38° C for >1 hr, hold pomalidomide until ANC ≥1000 per mcL. Resume at 1 mg/day less than 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. During cycle: continue at current dose. If platelet count <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.

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.

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 professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care professional 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 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 avoid donating blood while taking pomalidomide and for 1 mo following therapy.
Rep: 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 4 wk before, during therapy and interruptions of therapy, and for 4 wk 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. 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 wk 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.

Decrease progression of multiple myeloma and Kaposi sarcoma.

Pomalyst

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