General

**REMS Drug**

Pronunciation:
pom-a-lid-oh-mide

Trade Name(s)

• Pomalyst

Ther. Class.

antineoplastics

Pharm. Class.

immunomodulatory agents

Indications

Treatment of 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).

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 (NK) cell-mediated immunity and inhibits production of pro-inflammatory cytokines.

Therapeutic Effect(s):

Decreased progression of multiple myeloma.

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

Contraindication/Precautions

Contraindicated in:

• Hypersensitivity, cross-sensitivity with thalidomide may occur
• Blood should not be donated
• Serum creatinine >3.0 mg/dL
• Serum bilirubin >2.0 mg/dL and AST/ALT >3.0 × ULN
• OB:   May cause fetal harm/death
•  Lactation: Avoid breastfeeding.

Use Cautiously in:

• Rep:   Women of reproductive potential and men with female partners of reproductive potential
• Pedi:  Safety and effectiveness not established.

Adverse Reactions/Side Effects

CNS: confusion, dizziness, insomnia, fatigue, weakness

Resp: dyspnea

CV: DEEP VEIN THROMBOSIS/PULMONARY EMBOLISM, MI, STROKE, peripheral edema

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

GU: renal failure

Derm: dry skin, hyperhidrosis, night sweats, pruritus, rash, skin exfoliation

Endo: hyperglycemia

F and E: hypercalcemia, hypocalcemia, hypokalemia, hyponatremia

Hemat: ANEMIA, NEUTROPENIA, THROMBOCYTOPENIA, leukopenia, lymphopenia

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

Neuro: neuropathy, tremor

Misc: hypersensitivity reactions including ANGIOEDEMA, SKIN EXFOLIATION, and BULLAE, INFECTION, MALIGNANCY, fever, hypersensitivity reactions, chills

* 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

PO (Adults): 4 mg once daily on days 1–21 of 28-day cycle, repeated until disease progression; modifications recommended for neutropenia and/or thrombocytopenia;  Concurrent use of strong CYP1A2 inhibitor– ↓ dose of pomalidomide by 50%.

Renal Impairment 
PO (Adults): Hemodialysis– ↓ dose to 3 mg once daily; give dose after dialysis on hemodialysis days.

Hepatic Impairment 
PO (Adults): Moderate hepatic impairment (Child-Pugh Classes A or B)– ↓ dose to 3 mg once daily;  Severe hepatic impairment (Child-Pugh Class C)– ↓ dose to 2 mg once daily.

Availability

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

Lab Test Considerations:

Assess pregnancy status 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 CBC with differential, platelet count, hemoglobin and hematocrit weekly for first 8 wks of therapy and at least monthly thereafter. May require dose reduction.
• May cause neutropenia. If absolute neutrophil count (ANC) <500/mcL or febrile neutropenia (fever ≥38.5° and ANC <1000/mcL), interrupt pomalidomide therapy and follow CBC weekly. If ANC returns to ≥500/mcL resume pomalidomide at 3 mg/day. For each subsequent drop <500/mcL, interrupt therapy and resume at 1 mg/day less than the previous dose when ANC returns to ≥500/mcL.
• May cause thrombocytopenia. If platelets fall to <25,000/mcL interrupt pomalidomide therapy and follow CBC weekly. When platelets return to >50,000/mcL, resume at 3 mg/day. For each subsequent drop <25,000/mcL, interrupt therapy and resume at 1 mg/day less than the 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.
• May cause anemia, leukopenia, lymphopenia.
• May cause hyperglycemia, hyponatremia, hypokalemia, hypocalcamia, and hypercalcemia.

Potential Diagnoses

• Deficient knowledge, related to medication regimen (Patient/Family/Teaching) 

Implementation

• 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 who are not pregnant must comply with pregnancy testing and contraception requirements and males must comply with contraception requirements.
• PO Administer with water on an empty stomach, without regard to food. Swallow capsule whole; 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.
• Advise patient to notify health care professional if shortness of breath, chest pain, or arm or leg swelling 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 that they cannot donate blood and male patients cannot donate sperm while taking pomalidomide and for 1 mo following therapy.
• Rep:  Inform female patients 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.
• Rep:  Male patients receiving pomalidomide must always use a latex or synthetic condom during any contact with females with child-bearing potential, even if they have undergone a successful vasectomy.

Evaluation/Desired Outcomes

Reduction in clinical and laboratory symptoms of multiple myeloma.