pomalidomide

pomalidomide

(pom-a-lid-oh-mide) ,

Pomalyst

(trade name)

Classification

Therapeutic: antineoplastics
Pharmacologic: immunomodulatory agents
Pregnancy Category: X

Indications

Treatment of multiple myeloma in patients who have received at least 2 prior therapies including lenalidomide and bortezomib and have progressed on or within 60 days of completion of previous treatment.

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 effects

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

ROUTEONSETPEAKDURATION
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Contraindications/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; Obstetric: May cause fetal harm/death; Lactation: Should not be used by nursing mothers.
Use Cautiously in: Patients with reproductive potential (pregnancy should be excluded/prevented, contraception should be practiced by both male and female patients); Pediatric: Safety and effectiveness not been established.

Adverse Reactions/Side Effects

Central nervous system

  • confusion (most frequent)
  • dizziness (most frequent)
  • insomnia (most frequent)
  • fatigue
  • weakness

Respiratory

  • dyspnea (most frequent)

Cardiovascular

  • deep vein thrombosis/pulmonary embolism (life-threatening)
  • peripheral edema (most frequent)

Gastrointestinal

  • ↓ appetite (most frequent)
  • constipation (most frequent)
  • diarrhea (most frequent)
  • nausea (most frequent)
  • vomiting (most frequent)

Genitourinary

  • renal failure

Dermatologic

  • dry skin (most frequent)
  • hyperhidrosis (most frequent)
  • night sweats (most frequent)
  • pruritus (most frequent)
  • rash (most frequent)

Endocrinologic

  • hyperglycemia (most frequent)

Fluid and Electrolyte

  • hypercalcemia (most frequent)
  • hypocalcemia (most frequent)
  • hypokalemia (most frequent)
  • hyponatremia (most frequent)

Hematologic

  • anemia
  • neutropenia
  • thrombocytopenia (life-threatening)
  • leukopenia (most frequent)
  • lymphopenia (most frequent)

Musculoskeletal

  • arthralgia (most frequent)
  • back pain (most frequent)
  • bone pain (most frequent)
  • muscle spasms (most frequent)
  • muscle weakness (most frequent)
  • musculoskeletal pain (most frequent)
  • pain in extremity (most frequent)

Neurologic

  • neuropathy
  • tremor

Miscellaneous

  • infection
  • malignancy
  • fever (most frequent)
  • hypersensitivity reactions (most frequent)
  • chills

Interactions

Drug-Drug interaction

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

Oral (Adults) 4 mg daily on days 1–21 of 28-day cycle, repeated until disease progression; modifications recommended for neutropenia and/or thrombocytopenia.

Availability

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

Nursing implications

Nursing assessment

  • Assess pregnancy status prior to therapy. Effective contraception must be used for at least 4 wks prior to initiating therapy, during therapy, during dose interruptions, and for 4 wks following discontinuation of 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.
  • Assess for signs of deep venous thrombosis and pulmonary edema (dyspnea, chest pain, arm or leg swelling) periodically during therapy). Prophylactic anticoagulation may be considered.
  • Lab Test Considerations: 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 <25000/mcL, interrupt therapy and resume at 1 mg/day less than the previous dose when platelet count returns to ≥50,000/mcL.
    • May cause anemia, leukopenia, lymphopenia.
    • May cause hyperglycemia, hyponatremia, hypokalemia, hypocalcamia, and hypercalcemia.

Potential Nursing 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.
  • Oral: Administer with water on an empty stomach, at least 2 hrs before and 2 hrs after meals. 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.
  • 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.
  • 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.
  • 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 month following therapy.

Evaluation/Desired Outcomes

  • Reduction in clinical and laboratory symptoms of multiple myeloma.
References in periodicals archive ?
Celgene announced that the Phase III, randomized, open-label, international clinical study, OPTIMISMM, achieved its primary endpoint, showing a statistically significant and clinically meaningful improvement in progression-free survival for the pomalidomide arm versus the comparator arm.
Oncopeptides AB (STO:ONCO) on Saturday reported that interim data was presented at the American Society of Haematology (ASH) from the ongoing phase II study HORIZON, treating late-stage patients with Relapsed Refractory Multiple Myeloma (RRMM) that are also refractory to pomalidomide and/or daratumumab.
However, MUM1 may become a therapeutic target of PCNSL on the evidence that a novel class of immunomodulatory drugs, such as lenalidomide and pomalidomide, can treat patients with multiple myeloma and DLBCL via downregulation of MUM1 expression in CRBN-mediated signaling.
In addition, Triphase Accelerator is currently developing marizomib in combination with pomalidomide and dexamethasone in patients with relapsed and refractory multiple myeloma, and has received Orphan Drug designation for marizomib in multiple myeloma in the United States and the European Union.
The All Wales Medicines Strategy Group (AWMSG) has approved the use of pomalidomide in relapsed and refractory myeloma - a cancer which affects 230 in Wales each year.
Therefore, it is essential effective treatments like pomalidomide are available so that we are able to help our patients live longer.
lenalidomide and pomalidomide, have been synthesised and these possess reduced toxicity and greater efficacy (10,11).
The seven new antineoplastic agents are adotrastuzumab emtansine (Kadcyla) for HER2-positive breast cancer; afatinib (Gilotrif) for non-small cell lung cancer; dabrafenib (Tafinlar) for unresectable or metastatic melanoma; ibrutinib (Imbruvica) for mantle cell lymphoma or chronic lymphocytic leukemia; obinutuzumab (Gazyva) for chronic lymphocytic leukemia; pomalidomide (Pomalyst) for multiple myeloma; and trametinib (Mekinist) for unresectable or metastatic melanoma.
In recent years, researches have been done on immunomodulatory drugs, such as thalidomide, revlimid, and pomalidomide.
Several new agents have shown promising results in early phase clinical trials and are being explored as single agents or in combination with other agents in clinical trials like pomalidomide, (70) (a new IMiD) and carfilzomib, (71) (a second generation proteasome inhibitor).
Incidence of extramedullary disease in patients with multiple myeloma in the era of novel therapy, and the activity of pomalidomide on extramedullary myeloma.