Pomalidomide (Monograph)

Brand name: Pomalyst
Drug class: Antineoplastic Agents

Medically reviewed by Drugs.com on Jun 10, 2024. Written by ASHP.

[Web]

Introduction

Biologic response modifier; thalidomide analog with immunomodulatory, antineoplastic, and antiangiogenic activity.

Uses for Pomalidomide

Multiple Myeloma

Treatment of multiple myeloma in patients who received ≥2 prior therapies including a proteasome inhibitor and lenalidomide and demonstrated disease progression during or ≤60 days following completion of their last therapy (designated an orphan drug by FDA for use in multiple myeloma).

Kaposi Sarcoma

Treatment of Kaposi sarcoma in adult patients with acquired immunodeficiency syndrome (AIDS)-related Kaposi sarcoma after failure of highly active antiretroviral therapy (HAART).

Treatment of Kaposi sarcoma in adult patients who are HIV-negative.

Continued approval for this indication may be contingent upon verification of clinical benefit in confirmatory trials.

Designated an orphan drug by FDA for use in Kaposi sarcoma.

Pomalidomide Dosage and Administration

General

Pretreatment Screening

• Tests to exclude pregnancy must be performed within 10–14 days and again within 24 hours immediately prior to treatment initiation.

• Multiple myeloma: Do not begin a new treatment cycle until absolute neutrophil count (ANC) ≥500/mm³ and platelet count ≥50,000/mm³.

• Kaposi sarcoma: Do not begin a new treatment cycle until ANC ≥1000/mm³ and platelet count ≥75,000/mm³.

• Assess patients with multiple myeloma for risk factors for thromboembolism.

Patient Monitoring

• Multiple myeloma: CBCs weekly during first 8 weeks of therapy and at least monthly thereafter.

• Kaposi sarcoma: CBCs every 2 weeks for the first 3 months and monthly thereafter.

• Pregnancy tests weekly during the first month of therapy, then every 2 or 4 weeks in females with irregular or regular menstrual cycles, respectively.

• Development of second primary malignancies.

• Liver function tests (LFTs) monthly.

• Tumor lysis syndrome in patients with a high tumor burden.

Premedication and Prophylaxis

• Thromboprophylaxis recommended. Carefully assess patients receiving pomalidomide for risk factors for thromboembolism; base decisions regarding use of thromboprophylaxis and appropriate thromboprophylaxis regimens (e.g., aspirin, anticoagulant) on patient’s risk.

Dispensing and Administration Precautions

Handling and Disposal

• Consult specialized references for procedures for proper handling and disposal of antineoplastics.

• Avoid contact of capsule contents with skin or mucous membranes. If such contact occurs, wash affected areas of skin thoroughly with soap and water and rinse affected mucosa thoroughly with water.

REMS

• Distribution of pomalidomide is restricted because it is an analog of thalidomide (a known human teratogen that can cause severe birth defects).

• Must be obtained through a restricted distribution program (Pomalyst Risk Evaluation and Mitigation Strategy [REMS]) to help ensure that fetal exposure to pomalidomide does not occur. Clinicians, pharmacists, and patients must be registered in the program before they can prescribe, dispense, and receive pomalidomide; compliance with all terms outlined in the program is mandatory.

• The Pomalyst REMS program controls access to pomalidomide; educates participants (clinicians, pharmacists, patients) about the risks associated with pomalidomide and the procedural requirements for safe use; and monitors compliance with the registration, education, and safety requirements of the program.

• Prescribe and dispense no more than a 28-day supply at one time.

• For additional details on program requirements, contact Bristol Myers Squibb at 888-423-5436 or visit [Web].

Administration

Oral Administration

Administer orally with water once daily.

Administer without regard to food.

Swallow capsules whole; do not break, chew, or open capsules.

Dosage

Adults

Multiple Myeloma

Oral

4 mg once daily on days 1–21 of each 28-day cycle; in combination with dexamethasone (40 mg once daily [or 20 mg in those >75 years of age] on days 1, 8, 15, and 22 of each 28-day cycle used in clinical trials)

Continue until disease progression or unacceptable toxicity occurs.

Dosage Modification for Toxicity in Patients with Multiple Myeloma

If adverse effects occur, temporarily interrupt therapy, reduce dosage, and/or permanently discontinue pomalidomide as described in Table 1.

If angioedema, anaphylaxis, grade 4 rash, skin exfoliation, bullae, or any other severe dermatologic reaction occurs, permanently discontinue pomalidomide.

Kaposi Sarcoma

Oral

5 mg once daily on days 1–21 of each 28-day cycle.

Continue until disease progression or unacceptable toxicity.

Continue HV therapy with HAART in patients with AIDS-related Kaposi sarcoma.

Dosage Modification for Toxicity in Patients with Kaposi Sarcoma

If adverse effects occur, temporarily interrupt therapy, reduce dosage, and/or permanently discontinue pomalidomide as described in Table 2.

If angioedema, anaphylaxis, grade 4 rash, skin exfoliation, bullae, or any other severe dermatologic reaction occurs, permanently discontinue pomalidomide.

Dosage Modification for Concomitant Use with CYP1A2 Inhibitors

Avoid concomitant use with potent CYP1A2 inhibitors. If concomitant use cannot be avoided, reduce dosage to 2 mg daily.

Special Populations

Hepatic Impairment

Initial dosage reduction is necessary in patients with hepatic impairment (see Tables 3 and 4).

Renal Impairment

In patients with multiple myeloma and severe renal impairment requiring dialysis: Reduce initial dosage to 3 mg daily.

In patients with Kaposi sarcoma and severe renal impairment requiring dialysis: Reduce initial dosage to 4 mg daily.

Administer pomalidomide after completion of hemodialysis.

Geriatric Patients

No pomalidomide dosage adjustment recommended.

Cautions for Pomalidomide

Contraindications

• Pregnancy.

• Known hypersensitivity (e.g., angioedema, anaphylaxis) to pomalidomide or any ingredient in the formulation.

Warnings/Precautions

Warnings

Fetal/Neonatal Morbidity and Mortality

May cause fetal harm; contraindicated in pregnant women. Teratogenicity demonstrated in animals; structurally similar to thalidomide, a known human teratogen associated with severe birth defects and fetal death.

Pregnancy must be prevented (even in females with a history of infertility) by simultaneous use of 2 forms of effective contraception for ≥4 weeks before, throughout, and for 4 weeks after therapy, including during dosage interruptions. Must include at least 1 highly effective contraceptive method (e.g., intrauterine device [IUD], hormonal contraceptive, tubal ligation, vasectomized partner); other method may be an effective barrier method (e.g., latex or synthetic condom, diaphragm, cervical cap). Mandatory contraception not required for females who have undergone hysterectomy or bilateral oophorectomy, who are postmenopausal and have had no menses for ≥24 consecutive months, or who practice continuous abstinence from heterosexual contact.

Pomalidomide distributes into semen; sexually mature males (including those who have undergone successful vasectomy) must use a latex or synthetic condom each time they have sexual contact with a woman of childbearing potential during and for up to 28 days after therapy. Men must not donate semen during and for 4 weeks after therapy.

Patients must not donate blood during and for ≥1 month after therapy because of potential for any pomalidomide present in blood to be transfused into a pregnant woman.

Obtain 2 negative pregnancy test reports prior to initiating therapy in women of childbearing potential; tests to exclude pregnancy must be performed within 10–14 days and again within 24 hours immediately prior to treatment initiation. Repeat pregnancy tests weekly during the first month of therapy, then every 2 or 4 weeks in women with irregular or regular menstrual cycles, respectively.

Provide pregnancy testing and counseling if a patient misses her period or has abnormalities in menstrual bleeding. Discontinue drug during evaluation.

If pregnancy occurs, immediately discontinue treatment and apprise of potential fetal hazard. Refer patient to obstetrician-gynecologist experienced in reproductive toxicity for further evaluation and counseling. Report any suspected fetal exposure to FDA MedWatch Program at 800-FDA-1088 and to manufacturer at 888-423-5436.

Thromboembolic Events

Increased risk of venous and arterial thromboembolism (e.g., DVT, PE, MI, stroke).

Thromboprophylaxis is recommended. Carefully assess patients receiving pomalidomide for risk factors for thromboembolism; base decisions regarding use of thromboprophylaxis and appropriate thromboprophylaxis regimens (e.g., aspirin, anticoagulant) on patient’s risk. Risk is increased in patients with known risk factors (e.g., history of thrombosis); minimize modifiable risk factors (e.g., hyperlipidemia, hypertension, smoking).

Other Warnings and Precautions

Treatment-related Mortality

Increased mortality reported in patients with multiple myeloma receiving pembrolizumab in combination with a thalidomide analog and dexamethasone.

Patients with multiple myeloma should not receive an anti-programmed death receptor-1 (anti-PD-1) or anti-programmed-death ligand-1 (anti-PD-L1) in combination with a thalidomide analog and dexamethasone outside of a clinical trial.

Hematologic Effects

Risk of severe (grade 3 or 4) neutropenia, anemia, and/or thrombocytopenia in patients with multiple myeloma receiving pomalidomide in combination with low-dose dexamethasone. In the pivotal Kaposi sarcoma trial, neutropenia was the most commonly reported grade 3 or 4 adverse reaction.

In patients with multiple myeloma, monitor CBCs weekly during first 8 weeks of therapy and at least monthly thereafter.

In patients with Kaposi sarcoma, monitor CBCs every 2 weeks for the first 3 months and monthly thereafter.

If hematologic toxicity occurs, interrupt therapy and/or reduce dosage.

Hepatotoxicity

Hepatic failure, sometimes fatal, reported. Monitor liver function tests (LFTs) monthly; withhold therapy and consider dosage reduction for increased LFTs.

Cutaneous Reactions

Severe, and potentially fatal, cases of cutaneous reactions (Stevens-Johnson syndrome [SJS], toxic epidermal necrolysis [TEN], and drug reaction with eosinophilia and systemic symptoms [DRESS]) reported.

If grade 2 or 3 skin rash occurs, consider withholding or discontinuing pomalidomide. If grade 4 rash, exfoliative or bullous rash, or other severe cutaneous reactions (SJS, TEN, or DRESS) occur, permanently discontinue drug.

Dizziness and Confusion

Dizziness and confusion reported in patients receiving pomalidomide in combination with low-dose dexamethasone.

Advise patients to avoid situations where dizziness or confusional state may be a problem and avoid other medications that may cause dizziness or confusional state without adequate medical advice.

Neuropathy

Neuropathy (frequently peripheral neuropathy) reported in patients receiving pomalidomide in combination with low-dose dexamethasone.

Development of Second Primary Malignancy

Acute myelogenous leukemia (AML) reported in patients receiving pomalidomide as investigational therapy.

Tumor Lysis Syndrome

Tumor lysis syndrome may occur.

Risk is increased in patients with a high tumor burden. Monitor such patients and institute appropriate precautions.

Hypersensitivity Reactions

Angioedema, anaphylaxis, and anaphylactic reactions reported. Permanently discontinue pomalidomide if angioedema or anaphylaxis occur.

Specific Populations

Pregnancy

Contraindicated for use during pregnancy.

Lactation

Distributed into milk in rats; not known whether distributed into human milk. Discontinue breast-feeding during therapy.

Females of Reproductive Potential

May impair female fertility. See Fetal/Neonatal Morbidity and Mortality under Warnings for more information regarding effects of pomalidomide on reproductive potential.

Pediatric Use

Safety and efficacy not established in pediatric patients.

In 2 open-label studies evaluating pomalidomide in pediatric patients (4 to <17 years of age), no new safety concerns observed.

Geriatric Use

Multiple myeloma: No overall differences in efficacy in geriatric patients (≥65 years of age) compared with younger adults. Increased incidence of pneumonia compared with younger adults.

Kaposi sarcoma: Insufficient experience in patients ≥65 years of age to determine whether efficacy and safety are similar to those in younger adults.

Hepatic Impairment

Primarily metabolized in the liver. Increased AUC in patients with hepatic impairment; dosage adjustment required.

Renal Impairment

Pharmacokinetics not significantly altered by moderate (Cl_cr 30 to <60 mL/minute) or severe (Cl_cr 15 to <30 mL/minute) renal impairment.

Increased AUC and adverse events in patients with severe renal impairment receiving dialysis.

Common Adverse Effects

Combination therapy with low-dose dexamethasone in patients with multiple myeloma (≥30%): Fatigue and asthenia, neutropenia, anemia, constipation, nausea, diarrhea, dyspnea, upper -respiratory tract infections, back pain, pyrexia.

Monotherapy in patients with Kaposi sarcoma (≥30%): Decreased ANC, decreased WBC, decreased hemoglobin concentrations, decreased platelet count, decreased serum phosphate concentrations, decreased serum albumin concentrations, decreased serum calcium concentrations, increased S_cr concentrations, increased serum glucose concentrations, increased serum ALT concentrations, rash, constipation, fatigue, nausea, diarrhea.

Drug Interactions

Metabolized primarily by CYP1A2 and CYP3A4.

Does not inhibit or induce CYP isoenzymes in vitro.

Substrate of P-glycoprotein (P-gp); does not inhibit or induce P-gp or other transporters in vitro.

Drugs Affecting Hepatic Microsomal Enzymes

Potent CYP1A2 inhibitors: Increased pomalidomide exposure. Avoid concomitant use. If concomitant use cannot be avoided, reduce pomalidomide dosage.

Potent CYP1A2 inducers: Possible decreased pomalidomide exposure.

CYP3A4 inhibitors or inducers: No clinically significant alterations in pomalidomide exposure.

Drugs Affecting Efflux Transport Systems

P-gp inhibitors: No clinically significant alterations in pomalidomide exposure.

Specific Drugs and Foods

Pomalidomide Pharmacokinetics

Absorption

Bioavailability

Peak plasma pomalidomide concentrations are attained about 2–3 hours after oral administration.

AUC increases in an approximately dose-proportional manner.

Food

Administration with a high-fat, high-calorie meal decreased rate of absorption by 2.5 hours, mean peak plasma concentration by 27%, and AUC by 8%.

Special Populations

Age (61–85 years), sex, and race: No substantial effect on pharmacokinetics.

Distribution

Extent

Not known whether pomalidomide is distributed into human milk.

Distributed into semen.

Plasma Protein Binding

12–44%.

Elimination

Metabolism

Metabolized primarily by CYP1A2 and CYP3A4, with minor contributions from CYP2C19 and CYP2D6.

Elimination Route

Excreted in urine (73%) and feces (15%); minimal amounts of dose are recovered in urine and feces as unchanged drug.

Half-life

In healthy individuals, median half-life approximately 9.5 hours.

In patients with multiple myeloma or Kaposi sarcoma, median half-life approximately 7.5 hours.

Stability

Storage

Oral

Capsules

20–25°C (may be exposed to 15–30°C).

Actions

• A thalidomide analog with immunomodulatory, antineoplastic, and antiangiogenic activity.

• Induces direct cytotoxic and immunomodulatory effects following ubiquitination and degradation of substrate proteins (e.g., Aiolos, Ikaros).

• Inhibits production of proinflammatory cytokines (e.g., tumor necrosis factor [TNF; TNF-α], interleukin-6) and increases cytolytic T-cell and natural killer (NK) cell responses.

• Induces apoptosis and inhibits growth of hematopoietic tumor cells, including lenalidomide-resistant multiple myeloma cell lines.

• Synergistic antitumor effects demonstrated when combined with dexamethasone in lenalidomide-sensitive and lenalidomide-resistant cell lines.

• Inhibits angiogenesis in vitro and in mice bearing tumor xenografts.

Advice to Patients

• Educate patients regarding the Pomalyst Risk Evaluation and Mitigation Strategy (REMS) restricted distribution program for obtaining pomalidomide. (See REMS under Dosage and Administration.)

• Inform patients of the Pregnancy Exposure Registry that monitors pregnancy outcomes in females exposed to pomalidomide during pregnancy.

• Advise patients to swallow capsules intact and not to break, chew, or open capsules.

• Advise patients that a missed dose may be taken up to 12 hours after the scheduled administration time; if more than 12 hours have elapsed, the missed dose should be omitted and the regular dosing schedule resumed the following day. Importance of not taking 2 doses at the same time to make up for a missed dose.

• Risk of fetal harm. Advise women of childbearing potential to use effective methods of contraception beginning at least 4 weeks prior to initiation of therapy, throughout therapy, during dosage interruptions, and for at least 4 weeks after discontinuance of therapy; importance of obtaining pregnancy tests at appropriate intervals during therapy and of immediately discontinuing therapy and contacting their clinician if pregnancy is suspected. Advise men (including those who have successfully undergone vasectomy) to use a latex or synthetic condom during sexual encounters with women of childbearing potential; these contraceptive measures are required during and for at least 28 days after discontinuance of pomalidomide therapy. Availability of information on emergency contraception at 888-668-2528.

• Advise women to avoid breast-feeding while receiving pomalidomide therapy.

• Advise men to avoid donating semen while receiving pomalidomide and for 4 weeks after discontinuing therapy with the drug.

• Advise patients to avoid donating blood while receiving pomalidomide and for 1 month after discontinuing therapy with the drug.

• Risk of neutropenia, thrombocytopenia, and anemia. Importance of regular monitoring of blood cell counts during pomalidomide therapy. Importance of informing clinician if signs and symptoms of neutropenia, thrombocytopenia, or anemia occur.

• Risk of venous and arterial thromboembolic events; advise patients to seek medical care if shortness of breath, chest pain, or swelling of the arms or legs occurs.

• Risk of hepatotoxicity, including hepatic failure; advise patients to report signs and symptoms of hepatotoxicity to their clinician for evaluation.

• Risk of severe skin reactions; advise patients to seek medical care for signs and symptoms of Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), or drug reaction with eosinophilia and systemic symptoms (DRESS).

• Risk of dizziness or confusion; importance of avoiding activities where dizziness or confusion could cause serious harm to self or others. Importance of not taking other drugs that may cause dizziness or confusion without consulting their clinician.

• Risk of neuropathy. Importance of informing clinician if signs and symptoms of neuropathy occur.

• Possible risk of developing a second primary malignancy (i.e., acute myelogenous leukemia [AML]).

• Risk of tumor lysis syndrome. Importance of informing clinician if signs and symptoms of tumor lysis syndrome occur.

• Risk of severe hypersensitivity reactions; advise patients to seek medical care for signs and symptoms of hypersensitivity reactions.

• Advise patients that smoking may reduce the drug's efficacy.

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as any concomitant illnesses.

• Inform patients of other important precautionary information.

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care. For further information on the handling of antineoplastic agents, see the ASHP Guidelines on Handling Hazardous Drugs at [Web].

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Distribution of pomalidomide is restricted.

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