REMS: FDA approved a REMS for pomalidomide to ensure that the benefits outweigh the risk. The REMS may apply to one or more preparations of pomalidomide and consists of the following: elements to assure safe use and implementation system. See the FDA REMS page ([Web]). |
Pomalidomide, a thalidomide analog, is an immunomodulatory agent with antineoplastic and antiangiogenic activity.1, 13, 14, 17
Pomalidomide is used for the treatment of multiple myeloma in adult patients who have received at least 2 prior therapies including lenalidomide and a proteasome inhibitor and have demonstrated disease progression during or within 60 days following completion of their last therapy.1, 10, 11, 12, 17 Pomalidomide has been designated an orphan drug by FDA for use in multiple myeloma.7
The use of pomalidomide in patients with multiple myeloma is based principally on the results of a randomized, open-label, multicenter, phase 2 trial (MM-002) in adults with relapsed multiple myeloma who previously received lenalidomide and bortezomib.1, 8, 9, 20 Patients were enrolled if their disease was refractory to their most recent therapy (i.e., disease progression during or within 60 days following completion of their most recent therapy).1, 20 In this trial, 221 patients were randomized in a 1:1 ratio to receive pomalidomide (4 mg once daily on days 1-21 of a 28-day cycle) alone or in combination with low-dose dexamethasone (40 mg once daily on days 1, 8, 15, and 22 of a 28-day cycle; patients older than 75 years of age received reduced doses [i.e., 20 mg] of dexamethasone); treatment was continued until disease progression or unacceptable toxicity occurred or treatment was discontinued for other reasons.1, 9, 20 Patients who received pomalidomide alone could add low-dose dexamethasone to their treatment regimen upon disease progression.1, 20 All enrolled patients were required to receive thromboprophylaxis (i.e., aspirin 81-100 mg once daily or other antithrombotic therapy if aspirin was contraindicated).1, 9, 20 The primary end point of this study was progression-free survival; secondary end points included objective response rate, duration of response, time to response, and overall survival.9, 20 The median age of enrolled patients was 63 years, and patients had received a median of 5 prior therapies for multiple myeloma.1, 9, 20 Most of the patients (approximately 75%) had undergone stem cell transplantation and approximately 60% of patients had disease that was refractory to both bortezomib and lenalidomide.1, 20 A planned interim analysis indicated that patients receiving pomalidomide in combination with low-dose dexamethasone had a higher overall response rate than patients receiving pomalidomide alone (29.2 versus 7.4%), with a median response duration of 7.4 months; one patient receiving pomalidomide in combination with low-dose dexamethasone achieved a complete response compared with none of those receiving pomalidomide alone.1, 9 The median follow-up at the time of the interim analysis was 9.6 weeks.9 At the time of the final analysis at a median follow-up of 14.2 months, median progression-free survival was prolonged in patients receiving pomalidomide in combination with low-dose dexamethasone compared with patients receiving pomalidomide alone (4.6 versus 2.6 months); however, median overall survival was similar in both treatment groups (14.4 and 13.7 months for these respective treatments).20
Use of pomalidomide in combination with dexamethasone also was investigated in an open-label, multicenter, phase 3 trial (MM-003) in patients with relapsed or refractory multiple myeloma.1, 17, 21 In this trial, 455 patients were randomized in a 2:1 ratio to receive pomalidomide (4 mg once daily on days 1-21 of a 28-day cycle) in combination with low-dose dexamethasone (40 mg once daily on days 1, 8, 15, and 22 of a 28-day cycle) or high-dose dexamethasone alone (40 mg daily on days 1-4, 9-12, and 17-20 of a 28-day cycle); patients older than 75 years of age received reduced doses (i.e., 20 mg) of dexamethasone.1, 17, 21 Patients enrolled in the trial had received a median of 5 prior therapies.1 Most patients (74%) in this trial had disease that was refractory to both lenalidomide and bortezomib.1 Patients receiving pomalidomide in combination with low-dose dexamethasone had longer median progression-free survival compared with those receiving high-dose dexamethasone alone (3.6 versus 1.8 months).1 Median overall survival also was prolonged in patients receiving the combination of pomalidomide with low-dose dexamethasone compared with those receiving high-dose dexamethasone alone (12.4 versus 8.0 months).1
Pomalidomide also has been used in 3-drug combination regimens† in patients with relapsed or refractory multiple myeloma.22
Previously Treated Multiple Myeloma
The American Society of Clinical Oncology (ASCO) and Cancer Care Ontario (CCO) have published evidence-based recommendations for the treatment of multiple myeloma, including relapsed or refractory disease.47 ASCO and CCO state that prior therapies should be taken into consideration when selecting the treatment at first relapse.47 Treatment options include triplet combination therapy (two novel agents and a corticosteroid) or doublet combination therapy (one novel agent and a corticosteroid); novel agents include immunomodulatory drugs, proteasome inhibitors, and monoclonal antibodies (e.g., daratumumab, elotuzumab).47 For patients who are fit, triplet combination therapy is generally recommended over doublet combination therapy due to improved clinical outcomes.47 In patients with genetic high-risk disease, a triplet combination regimen with a proteasome inhibitor, immunomodulatory drug, and a corticosteroid should be the initial treatment, followed by one or two autologous hematopoietic stem cell transplantations, followed by proteasome inhibitor-based maintenance therapy until disease progression occurs.47
Treatment of relapsed multiple myeloma may be continued until disease progression.47 There are not enough data to recommend risk-based versus response-based duration of treatment.47
Pomalidomide is used for the treatment of adult patients with acquired immunodeficiency syndrome (AIDS)-related Kaposi sarcoma after failure of highly active antiretroviral therapy (HAART) or Kaposi sarcoma in adult patients who are human immunodeficiency virus (HIV)-negative.1 Pomalidomide has been designated an orphan drug by the FDA for use in Kaposi sarcoma.7 This indication is approved under accelerated approval based on overall response rate.1 Continued approval for this indication may be contingent upon verification of clinical benefit in confirmatory trials.1
The use of pomalidomide in patients with Kaposi sarcoma is based principally on the results of a single-arm, single-center, open-label clinical trial (Study 12-C-0047) conducted in 28 adults (10 HIV-negative and 18 HIV-positive).1, 23 In this study, patients received pomalidomide 5 mg orally once daily on days 1-21 of each 28-day cycle; therapy was continued until disease progression or unacceptable toxicity occurred.1, 23 All patients received thromboprophylaxis with aspirin 81 mg once daily during therapy.1, 23 The primary efficacy outcome was overall response rate.23 All patients were male and the median age of these patients was 52.5 years.1 The majority of patients had advanced disease (75%) and had received prior chemotherapy (75%).1 Overall response rate was 67% among HIV-positive patients and 80% among HIV-negative patients.1 The duration of response was 12.5 or 10.5 months in HIV-positive or HIV-negative patients, respectively.1
Dispensing and Administration Precautions
Pomalidomide capsules should be administered orally with water once daily.1 The drug can be administered without regard to food.1 The capsules should be swallowed intact and should not be broken, chewed, or opened.1 No more than a 28-day supply of pomalidomide should be prescribed and dispensed at one time.2
For the treatment of multiple myeloma in adults who have received at least 2 prior therapies including lenalidomide and a proteasome inhibitor, the recommended initial dosage of pomalidomide is 4 mg once daily on days 1-21 of each 28-day cycle in combination with dexamethasone.1 In clinical studies, therapy was continued for as long as the patient derived clinical benefit from the drug or until unacceptable toxicity occurred.1, 9 New cycles of therapy should not be undertaken until neutrophil counts reach or exceed 500/mm3 and platelet counts reach or exceed 50,000/mm3.1
Dosage Modification for Toxicity in Patients with Multiple Myeloma
Temporary interruption of therapy, dosage reduction, and/or permanent discontinuance of pomalidomide may be necessary in patients experiencing adverse effects (see Table 1).1
If angioedema, anaphylaxis, grade 4 rash, skin exfoliation, bullae, or any other severe dermatologic reaction occurs, pomalidomide should be permanently discontinued.1
Adverse Reaction and Severity | Pomalidomide Dosage Modification (Starting Dosage = 4 mg daily on days 1-21 of each 28-day cycle) |
|---|---|
Neutropenia: ANC <500/mm3 | First occurrence: Withhold therapy and monitor CBCs weekly; when ANC ≥500/mm3, then resume at a dosage reduced by 1 mg |
Subsequent occurrence: Withhold therapy until ANC ≥500/mm3, then resume at a dosage reduced by 1 mg | |
If a daily dosage of 1 mg is not tolerated, permanently discontinue pomalidomide | |
Febrile neutropenia (temperature of ≥38.5°C and ANC <1000/mm3) | Withhold therapy and monitor CBCs weekly; when ANC ≥500/mm3, then resume at a dosage reduced by 1 mg |
Thrombocytopenia: Platelet count <25,000/mm3 | First occurrence: Withhold therapy and monitor CBCs weekly; when platelet count ≥50,000/mm3, then resume at a dosage reduced by 1 mg |
Subsequent occurrence: Withhold therapy until platelet count ≥50,000/mm3, then resume at a dosage reduced by 1 mg | |
If a daily dosage of 1 mg is not tolerated, permanently discontinue pomalidomide | |
Non-hematologic adverse reactions: Grade 3 or 4 (excluding hypersensitivity or dermatologic reactions) | Withhold therapy; when toxicity resolves or improves to grade 2 or less, then resume at a dosage reduced by 1 mg |
For the treatment of Kaposi sarcoma in adult patients, the recommended initial dosage is 5 mg once daily on days 1-21 of each 28-day cycle.1 Treatment should be continued until disease progression or unacceptable toxicity occurs.1 In patients with AIDS-related Kaposi sarcoma, highly active antiretroviral therapy (HAART) should be continued.1 New cycles of pomalidomide should not be undertaken until ANC reaches or exceeds 1000/mm3 and platelet count reaches or exceeds 75,000/mm3.1
Dosage Modification for Toxicity in Patients with Kaposi Sarcoma
Temporary interruption of therapy, dosage reduction, and/or permanent discontinuance of pomalidomide may be necessary in patients experiencing adverse effects (see Table 2).1
If angioedema, anaphylaxis, grade 4 rash, skin exfoliation, bullae, or any other severe dermatologic reaction occurs, pomalidomide should be permanently discontinued.1
Adverse Reaction and Severity | Pomalidomide Dosage Modification (Starting Dosage = 5 mg daily on days 1-21 of each 28-day cycle) |
|---|---|
Neutropenia: ANC 500 to <1000/mm3 | Day 1 of cycle: Withhold therapy; when ANC ≥1000/mm3, resume at same dosage |
During cycle: Continue current dosage | |
ANC <500/mm3 | Withhold therapy; when ANC ≥1000/mm3, resume at same dosage |
Febrile neutropenia (ANC <1000/mm3 and single temperature of ≥38.3°C or sustained temperature of ≥38°C for >1 hour) | Withhold therapy; when ANC ≥1000/mm3, then resume at a dosage reduced by 1 mg |
If a daily dosage of 1 mg is not tolerated, permanently discontinue pomalidomide | |
Thrombocytopenia: Platelet count 25,000 to <50,000/mm3 | Day 1 of cycle: Withhold therapy; when platelet count ≥50,000/mm3, resume at same dosage |
During cycle: Continue current dosage | |
Platelet count <25,000/mm3 | Permanently discontinue pomalidomide |
Non-hematologic adverse reactions: Grade 3 or 4 (excluding hypersensitivity or dermatologic reactions) | Withhold therapy; when toxicity resolves or improves to grade 2 or less, then resume at a dosage reduced by 1 mg |
Dosage Modification for Concomitant Use with Cytochrome P-450 (CYP) 1A2 Inhibitors
Concomitant use with strong cytochrome P-450 (CYP) isoenzyme 1A2 inhibitors should be avoided.1 If concomitant use is necessary, the dosage of pomalidomide should be reduced to 2 mg daily.1
In patients with hepatic impairment, the manufacturer recommends reducing the initial dosage of pomalidomide as described in Tables 3 and 4.
Severity | Dose |
|---|---|
Mild (Child-Pugh class A) | 3 mg once daily |
Moderate (Child-Pugh class B) | 3 mg once daily |
Severe (Child-Pugh class C) | 2 mg once daily |
Severity | Dose |
|---|---|
Mild (Child-Pugh class A) | 3 mg once daily |
Moderate (Child-Pugh class B) | 3 mg once daily |
Severe (Child-Pugh class C) | 3 mg once daily |
In patients with multiple myeloma and severe renal impairment requiring dialysis, the recommended initial dosage of pomalidomide is 3 mg daily.1
In patients with Kaposi sarcoma and severe renal impairment requiring dialysis, the recommended initial dosage of pomalidomide is 4 mg daily.1
Pomalidomide should be administered after completion of hemodialysis.1
The manufacturer makes no specific dosage recommendations for geriatric patients.1
Fetal/Neonatal Morbidity and Mortality
Pomalidomide may cause fetal toxicity; pomalidomide is a structural analog of thalidomide, a known human teratogen, and teratogenic and other fetotoxic effects of pomalidomide (e.g., musculoskeletal anomalies and deformities; absence of internal organs, including bladder and thyroid; defects of internal organ systems, including cardiovascular, respiratory, renal, hepatic, and CNS abnormalities; increased fetal resorptions) have been demonstrated in animals.1 Therefore, pomalidomide is contraindicated in women who are pregnant and a boxed warning about the risk of teratogenicity and fetotoxicity has been included in the prescribing information for the drug.1, 2
All female patients of childbearing potential and all sexually mature males receiving pomalidomide must use effective contraceptive measures (which may include abstinence) to help ensure that fetal exposure to the drug does not occur.1 Contraceptive measures are indicated even in females with a history of infertility.1 The only females who do not need to observe mandatory contraceptive measures are those who have undergone hysterectomy or bilateral oophorectomy and those who are postmenopausal and have had no menses for 24 or more consecutive months.1, 2 All female patients of childbearing potential must use 2 reliable forms of contraception simultaneously (unless the patient chooses to remain continuously abstinent from engaging in heterosexual sexual contact) beginning at least 4 weeks prior to initiation of therapy, during therapy and treatment interruptions, and then for at least 4 weeks following discontinuance of pomalidomide therapy.1 At least one contraceptive method should be a highly effective method (intrauterine device [IUD], hormonal contraceptives, tubal ligation, vasectomized partner); the other may be an effective barrier method (latex or synthetic condom, diaphragm, cervical cap).1 Sexually mature males receiving pomalidomide must completely avoid unprotected sexual contact with women of childbearing potential and must not donate semen while receiving pomalidomide and for 4 weeks after discontinuing the drug.1 While receiving pomalidomide and for up to 28 days after discontinuing the drug, sexually mature males (including those who have successfully undergone vasectomy) must use a latex or synthetic condom each time they have sexual contact with a woman of childbearing potential.1
Because pomalidomide may cause fetal harm and because of the possibility that the drug may be present in blood and be transfused into a woman who is pregnant, patients receiving pomalidomide must not donate blood during therapy and for at least 1 month following discontinuance of the drug.1
All females of childbearing potential must be tested for pregnancy within 10-14 days and again within 24 hours immediately prior to initiation of pomalidomide therapy.1 The prescribing clinician should not provide the patient with a prescription for pomalidomide until reports of the pregnancy tests are available indicating that the results are negative.1 Pregnancy tests must then be repeated at regular intervals during pomalidomide therapy (i.e., weekly during the first month, then every 2 or 4 weeks in women with irregular or regular menstrual cycles, respectively).1 Pregnancy tests and counseling also should be performed if a patient misses her period or if there is any abnormality in menstrual bleeding.1 The drug should be discontinued during the evaluation period.1 If the drug is used during pregnancy or if the patient becomes pregnant while receiving the drug, pomalidomide should be immediately discontinued and the patient informed of the potential hazard to the fetus; the patient should be referred to an obstetrician/gynecologist experienced in reproductive toxicity, and the clinician should notify Bristol Myers Squibb (888-423-5436) and the US Food and Drug Administration (FDA) via the MedWatch program (800-332-1088).1
Serious venous and arterial thromboembolic events have been reported in patients receiving pomalidomide and a boxed warning about this risk has been included in the prescribing information for the drug.1, 8 Despite required thromboprophylaxis, 8% of patients treated with pomalidomide and low-dose dexamethasone in trial MM-003 had a thromboembolic event compared with 3.3% of patients treated with high-dose dexamethasone.1 Venous and arterial thromboembolic events occurred more frequently in patients receiving pomalidomide in combination with low-dose dexamethasone (4.7 and 3%, respectively) compared with patients receiving high-dose dexamethasone (1.3 and 1.3%, respectively).1
Patients with known risk factors (e.g., history of thrombosis) may be at greater risk and measures should be taken to minimize modifiable factors (e.g., hyperlipidemia, hypertension, smoking).1 The manufacturer recommends thromboprophylaxis in patients receiving pomalidomide.1 The manufacturer and some experts state that decisions regarding use of thromboprophylaxis and selection of an appropriate thromboprophylaxis regimen (e.g., aspirin, anticoagulant) should be based on careful assessment of the patient's risk factors for thromboembolism.1, 19
Other Warnings and Precautions
Increased mortality has been reported in clinical trials in patients with multiple myeloma receiving pembrolizumab in combination with a thalidomide analog and dexamethasone.1 The manufacturer of pomalidomide states that an anti-programmed death receptor-1 (anti-PD-1) or anti-programmed-death ligand-1 (anti-PD-L1) antibody should not be used in combination with a thalidomide analogue and dexamethasone in patients with multiple myeloma outside of a controlled clinical trial.1 FDA recommends that ongoing clinical trials evaluating an anti-PD-1 or anti-PD-L1 agent in combination with an immunomodulatory agent (e.g., pomalidomide) be evaluated for permanent discontinuance or protocol amendments.26
In the pivotal multiple myeloma trials, neutropenia was the most commonly reported grade 3 or 4 adverse reaction, followed by anemia and thrombocytopenia in patients receiving pomalidomide in combination with low-dose dexamethasone.1 Neutropenia of any grade occurred in 51% of patients receiving pomalidomide in combination with low-dose dexamethasone. 1 Grade 3 or 4 neutropenia or febrile neutropenia occurred in 46 or 8%, respectively, of patients receiving pomalidomide in combination with low-dose dexamethasone.1 Complete blood cell counts (CBCs) should be monitored weekly for the first 8 weeks of therapy and monthly thereafter.1 If hematologic toxicity occurs, dosage interruption and/or reduction may be required.1
In the pivotal Kaposi sarcoma trial, the most common adverse reactions were hematologic toxicities. 1 Grade 3 or 4 neutropenia occurred in 50% of patients receiving single-agent pomalidomide.1 CBCs should be monitored every 2 weeks for the first 3 months and monthly thereafter.1 If hematologic toxicity occurs, dosage interruption, reduction, or discontinuation may be required.1
Cases of hepatic failure, sometimes fatal, have occurred in patients treated with pomalidomide.1 Increased serum concentrations of ALT and bilirubin have also been reported in patients receiving pomalidomide.1 Liver function tests should be monitored monthly.1 If elevations in liver enzymes occur, temporarily interrupt pomalidomide therapy.1 When liver enzyme levels return to baseline values, resumption of pomalidomide therapy may be considered at a reduced dosage. 1
Severe cases of cutaneous reactions (i.e., Stevens-Johnson syndrome [SJS], toxic epidermal necrolysis [TEN], drug reaction with eosinophilia and systemic symptoms [DRESS]) have been reported.1 DRESS may present with a cutaneous reaction (such as rash or exfoliative dermatitis), eosinophilia, fever, and/or lymphadenopathy with systemic complications such as hepatitis, nephritis, pneumonitis, myocarditis, and/or pericarditis.1 These reactions can be fatal.1 For grade 2 or 3 skin rash, temporary interruption or discontinuance of pomalidomide should be considered.1 If grade 4 rash, exfoliative or bullous rash, or other severe cutaneous reactions (SJS, TEN, or DRESS) occur, pomalidomide should be permanently discontinued.1
In the pivotal multiple myeloma trials, dizziness or confusion occurred in 14 or 7%, respectively, of patients receiving pomalidomide in combination with low-dose dexamethasone; grade 3 or 4 dizziness occurred in 1% of patients, and grade 3 or 4 confusion occurred in 3% of patients.1 Instruct 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.1
In the pivotal multiple myeloma trials, neuropathy was reported in 18% of patients receiving pomalidomide in combination with low-dose dexamethasone, and peripheral neuropathy was reported in approximately 12% of patients.1 Grade 4 neuropathy occurred in none of the patients; however, grade 3 neuropathy occurred in 2% of patients in the MM-003 study.1
Development of Second Primary Malignancy
Acute myelogenous leukemia (AML) has been reported in patients receiving pomalidomide as investigational therapy for uses other than multiple myeloma.1
Tumor lysis syndrome may occur in patients receiving pomalidomide.1 Patients treated with pomalidomide with a high tumor burden are at risk for tumor lysis syndrome.1 Such patients should be monitored closely, and appropriate precautions should be instituted.1
Hypersensitivity reactions such as angioedema, anaphylaxis, and anaphylactic reactions have been reported in patients receiving pomalidomide.1 If angioedema or anaphylaxis occurs, pomalidomide should be permanently discontinued.1
Pomalidomide is a thalidomide analogue and is contraindicated for use during pregnancy.1 Based on animal studies, female fertility may be impaired with pomalidomide treatment.1
Pomalidomide is distributed into milk in rats; it is not known whether pomalidomide is distributed into milk in humans.1 Because many drugs are excreted in human milk and because of the potential for serious adverse reactions to pomalidomide in nursing infants, women should not breast-feed during therapy with pomalidomide.1
Females and Males of Reproductive Potential
Results of animal studies suggest that pomalidomide may impair female fertility.1
Safety and efficacy of pomalidomide have not been established in pediatric patients.1
Safety and efficacy of pomalidomide in pediatric patients (4 to less than 17 years of age) were assessed, but not established, in 2 open-label studies.1 New safety concerns were not observed in pediatric patients in these studies.1 When pomalidomide was administered at the same dose by body surface area, exposure in patients 4 to <17 years of age was similar to adult patients with multiple myeloma, but higher than exposure observed in adults with Kaposi sarcoma.1
In clinical trials evaluating pomalidomide in patients with multiple myeloma, 44% of patients were 65 years of age or older and 10% were 75 years of age or older.1 Although no overall differences in efficacy were observed between geriatric and younger patients, pneumonia occurred more frequently in patients 65 years of age or older compared with younger patients.1
In patients with Kaposi sarcoma, experience in patients 65 years of age or older is insufficient to determine whether they respond differently to pomalidomide than younger patients.1
Pomalidomide is primarily metabolized in the liver.1, 24 Following administration of a single-dose of pomalidomide, the AUC of pomalidomide increased by 51, 58, or 72% in patients with mild, moderate, or severe hepatic impairment, respectively, compared with patients with normal hepatic function.1, 24
Pomalidomide pharmacokinetic parameters were not significantly affected in patients with moderate (creatinine clearance 30 to less than 60 mL/minute) or severe (creatinine clearance 15 to less than 30 mL/minute) renal impairment relative to patients with normal renal function. 1
Approximately 73% of a radiolabeled dose of pomalidomide is excreted by the kidneys (primarily as metabolites) in healthy individuals.1 Following administration of a single-dose of pomalidomide, the AUC of pomalidomide increased by 38% and the rate of serious adverse events increased by 64% in patients with severe renal impairment requiring dialysis compared with patients with normal renal function.1 In patients with end-stage renal disease (creatinine clearance less than 15 mL/minute), the AUC of pomalidomide increased by 40% on non-dialysis days.1
In patients with severe renal impairment requiring dialysis, the estimated dialysis clearance is higher than the total body clearance of pomalidomide, indicating removal of pomalidomide from blood circulation during hemodialysis.1
Adverse effects reported in at least 30% of patients with multiple myeloma receiving pomalidomide in combination with low-dose dexamethasone include fatigue and asthenia, neutropenia, anemia, constipation, nausea, diarrhea, dyspnea, upper respiratory tract infection, back pain, and pyrexia.1
Adverse effects reported in at least 30% of patients with Kaposi sarcoma receiving pomalidomide include decreased absolute neutrophil count (ANC), decreased white blood cell count (WBC), decreased hemoglobin concentrations, decreased platelet count, decreased serum phosphate concentrations, decreased serum albumin concentrations, decreased serum calcium concentrations, increased serum creatinine concentrations, increased serum glucose concentrations, increased serum ALT concentrations, rash, constipation, fatigue, nausea, and diarrhea.1
Metabolism of pomalidomide is mediated primarily by cytochrome P-450 (CYP) isoenzymes 1A2 and CYP3A4, and to a lesser extent by CYP isoenzymes 2C19 and 2D6.1
Pomalidomide does not inhibit or induce CYP isoenzymes in vitro.1
Pomalidomide is a substrate of P-glycoprotein (P-gp).1
Pomalidomide does not inhibit or induce transporters in vitro.1
Drugs Affecting or Metabolized by Hepatic Microsomal Enzymes
Concomitant use of pomalidomide with the potent CYP3A4 inhibitor and P-gp inhibitor ketoconazole increased the AUC of pomalidomide by 19% in healthy male subjects; however, this is not considered clinically significant.1
Concomitant use of pomalidomide with the potent CYP3A4 inducer carbamazepine decreased AUC of pomalidomide by 20% in healthy male subjects; however, this is not considered clinically significant.1
Concomitant use of pomalidomide with the weak to moderate CYP3A4 inducer dexamethasone did not affect the pharmacokinetics of pomalidomide in patients with multiple myeloma.1
Concomitant use of pomalidomide with the potent CYP1A2 inhibitor fluvoxamine increased systemic exposure to pomalidomide by 125% in healthy subjects.1
Concomitant use with potent CYP1A2 inhibitors (e.g., ciprofloxacin, fluvoxamine) should be avoided; if concomitant use cannot be avoided, the dosage of pomalidomide should be reduced.1
Concomitant use of pomalidomide with drugs that induce CYP1A2 has not been studied; however, such concomitant use with CYP1A2 inducers may reduce pomalidomide exposure.1 Cigarette smoking (a potent CYP1A2 inducer) increased peak plasma concentration of pomalidomide and decreased the AUC of the drug.1, 26
Drugs Affecting Efflux Transport Systems
Concomitant use of pomalidomide with ketoconazole, a potent inhibitor of P-gp did not substantially affect pomalidomide exposure.1
Cigarette smoking may potentially reduce the AUC and efficacy of pomalidomide.1 Following a single 4-mg dose of pomalidomide, peak plasma concentrations of pomalidomide increased by 14% and AUC decreased by 32% in healthy male subjects who smoked 25 cigarettes per day compared with healthy non-smoker male subjects.1
Pomalidomide, a thalidomide analog, is an immunomodulatory agent with antineoplastic and antiangiogenic activity.1, 13, 14, 17 Cellular activities of pomalidomide are mediated through its target cereblon, a component of a cullin ring E3 ubiquitin ligase enzyme complex.1 In vitro, pomalidomide induces direct cytotoxic and immunomodulatory effects following ubiquitination and degradation of substrate proteins such as Aiolos and Ikaros.1 The drug has been shown to inhibit production of proinflammatory cytokines (e.g., tumor necrosis factor [TNF], interleukin-6) and increase cytolytic T-cell and natural killer (NK) cell responses.1, 13, 14 Pomalidomide has been shown to inhibit the growth of hematopoietic tumor cells, including lenalidomide-resistant multiple myeloma cell lines, by inducing apoptosis.1, 14 The drug has shown synergistic antitumor effects when combined with dexamethasone in lenalidomide-sensitive and lenalidomide-resistant cell lines.1 Pomalidomide has been shown to inhibit angiogenesis in vitro and in mice bearing tumor xenografts.1
Pomalidomide is extensively metabolized in the liver, principally by CYP-450 isoenzymes 1A2 and 3A4, with minor contributions from CYP isoenzymes 2C19 and 2D6.1, 13 Following multiple-dose oral administration (2 mg once daily for 4 days) in healthy men, pomalidomide concentrations in semen were approximately 67% of plasma concentrations at 4 hours after a dose (near-peak plasma concentrations).1 Administration of pomalidomide with a high-fat, high-calorie meal decreased the rate of absorption (time to peak concentrations delayed by 2.5 hours), mean peak plasma concentrations (decreased by 27%), and extent of absorption (AUC decreased by 8%).1 The median terminal half-life of pomalidomide in patients with multiple myeloma or Kaposi sarcoma is 7.5 hours.1, 13, 16 Following oral administration of a single 2-mg dose of radiolabeled pomalidomide, approximately 73% of the dose was recovered in urine and 15% was recovered in feces; unchanged drug accounted for only 2% of the dose recovered in urine and 8% of the dose recovered in feces.1, 13, 16
The pharmacokinetics of pomalidomide are not affected substantially by age (61-85 years), sex, and race.1
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].
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.
Because pomalidomide is an analog of thalidomide (a known human teratogen that can cause severe, life-threatening birth defects), distribution of pomalidomide is restricted.1, 2
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Oral | Capsules | 1 mg | Bristol Myers Squibb | |
2 mg | Pomalyst® | Bristol Myers Squibb | ||
3 mg | Pomalyst® | Bristol Myers Squibb | ||
4 mg | Pomalyst® | Bristol Myers Squibb |
1. Bristol Myers Squibb. Pomalyst® (pomalidomide) capsules prescribing information. Princeton, NJ; 2025 Feb.
2. US Food and Drug Administration. Pomalyst® (pomalidomide) NDA #204026: Risk evaluation mitigation strategy. From FDA website. Accessed 2021 Apr 29. [Web]
7. US Food and Drug Administration. Search orphan drug designations and approvals. From FDA website. Accessed 2024, May 20. [Web]
8. Celgene Corporation. Berkeley Heights, NJ: Personal communication.
9. US Food and Drug Administration. Center for Drug Evaluation and Research. Application number 204026Orig1s000: Medical review. From FDA website. [Web]
10. Leleu X, Attal M, Arnulf B et al. Pomalidomide plus low-dose dexamethasone is active and well tolerated in bortezomib and lenalidomide-refractory multiple myeloma: Intergroupe Francophone du Myélome 2009-02. Blood . 2013; 121:1968-75. [PubMed 23319574]
11. Lacy MQ, Hayman SR, Gertz MA et al. Pomalidomide (CC4047) plus low dose dexamethasone (Pom/dex) is active and well tolerated in lenalidomide refractory multiple myeloma (MM). Leukemia . 2010; 24:1934-9. [PubMed 20827286]
12. Lacy MQ, Hayman SR, Gertz MA et al. Pomalidomide (CC4047) plus low-dose dexamethasone as therapy for relapsed multiple myeloma. J Clin Oncol . 2009; 27:5008-14. [PubMed 19720894]
13. Hoffmann M, Kasserra C, Reyes J et al. Absorption, metabolism and excretion of [14C]pomalidomide in humans following oral administration. Cancer Chemother Pharmacol . 2013; 71:489-501. [PubMed 23203815]
14. Zhu YX, Kortuem KM, Stewart AK. Molecular mechanism of action of immune-modulatory drugs thalidomide, lenalidomide and pomalidomide in multiple myeloma. Leuk Lymphoma . 2013; 54:683-7. [PubMed 22966948]
16. Schey SA, Fields P, Bartlett JB et al. Phase I study of an immunomodulatory thalidomide analog, CC-4047, in relapsed or refractory multiple myeloma. J Clin Oncol . 2004; 22:3269-76. [PubMed 15249589]
17. Terpos E, Kanellias N, Christoulas D et al. Pomalidomide: a novel drug to treat relapsed and refractory multiple myeloma. Onco Targets Ther . 2013; 6:531-8. [PubMed 23690693]
19. Key NS, Khorana AA, Kuderer NM et al. Venous Thromboembolism Prophylaxis and Treatment in Patients With Cancer: ASCO Clinical Practice Guideline Update. J Clin Oncol . 2020; 38:496-520. [PubMed 31381464]
20. Richardson PG, Siegel DS, Vij R et al. Pomalidomide alone or in combination with low-dose dexamethasone in relapsed and refractory multiple myeloma: a randomized phase 2 study. Blood . 2014; 123:1826-32. [PubMed 24421329]
21. Miguel JS, Weisel K, Moreau P et al. Pomalidomide plus low-dose dexamethasone versus high-dose dexamethasone alone for patients with relapsed and refractory multiple myeloma (MM-003): a randomised, open-label, phase 3 trial. Lancet Oncol . 2013; 14:1055-1066. [PubMed 24007748]
22. Mushtaq A, Iftikhar A, Hassan H et al. Pomalidomide-Based Regimens for Treatment of Relapsed and Relapsed/Refractory Multiple Myeloma: Systematic Review and Meta-analysis of Phase 2 and 3 Clinical Trials. Clin Lymphoma Myeloma Leuk . 2019; 19:447-461. [PubMed 31060991]
23. Polizzotto MN, Uldrick TS, Wyvill KM et al. Pomalidomide for Symptomatic Kaposi's Sarcoma in People With and Without HIV Infection: A Phase I/II Study. J Clin Oncol . 2016; 34:4125-4131. [PubMed 27863194]
24. Li Y, Wang X, Liu L et al. An Open-Label, Phase 1 Study to Assess the Effects of Hepatic Impairment on Pomalidomide Pharmacokinetics. Clin Pharmacol Drug Dev . 2019; 8:346-354. [PubMed 29746728]
25. Li Y, Liu L, Wang X et al. In Vivo Assessment of the Effect of CYP1A2 Inhibition and Induction on Pomalidomide Pharmacokinetics in Healthy Subjects. J Clin Pharmacol . 2018; 58:1295-1304. [PubMed 29762875]
26. Food and Drug Administration. FDA drug safety communication: FDA alerts healthcare professionals and oncology clinical investigators about two clinical trials on hold evaluating Keytruda® (pembrolizumab) in patients with multiple myeloma. Silver Spring, MD; 2017 Sep 20. From the FDA website. [Web]
47. Mikhael J, Ismaila N, Cheung MC et al. Treatment of Multiple Myeloma: ASCO and CCO Joint Clinical Practice Guideline. J Clin Oncol . 2019; 37:1228-1263. [PubMed 30932732]