PDR MEMBER LOGIN:
  • PDR Search

    Required field
  • Advertisement
  • CLASSES

    Immunomodulators, Angiogenesis Inhibitors

    BOXED WARNING

    Hyperlipidemia, hypertension, myocardial infarction, stroke, thromboembolism, tobacco smoking

    Venous (e.g., deep venous thrombosis and pulmonary embolism) thromboembolism and arterial (e.g., myocardial infarction and stroke) thromboembolism have been reported in patients with multiple myeloma who received pomalidomide plus low-dose dexamethasone in clinical trials. A prior history of thrombosis, hyperlipidemia, hypertension, and/or tobacco smoking may increase the risk of thromboembolism with pomalidomide therapy; minimize modifiable risk factors if possible. Thromboprophylaxis is recommended in all patients; the choice of prophylactic regimen should be based on an assessment of a patient's underlying risk factors.

    Contraception requirements, dysfunctional uterine bleeding, infertility, male-mediated teratogenicity, menstrual irregularity, pregnancy testing, reproductive risk, sperm donation

    Counsel patients about the reproductive risk and contraception requirements during pomalidomide treatment. Do not initiate therapy in females of reproductive potential until pregnancy testing is performed twice with confirmed negative results. Administer the first test within 10 to 14 days and the second test 24 hours prior to prescribing pomalidomide. Once treatment is started, continue pregnancy testing weekly during the first 4 weeks of treatment, then every 4 weeks in females with regular menstrual cycles and every 2 weeks in females with irregular menstrual cycles. Effective contraception must be used by all females of reproductive potential for at least 4 weeks before beginning treatment, during therapy and dosage interruptions, and for 4 weeks following discontinuation of therapy. Women must commit to abstain from heterosexual intercourse or to use 2 methods of reliable birth control, including at least 1 highly effective method (e.g., intrauterine device (IUD), hormonal contraception, tubal ligation, or partner's vasectomy) and 1 additional effective method (e.g., latex condom, diaphragm, or cervical cap). Follow these contraceptive requirements even in patients with a history of infertility, unless a hysterectomy has been performed. Discontinue treatment, test for pregnancy, and counsel any woman of reproductive potential who experiences menstrual irregularity (e.g., dysfunctional uterine bleeding) or misses her period. Advise patients that if her doctor is not available, she can call 1-888-423-5436. Pomalidomide passes into semen and there is potential for male-mediated teratogenicity. Male patients must use barrier contraception (latex condom) during sexual intercourse with a woman of reproductive potential while on therapy, during interruptions, and for 4 weeks after discontinuing therapy, even if he has undergone successful vasectomy. Male patients should be warned against sperm donation during pomalidomide therapy and for 4 weeks after stopping therapy. Female infertility may be possible based on data in animal studies.[59487]

    DEA CLASS

    Rx

    DESCRIPTION

    Biologic response modifier with immunomodulatory, antiangiogenic, and antineoplastic properties
    Used for the treatment of multiple myeloma in patients who have received at least 2 prior therapies and have demonstrated disease progression on or within 60 days of completion of the last therapy
    Risk of birth defects or embryo-fetal death if used during pregnancy; prescribers, pharmacies, and patients must register in the POMALYST REMS program (1-888-423-5436)

    COMMON BRAND NAMES

    POMALYST

    HOW SUPPLIED

    POMALYST Oral Cap: 1mg, 2mg, 3mg, 4mg

    DOSAGE & INDICATIONS

    For the treatment of multiple myeloma.
    The FDA has designated pomalidomide as an orphan drug for the treatment of multiple myeloma.
    For the treatment of multiple myeloma in patients who have received at least 2 prior therapies including lenalidomide and a proteasome inhibitor and who had disease progression within 60 days of completing the last therapy, in combination with dexamethasone.
    Oral dosage
    Adults

    4 mg orally daily on days 1 to 21 repeated every 28 days until disease progression; give in combination with dexamethasone.[59487] Pomalidomide was administered with low-dose dexamethasone (LoDEX, 40 mg orally on days 1, 8, 15, and 22 of each 28-day cycle) in 2 randomized clinical studies.[58187] [58188] Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. Thromboembolism prophylaxis is recommended in all patients. Interruption or discontinuation of therapy and/or a dose reduction may be necessary in patients who develop toxicities.[59487] At a median follow-up time of 14.2 months, treatment with pomalidomide plus LoDEX resulted in a significantly improved progression-free survival (PFS) time (primary endpoint) compared with pomalidomide monotherapy (4.2 months vs. 2.7 months; hazard ratio (HR) = 0.68; 95% CI, 0.51 to 0.9; p = 0.003) in patients with relapsed or refractory multiple myeloma in a multicenter, randomized, open-label, phase 2 study (MM-003C study; n = 221; age range, 34 to 88 years; median of 5 prior therapies; range, 1 to 13 therapies). Prior to study enrollment, patients had previously received lenalidomide and bortezomib (100%), dexamethasone (99%), thalidomide (67%), and carfilzomib (23%); additionally, 74% of patients had received a stem cell transplant. All patients in this study received aspirin or another form of thromboprophylaxis if aspirin was contraindicated. Upon disease progression, 65 patients in the pomalidomide alone arm were allowed to cross-over to the pomalidomide plus LoDEX arm. The median overall survival (OS) time was not significantly improved with pomalidomide plus LoDEX arm compared with pomalidomide alone (16.5 months vs. 13.6 months; HR = 0.94; 95% CI, 0.7 to 1.28; p = 0.709).[58187] Treatment with pomalidomide plus LoDEX (n = 302) was compared with high-dose dexamethasone (HiDEX, given as 40 mg/day PO on days 1 to 4, 9 to 12, and 17 to 20 of each 28-day cycle) (n = 153) in patients with relapsed or refractory multiple myeloma in a multicenter, randomized, open-label, phase 3 trial (MM-003 study; age range, 35 to 87 years). All patients in this study had previously received at least 2 cycles of lenalidomide- and bortezomib-containing therapy and an adequate trial of an alkylating agent-containing regimen (median of 5 prior therapies; range, 2 to 17 therapies). At a median follow-up of 10 months, the median PFS time (primary endpoint) was significantly improved with pomalidomide plus LoDEX (4 months vs. 1.9 months; HR = 0.48; 95% CI, 0.39 to 0.6; p less than 0.0001). Physician's choice of thromboprophylaxis was given in all patients receiving pomalidomide or patients at high risk for developing thrombosis. Upon disease progression, 43 patients in the HiDEX arm were allowed to cross-over to treatment with single-agent pomalidomide. The median OS time was significantly improved with pomalidomide plus LoDEX compared with HiDEX (12.7 months vs. 8.1 months; HR = 0.74; 95% CI, 0.56 to 0.97; p = 0.0285). In a cohort of geriatric patients 76 years or older, treatment with pomalidomide plus LoDEX resulted in significantly increased PFS (HR = 0.36; 95% CI, 0.16 to 0.83) but not OS (HR = 0.4; 95% CI, 0.15 to 1.05) compared with HiDEX.[58188]

    For the treatment of multiple myeloma in patients who have received at least 2 prior therapies including lenalidomide and a proteasome inhibitor, in combination with daratumumab and dexamethasone†.
    NOTE: Daratumumab is FDA approved in combination with pomalidomide and dexamethasone for this indication.
    Oral dosage
    Adults

    4 mg orally daily on days 1 to 21 repeated every 28 days until disease progression; give in combination with daratumumab (16 mg/kg of actual body weight IV weekly on weeks 1 to 8 (8 doses), 16 mg/kg IV every other week on weeks 9 to 24 (8 doses), and then 16 mg/kg IV every 4 weeks starting on week 25) and dexamethasone (40 mg orally or IV once weekly or 20 mg orally or IV once weekly in patients older than 75 years or who had a body-mass index less than 18.5). Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. Thromboembolism prophylaxis is recommended in all patients. Interruption or discontinuation of therapy and/or a dose reduction may be necessary in patients who develop toxicities. The overall response rate (ORR) was 60% in patients with relapsed or refractory multiple myeloma who received daratumumab, pomalidomide, and low-dose dexamethasone in a nonrandomized, phase 1b trial (n = 103; EQUULEUS trial); the stringent complete response (CR) rate was 8% and the CR rate was 9%. At a median follow-up time of 13.1 months (range, 0.2 to 25.8 months), the median progression-free survival (PFS) and overall survival (OS) times were 8.8 months and 17.5 months, respectively; the estimated 12-month PFS and OS rates were 42% and 66%, respectively. Patients (median age, 64 years; range, 35 to 86 years) in this study had received a median of 4 prior therapies (range, 1 to 13 therapies); 74% of patients had previously received an autologous stem cell transplantation.

    For the treatment of multiple myeloma in patients who have received at least 2 prior therapies including lenalidomide and a proteasome inhibitor, in combination with elotuzumab and dexamethasone†.
    NOTE: Elotuzumab is FDA approved in combination with pomalidomide and dexamethasone for this indication.
    Oral dosage
    Adults

    4 mg orally daily on days 1 through 21 in combination with elotuzumab 10 mg/kg IV once weekly on cycles 1 and 2 (on days 1, 8, 15, and 22), then 20 mg/kg IV every 4 weeks (on day 1) starting on cycle 3 and oral dexamethasone (age 75 years or less, 28 mg; age over 75 years, 8 mg) at 3 to 24 hours prior to elotuzumab on days 1, 8, 15, and 22 on cycles 1 and 2 and on day 1 of subsequent cycles. Additionally, give oral dexamethasone (age 75 years or less, 40 mg; age over 75 years, 20 mg) at 3 to 24 hours prior to elotuzumab on days 8, 15, and 22 of cycles 3 and beyond. Repeat treatment cycles every 28 days until disease progression. Administer the following premedications 45 to 90 minutes prior to each elotuzumab infusion: acetaminophen 650 to 1,000 mg orally, diphenhydramine 25 to 50 mg orally or IV (or equivalent), ranitidine 50 mg IV or 150 mg orally (or equivalent), and dexamethasone 8 mg IV. At a minimum follow-up time of 9.1 months, the median investigator-assessed progression-free survival time was significantly improved with elotuzumab plus pomalidomide and dexamethasone (median number of treatment cycles, 9) compared with pomalidomide and dexamethasone alone (10.25 months vs. 4.67 months; hazard ratio (HR) = 0.54; 95% CI, 0.34 to 0.86; p = 0.0078) in patients with relapsed or refractory multiple myeloma in a randomized, phase 2 trial (n = 117; the ELOQUENT-3 trial). In this study, patients had received a median of 3 prior therapies; 70% of patients had refractory disease after both lenalidomide and a proteasome inhibitor and 55% of patients had previously received an autologous stem cell transplantation.[60354] Thromboembolism prophylaxis is recommended in all patients. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. Interruption or discontinuation of therapy and/or a dose reduction may be necessary in patients who develop toxicities.[59487]

    For the treatment of relapsed or refractory multiple myeloma in patients who have received 1 to 3 prior therapies including lenalidomide, in combination with bortezomib and dexamethasone†.
    Oral dosage
    Adults

    4 mg orally daily on days 1 to 14 repeated every 21 days in combination with bortezomib and dexamethasone was evaluated in a randomized, phase 3 trial (n = 559; the OPTIMISMM trial). Bortezomib was administered as follows: 1.3 mg/m2 IV or subcutaneously on days 1, 4, 8, and 11 on cycles 1 to 8 then 1.3 mg/m2 IV or subcutaneously on days 1 and 8 starting on cycle 9. Patients aged 75 years and younger received dexamethasone 20 mg orally on days 1, 2, 4, 5, 8, 9, 11, and 12 on cycles 1 to 8 and then 20 mg orally on days 1, 2, 8, and 9 starting on cycle 9; patients older than 75 years received dexamethasone 10 mg orally on days 1, 2, 4, 5, 8, 9, 11, and 12 on cycles 1 to 8 and then 10 mg orally on days 1, 2, 8, and 9 starting on cycle 9. Treatment cycles were repeated every 21 days until disease progression. All patients received low-dose aspirin, low-molecular-weight heparin, or other equivalent antithrombotic or anticoagulant treatment.[64412] Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. Interruption or discontinuation of therapy and/or a dose reduction may be necessary in patients who develop toxicities.[59487]

    MAXIMUM DOSAGE

    Adults

    4 mg/day PO.

    Geriatric

    4 mg/day PO.

    Adolescents

    Safety and efficacy have not been established.

    Children

    Safety and efficacy have not been established.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    Mild or moderate hepatic impairment (Child-Pugh classes A or B) at baseline: initial dose, 3 mg/day PO.
    Severe hepatic impairment (Child-Pugh class C) at baseline: initial dose, 2 mg/day PO.
    Treatment-related toxicity: for elevated hepatic enzymes (e.g., increased AST or ALT levels), hold pomalidomide; therapy may be resumed at a lower dose when hepatic enzymes levels return to baseline.

    Renal Impairment

    Severe renal impairment requiring dialysis at baseline: initial dose, 3 mg/day PO; administer after hemodialysis on dialysis days.
    Dosage Guidance with CYP1A2 Inhibitors/Inducers
    Strong CYP1A2 inhibitors: Avoid concomitant use if possible; consider an alternative agent. If concomitant use cannot be avoided, reduce the pomalidomide dose by 50%.
    Strong CYP1A2 inducers: Concomitant use has not been evaluated; use together with caution as pomalidomide exposure may be reduced.

    ADMINISTRATION

    All prescribers, patients, and pharmacists must comply with the conditions of the POMALYST REMS program when prescribing, dispensing, or receiving pomalidomide. Information about the drug and the program can be found at www.CelgeneRiskManagement.com or by calling 1-888-423-5436.
    Observe and exercise usual cautions for handling, administering, and disposal of cytotoxic drugs. Wash the exposed area immediately and thoroughly with soap and water if powder from pomalidomide capsules come into contact with skin; flush thoroughly with water if pomalidomide comes into contact with mucous membranes.

    Oral Administration
    Oral Solid Formulations

    Take pomalidomide with or without food at approximately the same time each day.
    Swallow capsules whole; do not crush, break, or chew.
    If a dose is missed, take within 12 hours of missing the dose. If more than 12 hours have passed, skip the dose of the day and take the dose the next day at the scheduled time.

    STORAGE

    POMALYST:
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F

    CONTRAINDICATIONS / PRECAUTIONS

    Angioedema, serious rash, thalidomide hypersensitivity

    Severe hypersensitivity reactions including serious rash (Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN)) and drug reaction with eosinophilia and systemic symptoms (DRESS) have been reported with pomalidomide therapy; some cases were fatal. Use is contraindicated in patients who have experienced an allergic reaction (e.g., angioedema or anaphylaxis) to pomalidomide. Therapy interruption or discontinuation should be considered in pomalidomide-treated patients who develop a grade 2 or 3 skin rash. Permanently discontinue pomalidomide if a patient develops angioedema, anaphylaxis, grade 4 rash, exfoliative or bullous rash, or SJS, TEN, or DRESS. Pomalidomide is a thalidomide analog; use caution in patients who have a history of thalidomide hypersensitivity.

    Hyperlipidemia, hypertension, myocardial infarction, stroke, thromboembolism, tobacco smoking

    Venous (e.g., deep venous thrombosis and pulmonary embolism) thromboembolism and arterial (e.g., myocardial infarction and stroke) thromboembolism have been reported in patients with multiple myeloma who received pomalidomide plus low-dose dexamethasone in clinical trials. A prior history of thrombosis, hyperlipidemia, hypertension, and/or tobacco smoking may increase the risk of thromboembolism with pomalidomide therapy; minimize modifiable risk factors if possible. Thromboprophylaxis is recommended in all patients; the choice of prophylactic regimen should be based on an assessment of a patient's underlying risk factors.

    Hepatic disease, hepatotoxicity

    Hepatotoxicity (e.g., elevated hepatic enzymes and hepatic failure) has been reported with pomalidomide therapy; death due to hepatic failure has occurred. Use pomalidomide with caution in patients with hepatic disease; an initial dose reduction is necessary in patients with hepatic impairment. Monitor liver function tests (LFTs) monthly. Therapy interruption, dose reduction, and/or discontinuation may be necessary in patients who develop hepatic toxicity.

    Anemia, bone marrow suppression, neutropenia, thrombocytopenia

    Bone marrow suppression/pancytopenia and severe anemia, neutropenia, and thrombocytopenia have been reported with pomalidomide use. Do not start a new cycle of therapy until the absolute neutrophil count is at least 500 cells/microliter (mcL) and the platelet count is at least 50,000 cells/mcL. Monitor complete blood counts weekly for the first 8 weeks and then monthly thereafter. Therapy interruption, dose reduction, and/or discontinuation may be necessary in patients who develop severe hematologic toxicity.

    Tumor lysis syndrome (TLS)

    Tumor lysis syndrome (TLS) has been reported with pomalidomide therapy. Monitor patients at risk for TLS (e.g., high tumor burden prior to treatment) for hyperkalemia, hyperphosphatemia, hyperuricemia, hypocalcemia, and decreased urine output. Take precautionary measures (e.g., hydration, uric acid lowering therapy) as appropriate to prevent electrolyte imbalances and renal toxicity.

    Blood donation

    Blood donation should not be considered by men or women receiving pomalidomide during or for 1 month after therapy because of the risk that this blood might be administered to a pregnant woman whose fetus must not be exposed to pomalidomide.

    Renal disease, renal failure, renal impairment

    Renal failure has been reported with pomalidomide therapy. Use pomalidomide with caution in patients with renal disease; an initial dose reduction is necessary in patients with severe renal impairment requiring dialysis.

    Treatment outside of a clinical trial

    The use of a PD-1 or PDL1 blocking antibody with a thalidomide analogue plus dexamethasone is not recommended for multiple myeloma treatment outside of a clinical trial. Two clinical trials were halted due to an increased risk of death in patients who received pembrolizumab and dexamethasone in combination with an immunomodulatory agent (lenalidomide or pomalidomide) for the treatment of multiple myeloma.

    Intrauterine fetal death, pregnancy

    Pomalidomide is contraindicated for use during pregnancy; females of reproductive potential should avoid pregnancy for at least 4 weeks prior to, during, and for at least 4 weeks after pomalidomide therapy. Pomalidomide is an analog of thalidomide, a known human teratogen that causes severe, life-threatening human birth defects. Pomalidomide produced malformations in the offspring of female rats and rabbits. It may cause birth defects or intrauterine fetal death if administered during pregnancy. In order to prevent fetal exposure, pomalidomide is only available through a restricted distribution program, the POMALYST REMS program. This program requires prescribers, pharmacists, and patients to comply with certain conditions prior to prescribing, dispensing, or receiving pomalidomide. It can be prescribed only by licensed prescribers who are registered in the POMALYST REMS program and understand the potential risk of teratogenicity if used during pregnancy. If pregnancy does occur during treatment, immediately discontinue pomalidomide. Prescribers are encouraged to report all cases of pregnancy to the Celgene Corporation at 1-888-423-5436 or to the FDA MedWatch program at 1-800-FDA-1088. Refer the patient to an obstetrician/gynecologist experienced in reproductive toxicity for further evaluation and counseling.

    Contraception requirements, dysfunctional uterine bleeding, infertility, male-mediated teratogenicity, menstrual irregularity, pregnancy testing, reproductive risk, sperm donation

    Counsel patients about the reproductive risk and contraception requirements during pomalidomide treatment. Do not initiate therapy in females of reproductive potential until pregnancy testing is performed twice with confirmed negative results. Administer the first test within 10 to 14 days and the second test 24 hours prior to prescribing pomalidomide. Once treatment is started, continue pregnancy testing weekly during the first 4 weeks of treatment, then every 4 weeks in females with regular menstrual cycles and every 2 weeks in females with irregular menstrual cycles. Effective contraception must be used by all females of reproductive potential for at least 4 weeks before beginning treatment, during therapy and dosage interruptions, and for 4 weeks following discontinuation of therapy. Women must commit to abstain from heterosexual intercourse or to use 2 methods of reliable birth control, including at least 1 highly effective method (e.g., intrauterine device (IUD), hormonal contraception, tubal ligation, or partner's vasectomy) and 1 additional effective method (e.g., latex condom, diaphragm, or cervical cap). Follow these contraceptive requirements even in patients with a history of infertility, unless a hysterectomy has been performed. Discontinue treatment, test for pregnancy, and counsel any woman of reproductive potential who experiences menstrual irregularity (e.g., dysfunctional uterine bleeding) or misses her period. Advise patients that if her doctor is not available, she can call 1-888-423-5436. Pomalidomide passes into semen and there is potential for male-mediated teratogenicity. Male patients must use barrier contraception (latex condom) during sexual intercourse with a woman of reproductive potential while on therapy, during interruptions, and for 4 weeks after discontinuing therapy, even if he has undergone successful vasectomy. Male patients should be warned against sperm donation during pomalidomide therapy and for 4 weeks after stopping therapy. Female infertility may be possible based on data in animal studies.[59487]

    Breast-feeding

    It is not known whether pomalidomide is excreted in human milk. Due to the potential for adverse reactions in nursing infants from pomalidomide, a decision should be made whether to discontinue breast-feeding or to discontinue pomalidomide, taking into account the importance of the drug to the mother.

    ADVERSE REACTIONS

    Severe

    neutropenia / Delayed / 4.7-48.3
    infection / Delayed / 0-28.6
    thrombocytopenia / Delayed / 18.8-22.0
    anemia / Delayed / 1.4-21.4
    asthenia / Delayed / 8.7-17.0
    fatigue / Early / 8.7-17.0
    dyspnea / Early / 5.7-12.5
    renal failure (unspecified) / Delayed / 10.3-12.5
    leukopenia / Delayed / 2.7-9.8
    back pain / Delayed / 5.0-9.8
    thromboembolism / Delayed / 8.0-8.0
    bone pain / Delayed / 0-7.3
    lymphopenia / Delayed / 1.0-7.1
    dehydration / Delayed / 5.4-5.4
    fever / Early / 0-5.0
    nausea / Early / 0-5.0
    diarrhea / Early / 0-5.0
    constipation / Delayed / 0-5.0
    arthralgia / Delayed / 0-5.0
    musculoskeletal pain / Early / 0-5.0
    muscle cramps / Delayed / 0-5.0
    hyperglycemia / Delayed / 0-5.0
    hypokalemia / Delayed / 0-5.0
    hyponatremia / Delayed / 0-5.0
    hypocalcemia / Delayed / 0-5.0
    rash / Early / 0-5.0
    headache / Early / 0-5.0
    pulmonary embolism / Delayed / 0-4.7
    thrombosis / Delayed / 0-4.7
    weakness / Early / 3.6-3.6
    confusion / Early / 3.0-3.0
    stroke / Early / 0-3.0
    myocardial infarction / Delayed / 0-3.0
    peripheral neuropathy / Delayed / 2.0-2.0
    elevated hepatic enzymes / Delayed / 1.0-1.7
    peripheral edema / Delayed / 1.3-1.3
    pelvic pain / Delayed / 1.3-1.3
    anorexia / Delayed / 1.0-1.0
    vomiting / Early / 1.0-1.0
    new primary malignancy / Delayed / 0-1.0
    hypercalcemia / Delayed / 0.9-0.9
    cough / Delayed / 0-0.7
    tremor / Early / 0-0.7
    dizziness / Early / 1.0
    pancytopenia / Delayed / Incidence not known
    GI bleeding / Delayed / Incidence not known
    bone fractures / Delayed / Incidence not known
    bronchospasm / Rapid / Incidence not known
    tumor lysis syndrome (TLS) / Delayed / Incidence not known
    interstitial nephritis / Delayed / Incidence not known
    toxic epidermal necrolysis / Delayed / Incidence not known
    Stevens-Johnson syndrome / Delayed / Incidence not known
    pericarditis / Delayed / Incidence not known
    Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) / Delayed / Incidence not known
    myocarditis / Delayed / Incidence not known
    heart failure / Delayed / Incidence not known
    atrial fibrillation / Early / Incidence not known
    hepatic failure / Delayed / Incidence not known
    anaphylactoid reactions / Rapid / Incidence not known
    angioedema / Rapid / Incidence not known
    teratogenesis / Delayed / Incidence not known
    fetal death / Delayed / Incidence not known
    organ transplant rejection / Delayed / Incidence not known

    Moderate

    chest pain (unspecified) / Early / 19.6-19.6
    hepatitis / Delayed / Incidence not known
    lymphadenopathy / Delayed / Incidence not known
    pneumonitis / Delayed / Incidence not known
    angina / Early / Incidence not known
    hypotension / Rapid / Incidence not known
    hyperbilirubinemia / Delayed / Incidence not known
    hypothyroidism / Delayed / Incidence not known
    hyperthyroidism / Delayed / Incidence not known

    Mild

    hyperhidrosis / Delayed / 5.0-16.1
    insomnia / Early / 16.1-16.1
    chills / Early / 12.5-12.5
    night sweats / Early / 12.5-12.5
    weight gain / Delayed / 10.7-10.7
    epistaxis / Delayed / 10.7-10.7
    xerosis / Delayed / 10.7-10.7
    weight loss / Delayed / 8.9-8.9
    pruritus / Rapid / 7.3-8.9
    anxiety / Delayed / 7.1-7.1
    syncope / Early / Incidence not known
    vertigo / Early / Incidence not known
    urticaria / Rapid / Incidence not known

    DRUG INTERACTIONS

    Acetaminophen; Butalbital: (Moderate) Use pomalidomide and barbiturates together with caution; decreased pomalidomide exposure may occur resulting in reduced pomalidomide effectiveness. Pomalidomide is a CYP1A2 substrate and barbiturates are CYP1A2 inducers.
    Acetaminophen; Butalbital; Caffeine: (Moderate) Use pomalidomide and barbiturates together with caution; decreased pomalidomide exposure may occur resulting in reduced pomalidomide effectiveness. Pomalidomide is a CYP1A2 substrate and barbiturates are CYP1A2 inducers.
    Acetaminophen; Butalbital; Caffeine; Codeine: (Moderate) Use pomalidomide and barbiturates together with caution; decreased pomalidomide exposure may occur resulting in reduced pomalidomide effectiveness. Pomalidomide is a CYP1A2 substrate and barbiturates are CYP1A2 inducers.
    Amiodarone: (Major) Avoid the concomitant use of pomalidomide and amiodarone; significantly increased pomalidomide exposure may occur increasing the risk of pomalidomide adverse events. If concomitant use is unavoidable, decrease the pomalidomide dose by 50% and monitor for pomalidomide adverse events. Pomalidomide is a CYP1A2 substrate and amiodarone inhibits CYP1A2. In healthy volunteers, the Cmax and AUC values for pomalidomide were increased by 24% and 125%, respectively, when pomalidomide was co-administered with a strong CYP1A2 inhibitor.
    Amobarbital: (Moderate) Use pomalidomide and barbiturates together with caution; decreased pomalidomide exposure may occur resulting in reduced pomalidomide effectiveness. Pomalidomide is a CYP1A2 substrate and barbiturates are CYP1A2 inducers.
    Aspirin, ASA; Butalbital; Caffeine: (Moderate) Use pomalidomide and barbiturates together with caution; decreased pomalidomide exposure may occur resulting in reduced pomalidomide effectiveness. Pomalidomide is a CYP1A2 substrate and barbiturates are CYP1A2 inducers.
    Aspirin, ASA; Butalbital; Caffeine; Codeine: (Moderate) Use pomalidomide and barbiturates together with caution; decreased pomalidomide exposure may occur resulting in reduced pomalidomide effectiveness. Pomalidomide is a CYP1A2 substrate and barbiturates are CYP1A2 inducers.
    Atropine; Hyoscyamine; Phenobarbital; Scopolamine: (Moderate) Use pomalidomide and barbiturates together with caution; decreased pomalidomide exposure may occur resulting in reduced pomalidomide effectiveness. Pomalidomide is a CYP1A2 substrate and barbiturates are CYP1A2 inducers.
    Barbiturates: (Moderate) Use pomalidomide and barbiturates together with caution; decreased pomalidomide exposure may occur resulting in reduced pomalidomide effectiveness. Pomalidomide is a CYP1A2 substrate and barbiturates are CYP1A2 inducers.
    Belladonna Alkaloids; Ergotamine; Phenobarbital: (Moderate) Use pomalidomide and barbiturates together with caution; decreased pomalidomide exposure may occur resulting in reduced pomalidomide effectiveness. Pomalidomide is a CYP1A2 substrate and barbiturates are CYP1A2 inducers.
    Butabarbital: (Moderate) Use pomalidomide and barbiturates together with caution; decreased pomalidomide exposure may occur resulting in reduced pomalidomide effectiveness. Pomalidomide is a CYP1A2 substrate and barbiturates are CYP1A2 inducers.
    Carbamazepine: (Minor) A decrease in pomalidomide exposure occurred when pomalidomide and carbamazepine were administered together in a drug interaction study. Pomalidomide is a substrate of CYP3A4 and CYP1A2 and carbamazepine is a strong CYP3A4 and moderate CYP1A2 inducer. In healthy male volunteers, the pomalidomide AUC value was decreased by 20% (90% CI, 13% to 27%) when pomalidomide was co-administered with carbamazepine.The authors did not consider this to be a clinically significant reduction, however it may be prudent to monitor for reduced efficacy of pomalidomide if coadministered with carbamazepine.
    Ciprofloxacin: (Major) Avoid the concomitant use of pomalidomide and ciprofloxacin; significantly increased pomalidomide exposure may occur increasing the risk of pomalidomide adverse events. If concomitant use is unavoidable, decrease the pomalidomide dose by 50% and monitor for pomalidomide adverse events. Pomalidomide is a CYP1A2 substrate and ciprofloxacin is a strong CYP1A2 inhibitor. In healthy volunteers, the Cmax and AUC values for pomalidomide were increased by 24% and 125%, respectively, when pomalidomide was co-administered with a strong CYP1A2 inhibitor.
    Clozapine: (Major) It is unclear if concurrent use of other drugs known to cause neutropenia (e.g., antineoplastic agents) increases the risk or severity of clozapine-induced neutropenia. Because there is no strong rationale for avoiding clozapine in patients treated with these drugs, consider increased absolute neutrophil count (ANC) monitoring and consult the treating oncologist.
    Dasabuvir; Ombitasvir; Paritaprevir; Ritonavir: (Moderate) Use pomalidomide and ritonavir together with caution; decreased pomalidomide exposure may occur resulting in reduced pomalidomide effectiveness. Pomalidomide is a CYP1A2 substrate and ritonavir is a CYP1A2 inducer.
    Deferasirox: (Major) Avoid the concomitant use of pomalidomide and deferasirox; significantly increased pomalidomide exposure may occur increasing the risk of pomalidomide adverse events. If concomitant use is unavoidable, decrease the pomalidomide dose by 50% and monitor for pomalidomide adverse events. Pomalidomide is a CYP1A2 substrate and deferasirox inhibits CYP1A2. In healthy volunteers, the Cmax and AUC values for pomalidomide were increased by 24% and 125%, respectively, when pomalidomide was co-administered with a strong CYP1A2 inhibitor. Additionally, the AUC value of a sensitive CYP1A2 substrate about doubled when deferasirox was co-administered with a sensitive CYP1A2 substrate in healthy volunteers.
    Denosumab: (Moderate) The safety and efficacy of denosumab use in patients with immunosuppression have not been evaluated. Patients receiving immunosuppressives along with denosumab may be at a greater risk of developing an infection and/or osteonecrosis of the jaw, a rare condition that has been reported during denosumab therapy.
    Fluvoxamine: (Major) Avoid the concomitant use of pomalidomide and fluvoxamine; significantly increased pomalidomide exposure occurred when these agents were administered together in a drug interaction study. If concomitant use is unavoidable, decrease the pomalidomide dose by 50% and monitor for pomalidomide adverse events. Pomalidomide is a CYP1A2 substrate and fluvoxamine is a strong CYP1A2 inhibitor. In healthy volunteers, the Cmax and AUC values for pomalidomide were increased by 24% and 125%, respectively, when pomalidomide was co-administered with fluvoxamine.
    Fosphenytoin: (Moderate) Use pomalidomide and phenytoin or fosphenytoin together with caution; decreased pomalidomide exposure may occur resulting in reduced pomalidomide effectiveness. Pomalidomide is a CYP1A2 substrate and phenytoin is a CYP1A2 inducer.
    Grapefruit juice: (Major) Pomalidomide is a substrate of CYP1A2, CYP3A, and P-glycoprotein (P-gp). Grapefruit juice is an inhibitor of P-gp. Avoid concomitant use of pomalidomide and grapefruit juice, particularly in combination with both a strong CYP1A2 and a strong CYP3A4 inhibitor. If coadministration of pomalidomide with grapefruit juice and these CYP inhibitors cannot be avoided, decrease the dose of pomalidomide by 50% and monitor for efficacy and toxicity. If pomalidomide is co-administered with grapefruit juice in the absence of both a CYP1A2 and CYP3A4 inhibitor, monitor closely for pomalidomide toxicity.
    Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Moderate) Use pomalidomide and rifampin together with caution; decreased pomalidomide exposure may occur resulting in reduced pomalidomide effectiveness. Pomalidomide is a CYP1A2 substrate and rifampin is a CYP1A2 inducer.
    Isoniazid, INH; Rifampin: (Moderate) Use pomalidomide and rifampin together with caution; decreased pomalidomide exposure may occur resulting in reduced pomalidomide effectiveness. Pomalidomide is a CYP1A2 substrate and rifampin is a CYP1A2 inducer.
    Ketoconazole: (Minor) A clinically insignificant increase in pomalidomide exposure occurred when pomalidomide and ketoconazole were administered together in a drug interaction study. Pomalidomide is a CYP3A4 and P-glycoprotein (P-gp) substrate and ketoconazole is a strong CYP3A4 and P-gp inhibitor. In 16 healthy male volunteers, the pomalidomide AUC value was increased by 19% when pomalidomide was co-administered with ketoconazole.
    Lopinavir; Ritonavir: (Moderate) Use pomalidomide and ritonavir together with caution; decreased pomalidomide exposure may occur resulting in reduced pomalidomide effectiveness. Pomalidomide is a CYP1A2 substrate and ritonavir is a CYP1A2 inducer.
    Mephobarbital: (Moderate) Use pomalidomide and barbiturates together with caution; decreased pomalidomide exposure may occur resulting in reduced pomalidomide effectiveness. Pomalidomide is a CYP1A2 substrate and barbiturates are CYP1A2 inducers.
    Methohexital: (Moderate) Use pomalidomide and barbiturates together with caution; decreased pomalidomide exposure may occur resulting in reduced pomalidomide effectiveness. Pomalidomide is a CYP1A2 substrate and barbiturates are CYP1A2 inducers.
    Mexiletine: (Moderate) Use pomalidomide and mexiletine together with caution; increased pomalidomide exposure may occur increasing the risk of pomalidomide adverse events. If these drugs are used together, monitor for pomalidomide adverse events; a pomalidomide dose adjustment may be necessary. Pomalidomide is a CYP1A2 substrate and mexiletine is a moderate CYP1A2 inhibitor. In healthy volunteers, the plasma levels of a sensitive CYP1A2 substrate increased by 72% (range 35% to 136%) when mexiletine was co-administered with a sensitive CYP1A2 substrate.
    Obeticholic Acid: (Major) Avoid the concomitant use of pomalidomide and obeticholic acid; significantly increased pomalidomide exposure may occur increasing the risk of pomalidomide adverse events. If concomitant use is unavoidable, decrease the pomalidomide dose by 50% and monitor for pomalidomide adverse events. Pomalidomide is a CYP1A2 substrate and obeticholic acid is a strong CYP1A2 inhibitor. In healthy volunteers, the Cmax and AUC values for pomalidomide were increased by 24% and 125%, respectively, when pomalidomide was co-administered with a strong CYP1A2 inhibitor.
    Ombitasvir; Paritaprevir; Ritonavir: (Moderate) Use pomalidomide and ritonavir together with caution; decreased pomalidomide exposure may occur resulting in reduced pomalidomide effectiveness. Pomalidomide is a CYP1A2 substrate and ritonavir is a CYP1A2 inducer.
    Pentobarbital: (Moderate) Use pomalidomide and barbiturates together with caution; decreased pomalidomide exposure may occur resulting in reduced pomalidomide effectiveness. Pomalidomide is a CYP1A2 substrate and barbiturates are CYP1A2 inducers.
    Phenobarbital: (Moderate) Use pomalidomide and barbiturates together with caution; decreased pomalidomide exposure may occur resulting in reduced pomalidomide effectiveness. Pomalidomide is a CYP1A2 substrate and barbiturates are CYP1A2 inducers.
    Phenytoin: (Moderate) Use pomalidomide and phenytoin together with caution; decreased pomalidomide exposure may occur resulting in reduced pomalidomide effectiveness. Pomalidomide is a CYP1A2 substrate and phenytoin is a CYP1A2 inducer.
    Primidone: (Moderate) Use pomalidomide and barbiturates together with caution; decreased pomalidomide exposure may occur resulting in reduced pomalidomide effectiveness. Pomalidomide is a CYP1A2 substrate and barbiturates are CYP1A2 inducers.
    Quinine: (Moderate) Use pomalidomide and quinine together with caution; decreased pomalidomide exposure may occur resulting in reduced pomalidomide effectiveness. Pomalidomide is a CYP1A2 substrate and quinine is a CYP1A2 inducer.
    Rifampin: (Moderate) Use pomalidomide and rifampin together with caution; decreased pomalidomide exposure may occur resulting in reduced pomalidomide effectiveness. Pomalidomide is a CYP1A2 substrate and rifampin is a CYP1A2 inducer.
    Ritonavir: (Moderate) Use pomalidomide and ritonavir together with caution; decreased pomalidomide exposure may occur resulting in reduced pomalidomide effectiveness. Pomalidomide is a CYP1A2 substrate and ritonavir is a CYP1A2 inducer.
    Secobarbital: (Moderate) Use pomalidomide and barbiturates together with caution; decreased pomalidomide exposure may occur resulting in reduced pomalidomide effectiveness. Pomalidomide is a CYP1A2 substrate and barbiturates are CYP1A2 inducers.
    St. John's Wort, Hypericum perforatum: (Moderate) Use pomalidomide and St. John's Wort, Hypericum perforatum, together with caution; decreased pomalidomide exposure may occur resulting in reduced pomalidomide effectiveness. Pomalidomide is a CYP1A2 substrate and St. John's Wort is a CYP1A2 inducer.
    Thiopental: (Moderate) Use pomalidomide and barbiturates together with caution; decreased pomalidomide exposure may occur resulting in reduced pomalidomide effectiveness. Pomalidomide is a CYP1A2 substrate and barbiturates are CYP1A2 inducers.
    Tobacco: (Moderate) Cigarette smoking may reduce pomalidomide exposure due to CYP1A2 induction. Patients should be advised that smoking tobacco may reduce the efficacy of pomalidomide.
    Vemurafenib: (Major) Avoid the concomitant use of pomalidomide and vemurafenib; significantly increased pomalidomide exposure may occur increasing the risk of pomalidomide adverse events. If concomitant use is unavoidable, decrease the pomalidomide dose by 50% and monitor for pomalidomide adverse events. Pomalidomide is a CYP1A2 substrate and vemurafenib is a strong CYP1A2 inhibitor. In healthy volunteers, the Cmax and AUC values for pomalidomide were increased by 24% and 125%, respectively, when pomalidomide was co-administered with a strong CYP1A2 inhibitor.
    Zileuton: (Moderate) Use pomalidomide and zileuton together with caution; increased pomalidomide exposure may occur increasing the risk of pomalidomide adverse events. If these drugs are used together, monitor for pomalidomide adverse events; a pomalidomide dose adjustment may be necessary. Pomalidomide is a CYP1A2 substrate and zileuton is a moderate CYP1A2 inhibitor. The Cmax increased by 73% and the AUC value approximately doubled for a sensitive CYP1A2 substrate when zileuton was co-administered with a sensitive CYP1A2 substrate in healthy volunteers.

    PREGNANCY AND LACTATION

    Pregnancy

    Counsel patients about the reproductive risk and contraception requirements during pomalidomide treatment. Do not initiate therapy in females of reproductive potential until pregnancy testing is performed twice with confirmed negative results. Administer the first test within 10 to 14 days and the second test 24 hours prior to prescribing pomalidomide. Once treatment is started, continue pregnancy testing weekly during the first 4 weeks of treatment, then every 4 weeks in females with regular menstrual cycles and every 2 weeks in females with irregular menstrual cycles. Effective contraception must be used by all females of reproductive potential for at least 4 weeks before beginning treatment, during therapy and dosage interruptions, and for 4 weeks following discontinuation of therapy. Women must commit to abstain from heterosexual intercourse or to use 2 methods of reliable birth control, including at least 1 highly effective method (e.g., intrauterine device (IUD), hormonal contraception, tubal ligation, or partner's vasectomy) and 1 additional effective method (e.g., latex condom, diaphragm, or cervical cap). Follow these contraceptive requirements even in patients with a history of infertility, unless a hysterectomy has been performed. Discontinue treatment, test for pregnancy, and counsel any woman of reproductive potential who experiences menstrual irregularity (e.g., dysfunctional uterine bleeding) or misses her period. Advise patients that if her doctor is not available, she can call 1-888-423-5436. Pomalidomide passes into semen and there is potential for male-mediated teratogenicity. Male patients must use barrier contraception (latex condom) during sexual intercourse with a woman of reproductive potential while on therapy, during interruptions, and for 4 weeks after discontinuing therapy, even if he has undergone successful vasectomy. Male patients should be warned against sperm donation during pomalidomide therapy and for 4 weeks after stopping therapy. Female infertility may be possible based on data in animal studies.[59487]

    MECHANISM OF ACTION

    The mechanism of action of pomalidomide is not fully understood. Pomalidomide, an analogue of thalidomide, is an immunomodulatory agent with antineoplastic activity. Pomalidomide has been shown in vitro to inhibit the proliferation of hematopoietic tumor cells and induce apoptosis. In addition, it inhibited the proliferation of multiple myeloma cell lines that were resistant to lenalidomide. Synergy with dexamethasone was shown in cell lines that were both lenalidomide-sensitive and lenalidomide-resistant. Pomalidomide enhanced T cell- and natural killer (NK) cell-mediated immunity and inhibited production of pro-inflammatory cytokines (e.g., tumor necrosis factor-alpha and interleukin-6) by monocytes. Pomalidomide demonstrated anti-angiogenic activity in a mouse tumor model and in the in vitro umbilical cord model.

    PHARMACOKINETICS

    Pomalidomide is administered orally. It is approximately 12% to 44% bound to plasma proteins; protein binding is not dependent on concentration. At steady state, the mean volume of distribution is 62 to138 liters (L). Pomalidomide does pass into semen. Following the administration of pomalidomide 2 mg/day PO for 4 days in healthy male subjects, the pomalidomide concentration in semen was about 67% of the plasma level at 4 hours post-dose. Pomalidomide is metabolized in the liver primarily by CYP1A2 and CYP3A4. The mean total body clearance is 7 to 10 L/hour. Following a radiolabeled dose of pomalidomide in healthy subjects, about 73% of the dose was excreted in the urine and 15% in the feces, with only 2% and 8% eliminated as unchanged drug in urine and feces, respectively. The mean elimination half-life is 9.5 hours in healthy subjects and 7.5 hours in multiple myeloma patients.
    Affected cytochrome P450 isoenzymes and drug transporters: CYP1A2, P-gp
    Pomalidomide is a substrate of CYP1A2, CYP3A4, and P-glycoprotein (P-gp); CYP2C19 and CYP2D6 are minor substrates in vitro. Concurrent use with strong CYP1A2 inhibitors should be avoided; the mean pomalidomide exposure was increased by 125% when pomalidomide was co-administered with a strong CYP1A2 inhibitor (fluvoxamine) in healthy subjects. However, pomalidomide exposure was not increased to a clinically significant extent when pomalidomide was co-administered with a strong CYP3A4 and P-gp inhibitor (ketoconazole), a strong CYP3A4 inducer (carbamazepine), or a weak to moderate inducer of CYP3A4 (dexamethasone) in drug interaction studies.

    Oral Route

    Following the administration of pomalidomide 4 mg/day PO alone or in combination with dexamethasone, the steady state AUC and Cmax values were 860 nanograms (ng)/mL x hour (coefficient of variance (CV), 37%) and 75 ng/mL (CV, 32%), respectively, in patients with multiple myeloma. The time to maximum plasma concentration (Tmax) is 2 to 3 hours post-dose.
    Effects of food: Compared with the fasted state, the mean AUC and Cmax values were decreased by 8% and 27%, respectively, and the Tmax was delayed by 2.5 hours when pomalidomide was administered with a high-fat (about 50% of the total caloric content), high-calorie (about 800 to 1000 calories) meal in healthy volunteers.