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使用说明书

【英文名】Pomalid (Pomalidomide Capsules)

【中文名】泊马度胺胶囊

【规  格】胶囊: 3mg（1mg、2mg、3mg、4mg）

【厂  家】印度   NATCO

 

 

适应证和用途
Pomalid是一种沙利度胺类似物适用为有多发性骨髓瘤患者曾接受至少两种既往治疗包括来那度胺[lenalidomide]和硼替佐米[bortezomib]和已证实疾病进展或末次治疗完成60天内。批准是根据反应率。尚未证明临床获益，例如改善活存或症状。

剂量和给药方法
重复28天疗程在第1-21天每天口服4mg直至疾病进展。

剂型和规格
胶囊：1mg，2mg，3mg和4mg。

禁忌证
妊娠

警告和注意事项
（1）血液学毒性：中性粒细胞减少是最常报道3/4级不良事件。监视患者血液学毒性，尤其是中性粒细胞减少。

 

不良反应
最常见不良反应(≥30%)包括疲乏和虚弱，中性粒细胞减少，贫血，便秘，恶心，腹泻，呼吸困难，上呼吸道感染，背痛和发热。

在特殊人群中使用
（1）哺乳母亲：终止药物或哺乳考虑药物对母亲的重要性。
（2）有血清肌酐 >3.0mg/dL患者中,避免Pomalid 。 

Pomalidomide

Class: Antineoplastic Agents
Chemical Name: 4-Amino-2-(2,6-dioxo-3-piperidinyl)-1H-isoindole-1,3(2H)-dione
Molecular Formula: C13H11N3O4
CAS Number: 19171-19-8
Brands: Pomalyst

 

 

 

Warning

Teratogenic Effects

· Potential risk of teratogenicity and fetotoxicity due to structural similarity to thalidomide, a known human teratogen that can cause severe, life-threatening birth defects if administered during pregnancy.1

· Contraindicated in pregnant women.1

· In women of childbearing potential, pregnancy must be excluded prior to treatment initiation with 2 negative pregnancy tests, and pregnancy must be prevented by abstinence or simultaneous use of 2 forms of reliable contraception.1 (See Fetal/Neonatal Morbidity and Mortality under Cautions.)

· Available only through a restricted distribution program.1 2 (See REMS and see Restricted Distribution Program under Dosage and Administration.)

Venous Thromboembolic Events

· Increased risk of venous thromboembolism (e.g., DVT, PE) in patients with multiple myeloma.1 (See Venous Thromboembolic Events under Cautions.)

· Thromboprophylaxis required in the pivotal multiple myeloma trial.1 Base decisions regarding thromboprophylaxis on careful assessment of patient’s risk factors.1 4 5 19

Risk Evaluation and Mitigation Strategy (REMS):

FDA approved a REMS for pomalidomide to ensure that the benefits outweigh the risks. 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 https://www.accessdata.fda.gov/scripts/cder/rems/.

 

 

 

Introduction

See also: Pomalyst

Biologic response modifier; thalidomide analog with immunomodulatory, antineoplastic, and antiangiogenic activity.1 13

 

Uses for PomalidomideMultiple Myeloma

Treatment of multiple myeloma in patients who have received ≥2 prior therapies including bortezomib 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).1 7 10 11 12 1517 Efficacy determined based on overall response rate in a noncomparative, open-label study in patients with relapsed multiple myeloma.1 8

 

Pomalidomide Dosage and AdministrationGeneral

· Carefully monitor CBCs during therapy.1 (See Hematologic Effects under Cautions.)

· Do not begin a new treatment cycle until ANC ≥500/mm3and platelet count ≥50,000/mm3.1

· Consult specialized references for procedures for proper handling and disposal of antineoplastics.1

Restricted Distribution Program

· Distribution of pomalidomide is restricted because it is an analog of thalidomide (a known human teratogen that can cause severe birth defects).1 2 (See Fetal/Neonatal Morbidity and Mortality under Cautions.)

· 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.1 2 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.1 2

· 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.2

· For additional details on program requirements, contact Celgene at 888-423-5436 or visit [Web].1

AdministrationOral Administration

Administer orally with water once daily.1

Administer at least 2 hours before or 2 hours after a meal.1

Swallow capsules whole; do not break, chew, or open capsules.1

Prescribe and dispense no more than a 28-day supply at one time.2

Avoid contact of capsule contents with skin or mucous membranes.1 If such contact occurs, wash affected areas of skin thoroughly with soap and water and rinse affected mucosa thoroughly with water.1

DosageAdultsMultiple MyelomaOral

4 mg once daily on days 1–21 of each 28-day cycle; may be used in combination with low-dose dexamethasone (40 mg once daily on days 1, 8, 15, and 22 of each 28-day cycle used in clinical trials).1 15

In the pivotal trial, treatment could be continued until disease progression or unacceptable toxicity occurred.1

Dosage Modification for Toxicity in Patients with Multiple MyelomaOral

Adjust dosage in decrements of 1 mg daily.1

If dosage of 1 mg daily is not tolerated, discontinue therapy.1

Hematologic Toxicity

For first occurrence of neutropenia (ANC <500/mm3), febrile neutropenia (temperature ≥38.5°C and ANC <1000/mm3), or thrombocytopenia (platelet count <25,000/mm3), withhold therapy and monitor CBC weekly.1 When ANC is ≥500/mm3 and platelet count is ≥50,000/mm3, may resume therapy at reduced dosage of 3 mg daily.1

For subsequent occurrences of neutropenia (ANC <500/mm3) or thrombocytopenia (platelet count <25,000/mm3), interrupt therapy until ANC is ≥500/mm3 and platelet count is ≥50,000/mm3; when resuming therapy following recovery, further reduce dosage by 1 mg daily.1 (See Hematologic Effects under Cautions.)

Grade 3 or 4 Toxicity

If grade 3 or 4 toxicities other than neutropenia or thrombocytopenia occur, interrupt therapy until symptoms improve to grade ≤2; resume therapy at reduced dosage of 1 mg daily less than previous dosage.1

Special PopulationsHepatic Impairment

Avoid use in patients with ALT and/or AST >3 times ULN and bilirubin >2 mg/dL.1 (See Hepatic Impairment under Cautions.)

Renal Impairment

Avoid use in patients with Scr >3 mg/dL.1 (See Renal Impairment under Cautions.)

Geriatric Patients

No pomalidomide dosage adjustment required.1 Concomitant dexamethasone dosage reduced to 20 mg once daily on days 1, 8, 15, and 22 of each 28-day cycle in patients >75 years of age in multiple myeloma trials.1 15

Cautions for PomalidomideContraindications

· Pregnancy.1 (See Boxed Warning and see Fetal/Neonatal Morbidity and Mortality under Cautions.)

Warnings/PrecautionsWarningsFetal/Neonatal Morbidity and Mortality

May cause fetal harm; contraindicated in pregnant women.1 Teratogenicity demonstrated in animals; structurally similar to thalidomide, a known human teratogen associated with severe birth defects and fetal death.1 (See Restricted Distribution Program under Dosage and Administration.)

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.1 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).1 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.1 2

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.1 Men must not donate semen during and for 4 weeks after therapy.1

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.1

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.1 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.1

Provide pregnancy testing and counseling if a patient misses her period or has abnormalities in menstrual bleeding.1 Discontinue drug during evaluation.1

If pregnancy occurs, immediately discontinue treatment and apprise of potential fetal hazard.1 Refer patient to obstetrician-gynecologist experienced in reproductive toxicity for further evaluation and counseling.1 Report any suspected fetal exposure to FDA MedWatch Program at 800-FDA-1088 and to manufacturer at 888-423-5436.1

Venous Thromboembolic Events

Increased risk of venous thromboembolism (e.g., DVT, PE) in patients with multiple myeloma.1

Monitor for signs and symptoms of thromboembolism (e.g., shortness of breath, chest pain, arm or leg swelling).1

Thromboprophylaxis (aspirin 81–100 mg daily, or another antithrombotic agent if aspirin contraindicated) required in all patients receiving pomalidomide alone or in combination with low-dose dexamethasone in the pivotal multiple myeloma trial.1 9 Carefully assess multiple myeloma 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.1 4 5 19

Sensitivity ReactionsHypersensitivity Reactions

Risk of hypersensitivity reactions may be increased in patients who have had serious hypersensitivity reactions to thalidomide or lenalidomide.1

Other Warnings and PrecautionsHematologic Effects

Risk of severe (grade 3 or 4) neutropenia, anemia, and/or thrombocytopenia.1

Perform CBCs weekly during first 8 weeks of therapy and at least monthly thereafter.1

If hematologic toxicity occurs, interrupt therapy and/or reduce dosage.1 (See Dosage Modification for Toxicity in Patients with Multiple Myeloma under Dosage and Administration.)

Nervous System Effects

Dizziness, confusion, and neuropathy (frequently peripheral neuropathy) reported.1 (See Advice to Patients.)

Development of Second Primary Malignancy

Acute myelogenous leukemia (AML) reported in patients receiving pomalidomide as investigational therapy.1

Specific PopulationsPregnancy

Category X.1 (See Fetal/Neonatal Morbidity and Mortality under Cautions.)

Lactation

Distributed into milk in rats; not known whether distributed into human milk.1 Discontinue nursing or drug.1

Pediatric Use

Safety and efficacy not established in pediatric patients <18 years of age.1

Geriatric Use

No overall differences in efficacy in geriatric patients (≥65 years of age) compared with younger adults.1Increased incidence of pneumonia compared with younger adults.1

Hepatic Impairment

Safety and efficacy not established in patients with baseline ALT or AST concentrations >3 times ULN and bilirubin concentration >2 mg/dL.1

Renal Impairment

Safety and efficacy not established in patients with baseline Scr >3 mg/dL.1

Common Adverse Effects

Fatigue,1 asthenia,1 10 pyrexia,1 peripheral edema,1 neutropenia,1 10 anemia,1 10 thrombocytopenia,1 10constipation,1 diarrhea,1 nausea,1 pneumonia,1 upper respiratory tract infection,1 back pain,1musculoskeletal chest pain,1 dyspnea,1 cough,1 decreased appetite,1 hypercalcemia,1 rash,1 dizziness.1

Interactions for Pomalidomide

Metabolized primarily by CYP1A2 and CYP3A4.1 13

Does not inhibit or induce CYP isoenzymes in vitro.1

Substrate of P-glycoprotein (P-gp); does not inhibit or induce P-gp or other transporters in vitro.1

No formal drug interaction studies to date.1

Drugs Affecting Hepatic Microsomal Enzymes

Potent CYP1A2 or 3A inhibitors: Possible increased pomalidomide exposure.1 Avoid concomitant use.1

Potent CYP1A2 or 3A inducers: Possible decreased pomalidomide exposure.1 Avoid concomitant use.1

Drugs Affecting Efflux Transport Systems

Potent inhibitors of P-gp: Possible increased pomalidomide exposure.1 Avoid concomitant use.1

Potent inducers of P-gp: Possible decreased pomalidomide exposure.1 Avoid concomitant use.1

Specific Drugs

Drug	Interaction	Comments
Cigarette smoking	Possible decreased exposure to pomalidomide and reduced efficacy1	Avoid concomitant use1
Dexamethasone	Pharmacokinetics of pomalidomide unchanged
Ketoconazole	Possible increased exposure to pomalidomide1	Avoid concomitant use1
Rifampin	Possible decreased exposure to pomalidomide1	Avoid concomitant use1

Pomalidomide PharmacokineticsAbsorptionBioavailability

Peak plasma pomalidomide concentrations are attained about 2–3 hours after oral administration.1

AUC increases in an approximately dose-proportional manner.1

DistributionExtent

Not known whether pomalidomide is distributed into human milk.1

Distributed into semen.1 (See Fetal/Neonatal Morbidity and Mortality under Cautions.)

Plasma Protein Binding

12–44%.1

EliminationMetabolism

Metabolized primarily by CYP1A2 and CYP3A4, with minor contributions from CYP2C19 and CYP2D6.1 13

Elimination Route

Excreted in urine (73%) and feces (15%); minimal amounts of dose are recovered in urine and feces as unchanged drug.1 13 16

Half-life

In healthy individuals, median half-life approximately 9.5 hours.1

In patients with multiple myeloma, median half-life approximately 7.5 hours.1 13 16

StabilityStorageOralCapsules

20–25°C (may be exposed to 15–30°C).1

Actions

· A thalidomide analog with immunomodulatory, antineoplastic, and antiangiogenic activity.1 13 14 17

· 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.1 13 14

· Induces apoptosis and inhibits growth of hematopoietic tumor cells, including lenalidomide-resistant multiple myeloma cell lines.1 14

· Synergistic antitumor effects demonstrated when combined with dexamethasone in lenalidomide-sensitive and lenalidomide-resistant cell lines.1

· Inhibits angiogenesis in vitro and in mice bearing tumor xenografts.1

Advice to Patients

· Importance of educating patients regarding the Pomalyst REMS restricted distribution program for obtaining pomalidomide.1 (See Restricted Distribution Program under Dosage and Administration.)

· Importance of swallowing capsules intact and not breaking, chewing, or opening capsules.1

· Importance of not taking 2 doses at the same time to make up for a missed dose.1 A missed dose may be taken up to 12 hours after the scheduled administration time; if >12 hours have elapsed, omit the missed dose and resume the regular dosing schedule the next day.1

· Risk of fetal harm.1 Necessity of advising women of childbearing potential to use effective methods of contraception beginning 4 weeks before initiation of therapy, throughout therapy, during dosage interruptions, and for ≥4 weeks after discontinuance of therapy (see Fetal/Neonatal Morbidity and Mortality under Cautions); importance of obtaining pregnancy tests at appropriate intervals and of immediately discontinuing therapy and contacting their clinician if pregnancy is suspected.1 Necessity of advising men (including those who have successfully undergone vasectomy) to use a latex or synthetic condom during sexual encounters with women of childbearing potential during and for ≥28 days after discontinuance of therapy.1 Availability of information on emergency contraception at 888-668-2528.1

· Importance of advising women to avoid breast-feeding while receiving pomalidomide therapy.1

· Importance of advising men to avoid donating semen while receiving pomalidomide and for 4 weeks after discontinuing the drug.1

· Importance of advising patients to avoid donating blood while receiving pomalidomide and for 1 month after discontinuing the drug.1

· Risk of neutropenia, thrombocytopenia, and anemia.1 Importance of regular monitoring of blood cell counts.1 Importance of informing clinician if signs and symptoms of neutropenia, thrombocytopenia, or anemia occur.1

· Risk of severe hypersensitivity reactions in patients who have had hypersensitivity reactions to thalidomide or lenalidomide.1

· Risk of venous thromboembolic events; importance of seeking medical care if shortness of breath, chest pain, or swelling of the arms or legs occurs.1

· Risk of dizziness or confusion; importance of avoiding activities where dizziness or confusion could cause serious harm to self or others.1 Importance of not taking other drugs that may cause dizziness or confusion without consulting clinician.1

· Risk of neuropathy.1 Importance of informing clinician if signs and symptoms of neuropathy occur.1

· Possible risk of developing a second primary malignancy (i.e., AML).1

· Importance of not smoking during pomalidomide therapy, since smoking may reduce the drug's efficacy.1

· 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.1

· Importance of informing patients of other important precautionary information.1 (See Cautions.)

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.1 2 (See REMS and see Restricted Distribution Program under Dosage and Administration.)

Pomalidomide
Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Oral	Capsules	1 mg	Pomalyst	Celgene
		2 mg	Pomalyst	Celgene
		3 mg	Pomalyst	Celgene
		4 mg	Pomalyst	Celgene

AHFS DI Essentials. © Copyright 2018, Selected Revisions November 1, 2013. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.