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Thalidomide

Class: Immunomodulatory Agents
ATC Class: L04AX02
VA Class: IM900
Chemical Name: (±)-2-(2,6-Dioxo-3-piperidinyl)-1H-isoindole-1,3(2H)-dione
Molecular Formula: C13H10N2O4
CAS Number: 50-35-1
Brands: Thalomid

Medically reviewed by Drugs.com. Last updated on Jan 27, 2020.

Warning

    Teratogenic Effects
  • Known human teratogen; extremely high risk of severe, life-threatening birth defects if administered during pregnancy. Single dose (regardless of dosage strength) can cause teratogenic effects.

  • Major human fetal abnormalities include skeletal deformities (e.g., amelia [absence of legs and/or arms], absence of bones, phocomelia [short legs and/or arms], bone hypoplasia); external ear deformities (e.g., anotia, microtia or micro pinna, small or absent auditory canals); facial palsy; ocular abnormalities (e.g., anophthalmos and microphthalmos); congenital heart defects; renal and urinary tract malformations; genital malformations; and GI tract malformations.

  • Mortality rate at or shortly after birth in neonates with thalidomide-induced abnormalities about 40%.

    Teratogenicity Precautions
  • Contraindicated in pregnant women; use in females of childbearing potential only when alternative therapies considered inappropriate.

  • Pregnancy must be excluded by negative pregnancy test (sensitivity to detect human serum chorionic gonadotropin [HCG] concentrations of 50 million IU/mL) ≤24 hours before treatment initiation. Repeat pregnancy tests throughout therapy (i.e., once weekly during first month, then monthly or every 2 weeks in women with regular or irregular menstrual cycles, respectively).

  • Pregnancy must be prevented (even in females with a history of infertility) by simultaneous use of 2 forms of reliable contraception for ≥4 weeks prior to, throughout, and for 4 weeks after completion of therapy. (See Fetal/Neonatal Morbidity and Mortality under Cautions.) Mandatory contraception not required for females who have undergone hysterectomy, are postmenopausal and have had no menses for ≥24 consecutive months, or practice continuous abstinence from heterosexual contact.

  • Sexually mature males (including successfully vasectomized men) must completely avoid unprotected sexual contact with women of childbearing potential (i.e., use latex condom throughout and for ≥4 weeks after thalidomide therapy) because thalidomide distributes into semen.

  • Provide pregnancy tests and counseling if a patient misses her period or has abnormalities in menstrual bleeding.

  • If pregnancy occurs, immediately discontinue treatment. Refer patient to obstetrician-gynecologist experienced in reproductive toxicity for further evaluation and counseling. Report any suspected fetal exposure to FDA MedWatch Program at 1-800-FDA-1088 and to manufacturer at 1-888-423-5436.

    Restricted Distribution Program
  • Available only through restricted distribution program, the System for Thalidomide Education and Prescribing Safety (STEPS), designed to help ensure that fetal exposure does not occur. (See Restricted Distribution under Dosage and Administration.)

  • Limits access to thalidomide to prescribing clinicians, pharmacies, and patients who are registered in program and mandates compliance with registration, education, and safety requirements.

  • Registered prescribing clinicians must understand risks of teratogenicity if used during pregnancy and must not provide a prescription until a documented negative pregnancy test available.

  • Patient or parent/legal guardian (for minors 12–18 years of age) must be capable of understanding and complying with patient registration, education, patient survey, and safety requirements, including mandatory contraceptive measures and pregnancy testing.

  • Provide oral and written warnings of risk of possible contraceptive failure, hazards of using drug during pregnancy, exposing fetus to drug, and presence of drug in semen.

  • Patient or parent/legal guardian must provide written acknowledgment of understanding of these warnings and need for mandatory contraceptive measures.

    Venous Thromboembolism
  • Increased risk of venous thromboembolism (e.g., DVT, pulmonary embolism) in patients with multiple myeloma, especially when used in combination with chemotherapy, including dexamethasone.

  • Monitor for signs and symptoms of thromboembolism.

  • Base decisions regarding thromboprophylaxis on careful assessment of patient’s risk factors. (See Thrombotic Events under Cautions.)

Risk Evaluation and Mitigation Strategy (REMS):

FDA approved a REMS for thalidomide to ensure that the benefits outweigh the risks. The REMS may apply to one or more preparations of thalidomide and consists of the following: elements to assure safe use and implementation system. See https://www.accessdata.fda.gov/scripts/cder/rems/.

Introduction

Biologic response modifier; has immunomodulatory, anti-inflammatory, antiangiogenic, and sedative and hypnotic activities.

Uses for Thalidomide

Erythema Nodosum Leprosum

Acute treatment of cutaneous manifestations of moderate to severe erythema nodosum leprosum (ENL) reactions (lepra type 2 reactions); (designated an orphan drug by FDA for this use).

Suggested by some clinicians as drug of choice for treatment of moderate to severe ENL reactions, especially severe, recurrent reactions.

Maintenance therapy for prevention and suppression of cutaneous manifestations of ENL recurrence.

Designated an orphan drug by FDA for treatment and maintenance of reactional lepromatous leprosy.

Used in conjunction with corticosteroid therapy for acute treatment of ENL reactions complicated by moderate to severe neuritis. Should not be used as monotherapy in such patients.

Undertake therapy for leprosy in consultation with an expert.

Multiple Myeloma

Induction therapy (in combination with dexamethasone) in patients with newly diagnosed multiple myeloma (designated an orphan drug by FDA for this use).

Combination therapy with dexamethasone more effective than dexamethasone monotherapy in achieving partial response (decreased concentrations of monoclonal immunoglobulins [e.g., myeloma or Bence-Jones proteins] in serum or urine) in patients with newly diagnosed multiple myeloma. Effect of combination therapy on survival in such patients not established.

Use with bortezomib and dexamethasone may be considered a reasonable choice (accepted, with possible conditions) as induction therapy for newly diagnosed multiple myeloma in transplant-eligible patients (see Multiple Myeloma under Dosage and Administration); however, use of a modified bortezomib-thalidomide-dexamethasone regimen using reduced thalidomide and bortezomib dosages is not fully established because of unclear risk/benefit and/or inadequate experience. Consider performance status and preexisting conditions (e.g., peripheral neuropathy) when selecting a combination chemotherapy regimen.

Other Neoplastic Diseases

Has also been used for treatment of melanoma, ovarian cancer, myelodysplastic syndrome (MDS), advanced pancreatic cancer, primary brain tumors (designated an orphan drug by FDA for this use), androgen-independent prostate cancer, and renal carcinoma.

Inflammatory and/or Dermatologic Disorders

Has been used for treatment of a variety of severe, refractory (e.g., unresponsive to other appropriate agents [e.g., corticosteroids]), inflammatory and/or dermatologic disorders (e.g., erosive lichen planus, erythema multiforme, lupus erythematosus, prurigo nodularis, actinic prurigo, cutaneous Langerhans cell histiocytosis, uremic pruritus, porphyria cutanea tarda, and pyoderma gangrenosum).

Has been used to treat dermatologic, mucocutaneous, and arthritic manifestations of Behcet’s syndrome.

HIV-associated Aphthous Ulcers

Has been used for treatment of HIV-associated aphthous ulcers. However, increases in HIV viral load reported. (See Effects on HIV Viral Load under Cautions.)

May be effective in patients with recurrent ulcers refractory to other therapies (e.g., corticosteroids). Recommended as alternative therapy; not a drug of first choice.

HIV-associated Wasting Syndrome

Has been used for treatment of HIV-associated wasting syndrome (designated an orphan drug by FDA for this use). However, increases in HIV viral load reported. (See Effects on HIV Viral Load under Cautions.)

HIV-associated Diarrhea

Has been used for treatment of HIV-associated diarrhea. However, increases in HIV viral load reported. (See Effects on HIV Viral Load under Cautions.)

AIDS-related Kaposi’s Sarcoma

Has been used for treatment of AIDS-related Kaposi’s sarcoma (designated an orphan drug by FDA for this use). However, increases in HIV viral load reported. (See Effects on HIV Viral Load under Cautions.)

Mycobacterium Infections

Has been used as an adjunct to anti-infective agents in treatment of mycobacterial infections, including Mycobacterium tuberculosis and M. avium complex (MAC) infections, in HIV-infected patients. However, increases in HIV viral load reported. (See Effects on HIV Viral Load under Cautions.)

Graft-versus-host Disease

Has been used for treatment of graft-versus-host disease (GVHD) in bone marrow transplant recipients (designated an orphan drug by FDA for this use).

Should not be used for prophylaxis of chronic GVHD.

Also has been used with some success in the treatment of GVHD in adult peripheral blood stem cell transplant recipients.

Recurrent Aphthous Stomatitis

Has been used for treatment of severe aphthous oral ulcers.

Crohn’s Disease

Has been used for treatment of refractory Crohn’s disease (designated an orphan drug by FDA for this use).

Rheumatic Diseases

Has been used for treatment of refractory ankylosing spondylitis and refractory rheumatoid arthritis.

Sarcoidosis

Has been used for treatment of sarcoidosis.

Thalidomide Dosage and Administration

General

ENL

  • In patients with moderate to severe neuritis associated with severe ENL reactions receiving concomitant corticosteroid therapy, taper corticosteroid dosage and discontinue when neuritis has subsided.

Administration

Restricted Distribution

Distribution of thalidomide is restricted because of known, severe teratogenic effects. (See Boxed Warning and see Fetal/Neonatal Morbidity and Mortality under Cautions.)

A special restricted distribution program, called STEPS, for thalidomide was approved by FDA. The program requires registration of clinicians, pharmacies, and patients; all must agree to accept specific responsibilities (e.g., mandatory contraceptive measures, pregnancy testing) designed to minimize pregnancy exposures in order to prescribe, dispense, or use thalidomide.

STEPS program ensures appropriately timed and properly documented pregnancy testing and counseling of patients before, during, and following thalidomide therapy.

Prior to initiation of therapy, females must certify that they are not pregnant or not of childbearing potential (i.e., hysterectomy, postmenopausal [no menses for ≥24 consecutive months]).

To facilitate pregnancy testing and counseling in accordance with STEPS program, prescribe and dispense ≤28-day supply of drug. Refills require new prescription and another authorization from STEPS program; automatic refills not allowed.

Registering pharmacist must agree to inform all staff pharmacists of dispensing procedures for drug. Before dispensing thalidomide, activate authorization number on every prescription by calling Celgene Customer Care Center at 1-888-423-5436 and obtaining a confirmation number; write confirmation number on thalidomide prescription. Verify that each prescription was written within ≤7 days. Dispense blister packs containing drug intact (i.e., drug cannot be repackaged).

Oral Administration

Administer orally with water ≥1 hour after a meal.

Usually administer as a single daily dose, preferably at bedtime (to minimize sedative effects of drug) with water and ≥1 hour after evening meal.

May administer a high daily dosage (e.g., ≤400 mg daily) as a single dose at bedtime or, alternatively, in divided doses with water ≥1 hour after meals.

Dosage

Pediatric Patients

ENL
Oral

Children ≥12 years of age weighing <50 kg: Initially, administer at lower end of dosage range (e.g., 100 mg daily).

Children ≥12 years of age weighing ≥50 kg: Initially, 100–300 mg once daily. For treatment of severe cutaneous reactions or in patients who previously required high dosages to control a reaction, may initiate at ≤400 mg once daily at bedtime or in divided doses.

Continue therapy until signs and symptoms of active ENL reaction have subsided (usually ≥2 weeks). Gradually taper daily dosage in 50-mg decrements every 2–4 weeks until drug withdrawn or recurrence of ENL occurs.

Maintenance therapy in patients who have recurrence of ENL during tapering and those who have a documented history of recurrences: Institute minimum dosage as required to control ENL reaction. Attempt gradual decrease (i.e., 50-mg decrements every 2–4 weeks) and withdrawal every 3–6 months.

Adults

ENL
Oral

Patients weighing <50 kg: Initially, administer at lower end of dosage range (e.g., 100 mg daily).

Patients weighing ≥50 kg: Initially, 100–300 mg once daily. For treatment of severe cutaneous reactions or in patients who previously required high dosages to control a reaction, may initiate at ≤400 mg once daily at bedtime or in divided doses.

Continue until signs and symptoms of active ENL reaction have subsided (usually ≥2 weeks). Gradually taper daily dosage in 50-mg decrements every 2–4 weeks until drug withdrawn or recurrence of ENL occurs.

Maintenance therapy in patients who have recurrence of ENL during tapering and those who have a documented history of recurrences: Institute minimum dosage as required to control ENL reaction. Attempt gradual decrease (i.e., 50-mg decrements every 2–4 weeks) and withdrawal every 3–6 months.

Multiple Myeloma
Induction Therapy Prior to Stem-cell Transplantation in Newly Diagnosed Multiple Myeloma
Oral

Thalidomide and dexamethasone: Thalidomide 200 mg once daily combined with dexamethasone 40 mg daily on days 1–4, 9–12, and 17–20 of a 28-day cycle, with cycles repeated at 28-day intervals. Reduce dosage or temporarily discontinue if adverse effects such as constipation, oversedation, or peripheral neuropathy occur. Once adverse effects subside, reinitiate at lower or previous dosage, based on clinical judgment.

Thalidomide, bortezomib, and dexamethasone: Thalidomide 200 mg daily (after initial dosage escalation during cycle 1 with 100 mg on days 1–14 followed by 200 mg daily thereafter) along with bortezomib 1.3 mg/m2 by IV injection twice weekly for 2 weeks (days 1, 4, 8, and 11) and dexamethasone 40 mg orally on days 1, 2, 4, 5, 8, 9, 11, and 12. Treatment cycles repeated every 21 days for 3 cycles.

Thalidomide, bortezomib, and dexamethasone: Thalidomide 200 mg daily (after initial dosage escalation during cycle 1 with 50 mg on days 1–14 followed by 100 mg on days 15–28) along with bortezomib 1.3 mg/m2 by IV injection twice weekly for 2 weeks (days 1, 4, 8, and 11) and dexamethasone 40 mg orally on days 1–4 and 9–12. Treatment cycles repeated every 4 weeks for 6 cycles.

Thalidomide, bortezomib, and dexamethasone: Thalidomide 100 mg daily along with bortezomib 1.3 mg/m2 by sub-Q or IV injection twice weekly for 2 weeks (days 1, 4, 8, and 11) and dexamethasone 40 mg orally on days 1–4 and 9–12. Treatment cycles repeated every 3 weeks for 4 cycles.

Recurrent Aphthous Stomatitis†
Oral

100–300 mg daily for 1–6 weeks has been used. May be necessary to use higher dosages (e.g., 400–600 mg daily). Optimal duration of therapy unknown; may relapse following discontinuance of drug.

Maintenance therapy to prevent or treat relapse: 50–100 mg daily.

Crohn’s Disease†
Oral

50–300 mg daily has been used.

Graft-versus-host Disease†
Oral

800 mg to 1.6 g daily for a median duration of 240 days has been used in a clinical trial.

Prescribing Limits

Pediatric Patients

ENL
Oral

Children ≥12 years of age weighing ≥50 kg: Maximum 400 mg daily.

Adults

ENL
Oral

Patients weighing ≥50 kg: Maximum 400 mg daily.

Special Populations

No dosage adjustment required in patients undergoing hemodialysis.

Cautions for Thalidomide

Contraindications

  • Pregnant women. (See Boxed Warning and see Fetal/Neonatal Morbidity and Mortality under Cautions.)

  • Females of childbearing potential and sexually mature males, unless they comply with all special conditions required by manufacturer and STEPS program. (See Boxed Warning and see Fetal/Neonatal Morbidity and Mortality under Cautions.)

  • Known hypersensitivity to thalidomide or any ingredient in formulation. (See Sensitivity Reactions under Cautions.)

Warnings/Precautions

Warnings

Fetal/Neonatal Morbidity and Mortality

Extremely high risk of severe birth defects (possibly life-threatening) if pregnancy occurs while receiving thalidomide in any amount. (See Boxed Warning.)

High risk of severe teratogenicity (e.g., phocomelia, death to the fetus) especially during critical period of pregnancy (i.e., 35–50 days after the last menstrual period); potentially significant risk outside this critical period.

Contraindicated in female patients who are or who may become pregnant.

Women of childbearing potential must use 2 forms of effective contraception ≥4 weeks prior to, throughout, and following completion of therapy. Use a highly effective birth control method (intrauterine device [IUD]; oral, injectable, or implanted hormonal contraceptives; tubal ligation; vasectomized partner) and effective barrier method (latex condom, diaphragm, cervical cap). If either IUD or hormonal contraceptive use contraindicated, may use another highly effective method or 2 simultaneous effective barrier methods.

Thalidomide distributes into semen; risk to fetus from semen of male patients receiving thalidomide unknown. Sexually mature males (including those who have successfully undergone vasectomy) receiving thalidomide must use a latex condom each time they have sexual contact with a woman of childbearing potential during therapy and for 4 weeks following completion of therapy.

If clinician not available, information about emergency contraception (including information regarding clinicians who provide emergency contraceptive services) can be obtained by calling 1-888-668-2528 or by using other sources (e.g., ).

Thrombotic Events

Increased risk of venous thromboembolism (e.g., DVT, pulmonary embolism) in patients with multiple myeloma, especially when used in combination with chemotherapy, including dexamethasone.

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

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

International Myeloma Working Group (IMWG) recommends aspirin for thalidomide-treated multiple myeloma patients with ≤1 individual and/or myeloma-related risk factor and a low molecular weight heparin (LMWH) for those with ≥2 such risk factors. IMWG also recommends that thromboprophylaxis with an LMWH be considered in patients receiving thalidomide with high-dose dexamethasone, doxorubicin, or multiple antineoplastic agents, independent of additional risk factors. IMWG states full-dose warfarin (INR 2–3) is an alternative to LMWHs, but clinical experience is limited.

ASCO recommends pharmacologic thromboprophylaxis for multiple myeloma patients receiving thalidomide with dexamethasone or antineoplastic agents. Those at lower risk for thromboembolism may receive aspirin or an LMWH; those at higher risk should receive an LMWH.

DVT and pulmonary embolism also reported in patients with ENL.

Peripheral Neuropathy

Potentially severe and irreversible nerve damage (i.e., polyneuritis or peripheral neuropathy); generally reported with chronic use, but has occurred with relatively short-term use and after discontinuance of therapy.

Correlation with cumulative thalidomide dose unclear.

Differentiation of neuropathologic symptoms caused by thalidomide and changes caused by underlying disease (i.e., ENL, HIV infection) may be difficult.

Evaluate patients for signs and symptoms of peripheral neuropathy (e.g., numbness, tingling, pain or a burning sensation in the hands and feet), and counsel and question patients regularly during therapy (i.e., monthly for first 3 months of thalidomide treatment, and periodically thereafter).

Consider using electrophysiologic testing, consisting of sensory nerve action potential (SNAP) amplitude measurement at baseline and every 6 months thereafter to detect asymptomatic neuropathy.

If manifestations of peripheral neuropathy develop, discontinue therapy immediately (if clinically appropriate) to minimize further damage. Usually, resume treatment only if manifestations of neuropathy return to baseline.

Use concomitantly with drugs known to be associated with peripheral neuropathy with caution. (See Specific Drugs under Interactions.)

Other Nervous System Effects

Drowsiness and somnolence occur frequently.

Cardiovascular Effects

Possible orthostatic hypotension and dizziness. (See Advice to Patients.)

Hematologic Effects

Decreased leukocyte counts, including neutropenia, reported. Do not initiate therapy in patients with ANC <750/mm3. Routinely monitor leukocyte and differential counts, especially in those prone to neutropenia (e.g., HIV-infected patients). If ANC decreases to <750/mm3, reevaluate drug regimen. If neutropenia persists, consider withholding drug if clinically appropriate.

Effects on HIV Viral Load

Increases in HIV viral load (i.e., plasma HIV-1 RNA concentrations) reported.

Measure plasma HIV-1 RNA concentrations in HIV-seropositive patients after first and third months of treatment and every 3 months thereafter.

Sensitivity Reactions

Hypersensitivity reactions (e.g., erythematous macular rash associated with fever, tachycardia, hypotension) reported. Discontinue if signs and symptoms of hypersensitivity are severe. If therapy resumed and reaction recurs, permanently discontinue.

Severe, potentially fatal skin reactions, including Stevens-Johnson syndrome and toxic epidermal necrolysis, reported. Discontinue if rash occurs; resume therapy only after appropriate clinical evaluation. Do not resume therapy if rash is exfoliative, purpuric, or bullous, or if Stevens-Johnson syndrome or toxic epidermal necrolysis suspected.

General Precautions

Environmental Exposure of Patients and Health-care Providers

Potential risks of birth defects from environmental exposure through cutaneous absorption or inhalation of drug powder by sexually mature females unknown. Birth defects reported only following oral ingestion of thalidomide.

Do not extensively handle or open drug capsules; maintain storage in blister packs until ingestion. If accidental skin contact with opened capsules or drug powder occurs, wash affected area with soap and water.

Thalidomide present in serum and semen of patients receiving drug. When treating patients receiving drug, use precautions (e.g., use of gloves, wash skin exposed to body fluids) to minimize exposure to patient’s body fluids.

Bradycardia

Bradycardia, possibly requiring medical intervention, reported; clinical importance and underlying etiology unknown.

Seizures

Seizures, including tonic-clonic (grand mal) seizures, reported, usually in patients with predisposing risk factors. Epileptogenic activity of thalidomide unknown.

Monitor patients with a history of seizures or other risk factors closely for clinical changes that could precipitate acute seizure activity.

Specific Populations

Pregnancy

Category X. (See Boxed Warnings and see Fetal/Neonatal Morbidity and Mortality under Cautions.)

Lactation

Not known whether thalidomide is distributed into milk. Discontinue nursing or the drug.

Pediatric Use

Safety and efficacy not established in children <12 years of age.

For information on patients 12–18 years of age, see Boxed Warning.

Geriatric Use

No substantial differences in safety and efficacy relative to younger adults, but increased sensitivity cannot be ruled out.

Possibility exists of greater sensitivity to the drug in some geriatric individuals.

Common Adverse Effects

Somnolence, dizziness, rash.

Interactions for Thalidomide

Limited hepatic metabolism; only parent compound appears to be metabolized by CYP-450 isoenzymes.

Specific Drugs

Drug

Interaction

Comments

Antineoplastic agents (e.g., cisplatin, paclitaxel, vincristine)

Increased risk of neuropathy

Use concomitantly with caution

Antiretroviral agents (e.g., didanosine)

Increased risk of neuropathy

Use concomitantly with caution

CNS depressants (e.g., alcohol, barbiturates, chlorpromazine)

Potential additive sedative effects

Contraceptives, oral

Pharmacokinetic interaction unlikely

Thalidomide Pharmacokinetics

Absorption

Bioavailability

Absolute bioavailability not determined; racemic drug has poor aqueous solubility.

Slowly absorbed from GI tract; mean peak plasma concentrations generally attained 2.5–6 hours after oral dose.

Food

Food decreases rate but not does not substantially affect extent of absorption.

Special Populations

Pharmacokinetics similar in HIV-infected patients and in healthy individuals.

Pharmacokinetics not established in pediatric and adolescent patients (<18 years of age).

Bioavailability may be greater in patients with leprosy than in healthy individuals.

Distribution

Extent

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

Crosses placenta in humans and animals, resulting in fetal malformations. (See Boxed Warning and see Fetal/Neonatal Morbidity and Mortality under Cautions.)

Plasma Protein Binding

55 and 66% for R- and S-enantiomers, respectively.

Elimination

Metabolism

Principally, rapid nonenzymatic spontaneous hydrolysis in plasma. Insufficient evidence exists that formation of active metabolites required for thalidomide’s effects.

Hepatic metabolism limited, and only parent compound appears to be metabolized by CYP-450 isoenzymes.

Elimination Route

Predominantly nonrenal; <0.7% excreted in urine as unchanged drug.

Half-life

Averages approximately 5–7 hours in healthy individuals.

Averages 6.9 hours and 4.98 hours in leprosy patients and multiple myeloma patients, respectively.

Special Populations

In patients with severe renal impairment, accumulation of drug does not occur. Mean total clearance increased 2.5-fold in patients undergoing hemodialysis. (See Special Populations under Dosage and Administration.)

Stability

Storage

Oral

Capsules

25°C (may be exposed to 15–30°C); protect from light.

Actions

  • In patients with ENL, activates T cells and modulates production of cytokines TNF-α, interleukin-2 (IL-2), interleukin-12 (IL-12), and interferon-γ by T cells.

  • Induces down-modulation of selected cell surface adhesion molecules involved in leukocyte migration, resulting in decreased dermal infiltrations of leukocytes (e.g., neutrophils) in ENL lesions.

  • In multiple myeloma patients, inhibits TNF-α expression by bone marrow stromal cells, resulting in inhibition of growth of multiple myeloma cells. Enhances T cell activation, releasing cytokines IL-2 and interferon-γ. These cytokines activate natural killer cells causing lysis of multiple myeloma cells.

  • Impairs angiogenesis in bone marrow by decreasing fibroblast growth factor (FGF-2) and vascular endothelial growth factor (VEGF) production.

  • Decreases production of selected cell surface adhesion molecules involved in binding multiple myeloma cells to bone marrow stromal cells.

  • Suppresses production of prostaglandins by macrophages.

  • Modulates interleukin-10 (IL-10) and IL-12 production by peripheral blood mononuclear cells and T cells.

  • Inhibits angiogenesis; teratogenic effects may be related to such effects.

Advice to Patients

  • Importance of comprehensive counseling on benefits and risks (e.g., severe, potentially life-threatening birth defects) of drug. (See Boxed Warning.)

  • Importance of taking thalidomide only as prescribed, and in compliance with requirements of STEPS program. (See Restricted Distribution under Dosage and Administration.)

  • Importance of providing patients with copy of video titled Important Information for Men and Women Taking Thalomid (thalidomide) and/or patient brochure provided by manufacturer.

  • Importance of warning women of childbearing potential not to take drug if pregnant, breast-feeding, or able to get pregnant (e.g., not using required methods of birth control).

  • Necessity of advising women of childbearing potential to avoid pregnancy by using mandatory contraceptive measures, unless she abstains from heterosexual contact. (See Boxed Warning and see Fetal/Neonatal Morbidity and Mortality under Cautions.)

  • Importance of immediately discontinuing therapy if pregnancy suspected.

  • Importance of women of childbearing potential informing clinicians of pregnancy, suspected pregnancy, missed menstrual period, unusual menstrual bleeding, or cessation of using contraceptive measures.

  • Importance of informing patient how to obtain information about emergency contraception (including information regarding clinicians who provide emergency contraceptive services) if clinician not available. (See Fetal/Neonatal Morbidity and Mortality under Cautions.)

  • Importance of informing sexually mature male patients (including those who have undergone a vasectomy) of necessity using a latex condom when engaging in sexual contact with a woman of childbearing potential or a pregnant women. (See Fetal/Neonatal Morbidity and Mortality under Cautions.)

  • Importance of male patients informing clinician of unprotected heterosexual sexual contact during therapy and first 4 weeks after drug discontinuance. Importance of male patients informing clinician of suspected pregnancy of their sexual partner.

  • Importance of avoiding extensive handling or opening of drug capsules. Importance of maintaining storage of drug capsules in blister packs until ingestion. (See Environmental Exposure of Patients and Health-care Providers under Cautions.)

  • Importance of advising patients not to share drug with anyone else (even if other individual has similar symptoms) and of not donating blood or semen while receiving drug.

  • Importance of keeping thalidomide out of reach of children and from women of childbearing potential, unless part of STEPS program.

  • Importance of advising patients of risk of dizziness and orthostatic hypotension. Importance of sitting upright for a few minutes before standing up from reclining position.

  • Risk of drowsiness and somnolence; importance of avoiding situations where such drowsiness could create a problem. Risk of impaired ability to perform tasks that require mental alertness or physical coordination (e.g., operating machinery, driving a motor vehicle). Importance of warning patients not to take any other drugs or alcohol that may cause drowsiness without consulting their clinician. (See Specific Drugs under Interactions.)

  • Importance of immediately reporting initial symptoms (e.g., numbness, tingling, pain or a burning sensation in hands and feet) of peripheral neuropathy to clinician.

  • Importance of contacting clinician if symptoms of thromboembolism (e.g., shortness of breath, chest pain, arm or leg swelling) develop.

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

  • Importance of informing patients of other important precautionary information. (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.

Because thalidomide is a known human teratogen and can cause severe, life-threatening birth defects if administered during pregnancy, commercially available thalidomide must be obtained through a restricted distribution program, the System for Thalidomide Education and Prescribing Safety (STEPS), designed to help ensure that fetal exposure to the drug does not occur. See Restricted Distribution Program under Dosage and Administration.

Thalidomide

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Capsules

50 mg

Thalomid

Celgene

100 mg

Thalomid

Celgene

150 mg

Thalomid

Celgene

200 mg

Thalomid

Celgene

AHFS DI Essentials™. © Copyright 2021, Selected Revisions January 27, 2020. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

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