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
- Teratogenic Effects
Known human teratogen; extremely high risk of severe, life-threatening birth defects if administered during pregnancy.1 2 3 4 5 11 12 15 20 21 52 53 54 Single dose (regardless of dosage strength) can cause teratogenic effects.1 2 3 4 5 15 52 1
Major human fetal abnormalities include skeletal deformities (e.g., amelia [absence of legs and/or arms],1 5 15 absence of bones,1 15 phocomelia [short legs and/or arms],1 4 5 15 54 bone hypoplasia);1 15 external ear deformities (e.g., anotia,1 15 microtia or micro pinna,1 15 small or absent auditory canals);1 5 15 facial palsy;1 15 ocular abnormalities2 5 15 (e.g., anophthalmos1 15 and microphthalmos); 1 15 congenital heart defects;1 5 15 21 renal and urinary tract malformations;15 21 genital malformations;1 15 21 and GI tract malformations.5 15
- Teratogenicity Precautions
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.1 9 22 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).1 9 22
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.1 9 22 (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.1 22
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.1
Provide pregnancy tests and counseling if a patient misses her period or has abnormalities in menstrual bleeding.1
If pregnancy occurs, immediately discontinue treatment.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 1-800-FDA-1088 and to manufacturer at 1-888-423-5436.1
- 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.1 9 17 20 22 (See Restricted Distribution under Dosage and Administration.)
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.1 22
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.1
Patient or parent/legal guardian must provide written acknowledgment of understanding of these warnings and need for mandatory contraceptive measures.1
- 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.1
Monitor for signs and symptoms of thromboembolism.1
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 the FDA REMS page () or the ASHP REMS Resource Center ().
Uses for Thalidomide
Erythema Nodosum Leprosum
Acute treatment of cutaneous manifestations of moderate to severe erythema nodosum leprosum (ENL) reactions (lepra type 2 reactions);1 9 10 13 34 35 39 44 76 86 89 111 113 114 218 220 232 233 234 235 237 238 (designated an orphan drug by FDA for this use).28
Designated an orphan drug by FDA for treatment and maintenance of reactional lepromatous leprosy.28
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.1 242 243 Effect of combination therapy on survival in such patients not established.1
Other Neoplastic Diseases
Has also been used for treatment of melanoma†,9 175 232 237 ovarian cancer†,9 myelodysplastic syndrome (MDS)†,229 advanced pancreatic cancer†,229 primary brain tumors† (designated an orphan drug by FDA for this use),9 28 29 169 174 175 229 androgen-independent prostate cancer†,9 168 and renal carcinoma†.9 175
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]),9 93 156 186 inflammatory and/or dermatologic disorders (e.g., erosive lichen planus†,9 104 127 215 219 232 erythema multiforme†,181 182 215 218 219 232 237 lupus erythematosus†,3 4 9 53 59 104 110 121 122 123 124 196 215 218 219 220 229 237 prurigo nodularis†,9 59 60 94 104 117 118 215 219 229 232 actinic prurigo†,104 119 cutaneous Langerhans cell histiocytosis†,4 104 183 184 232 uremic pruritus†,104 180 215 237 237 porphyria cutanea tarda†,195 215 and pyoderma gangrenosum†).4 5 9 53 104 125 126 219 232 237
HIV-associated Aphthous Ulcers
Has been used for treatment of HIV-associated aphthous ulcers†.9 48 112 142 143 144 146 147 221 223 237 However, increases in HIV viral load reported.1 12 53 54 (See Effects on HIV Viral Load under Cautions.)
May be effective in patients with recurrent ulcers refractory to other therapies (e.g., corticosteroids).55 142 143 144 147 221 Recommended as alternative therapy; not a drug of first choice.55 102 186
HIV-associated Wasting Syndrome
Has been used for treatment of HIV-associated wasting syndrome†9 11 41 48 50 112 140 141 224 (designated an orphan drug by FDA for this use).28 However, increases in HIV viral load reported.1 12 53 54 (See Effects on HIV Viral Load under Cautions.)
AIDS-related Kaposi’s Sarcoma
Has been used for treatment of AIDS-related Kaposi’s sarcoma†9 30 48 115 170 227 (designated an orphan drug by FDA for this use).28 However, increases in HIV viral load reported.1 12 53 54 (See Effects on HIV Viral Load under Cautions.)
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.40 42 53 However, increases in HIV viral load reported.1 12 53 54 (See Effects on HIV Viral Load under Cautions.)
Recurrent Aphthous Stomatitis
Thalidomide Dosage and Administration
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.1
A special restricted distribution program, called STEPS, for thalidomide was approved by FDA.1 9 54 185 186 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.1 9 22
To facilitate pregnancy testing and counseling in accordance with STEPS program, prescribe and dispense ≤28-day supply of drug.9 1 Refills require new prescription and another authorization from STEPS program; automatic refills not allowed.1 9 22
Registering pharmacist must agree to inform all staff pharmacists of dispensing procedures for drug.1 9 22 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.1 Verify that each prescription was written within ≤7 days.1 9 Dispense blister packs containing drug intact (i.e., drug cannot be repackaged).1
Administer orally with water ≥1 hour after a meal.1
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.1
Children ≥12 years of age weighing <50 kg: Initially, administer at lower end of dosage range (e.g., 100 mg daily).1
Children ≥12 years of age weighing ≥50 kg: Initially, 100–300 mg once daily.1 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.1
Continue therapy until signs and symptoms of active ENL reaction have subsided (usually ≥2 weeks).1 Gradually taper daily dosage in 50-mg decrements every 2–4 weeks until drug withdrawn or recurrence of ENL occurs.1
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.1 Attempt gradual decrease (i.e., 50-mg decrements every 2–4 weeks) and withdrawal every 3–6 months.1
Patients weighing <50 kg: Initially, administer at lower end of dosage range (e.g., 100 mg daily).1
Patients weighing ≥50 kg: Initially, 100–300 mg once daily.1 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.1
Continue until signs and symptoms of active ENL reaction have subsided (usually ≥2 weeks).1 Gradually taper daily dosage in 50-mg decrements every 2–4 weeks until drug withdrawn or recurrence of ENL occurs.1
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.1 Attempt gradual decrease (i.e., 50-mg decrements every 2–4 weeks) and withdrawal every 3–6 months.1
Induction therapy: 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.1
Reduce dosage or temporarily discontinue if adverse effects such as constipation, oversedation, or peripheral neuropathy occur.1 Once adverse effects subside, reinitiate at lower or previous dosage, based on clinical judgment.1
Recurrent Aphthous Stomatitis†
100–300 mg daily for 1–6 weeks has been used.9 148 149 150 May be necessary to use higher dosages (e.g., 400–600 mg daily).9 148 149 150 Optimal duration of therapy unknown; may relapse following discontinuance of drug.9 148 149
800 mg to 1.6 g daily for a median duration of 240 days has been used in a clinical trial.153
Children ≥12 years of age weighing ≥50 kg: Maximum 400 mg daily.1
Patients weighing ≥50 kg: Maximum 400 mg daily.1
Cautions for Thalidomide
Pregnant women.1 (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.1 22 (See Boxed Warning and see Fetal/Neonatal Morbidity and Mortality under Cautions.)
Known hypersensitivity to thalidomide or any ingredient in formulation.1 (See Sensitivity Reactions under Cautions.)
Fetal/Neonatal Morbidity and Mortality
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.1
Contraindicated in female patients who are or who may become pregnant.1
Women of childbearing potential must use 2 forms of effective contraception ≥4 weeks prior to, throughout, and following completion of therapy.1 22 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).1 22 If either IUD or hormonal contraceptive use contraindicated, may use another highly effective method or 2 simultaneous effective barrier methods.1
Thalidomide distributes into semen;1 risk to fetus from semen of male patients receiving thalidomide unknown.1 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.1
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., ).1 24
Increased risk of venous thromboembolism (e.g., DVT, pulmonary embolism) in patients with multiple myeloma, especially when used in combination with chemotherapy, including dexamethasone.1
Monitor for signs and symptoms of thromboembolism (e.g., shortness of breath, chest pain, arm or leg swelling).1
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.251 252 253 254
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.253 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.253 IMWG states full-dose warfarin (INR 2–3) is an alternative to LMWHs, but clinical experience is limited.253
ASCO recommends pharmacologic thromboprophylaxis for multiple myeloma patients receiving thalidomide with dexamethasone or antineoplastic agents.254 Those at lower risk for thromboembolism may receive aspirin or an LMWH; those at higher risk should receive an LMWH.254
DVT and pulmonary embolism also reported in patients with ENL.240
Potentially severe and irreversible nerve damage (i.e., polyneuritis or peripheral neuropathy);1 3 4 5 20 41 53 54 57 59 60 61 62 generally reported with chronic use,1 53 60 but has occurred with relatively short-term use1 58 61 62 and after discontinuance of therapy.1
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).1 4
Consider using electrophysiologic testing, consisting of sensory nerve action potential (SNAP) amplitude measurement at baseline and every 6 months thereafter to detect asymptomatic neuropathy.1
If manifestations of peripheral neuropathy develop, discontinue therapy immediately (if clinically appropriate) to minimize further damage.1 Usually, resume treatment only if manifestations of neuropathy return to baseline.1
Use concomitantly with drugs known to be associated with peripheral neuropathy with caution.1 (See Specific Drugs under Interactions.)
Other Nervous System Effects
Decreased leukocyte counts, including neutropenia, reported.1 34 53 54 Do not initiate therapy in patients with ANC <750/mm3.1 Routinely monitor leukocyte and differential counts, especially in those prone to neutropenia (e.g., HIV-infected patients).1 If ANC decreases to <750/mm3, reevaluate drug regimen.1 20 If neutropenia persists, consider withholding drug if clinically appropriate.1 20
Effects on HIV Viral Load
Measure plasma HIV-1 RNA concentrations in HIV-seropositive patients after first and third months of treatment and every 3 months thereafter.1
Hypersensitivity reactions (e.g., erythematous macular rash associated with fever, tachycardia, hypotension) reported.1 Discontinue if signs and symptoms of hypersensitivity are severe.1 If therapy resumed and reaction recurs, permanently discontinue.1
Severe, potentially fatal skin reactions, including Stevens-Johnson syndrome and toxic epidermal necrolysis, reported.1 197 212 214 217 Discontinue if rash occurs; resume therapy only after appropriate clinical evaluation.1 Do not resume therapy if rash is exfoliative, purpuric, or bullous, or if Stevens-Johnson syndrome or toxic epidermal necrolysis suspected.1
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.1 Birth defects reported only following oral ingestion of thalidomide.1
Do not extensively handle or open drug capsules; maintain storage in blister packs until ingestion.1 If accidental skin contact with opened capsules or drug powder occurs, wash affected area with soap and water.1
Thalidomide present in serum and semen of patients receiving drug.1 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.1
Bradycardia, possibly requiring medical intervention, reported; clinical importance and underlying etiology unknown.1
Monitor patients with a history of seizures or other risk factors closely for clinical changes that could precipitate acute seizure activity.1
Category X.1 (See Boxed Warnings and see Fetal/Neonatal Morbidity and Mortality under Cautions.)
For information on patients 12–18 years of age, see Boxed Warning.1
No substantial differences in safety and efficacy relative to younger adults, but increased sensitivity cannot be ruled out.1
Possibility exists of greater sensitivity to the drug in some geriatric individuals.1
Common Adverse Effects
Somnolence, dizziness, rash.1
Interactions for Thalidomide
Antineoplastic agents (e.g., cisplatin, paclitaxel, vincristine)
Antiretroviral agents (e.g., didanosine)
CNS depressants (e.g., alcohol, barbiturates, chlorpromazine)
Potential additive sedative effects 1
Rauwolfia alkaloids (reserpine)
Potential additive sedative effects 1
Food decreases rate but not does not substantially affect extent of absorption.1
Pharmacokinetics similar in HIV-infected patients and in healthy individuals.1
Pharmacokinetics not established in pediatric and adolescent patients (<18 years of age).1
Bioavailability may be greater in patients with leprosy than in healthy individuals.1
Distributes into semen.1 (See Fetal/Neonatal Morbidity and Mortality under Cautions.)
Plasma Protein Binding
Averages approximately 5–7 hours in healthy individuals.1
In patients with severe renal impairment, accumulation of drug does not occur.2 6 92 Mean total clearance increased 2.5-fold in patients undergoing hemodialysis.1 245 (See Special Populations under Dosage and Administration.)
25°C (may be exposed to 15–30°C); protect from light.1
Induces down-modulation of selected cell surface adhesion molecules involved in leukocyte migration,1 2 6 14 45 248 resulting in decreased dermal infiltrations of leukocytes (e.g., neutrophils) in ENL lesions.2 14 44
In multiple myeloma patients, inhibits TNF-α expression by bone marrow stromal cells, resulting in inhibition of growth of multiple myeloma cells.248 Enhances T cell activation, releasing cytokines IL-2 and interferon-γ.1 248 These cytokines activate natural killer cells causing lysis of multiple myeloma cells.1 243 248
Impairs angiogenesis in bone marrow by decreasing fibroblast growth factor (FGF-2) and vascular endothelial growth factor (VEGF) production.243
Suppresses production of prostaglandins by macrophages.1
Advice to Patients
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).1
Necessity of advising women of childbearing potential to avoid pregnancy by using mandatory contraceptive measures, unless she abstains from heterosexual contact.1 9 22 (See Boxed Warning and see Fetal/Neonatal Morbidity and Mortality under Cautions.)
Importance of immediately discontinuing therapy if pregnancy suspected.1
Importance of women of childbearing potential informing clinicians of pregnancy, suspected pregnancy, missed menstrual period, unusual menstrual bleeding, or cessation of using contraceptive measures.1
Importance of informing patient how to obtain information about emergency contraception (including information regarding clinicians who provide emergency contraceptive services) if clinician not available.1 24 (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.1 (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.1 Importance of male patients informing clinician of suspected pregnancy of their sexual partner.1
Importance of avoiding extensive handling or opening of drug capsules.1 Importance of maintaining storage of drug capsules in blister packs until ingestion.1 (See Environmental Exposure of Patients and Health-care Providers under Cautions.)
Importance of keeping thalidomide out of reach of children and from women of childbearing potential, unless part of STEPS program.1
Risk of drowsiness and somnolence; importance of avoiding situations where such drowsiness could create a problem.1 Risk of impaired ability to perform tasks that require mental alertness or physical coordination (e.g., operating machinery, driving a motor vehicle).1 Importance of warning patients not to take any other drugs or alcohol that may cause drowsiness without consulting their clinician.1 (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.1
Importance of contacting clinician if symptoms of thromboembolism (e.g., shortness of breath, chest pain, arm or leg swelling) develop.1
Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription or OTC drugs and herbal supplements, as well as concomitant illnesses.1
Importance of informing patients of other important precautionary information.1 (See Cautions.)
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
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.
AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions November 1, 2013. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.
1. Celgene. Thalomid (thalidomide) capsules prescribing information. Warren, NJ; 2007 Feb.
2. Zwingenberger K, Wnendt S. Immunomodulation by thalidomide: systematic review of the literature and of unpublished observations. J Inflamm. 1995-96; 46:177-211.
3. Anon. New uses of thalidomide. Med Lett Drugs Ther. 1996; 38:15-6. [PubMed 8592478]
4. Tseng S, Pak G, Washenik K et al. Rediscovering thalidomide: a review of its mechanism of action, side effects, and potential uses. J Am Acad Dermatol. 1996; 35:969-79. [IDIS 380118] [PubMed 8959957]
5. Gunzler V. Thalidomide in human immunodeficiency virus (HIV) patients. A review of safety considerations. Drug Saf. 1992; 7:116-34. [PubMed 1605898]
6. Schuler U, Ehninger G. Thalidomide: rationale for renewed use in immunological disorders. Drug Saf. 1995; 12:364-9. [PubMed 8527011]
7. Sampaio, EP, Sarno EN et al. Thalidomide selectively inhibits tumor necrosis factor α production by stimulated human monocytes. J Exp Med. 1991; 173:699-703. [PubMed 1997652]
8. Makonkawkeyoon S, Limson-Pobre RN, Moreira AL et al. Thalidomide inhibits the replication of human immunodeficiency virus type 1. Proc Natl Acad Sci USA. 1993; 90:5974-8. [PubMed 8327469]
9. Celgene, Warren, NJ: Personal communication.
10. Gelber RH. Leprosy (Hansen’s disease). In: Mandell GL, Bennett JE, Dolin R, eds. Mandell, Douglas and Bennett’s principles and practice of infectious diseases. 4th ed. New York, NY: Churchill Livingstone; 1995:2243-50.
11. Balog DL, Epstein ME, Amodio-Groton MI. HIV wasting syndrome: treatment update. Ann Pharmacother. 1998; 32:446-58. [IDIS 403355] [PubMed 9562141]
12. Jacobson JM, Greenspan JS, Spritzler J et al. Thalidomide for the treatment of oral aphthous ulcers in patients with human immunodeficiency virus infection. N Engl J Med. 1997; 336:1487-93. [IDIS 384850] [PubMed 9154767]
13. Sampaio EP, Moreira AL, Sarno EN et al. Prolonged treatment with recombinant interferon γ induces erythema nodosum leprosum in lepromatous leprosy patients. J Exp Med. 1992; 175:1729-37. [PubMed 1588290]
14. Nogueira AC, Neubert R, Helge H et al. Thalidomide and the immune system. Simultaneous up- and down-regulation of different integrin receptors on human white blood cells. Life Sci. 1994; 55:77-92. [PubMed 7516993]
15. Smithells RW, Newman CG. Recognition of thalidomide defects. J Med Genet. 1992; 29:716-23. [PubMed 1433232]
16. Burkholz, H. Giving thalidomide a second chance. FDA Consumer. 1997; September-October:12-14.
17. Food and Drug Administration. FDA approves thalidomide for Hansen’s disease side effect, imposes unprecedented restrictions on distribution. FDA Talk Paper. July 16, 1998.
18. Celgene. Thalomid (thalidomide). System for thalidomide education and prescribing safety. May 26, 1999. From web site.
19. Jaggers LD. FDA approval of thalidomide. Memorandum to presidents and executive officers, state societies of health-system pharmacists ASHP Public Relations Network. 1998; July 17.
20. Food and Drug Administration Center for Drug Evaluation and Research. Frequently asked questions concerning thalidomide. July 17, 1998. From web site.
21. Food and Drug Administration Center for Drug Evaluation and Research. Thalidomide. Important patient information. July 17, 1998. From web site.
22. Zeldis JB, Williams BA, Thomas SD et al. S.T.E.P.S.: a comprehensive program for controlling and monitoring access to thalidomide. Clin Ther. 1999; 21:319-30. [IDIS 426750] [PubMed 10211535]
23. Anon. Celgene Thalomid initial availability will be limited to 500 physicians. F-D-C Rep. 1998; Jul 20:3-4.
24. Stewart F. Promoting emergency contraception. Hosp Pract. 1998; (Aug 15):61-75.
25. Oral contraceptives interaction: ritonavir (Norvir). In: Hansten PD, Horn JR. Drug interactions analysis and management. Vancouver, WA: Applied Therapeutics, Inc; 1997: N.32.
26. Ethinyl estradiol (Ortho-Novum 1/35) drug interaction: Indinavir (Crixivan). In: Hansten PD, Horn JR. Drug interactions analysis and management. Vancouver, WA: Applied Therapeutics, Inc; 1997: N.49.
27. Merck Index. 12th ed. Budavari S, O’Neil MJ, Smith A et al, eds. Whitehouse Station, NJ: Merck & Co., Inc. 1996:1580.
28. Food and Drug Administration. List of orphan designations and approvals. Oct. 4, 2007. From web site.
29. Kaba SE, Kyritis AP. Recognition and management of gliomas. Drugs. 1997; 53:235-44. [PubMed 9028743]
30. Soler RA, Howard M, Brink NS et al. Regression of AIDS-related Kaposi’s sarcoma during therapy with thalidomide. Clin Infect Dis. 1996; 23:501-3. [IDIS 375074] [PubMed 8879772]
31. Levine AM. Editorial response: regression of AIDS-related Kaposi’s sarcoma during therapy with thalidomide. Clin Infect Dis. 1996; 23:504-5.
32. Gasparini G, Harris AL. Clinical importance of the determination of tumor angiogenesis in breast carcinoma: much more than a new prognostic tool. J Clin Oncol. 1995; 13:765-82. [IDIS 343797] [PubMed 7533829]
33. Ashby J, Tinwell H. Is thalidomide mutagenic? Nature. 1995; 375:453. Letter.
34. Iyer CG, Languillon J, Ramanujam K et al. WHO co-ordinated short-term double-blind trial with thalidomide in the treatment of acute lepra reactions in male lepromatous patients. Bull World Health Organ. 1971; 45:719-32. [PubMed 4947831]
35. Waters MF. An internally-controlled double blind trial of thalidomide in severe erythema nodosum leprosum. Lepr Rev. 1971; 42:26-42. [PubMed 4338720]
36. McBride WG. Thalidomide may be a mutagen. BMJ. 1994; 308:1635-6. [IDIS 331775] [PubMed 8025439]
37. Read AP. Thalidomide may be a mutagen. BMJ. 1994; 308:1635-6.
38. Smithells D. Does thalidomide cause second generation birth defects? Drug Saf. 1998; 19:339-41.
39. Sheskin J, Convit J. Results of a double blind study of the influence of thalidomide on the lepra reaction. Int J Lepr Other Mycobact Dis. 1969; 37:135-46. [PubMed 4900407]
40. Tramontana JM, Utaipat U, Molloy A et al. Thalidomide treatment reduces tumor necrosis factor α production and enhances weight gain in patients with pulmonary tuberculosis. Mol Med. 1995; 1:384-97. [PubMed 8521296]
41. Reyes-Teran G, Sierra-Madero JG, Martinez del Cerro V et al. Effects of thalidomide on HIV-associated wasting syndrome: a randomized, double-blind, placebo-controlled clinical trial. AIDS. 1996; 10:1501-7. [PubMed 8931784]
42. Klausner JD, Makonkawkeyoon S, Akarasewi P et al. The effect of thalidomide on the pathogenesis of human immunodeficiency virus type 1 and M. tuberculosis infection. J Acquir Immune Defic Syndr Hum Retrovirol. 1996; 11:247-57. [PubMed 8603261]
43. Aukrust P, Liabakk NB, Muller F et al. Serum levels of tumor necrosis factor-α (TNFα) and soluble TNF receptors in human immunodeficiency virus type 1 infection—correlations to clinical, immunologic, and virologic parameters. J Infect Dis. 1994; 169:420-4. [PubMed 7906293]
44. Sampaio EP, Kaplan G, Miranda A et al. The influence of thalidomide on the clinical and immunologic manifestation of erythema nodosum leprosum. J Infect Dis. 1993; 168:408-14. [IDIS 318757] [PubMed 8335978]
45. Sarno EN, Grau GE, Vieira LM et al. Serum levels of tumour necrosis factor-alpha and interleukin 1β during leprosy reactional states. Clin Exp Immunol. 1991; 84:103-8. [PubMed 2015700]
46. Gordon GB, Spielberg SP, Blake DA et al. Thalidomide teratogenesis: evidence for a toxic arene oxide metabolite. Proc Natl Acad Sci USA. 1981; 78:2545-8. [PubMed 6941308]
47. Munis JR, Richman DD, Kornbluth RS. Human immunodeficiency virus-1 infection of macrophages in vitro neither induces tumor necrosis factor (TNF)/cachectin gene expression nor alters TNF/cachectin induction by lipopolysaccharide. J Clin Invest. 1990; 85:591-6. [PubMed 2298923]
48. AIDS Clinical Trials Information Service (ACTIS). AIDSTRIALS Database. July 12, 1999. From web site.
49. Hamuryudan V, Mat C, Saip S et al. Thalidomide in the treatment of the mucocutaneous lesions of the Behcet syndrome. Ann Intern Med. 1998; 128:443-50. [IDIS 401948] [PubMed 9499327]
50. Sharp M, Getty J, Klausner JD. Thalidomide use is associated with weight gain in HIV-1 positive clients. J Acquir Immune Defic Syndr. 1997; 15:392.
51. Piscitelli SC, Figg WD, Hahn B et al. Single-dose pharmacokinetics of thalidomide in human immunodeficiency virus-infected patients. Antimicrob Agents Chemother. 1997; 41:2797-9. [IDIS 397017] [PubMed 9420064]
52. Vanchieri C. Preparing for thalidomide’s comeback. Ann Intern Med. 1997; 127:951-2. [PubMed 9446509]
53. Anon. Thalidomide. Med Lett Drugs Ther. 1998; 40:103-4. [PubMed 9813597]
54. Nightingale SL. From the Food and Drug Administration. Thalidomide approved for erythema nodosum leprosum. JAMA. 1998; 280:872. [PubMed 9739956]
55. Weidle PJ. Thalidomide for aphthous ulcers in patients infected with the human immunodeficiency virus. Am J Health-Syst Pharm. 1996; 53:368,371-2,378. [IDIS 360611] [PubMed 8673657]
56. Sharpstone D, Rowbottom A, Francis N et al. Thalidomide: a novel therapy for microsporidiosis. Gastroenterology. 1997; 112:1823-9. [IDIS 387096] [PubMed 9178672]
57. Gagnon B, Bruera E. A review of the drug treatment of cachexia associated with cancer. Drugs. 1998; 55:675-88. [PubMed 9585863]
58. Haslett P, Tramontana J, Burroughs M et al. Adverse reactions to thalidomide in patients infected with human immunodeficiency virus. Clin Infect Dis. 1997; 24:1223-7. [IDIS 388568] [PubMed 9195087]
59. Clemmensen OJ, Olsen PZ, Andersen KE. Thalidomide neurotoxicity. Arch Dermatol. 1984; 120:338-41. [IDIS 182077] [PubMed 6703734]
60. Wulff CH, Hoyer H, Asboe-Hansen G et al. Development of polyneuropathy during thalidomide therapy. Br J Dermatol. 1985; 112:475-80. [IDIS 199338] [PubMed 2986670]
61. Ochonisky S, Verroust J, Bastuji-Garin S et al. Thalidomide neuropathy incidence and clinicoelectrophysiologic findings in 42 patients. Arch Dermatol. 1994; 130:66-9. [IDIS 324064] [PubMed 8285742]
62. Aronson IK, Yu R, West DP et al. Thalidomide-induced peripheral neuropathy. Arch Dermatol. 1984; 120:1466-70. [IDIS 192481] [PubMed 6093713]
63. Jacobus Pharmaceutical Company Inc. Dapsone USP prescribing information. Princeton, NJ; 1985 Jun.
64. Jacobson RR. Treatment. In: Hastings RC, ed. Leprosy. New York: Churchill Livingstone; 1985:193-222.
65. Geigy Pharmaceuticals. Lamprene (clofazimine) prescribing information. Ardsley, NY; 1986 Dec.
66. Jolliffe DS. Leprosy reactional states and their treatment. Br J Dermatol. 1977; 97:345-51. [PubMed 336075]
67. Beeching NJ, Ellis CJ. Leprosy and its chemotherapy. J Antimicrob Chemother. 1982; 10:81-7. [PubMed 6749788]
68. Morgan J. Management of steroid-dependency with clofazimine [Lamprene or B 663 (Geigy)]. Lepr Rev. 1970; 41:229-32. [PubMed 5515679]
69. Yawalkar SJ, Vischer W. Lamprene (clofazimine) in leprosy. Lepr Rev. 1979; 50:135-44. [PubMed 396428]
70. Farb H, West DP, Pedvis-Leftick A. Clofazimine in pregnancy complicated by leprosy. Obstet Gynecol. 1982; 59:122-3. [IDIS 145212] [PubMed 7078842]
71. Duncan ME, Pearson JM. The association of pregnancy and leprosy—erythema nodosum leprosum in pregnancy and lactation. Lepr Rev. 1984; 55:129-42. [PubMed 6748844]
72. Gaudino M (Ciba-Geigy Corporation, Summit, NJ): Personal communication; 1987 Oct 23.
73. Reviewers’ comments (personal observations) on Clofazimine 8:40.
74. Centers for Disease Control and Prevention. Tuberculosis/Mycobacteriology Branch. Nov 6, 1998. From web site.
75. Mehta P, Kedar A, Graham-Pole S et al. Thalidomide in children undergoing bone marrow transplantation: series at a single institution and review of the literature. Pediatrics. 1999; 103:e44.
76. Jacobson RR, Krahenbuhl JL. Leprosy. Lancet. 1999; 353:655-60. [IDIS 421539] [PubMed 10030346]
77. Shek LP, Lee YS, Lee BW et al. Thalidomide responsiveness in an infant with Behcet’s syndrome. Pediatrics. 1999; 103:1295-7. [IDIS 430017] [PubMed 10353947]
78. Scheffler MR, Colburn W, Kook KA et al. Thalidomide does not alter estrogen-progesterone hormone single dose pharmacokinetics. Clin Pharmacol Ther. 1999; 65:483-90. [IDIS 425537] [PubMed 10340913]
79. Trapnell CB, Donahue SR, Collins JM et al. Thalidomide does not alter the pharmacokinetics of ethinyl estradiol and norethindrone. Clin Pharmacol Ther. 1998; 64:597-602. [IDIS 416897] [PubMed 9871424]
80. Rea TH, Sieling PA. Delayed-type hypersensitivity reactions followed by erythema nodosum leprosum. Int J Lepr Other Mycobact Dis. 1998; 66:316-27. [PubMed 9934358]
81. Sugumaran DS. Leprosy reactions—complications of steroid therapy. Int J Lepr Other Mycobact Dis. 1998; 66:10-5. [PubMed 9614834]
82. Schreuder PAM. The occurrence of reactions and impairments in leprosy: experience in the leprosy control program of three provinces in Northeastern Thailand, 1978–1995. II. Reactions. Int J Lepr Other Mycobact Dis. 1998; 66:159-69. [PubMed 9728448]
83. Partida-Sanchez S, Favila-Castillo L, Pedraza-Sanchez S et al. IgG antibody subclasses, tumor necrosis factor and IFN-γ levels in patients with type II lepra reaction on thalidomide treatment. Int Arch Allergy Immunol. 1998; 116:60-6. [PubMed 9623511]
84. Bhargava P, Mal Kuldeep C, Mathur NK. Erythema nodosum leprosum in subgroups of lepromatous leprosy. Lepr Rev. 1998; 68:373-85.
85. de Carsalade GY, Wallach D, Spindler E et al. Daily multidrug therapy for leprosy; results of a fourteen-year experience. Int J Lepr Other Mycobact Dis. 1997; 65:37-44. [PubMed 9207752]
86. Meyerson MS. Erythema nodosum leprosum. Int J Dermatol. 1996; 35:389-92. [PubMed 8737869]
87. Kifayet A, Shahid F, Lucas S et al. Erythema nodosum leprosum is associated with up-regulation of polyclonal IgG1 antibody synthesis. Clin Exp Immunol. 1996; 106:447-53. [PubMed 8973611]
88. Willcox ML. The impact of multiple drug therapy on leprosy disabilities. Lepr Rev. 1997; 68:350-66. [PubMed 9503872]
89. Lockwood DNJ. The management of erythema nodosum leprosum: current and future options. Lepr Rev. 1996; 67:253-9. [PubMed 9033196]
90. Shannon EJ, Morales MJ, Sandoval F. Immunomodulatory assays to study structure—activity relationships of thalidomide. Immunopharmacology. 1997; 35:203-12. [PubMed 9043933]
91. Foss NT, Brandt de Oliveira E, Lopes Silva C. Correlation between TNF production, increase of plasma C-reactive protein level and suppression of T lymphocyte response to concanavalin A during erythema nodosum leprosum. Int J Lepr Other Mycobact Dis. 1993; 61:218-26. [PubMed 8371031]
92. Shannon EJ, Sandoval F, Krahenbuhl JL. Hydrolysis of thalidomide abrogates its ability to enhance mononuclear cell synthesis of IL-2 as well as its ability to suppress the synthesis of TNF-α. Immunopharmacology. 1997; 36:9-15. [PubMed 9129992]
93. Ghate JV, Jorizzo JL. Behcet’s disease and complex aphthosis. J Am Acad Dermatol. 1999; 40:1-18. [IDIS 421218] [PubMed 9922007]
94. Herranz P, Pizarro A, de Lucas R et al. Treatment of AIDS-associated prurigo nodularis with thalidomide. Clin Exp Dermatol. 1998; 23:233-4. [PubMed 10233821]
95. Weinstein TA, Sciubba JJ, Levine J. Thalidomide for the treatment of oral aphthous ulcers in Crohn’s disease. J Ped Gastroenterol Nutr. 1999; 28:214-6.
96. Figg WD, Raje S, Bauer KS et al. Pharmacokinetics of thalidomide in an elderly prostate cancer population. J Pharm Sci. 1999; 88:121-5. [IDIS 421269] [PubMed 9874712]
97. Wolkenstein P, Latarjet J, Roujeau JC et al. Randomised comparison of thalidomide versus placebo in toxic epidermal necrolysis. Lancet. 1998; 352:1586-9. [IDIS 418383] [PubMed 9843104]
98. Breban M, Gombert B, Amor B et al. Efficacy of thalidomide in the treatment of refractory ankylosing spondylitis. Arthritis Rheumatism. 1999; 42:580-1. [IDIS 425670] [PubMed 10088786]
99. Rousseau L, Beylot-Barry M, Doutre MS et al. Cutaneous sarcoidosis successfully treated with low doses of thalidomide. Arch Dermatol. 1998; 134:1045-6. [IDIS 413161] [PubMed 9722748]
100. Berenson JR, Bergsagel PL, Munshi N. Initiation and maintenance of multiple myeloma. Semin Hematol. 1999; 36:9-13. [PubMed 9989483]
101. Forsyth CJ, Cremer PD, Torzillo P. Thalidomide responsive chronic pulmonary GVHD. Bone Marrow Transplant. 1996; 17:291-3. [IDIS 361577] [PubMed 8640183]
102. Birnkrant D. Thalidomide for aphthous ulcers in HIV infection. N Engl J Med. 1997; 337:1086-7. [IDIS 393099] [PubMed 9324641]
103. Thalidomide for aphthous ulcers in HIV infection. N Engl J Med. 1997; 337:1087. Letter.
104. Stirling DI. Thalidomide and its impact in dermatology. Sem Cutan Med Surg. 1998; 17:231-42.
105. Eriksson T, Bjorkman S, Roth B et al. Hydroxylated metabolites of thalidomide: formation in-vitro and in-vivo in man. J Pharm Pharmacol. 1998; 50:1409-16. [IDIS 421424] [PubMed 10052858]
106. Eriksson T, Bjorkman S, Roth B et al. Stereospecific determination, chiral inversion in vitro and pharmacokinetics in humans of the enantiomers of thalidomide. Chirality. 1995; 7:44-52. [PubMed 7702998]
107. Chen TL, Vogelsang GB, Petty BG et al. Plasma pharmacokinetics and urinary excretion of thalidomide after oral dosing in healthy male volunteers. Drug Metab Dispos. 1989; 17:402-5. [IDIS 305210] [PubMed 2571480]
108. Eriksson T, Bjorkman S, Roth B et al. Enantiomers of thalidomide: blood distribution and the influence of serum albumin on chiral inversion and hydrolysis. Chirality. 1998; 10:223-8. [PubMed 9499573]
109. Heney D, Norfolk DR, Wheeldon J et al. Thalidomide treatment for chronic graft-versus-host disease. Br J Haematol. 1991; 78:23-7. [PubMed 2043478]
110. Lagueny A, Rommel A, Vignolly B et al. Thalidomide neuropathy: an electrophysiologic study. Muscle Nerve. 1986; 9:837-44. [PubMed 3023998]
111. WHO Expert Committee on Leprosy. WHO expert committee on Leprosy. World Health Organ Tech Rep Ser. 1998; 874:1-43. [PubMed 9627517]
112. Calabrese L. Resztak K. Thalidomide revisited: pharmacology and clinical applications. Exp Opin Invest Drugs. 1998; 7:2043-60.
113. Hastings RC, Trautman JR, Enna CD et al. Thalidomide in the treatment of erythema nodosum leprosum with a note on selected laboratory abnormalities in erythema nodosum leprosum. Clin Pharmacol Ther. 1970; 11:481-7. [PubMed 4913866]
114. Pearson JMH, Vedagiri M. Treatment of moderately severe erythema nodosum leprosum with thalidomide—a double-blind controlled trial. Lepr Rev. 1969; 40:111-6. [PubMed 4893253]
115. National Institutes of Health, Food and Drug Administration, Centers for Disease Control and Prevention. Thalidomide: potential benefits and risks. Open public scientific workshop. Bethesda, MD: 1997 Sep 9-10.
116. Fullerton PM, O’sullivan DJ. Thalidomide neuropathy: a clinical, electrophysiological, and histological follow-up study. J Neurol, Neurosurg, Psy. 1968; 31:543.
117. Winkelmann RK, Connolly SM, Doyle JA et al. Thalidomide treatment of prurigo nodularis. Acta Derm Venereol. 1984; 64:412-7. [PubMed 6208720]
118. van den Broek H. Treatment of prurigo nodularis with thalidomide. Arch Dermatol. 1980; 116:571-2. [IDIS 119877] [PubMed 7377791]
119. Lovell CR, Hawk JLM, Calnan CD et al. Thalidomide in actinic prurigo. Br J Dermatol. 1983; 108:467-71. [IDIS 169964] [PubMed 6838772]
120. Grosshans E, Illy G. Thalidomide therapy for inflammatory dermatoses. Int J Derm. 1984; 23:596-601.
121. Stevens RJ, Andujar C, Edwards CJ et al. Thalidomide in the treatment of the cutaneous manifestations of lupus erythematosus: experience in sixteen consecutive patients. Br J Rheumatol. 1997; 36:353-9. [PubMed 9133968]
122. Naafs B, Faber WR. Thalidomide therapy: an open trial. Int J Derm. 1985; 24:131-4. [PubMed 2985516]
123. Holm AL, Bowers KE, McMeekin TO et al. Chronic cutaneous lupus erythematosus treated with thalidomide. Arch Dermatol. 1993; 129:1548-50. [IDIS 322832] [PubMed 8250576]
124. Atra E, Sato EI. Treatment of the cutaneous lesions of systemic lupus erythematosus with thalidomide. Clin Exp Rheumatol. 1993; 11:487-93. [PubMed 8275583]
125. Munro CS, Cox NH. Pyoderma gangrenosum associated with Behcet’s syndrome—response to thalidomide. Clin Exp Dermatol. 1988; 13:408-10. [PubMed 3256462]
126. Rustin MHA, Gilkes JJH, Robinson JWE. Pyoderma gangrenosum associated with Behcet’s disease: treatment with thalidomide. J Am Acad Dermatol. 1990; 23:941-4. [PubMed 2254485]
127. Dereure O, Basset-Sequin N, Guilhou JJ et al. Erosive lichen planus: dramatic results to thalidomide. Arch Dermatol. 1996; 132:1392-3. [IDIS 375428] [PubMed 8915327]
128. Hamza MH. Treatment of Behcet’s disease with thalidomide. Clin Rheumatol. 1986; 5:365-71. [PubMed 3780143]
129. Jorizzo JL, Schmalstieg FC, Solomon AR et al. Thalidomide effects in Behcet’s syndrome and pustular vasculitis. Arch Intern Med. 1986; 146:878-81. [IDIS 216378] [PubMed 3963978]
130. Eisenbud L, Horowitz I, Kay B et al. Recurrent aphthous stomatitis of the Behcet’s syndrome: successful treatment with thalidomide. Oral Surg Oral Med Pathol. 1987; 64:289-2.
131. Mangelsdorf HC, White WL, Jorizzo JL. Behcet’s disease: report of twenty-five patients from the United States with prominent mucocutaneous involvement. J Am Acad Dermatol. 1996; 34:745-50. [IDIS 366314] [PubMed 8632067]
132. Ramselaar CG, Boone RM, Kluin-Nelemans HC. Thalidomide in the treatment of neuro-Behcet’s syndrome. Br J Dermatol. 1986; 115:367-70. [IDIS 230703] [PubMed 3756093]
133. Larsson H. Treatment of severe colitis in Behcet’s syndrome with thalidomide (CG-217). J Intern Med. 1990; 228:405-7. [IDIS 273420] [PubMed 2266351]
134. Lewis DA, Amerasinghe CN, Murphy SM. Successful treatment of Behcet’s syndrome in an African female patient with thalidomide. Int J STD AIDS. 1996; 7:518-20. [PubMed 9116070]
135. Powell RJ, Allen BR, Jenkins JS et al. Investigation and treatment of orogenital ulceration; studies on a possible mode of action of thalidomide. Br J Dermatol. 1985; 113(Suppl 28):141-4. [IDIS 203222] [PubMed 4040386]
136. Postema PTE, den Haan P, van Hagen PM et al. Treatment of colitis in Behcet’s disease with thalidomide. Eur J Gastroenterol Hepatol. 1996; 8:929-31. [PubMed 8889464]
137. Saylan T, Saltik I. Thalidomide in the treatment of Behcet’s syndrome. Arch Dermatol. 1982; 118:536. [IDIS 154935] [PubMed 7103519]
138. Satnis HR. Aphthous stomatitis and its management. Curr Opin Dent. 1991; 1:763-8. [PubMed 1807480]
139. Bonnethlane JM, Royer C, Bedane C. Thalidomide and recurrent aphthous stomatitis: a follow-up study. Dermatology. 1996; 193:321-3. [PubMed 8993957]
140. Haslett P, Hempstead M, Seidman C et al. The metabolic and immunologic effects of short-term thalidomide treatment of patients infected with the human immunodeficiency virus. AIDS Res Hum Retroviruses. 1997; 13:1047-54. [PubMed 9264292]
141. Kaplan G, Schambelan M, Gottlieb M et al. Thalidomide reverses cachexia in HIV-wasting syndrome. 5th Conference on Retroviruses and Opportunistic Infections. 1998. Abstract No. 476.
142. Nicolau DP, West TE. Thalidomide: treatment of severe recurrent aphthous stomatitis in patients with AIDS. DICP. 1990; 24:1054-6. [IDIS 274665] [PubMed 2275226]
143. Beliomo A, Schorr-Lesnick B. Thalidomide treatment for idiopathic esophageal ulcers in patients with HIV. Gastrointest Endosc. 1996; 44:729-1. [PubMed 8979067]
144. Ball SC, Sepkowitz KA, Jacobs JL. Thalidomide for treatment of oral aphthous ulcers in patients with human immunodeficiency virus: case report and review. Am J Gastroenterol. 1997; 92:169-70. [IDIS 380232] [PubMed 8995965]
145. Ghigloiotti G, Repetto T, Farris A et al. Thalidomide: treatment of choice for aphthous ulcers in patients seropositive for human immunodeficiency virus. J Am Acad Dermatol. 1993; 28:271-2. [PubMed 8432932]
146. Naum SM, Molloy PJ, Kania RJ et al. Use of thalidomide in treatment and maintenance of idiopathic esophageal ulcers in HIV+ individuals. Dig Dis Sci. 1995; 40:1147-8. [IDIS 346249] [PubMed 7729278]
147. Paterson DL, Georghiou PR, Allworth AM et al. Thalidomide as treatment of refractory aphthous ulceration related to human immunodeficiency virus infection. Clin Infect Dis. 1995; 20:250-4. [IDIS 343228] [PubMed 7742424]
148. Grinspan D. Significant response of oral aphthosis to thalidomide treatment. J Am Acad Dermatol. 1985; 12:85-90. [PubMed 3980807]
149. Grinspan D, Blanco GF, Aguero S. Treatment of aphthae with thalidomide. J Am Acad Dermatol. 1989; 20:1060-3. [PubMed 2754056]
150. Revuz J, Guillaume JC, Janier M et al. Crossover study of thalidomide vs placebo in severe recurrent aphthous stomatitis. Arch Dermatol. 1990; 126:923-7. [IDIS 269834] [PubMed 2193629]
151. Rovelli A, Arrigo C, Nesi F et al. The role of thalidomide int he treatment of refractory chronic graft-versus-host disease following bone marrow transplantation in children. Bone Marrow Transplant. 1998; 21:577-81. [IDIS 403884] [PubMed 9543061]
152. Cole CH, Rogers PCJ, Pritchard S et al. Thalidomide in the management of chronic graft-versus-host disease in children following bone marrow transplantation. Bone Marrow Transplant. 1994; 14:937-42. [IDIS 342192] [PubMed 7711671]
153. Vogelsang GB, Farmer ER, Hess AD et al. Thalidomide for the treatment of chronic graft-versus-host disease. N Engl J Med. 1992; 326:1055-8. [IDIS 294301] [PubMed 1549151]
154. Holler E, Hintermeier-Knabe R, Mittermuller J et al. Role of tumor necrosis factor alpha in acute graft-versus-host disease and complications following allogeneic bone marrow transplantation. Transplant Proceed. 1993; 25:1234-6.
155. Parker PM, Chao N, Nademanee A et al. Thalidomide as salvage therapy for chronic graft-versus-host disease. Blood. 1995; 86:3604-9. [IDIS 356811] [PubMed 7579470]
156. Stevens RJ. The place of thalidomide in the treatment of inflammatory disease. Lupus. 1996; 5:257-8. [PubMed 8869894]
157. Waters MF, Laing AB, Ambikapathy A et al. Treatment of ulcerative colitis with thalidomide. Br Med J. 1979; 1:792. [PubMed 435799]
158. Wettstein AR, Meagher AP. Thalidomide in Crohn’s disease. Lancet. 1997; 350:1445-2. [IDIS 396881] [PubMed 9371171]
159. Odeka EB, Miller V. Thalidomide in oral Crohn’s disease refractory to conventional medical treatment. J Pediatr Gastroenterol. 1997; 25:250-1.
160. Kulkarni S, Powles R, Mehta J et al. Thalidomide in GVHD—anti-GVHD effect separable from the antiangiogenesis? Blood. 1998; 92(Suppl 1):344b. Abstract No. 4482.
161. Singhal S, Mehta J, Eddlemon P et al. Marked anti-tumor effect from anti-angiogenesis (AA) therapy with thalidomide (T) in high risk refractory multiple myeloma (MM). Blood. 1998; 92(Suppl 1):318a.
162. Barlogie B, Desikan R, Munshi N et al. Single course D.T. pace anti-angiochemotherapy effects CR in plasma cell leukemia and fulminant multiple myeloma (MM). Blood. 1998; 92(Suppl 1):273b.
163. Lim SH, Maclean R. Thalidomide in IgA multiple myeloma. Blood. 1998; 92(Suppl 1):279b.
164. D’Amato RJ, Loughnan MS, Flynn E et al. Thalidomide is an inhibitor of angiogenesis. Proc Natl Acad Sci. 1994; 91:4082-5. [PubMed 7513432]
165. Pluda JM. Tumor-associated angiogenesis: mechanisms, clinical implications, and therapeutic strategies. Semin Oncol. 1997; 24:203-18. [PubMed 9129690]
166. Ching LM, Zu ZF, Gummer BH et al. Effect of thalidomide on tumour necrosis factor production and anti-tumour activity induced by 5,6-dimethylxanthenone-4-acetic acid. Br J Cancer. 1995; 72:339-43. [PubMed 7640215]
167. Bauer KS, Dixon SC, Figg WD. Inhibition of angiogenesis by thalidomide requires metabolic activation, which is species-dependent. Biochem Pharmacol. 1998; 55:1827-34. [PubMed 9714301]
168. Figg WD, Bergan R, Brawley O et al. Randomized phase II study of thalidomide in androgen-independent prostate cancer (AIPC). Proceedings of ASCO. 1997. Abstract No. 1189.
169. Fine HA, Loeffler JS, Kyritsis A et al. A phase II trial of the anti-angiogenic agent, thalidomide, in patients with recurrent high-grad gliomas. Proceedings of ASCO. 1997. Abstract No. 1372.
170. Politi P, Reboredo G, Losso M et al. Phase I trial of thalidomide (T) in AIDS-related kaposi sarcoma (KS). Proceedings of ASCO. 1998. Abstract No. 161.
171. Long G, Vredenburgh J, Rizzieri DA et al. Pilot trial of thalidomide post-autologous peripheral blood progenitor cell transplantation (PBPC) in patients with metastatic breast cancer. Proceedings of ASCO. 1998. Abstract No. 697.
172. Watanabe S, Pituskin E, Calder K et al. Thalidomide (T) in the symptomatic treatment of cachexia in patients (pts) with terminal cancer. Proceedings of ASCO Atlanta, CA 1999. Abstract No. 180.
173. Baidas SM, Isaacs C, Crawford J et al. A phase II evaluation of thalidomide in patients with metastatic breast cancer. Proceedings of ASCO Atlanta, CA 1999. Abstract No. 475.
174. Glass J, Gruber ML, Nirenberg A et al. Phase I/II study of carboplatin and thalidomide in recurrent glioblastoma multiforme. Proceedings of ASCO Atlanta, CA 1999. Abstract No. 551.
175. Marx GM, Levi JA, Bell DR et al. A phase I/II trial of thalidomide as an antiangiogenic agent in the treatment of advanced cancer. Proceedings of ASCO Atlanta, CA 1999. Abstract No. 1751.
176. Noormohamed FH, Youle MS, Higgs CJ et al. Pharmacokinetics and hemodynamic effects of single oral doses of thalidomide in asymptomatic human immunodeficiency virus-infected subjects. AIDS Res Hum Retroviruses. 1999; 15:1047-52. [PubMed 10461824]
177. Thalidomide Victims Association of Canada. Living in a world with thalidomide: a new reality. Aug 20, 1999. From web site.
178. Gutierrez-Rodriguez O. A promising new treatment for rheumatoid arthritis. Arthritis Rheum. 1984; 27:1118-21. [IDIS 191707] [PubMed 6237660]
179. Huizinga TWJ, Dijkmans BAC, van der Velde E et al. An open study of pentoxyfylline and thalidomide as adjuvant therapy in the treatment of rheumatoid arthritis. Ann Rheum Dis. 1996; 55:833-6. [IDIS 377804] [PubMed 8976641]
180. Silva SR, Viana PC, Lugon NV et al. Thalidomide for the treatment of uremic pruritus: a crossover randomized double-blind trial. Nephron. 1994; 67:270-3. [PubMed 7936015]
181. Engeser P, Klimm HD. Therapy of recurrent exudative erythema multiforme. Effectiveness of thalidomide—report of a case. Fortschr Med. 1999; 117:39-40. [PubMed 10365532]
182. Cherouati K, Claudy A, Souteyrand P et al. Treatment by thalidomide of chronic multiforme erythema: its recurrent and continuous variants. A retrospective study of 26 patients. Ann Dermatol Venereol. 1996; 123:375-7. [PubMed 8959059]
183. Thomas L, Ducros B, Secchi T et al. Successful treatment of adult’s Langerhans cell histiocytosis with thalidomide. Report of two cases and literature review. Arch Dermatol. 1993; 129:1261-4. [IDIS 320686] [PubMed 8215489]
184. Meunier L, Marck Y, Ribeyre C et al. Adult cutaneous Langerhans cell histiocytosis: remission with thalidomide. Br J Dermatol. 1995; 132:168. [IDIS 342084] [PubMed 7756144]
185. Grünenthal GMBH, Aachen, Germany: Personal communication.
186. Reviewer’s comments (personal observations).
187. Welles L, Little R, Wyvill K et al. Preliminary results of a phase II study of oral thalidomide in patients with HIV infection and Kaposi’s Sarcoma (KS). J Acquir Immune Defic Syndr. 1997; 14: A21.
188. Warren R, Cole G. Reports of second generation thalidomide children: media reports that thalidomide disabilities can be inherited are false! Thalidomide Victims Association of Canada. August 30, 1997. From web site, 1999 Nov 2.
189. Chao NJ, Parker PM, Niland JC et al. Paradoxical effect of thalidomide prophylaxis on chronic graft-vs.-host disease. Biol Blood Marrow Transplant. 1996; 2:86-92. [PubMed 9118303]
190. Haslett PAJ, Corral LG, Albert M et al. Thalidomide costimulates primary human T lymphocytes, preferentially inducing proliferation, cytokine production, and cytotoxic responses in the CD8+ subset. J Exp Med. 1998; 187:1885-92. [PubMed 9607928]
191. Corral LG, Haslett PAJ, Muller GW et al. Differential cytokine modulation and T cell activation by two distinct classes of thalidomide analogues that are potent inhibitors of TNF-α. J Immunol. 1999; 163: 380-6. [PubMed 10384139]
192. Ashby J, Tinwell H, Callander RD et al. Thalidomide: lack of mutagenic activity across phyla and genetic endpoints. Mut Res. 1997; 396:45-64.
193. Ridoux O, Drancourt M. Lack of in vitro antimicrosporidian activity of thalidomide. Antimicrob Agents Chemother. 1999; 2305-6.
194. Haslett PAJ, Klausner JD, Makonkawkeyoon S et al. Thalidomide stimulates T cell responses and interleukin 12 production in HIV-infected patients. AIDS Res Hum Retroviruses. 1999; 15:1169-79. [PubMed 10480630]
195. Monastirli A, Georgiou S, Bolsen K et al. Treatment of porphyria cutanea tarda with oral thalidomide. Skin Pharmacol Appl Skin Physiol. 1999; 12:305-11. [PubMed 10545826]
196. Duong DJ, Spigel GT, Moxley RT et al. American experience with low-dose thalidomide therapy for severe cutaneous lupus erythematosus. Arch Dermatol. 1999; 135:1079-87. [IDIS 436065] [PubMed 10490113]
197. Horowitz SB, Stirling AL. Thalidomide-induced toxic epidermal necrolysis. Pharmacotherapy. 1999; 19:1177-80. [IDIS 434124] [PubMed 10512068]
198. Durie BGM, Stepan DE. Efficacy of low dose thalidomide (T) in multiple myeloma. Presented at 7th annual international multiple myeloma workshop. Stockholm, Sweden: 1999 Sep 1-5. Abstract No. O9.
199. Weber DM, Gavino M, Delasalle K et al. Thalidomide for refractory multiple myeloma. Presented at 7th annual international multiple myeloma workshop. Stockholm, Sweden: 1999 Sep 105. Abstract No. P77.
200. Singhal S, Mehta J, Desikan et al. Antitumor activity of thalidomide in refractory multiple myeloma. N Engl J Med. 1999; 341:1565-71. [IDIS 435753] [PubMed 10564685]
201. Raje N, Anderson K. Thalidomide: a revival story. N Engl J Med. 1999; 341:606-9.
202. Scribano M, Prantera C. Review article: medical treatment of moderate to severe Crohn’s disease. Aliment Pharmacol Ther. 2003; 17(Suppl. 2):23-30. [PubMed 12786609]
203. Podolsky DK. Inflammatory bowel disease. N Engl J Med. 2002; 347:417-29. [IDIS 484721] [PubMed 12167685]
204. Vasiliauskas EA, Kam LY, Abreu-Martin MT et al. An open-label pilot study of low-dose thalidomide in chronically active, steroid-dependent Crohn’s disease. Gastroenterology. 1999; 117:1278-87. [IDIS 450746] [PubMed 10579968]
205. Ehrenpreis ED, Kane SV, Cohen LB et al. Thalidomide therapy for patients with refractory Crohn’s disease: an open-label trial. Gastroenterology. 1999; 117:1271-7. [IDIS 450745] [PubMed 10579967]
206. Sabate JM, Villarejo J, Lemann M et al. An open-label study of thalidomide for maintenance therapy in responders to infliximab in chronically active and fistulizing refractory Crohn’s disease. Aliment Pharmacol Ther. 2002; 16:1117-24. [PubMed 12030953]
207. Hershfield NB.. Disappearance of Crohn’s ulcers in the terminal ileum after thalidomide therapy. Can J Gastroenterol. 2004; 18:101-4. [PubMed 14997219]
208. Bousvaros A, Mueller B. Thalidomide in gastrointestinal disorders. Drugs. 2001; 61:777-87. [PubMed 11398909]
209. Bauditz J, Wedel S, Lochs H. Thalidomide reduces tumour necrosis factor α and interleukin 12 production in patients with chronic active Crohn’s disease. Gut. 2002; 50:196-200. [IDIS 477105] [PubMed 11788559]
210. Yasui K, Uchida N, Akazawa Y et al. Thalidomide for treatment of intestinal involvement of juvenile-onset Behçet disease. Inflamm Bowel Dis. 2008; 14:396-400. [PubMed 17973303]
211. Majumdar S, Mockenhaupt M, Roujeau J et al. Interventions for toxic epidermal necrolysis. Cochrane Database of Syst Rev. 2002; 4:CD001435.
212. Hall VC, El-Azhary RA, Bouwhuis S et al. Dermatologic side effects of thalidomide in patients with multiple myeloma. J Am Acad Dermatol.2003; 48:548-52. [PubMed 12664018]
213. Wines NY, Cooper AJ, Wines MP. Thalidomide in dermatology. Australas J Dermatol. 2002; 43:229-38. [PubMed 12423428]
214. Rajkumar SV, Gertz MA, Witzig TE. Life-threatening toxic epidermal necrolysis with thalidomide therapy for myeloma. NEJM. 2000; 343:972-3. [PubMed 11012329]
215. Paghdal K, Schwartz R. Thalidomide and its dermatologic uses. Acta Dermatovenerol Croat. 2007; 15:39-44. [PubMed 17433179]
216. Shek LPC, Lim DLC. Thalidomide in Behçet disease. Biomed Pharmacother. 2002; 56:31-5. [PubMed 11908493]
217. Colagrande M, Di Ianni M, Coletti G et al. Toxic epidermal necrolysis in a patient with primary myelofibrosis receiving thalidomide therapy. Int J Hematol. 2009; 89:76-9. [PubMed 19052692]
218. Nasca MR, Micali G, Cheigh NH et al. Dermatologic and nondermatologic uses of thalidomide. Ann Pharmacother. 2003; 37:1307-20. [PubMed 12921515]
219. Wu JJ, Huang DB, Pang KR et al. Thalidomide: dermatological indications, mechanisms of action and side-effects. Br J Dermatol. 2005; 153:254-273. [PubMed 16086735]
220. Moraes M, Russo G. Thalidomide and its dermatologic uses. Am J Med Sci. 2001; 321:321-6. [PubMed 11370795]
221. Shetty. Thalidomide in the management of recurrent aphthous ulcerations in patients who are HIV-positive: a review and case reports. Spec Care Dentist. 2005; 25:236-41.
222. Letsinger JA, McCarty MA, Jorizzo JI. Complex aphthosis: a large case series with evaluation algorithm and therapeutic ladder from topicals to thalidomide. J Am Acad Dermatology.2005; 52:500-8.
223. Shetty KM. Current role of thalidomide in HIV-positive patients with recurrent aphthous ulcerations. Gen Dent. 2007; 55:537-42. [PubMed 18050580]
224. Corcoran C, Grinspoon S. Treatment for wasting in patients with the Acquired Immunodeficiency Syndrome. N Engl J Med. 1999; 340:1740-50. [IDIS 425644] [PubMed 10352167]
225. Kaplan G, Thomas S, Fierer DS et al. Thalidomide for the treatment of AIDS-associated wasting. IDS Res and Human Retroviruses. 2000; 16:1345-55.
226. M’barek LB, Fardet L, Mebazaa A et al. A retrospective analysis of thalidomide therapy in non-HIV-related Kaposi’s sarcoma. Dermatology. 2007; 215:202-5.
227. Little RF, Wyvill KM, Pluda JM et al. Activity of thalidomide in AIDS-related Kaposi’s sarcoma. J Clin Oncol. 2000; 18:2593-602. [PubMed 10893291]
228. Johnson L, Jarvis JN, Wilkins EGL et al. Thalidomide treatment for refractory HIV-associated colitis: a case series.Clin Infect Dis. 2008; 47:133-6. [PubMed 18494607]
229. Teo SK, Stirling DI, Zeldis JB. Thalidomide as a novel therapeutic agent: new uses for an old product. Drug Discov. 2005; 10:107-14.
230. Bariol C, Meagher AP, Vickers CR et al. Thalidomide for inflammatory bowel disease. J Gastroenterol Hepatol. 2002; 17:135-9. [PubMed 11966942]
231. Kane S, Stone LJ, Ehrenpreis E. Thalidomide as “salvage” therapy for patients with delayed hypersensitivity response to infliximab: a case series. J Clin Gastroenterol. 35:149-50.
232. Shanhbag PS, Viswanath V, Torsekar RG. Thalidomide: current status. Ind J Dermatol Venereol Lepro. 2006; 72:75-80.
233. Walker SL, Waters MF, Lockwood DN. The role of thalidomide in the management of erythema nodosum leprosum. Lepr Rev. 2007; 78:197-215. [PubMed 18035771]
234. Feuth M, Brandsma JW, Faber WR et al. Erythema nodosum leprosum in Nepal: a retrospective study of clinical features and response to treatment with prednisolone or thalidomide. Lepr Rev. 2008; 79:254-69. [PubMed 19009975]
235. Kaur I, Dogra S, Narang T et al. Comparative efficacy of thalidomide and prednisolone in the treatment of moderate to severe erythema nodosum leprosum; a randomized study. Australas J Dermatol. 2009; 50:181-5. [PubMed 19659979]
236. Tsukagoshi S. Action mechanism of thalidomide in treatment of multiple myeloma. (Japanese; with English abstract.)Nippon Rinsho. 2007; 65:2291-5.
237. Rosenbach M, Werth VP. Dermatologic therapeutics: thalidomide. A practical guide. Dermatol Ther. 2007 ; 20:175-86. [PubMed 17970884]
238. Villahermosa LG, Fajardo TT, Jr., Abalos RM et al. A randomized, double-blind, double-dummy, controlled dose comparison of thalidomide for treatment of erythema nodosum leprosorum. Am J Trop Med Hyg. 2005; 72: 518 -26. [PubMed 15891124]
239. Nair V, Sharma A, Ghosh I et al. Extensive chronic graft-versus-host disease of skin successfully treated with thalidomide. J Assoc Physicians India. 2005; 53:988-90. Links , Arora S, Sahai K, Dutta V. [PubMed 16515241]
240. Fabi SG, Hill C, Witherspoon JN et al. Frequency of thromboembolic events associated with thalidomide in the non-cancer setting: a case report and review of the literature. J Drugs Dermatol. 2009; 8:765-9. [PubMed 19663116]
241. Howell E, Johnson SM. Venous thrombosis occurring after initiation of thalidomide for the treatment of cicatricial pemphigoid. J Drugs Dermatol. 2004; 3:83-5. [PubMed 14964754]
242. Rajkumar SV, Blood E, Vesole D et al. Phase III clinical trial of thalidomide plus dexamethasone compared with dexamethasone alone in newly diagnosed multiple myeloma: a clinical trial coordinated by the Eastern Cooperative Oncology Group. J Clin Oncol. 2006; 24:431-6. [PubMed 16365178]
243. Sirohi B, Powles R. Multiple myeloma. Lancet. 2004; 363:875-7. [PubMed 15031034]
244. Haslett PA, Roche P, Butlin CR et al. Effective treatment of erythema nodosum leprosum with thalidomide is associated with immune stimulation. J Infect Dis. 2005; 192:2045-53. [PubMed 16288366]
245. Eriksson T, Hoglund P, Turesson I et al. Pharmacokinetics of thalidomide in patients with impaired renal function and while on and off dialysis. J Pharm Pharmacol. 2003; 55:1701-6. [PubMed 14738599]
246. Okafor MC. Thalidomide for erythema nodosum leprosum and other applications. Pharmacotherapy. 2003; 23:481-93. [PubMed 12680478]
247. Du W, Hattori Y, Hashiguchi A et al. Tumor angiogenesis in the bone marrow of mulitple myeloma patients and its alteration by thalidomide treatment. Pathol Int. 2004; 54:285-94. [PubMed 15086832]
248. Teo SK. Properties of thalidomide and its analogues: implications for anticancer therapy. AAPS J. 2005; 7:E14-9. [PubMed 16146335]
249. Richardson P, Schlossman R, Jagannath S et al. Thalidomide for patients with relapsed multiple myeloma after high-dose chemotherapy and stem-cell transplantation: results of an open-label multicenter phase 2 study of efficacy, toxicity, and biological activity. Mayo Clin Proc. 2004; 79:875-82. [PubMed 15244383]
251. Celgene Corporation. Thalomid (thalidomide) capsules prescribing information. Summit, NJ; 2013 Feb.
252. National Comprehensive Cancer Network (NCCN). Clinical practice guidelines in oncology: venous thromboembolic disease. Version 2.2013.
253. Palumbo A, Rajkumar SV, Dimopoulos MA et al. Prevention of thalidomide- and lenalidomide-associated thrombosis in myeloma. Leukemia. 2008; 22:414-23. [PubMed 18094721]
254. Lyman GH, Khorana AA, Kuderer NM et al. Venous thromboembolism prophylaxis and treatment in patients with cancer: American Society of Clinical Oncology clinical practice guideline update. J Clin Oncol. 2013; 31:2189-204. [PubMed 23669224]
More about thalidomide
- Other brands: Thalomid