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  • CLASSES

    Drugs For The Treatment of Leprosy
    Immunomodulators, Angiogenesis Inhibitors
    Other Immunosuppressants

    BOXED WARNING

    Myocardial infarction, stroke, thromboembolic disease

    Venous (e.g., pulmonary embolism, deep vein thrombosis) and arterial (e.g., stroke, myocardial infarction (MI)) thromboembolic disease has been reported in patients with multiple myeloma who received thalidomide. Using thalidomide in combination with chemotherapy agents, including dexamethasone, may increase the risk of thromboembolism (TE); use caution when administering thalidomide with chemotherapy agents or other agents that may increase the risk of TE (e.g., estrogen-containing contraceptives). Monitor patients for signs and symptoms of a blood clot such as dyspnea, chest pain, and arm or leg swelling; a stroke such as sudden numbness or weakness (especially on one side of the body), severe headache or confusion, or problems with vision, speech, or balance; and a MI such as feeling sweaty, shortness of breath, feeling sick or vomiting, and/or chest pain that may spread to the arms, neck, jaw, back, or stomach. Consider thromboprophylaxis based on an assessment of individual patients’ underlying risk factors.

    Contraception requirements, male-mediated teratogenicity, menstrual irregularity, pregnancy testing, reproductive risk

    Counsel patients about the reproductive risk of thalidomide and discuss contraception requirements with both men and females of childbearing potential. Thalidomide may cause severe birth defects or fetal death; defects may occur with even 1 dose to a pregnant female. Thalidomide therapy should not be initiated in females of reproductive potential until negative results from 2 pregnancy tests are confirmed. The first test should be done within 10 to 14 days and the second test within 24 hours prior to prescribing thalidomide. Once treatment is started, pregnancy testing should occur weekly during the first month of treatment, then every month in females with regular menstrual cycles. If the female patient's menstrual cycles are irregular, pregnancy testing should occur every 2 weeks. If any woman of reproductive potential experiences menstrual irregularity or misses her period while receiving thalidomide, treatment must be discontinued and pregnancy testing and counseling should be performed. Effective contraception must be used by all females of reproductive potential for at least 4 weeks before beginning treatment, during therapy and dosage interruptions, and for 4 weeks following discontinuation of therapy. Women must commit to abstain from heterosexual intercourse or to use 2 methods of reliable birth control, including at least 1 highly effective method (e.g., intrauterine devices (IUD), hormonal contraception, tubal ligation, or partner's vasectomy) and 1 additional effective method (e.g., latex condom, diaphragm, or cervical cap). These contraceptive measures should be taken even in patients with a history of infertility, unless a hysterectomy has been performed. Women requiring medications that may interfere with the effectiveness of hormonal contraception (e.g., HIV-protease inhibitors, griseofulvin, modafinil, penicillins, rifampin, rifabutin, phenytoin, carbamazepine, or certain herbal supplements such as St. John’s Wort) must use 2 other effective or highly effective methods of contraception. Some contraceptive methods such as IUD or contraceptive implants may increase the risk for infection or bleeding either at insertion, removal, or during use. Additionally, estrogen-containing contraceptives may increase the risk of blood clot formation. Consider these risks when choosing contraceptive measures. Thalidomide is passed into the semen and there is a potential for male-mediated teratogenicity. Therefore, a male patient must use barrier contraception (latex condom) during sexual intercourse with a woman of reproductive potential while on therapy and for 4 weeks after discontinuing thalidomide therapy, even if he has undergone successful vasectomy. Male patients should not donate sperm while taking thalidomide and for 4 weeks after stopping therapy. If the patient is less than 18 years of age, their parent or legal guardian must agree to ensure compliance with these conditions.

    DEA CLASS

    Rx

    DESCRIPTION

    Biologic response modifier with immunomodulatory, antiangiogenic, and antitumor properties
    FDA approved for the acute treatment of the cutaneous manifestations of moderate to severe erythema nodosum leprosum (ENL) and as maintenance therapy for prevention and suppression of the cutaneous manifestations of ENL recurrence; it is also FDA in combination with dexamethasone for the treatment of patients with newly diagnosed multiple myeloma
    Pregnancy category X agent than may cause birth defects or embryo-fetal death; prescribers, pharmacies, and patients must register in the THALOMID REMS program to prescribe, dispense, or receive thalidomide (1—888—423—5436)

    COMMON BRAND NAMES

    Thalomid

    HOW SUPPLIED

    Thalomid Oral Cap: 50mg, 100mg, 150mg, 200mg

    DOSAGE & INDICATIONS

    For the treatment of erythema nodosum leprosum (ENL).
    NOTE: The FDA has designated thalidomide as an orphan drug for the treatment of erythema nodosum leprosum.
    for the acute treatment of the cutaneous manifestations of moderate to severe erythema ENL.
    Oral dosage
    Children 12 years of age, Adolescents, and Adults

    100—300 mg orally once daily is the usual initial dosage range; administration at bedtime and at least 1 hour after the evening meal is recommended. Concomitant corticosteroid therapy should be given in patients with moderate to severe neuritis associated with a severe ENL reaction; taper steroids after the neuritis resolves. Start thalidomide at the lower end of the dosing range in patients weighing less than 50 kg. Patients who have a severe cutaneous ENL reaction or who have previously required higher doses to control the reaction may start thalidomide at 400 mg/day orally; the daily dose may be taken at bedtime or in divided doses. Therapy is usually continued at least 2 weeks or until signs and symptoms of active reaction resolve. After treatment, taper therapy by decreasing the thalidomide dose by 50 mg every 2 to 4 weeks. Consider therapy interruption, a dose reduction, or therapy discontinuation in patients who develop grade 3 or 4 adverse reactions.

    as maintenance therapy for the prevention and suppression of the cutaneous manifestations of recurrent ENL.
    Oral dosage
    Children 12 years of age, Adolescents, and Adults

    Use the minimum dose necessary to control the cutaneous ENL reaction in patients who require maintenance therapy or who flare when thalidomide was tapered after an acute cutaneous reaction. Every 3 to 6 months, attempt to taper therapy by decreasing the thalidomide dose by 50 mg every 2 to 4 weeks. Consider therapy interruption, a dose reduction, or therapy discontinuation in patients who develop grade 3 or 4 adverse reactions.

    For the treatment of multiple myeloma.
    NOTE: The FDA has designated thalidomide as an orphan drug for the treatment of multiple myeloma.
    For newly diagnosed multiple myeloma, in combination with dexamethasone.
    Oral dosage
    Adults

    200 mg orally once daily in combination with dexamethasone 40 mg orally on days 1 to 4, 9 to 12, and 17 to 20; administration at bedtime and at least 1 hour after the evening meal is recommended. Treatment cycles are repeated every 28 days. Consider therapy interruption, a dose reduction, or therapy discontinuation in patients who develop grade 3 or 4 adverse reactions.

    For newly diagnosed multiple myeloma, in combination with Total Therapy 2 regimen†.
    Oral dosage
    Adults and Elderly patients 75 years or younger

    400 mg/day PO during induction chemotherapy (withheld on day 5 of cycle 3 during peripheral blood stem-cell collection), thalidomide 100 mg/day PO after each transplant (when platelet count > 50,000/mm3), thalidomide 200 mg/day during consolidation therapy, and maintenance therapy with thalidomide 100 mg/day for 1 year and then thalidomide 50 mg every other day until relapse or unacceptable toxicity. Concurrent thalidomide administration was studied as part of the Total Therapy 2 regimen in combination with 4 cycles of induction chemotherapy, 2 (tandem) autologous stem-cell transplants, and 4 cycles of consolidation therapy. Supportive medications included filgrastim, prophylactic antibiotics, histamine H2 blockers, and erythropoietin (as necessary); low molecular weight heparin was given as thromboprophylaxis.

    For relapsed or refractory multiple myeloma, in combination with dexamethasone†.
    NOTE: Thalidomide has been designated an orphan drug by the FDA for this indication.
    Oral dosage
    Adults

    Multiple regimens have been studied. Thalidomide 100 mg/day PO plus dexamethasone 40 mg/day PO on days 1—4 repeated monthly (median time to max response, 4 months; duration of therapy range, 4—36 months); and, thalidomide 200 mg/day PO at bedtime (increased by 100 mg every 7 days to a max dose of 600 mg/day) plus dexamethasone 20 mg/m2/day PO for 5 days repeated every 15 days followed by thalidomide 100—150 mg/day continuously plus dexamethasone for 5 consecutive days/month were administered in responding patients (median time to remission, 2 months; mean dose at 2 months, 270 mg/day) have been studied in clinical trials.

    For newly diagnosed multiple myeloma in elderly or transplant ineligible patients, in combination with melphalan and prednisone†.
    Oral dosage
    Elderly patients

    The optimal dosage of thalidomide plus melphalan and prednisone has not been clearly established and dosages have varied in randomized controlled trials. Thalidomide 200 mg/day PO for 2—4 weeks escalated up to a maximum dose of 400 mg/day if no severe adverse events occurred (median therapy duration of 11 months) plus melphalan 0.25 mg/kg daily for 4 days and prednisone 2 mg/kg daily for 4 days repeated every 6 weeks for 12 cycles was studied in previously untreated patients with multiple myeloma who were between 65 and 75 years of age in one study. Thalidomide was stopped after day 4 of the last cycle. Most patients in this study took a thalidomide dose of 200 mg/day or less. In another study, patients aged 75 years and older received thalidomide 100 mg/day PO at bedtime (median therapy duration of 13.5 months) plus melphalan 0.2 mg/kg daily for 4 days and prednisone 2 mg/kg daily for 4 days repeated every 6 weeks for 12 cycles.

    For newly diagnosed multiple myeloma as induction therapy prior to autologous stem-cell transplantation, in combination with bortezomib and dexamethasone†.
    Oral dosage
    Adults <= 65 years

    100 mg PO daily for the first 14 days (cycle 1 only) then 200 mg PO daily thereafter plus bortezomib 1.3 mg/m2 IV on days 1, 4, 8, and 11 and dexamethasone 40 mg on days 1, 2, 4, 5, 8, 9, 11, and 12 (VTD regimen) repeated every 21 days for 3 cycles prior to a double (tandem) autologous stem-cell transplant (ASCT) was studied in a multicenter, randomized, phase III study. Patients randomized to induction therapy with VTD also received two 35-day consolidation cycles with VTD (bortezomib 1.3 mg/m2 IV on days 1, 8, 15, and 22 plus thalidomide 100 mg PO daily and dexamethasone 40 mg on days 1, 2, 8, 9, 15, 16, 22, and 23) following the second transplantation. Patients also received maintenance therapy with dexamethasone 40 mg PO on days 1—4 every 28 days until relapse or disease progression. Additionally, thalidomide 200 mg PO daily (dose escalation as follows in the first cycle: 50 mg/day on days 1—14 and 100 mg/day on days 15—28) plus bortezomib 1.3 mg/m2 IV on days 1, 4, 8, and 11 and dexamethasone 40 mg on days 1—4 and 9—12 repeated every 4 weeks for 6 cycles prior to an ASCT was studied in another randomized, phase III study. In this study, patients who received up to 3 years of maintenance therapy (starting 3 months after ASCT) with thalidomide (100 mg/day) plus bortezomib (1.3 mg/m2 IV on days 1, 4, 8, and 11 repeated every 3 months) had significantly improved 2-year progression-free survival compared with thalidomide or interferon alfa-2b maintenance therapy.

    For the treatment of AIDS-associated wasting syndrome† and cancer cachexia†.
    NOTE: Thalidomide has been designated an orphan drug by the FDA for this indication.
    Oral dosage
    Adults

    Thalidomide 100 mg PO once daily at bedtime is the typical dose with a range of 50—200 mg/day PO. In patients with AIDS-associated wasting syndrome, thalidomide has shown to increase lean body mass 10.5% from baseline after 24 weeks of treatment. Weight gain has continued with continued treatment with thalidomide.

    For the treatment of recurrent aphthous ulcer† and stomatitis† in severely immunocompromised patients.
    NOTE: Thalidomide has been designated an orphan drug by the FDA for this indication.
    Oral dosage
    Adults

    Thalidomide 100—200 mg PO once daily at bedtime has been studied. If the patient does not respond to lower doses, thalidomide may be increased to 400—600 mg/day PO. In patients with HIV-related aphthous ulcers, > 90% of patients experienced healing of ulcers, decreased pain, improved appetite and increased sense of well-being following 7—28 days of treatment with thalidomide. Once the ulcers have healed thalidomide is usually discontinued. Retreatment with thalidomide if the ulcers recur is effective.

    For the treatment of chronic graft-versus-host-disease (GVHD)† in combination with steroids and either cyclosporine or tacrolimus.
    NOTE: Thalidomide has been designated an orphan drug by the FDA for this indication.
    Oral dosage
    Adults and Adolescents

    Dosage for this indication not established. 200 mg PO once daily, gradually increased to a target dose of 200 mg PO four times daily has been studied. Drug discontinuation due to intolerance in the thalidomide group was high (>90%). Thalidomide has been given in combination with prednisone and a calcineurin inhibitor (cyclosporine or tacrolimus).

    Children

    Dosage for this indication not established. 3 mg/kg PO once daily (if patient < 67 kg), gradually increased to a target dose of 3 mg/kg PO four times daily has been studied. Drug discontinuation due to intolerance in the thalidomide group was high (>90%). Thalidomide has been given in combination with prednisone and a calcineurin inhibitor (cyclosporine or tacrolimus).

    For the treatment of AIDS-related Kaposi's sarcoma†.
    NOTE: Thalidomide has been designated an orphan drug by the FDA for this indication.
    Oral dosage
    Adults

    200 mg/day PO escalatied by 200 mg/day every 2 weeks as tolerated to a maximum of 1000 mg/day was given to patients for 52 weeks in a phase II study of 20 male patients; the overall response rate was 47%.

    For the treatment of primary malignant glioma† (including astrocytoma†).
    NOTE: Thalidomide has been designated an orphan drug by the FDA for this indication.
    For the treatment of recurrent primary malignant glioma†, including astrocytoma† as a single-agent.
    Oral dosage
    Adults

    800—1200 mg PO per day has been studied. In a phase II study of single-agent thalidomide in recurrent high-grade gliomas, results showed an ORR of 6%, median TTP = 10 weeks and median OS = 28 weeks, leading authors to conclude that single-agent thalidomide was not effective. Toxicities included seizures, constipation, neuropathy and somnolence.

    For the treatment of primary malignant glioma, including astrocytoma in combination with chemotherapy or radiation therapy†.
    Oral dosage
    Adults

    Thalidomide has been used in combination with various chemotherapy agents and/or radiation therapy. In a phase II trial, thalidomide 800—1200 mg PO per day was given with carmustine 200mg/m2 intravenously every 6 weeks. Alternately, a starting dose of thalidomide 100 mg PO per day (escalated by 100 mg PO per day up to a dose of 400 mg PO per day) was given with irinotecan 350—700 mg/m2 (depending on anti-epileptic regimen). Additionally, temozolomide 150—200 mg/m2/day PO on days 1—5 every 28 days plus radiation therapy (6 weeks) was given in combination with thalidomide 200 mg PO per day (beginning on day 7) dose escalated by 100—200 mg PO per day every 7—14 days to a maximum dose of 1200 mg PO per day.

    For the treatment of myelodysplastic syndrome (MDS)†.
    Oral dosage
    Adults

    As a single agent, thalidomide 100 mg/day PO escalated to 400 mg/day PO was used in one trial. Of the 51 evaluable patients, 31% responded to therapy including some patients becoming transfusion independent. No cytogenetic or complete responses were seen, but some patients showed hematologic improvement. Patients who responded had lower baseline blast counts, shorter duration of pretherapy platelet transfusions, and higher platelet counts.

    For the treatment of discoid lupus erythematosus†, subacute cutaneous lupus erythematosus†, chronic cutaneous lupus erythematosus†, and the cutaneous manifestations of systemic lupus erythematosus (SLE)†.
    Oral dosage
    Adults

    In patients who are refractory to previous treatment, initial doses of thalidomide of 50—400 mg/day PO until clinical response is achieved have been given. Doses are gradually tapered and maintained at 25—100 mg PO once daily. Retreatment for relapse with thalidomide 25—100 mg/day PO is usually effective.

    For the treatment of Behcet's syndrome†.
    Oral dosage
    Adults

    Thalidomide 100—400 mg/day PO daily for up to 38 months has been effective in improving arthritis, ocular manifestations and skin lesions associated with Behcet's syndrome.

    For the treatment of prurigo†, specifically, prurigo nodularis†.
    Oral dosage
    Adults

    Thalidomide 50—300 mg/day PO for an average duration of 12 months produced immediate and pronounced relief of intense pruritus and a significant decrease in the number of skin lesions.

    For the treatment of Crohn's disease†.
    NOTE: Thalidomide has been designated an orphan drug by the FDA for this indication.
    In patients with steroid-dependent disease†.
    Oral dosage
    Adults

    In a pilot study, 12 patients received thalidomide 50 mg or 100 mg PO once daily at bedtime for 12 weeks. All patients were able to reduce their steroid dosage by >= 50% and 44% of patients discontinued all steroid therapy. In weeks 5—12, 70% of patients responded and 20% achieved a complete remission.

    In patients with refractory Crohn's disease†.
    Oral dosage
    Adults

    In an open trial, 22 patients with refractory Crohn's disease were treated with thalidomide 200 mg or 300 mg PO once daily at bedtime for 12 weeks. At 4 weeks of treatment, there were 12 clinical responses and 4 clinical remissions. At 12 weeks of therapy, 9 (3 luminal and 6 fistula patients) patients achieved a clinical remission.

    †Indicates off-label use

    MAXIMUM DOSAGE

    Adults

    200 mg/day PO for multiple myeloma and 400 mg/day PO for ENL.

    Adolescents

    Safety and efficacy have not been established.

    Children

    Safety and efficacy have not been established.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.

    Renal Impairment

    Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.

    ADMINISTRATION

    All prescribers, patients, and pharmacists must comply with the conditions of the THALOMID REMS program when prescribing, dispensing, or receiving thalidomide. Information about the drug and the program can be found at www.celgeneriskmanagement.com or by calling 1—888—423—5436.
    CAUTION: Observe and exercise usual cautions for handling, administering, and disposal of cytotoxic drugs. Maintain storage of capsules in blister packs until taken. Wash the exposed area immediately and thoroughly with soap and water if powder from thalidomide capsules come into contact with skin; flush thoroughly with water if thalidomide comes into contact with mucous membranes.[49713]

    Oral Administration
    Oral Solid Formulations

    Take thalidomide once daily at least 1 hour after the evening meal, preferably at bedtime.
    Swallow capsules whole; do not crush, break, or chew.
    If a dose is missed, take within 12 hours of missing the dose. If more than 12 hours have passed, skip the dose of the day and take the dose the next day at the scheduled time.
    No more than a 28-day supply should be dispensed at one time.

    STORAGE

    Thalomid:
    - Protect from light
    - Store at 77 degrees F; excursions permitted to 59-86 degrees F

    CONTRAINDICATIONS / PRECAUTIONS

    Exfoliative dermatitis, thalidomide hypersensitivity

    Thalidomide is contraindicated for use by patients with thalidomide hypersensitivity. Serious dermatologic reactions including Stevens-Johnson syndrome and toxic epidermal necrolysis (TEN) have been reported. Thalidomide should be discontinued if a skin rash occurs and should only be restarted after appropriate clinical evaluation. If purpura, bullous rash, or exfoliative dermatitis is present or if Stevens-Johnson syndrome or TEN is suspected, the use of thalidomide should not be resumed.

    Myocardial infarction, stroke, thromboembolic disease

    Venous (e.g., pulmonary embolism, deep vein thrombosis) and arterial (e.g., stroke, myocardial infarction (MI)) thromboembolic disease has been reported in patients with multiple myeloma who received thalidomide. Using thalidomide in combination with chemotherapy agents, including dexamethasone, may increase the risk of thromboembolism (TE); use caution when administering thalidomide with chemotherapy agents or other agents that may increase the risk of TE (e.g., estrogen-containing contraceptives). Monitor patients for signs and symptoms of a blood clot such as dyspnea, chest pain, and arm or leg swelling; a stroke such as sudden numbness or weakness (especially on one side of the body), severe headache or confusion, or problems with vision, speech, or balance; and a MI such as feeling sweaty, shortness of breath, feeling sick or vomiting, and/or chest pain that may spread to the arms, neck, jaw, back, or stomach. Consider thromboprophylaxis based on an assessment of individual patients’ underlying risk factors.

    Peripheral neuropathy

    Patients with pre-existing peripheral neuropathy or taking other agents known to cause peripheral neuropathy should be closely monitored during treatment with thalidomide. Thalidomide may cause severe and possibly irreversible neuropathies, usually after chronic use. Patients should be examined monthly for the first 3 months of thalidomide therapy and then routinely from then on to detect any early signs of peripheral neuropathy. Clinicians should consider electrophysiologic testing consisting of measurement of sensory nerve action potential (SNAP) amplitudes at baseline and then every 6 months to detect asymptomatic neuropathies.

    Bleeding, GI bleeding, neutropenia, thrombocytopenia

    Hematologic toxicity (e.g., neutropenia and thrombocytopenia) has been reported with thalidomide use. Do not start therapy in patients who have an absolute neutrophil count (ANC) of less than 750 cells/mm3. Monitor complete blood counts (including a differential and platelet counts) at baseline and periodically during therapy, especially in patients predisposed to neutropenia (e.g., HIV-seropositive patients). If the ANC is decreased to less than 750 cells/mm3 during therapy, re-evaluate and consider holding thalidomide therapy if the neutropenia persists. Observe patients for signs and symptoms of bleeding including petechiae, epistaxis, and GI bleeding; patients receiving concomitant medications that may also cause bleeding may be at increased risk for serious bleeding. If grade 3 or 4 thrombocytopenia occurs, consider therapy interruption, a dose reduction, or therapy discontinuation.

    Driving or operating machinery

    Patients should be cautioned about driving or operating machinery during thalidomide therapy due to somnolence and drowsiness associated with thalidomide therapy. Patients should also be warned of the potential additive effects with other medications such as barbiturates, H1-blockers, and ethanol.

    Orthostatic hypotension

    Thalidomide may cause dizziness and orthostatic hypotension. Patients should be cautioned to sit upright for a few minutes before standing up from a lying or seated position.

    Human immunodeficiency virus (HIV) infection

    Thalidomide has been associated with an increase in HIV-RNA levels in human immunodeficiency virus (HIV) infection-seropositive patients in controlled trials. The clinical significance of this increase is unknown and appears to be a transient effect. These studies were performed prior to the availability of effective combination antiretroviral therapy. In HIV-seropositive patients, it is recommended to monitor viral load after the first and third months of thalidomide treatment and every 3 months thereafter.

    Seizure disorder, seizures

    Seizures have been reported during post-marketing of thalidomide. Most patients had disorders that may have predisposed them to seizure activity, and it is not currently known whether thalidomide has any epileptogenic influence. During therapy with thalidomide, patients with a history of a seizure disorder or with other risk factors for the development of seizures should be monitored closely for clinical changes that could precipitate acute seizure activity.

    Children, infants, neonates

    The safety and effectiveness of thalidomide have not been determined in neonates, infants and children under the age of 12 years.

    Accidental exposure

    Although the only type of thalidomide exposure known to result in drug-induced birth defects are as a result of direct oral ingestion of thalidomide, avoid accidental exposure to non-intact capsules or the powder from inside the capsules. No specific data are available regarding the cutaneous absorption or inhalation of thalidomide in women of child-bearing potential and whether these exposures may result in any birth defects. Patients should be instructed to not extensively handle or open thalidomide capsules and to maintain storage of capsules in blister packs until taken. If healthcare providers or other care givers are exposed to body fluids from patients receiving thalidomide, appropriate precautions should be utilized, such as wearing gloves to prevent the potential cutaneous exposure to thalidomide. If there is contact with non-intact thalidomide capsules or the powder contents, the exposed area should be washed with soap and water.

    Intrauterine fetal death, pregnancy

    Thalidomide is classified as pregnancy risk category X and it’s use is contraindicated in pregnancy. Thalidomide is a known human teratogen and even a single dose taken by a pregnant woman may cause severe birth defects; intrauterine fetal death may also occur. Severe and life-threatening birth defects such as amelia; phocomelia; hypoplasticity of the bones; absence of bones; external ear abnormalities; facial palsy; eye abnormalities; congenital heart defects; alimentary tract, urinary tract, and genital malformations; and death at or shortly after birth have been reported in human infants. Thalidomide therapy should not be initiated in females of reproductive potential until negative results from 2 pregnancy tests are confirmed. The first test should be done within 10 to 14 days and the second test within 24 hours prior to prescribing thalidomide. Once treatment is started, additional pregnancy tests should occur weekly during the first month of treatment, then every month in females with regular menstrual cycles (more frequently if pregnancy is suspected or if menstrual cycles are irregular). Both men and women must comply with the need for adequate contraception to prevent pregnancy. In order to prevent fetal exposure during pregnancy, thalidomide is only available through a restricted distribution program, the THALOMID REMS program. This program requires prescribers, pharmacists, and patients to comply with certain conditions prior to prescribing, dispensing, or receiving thalidomide. It can be prescribed only by licensed prescribers who are registered in the THALOMID REMS program and understand the potential risk of teratogenicity if used during pregnancy. If the patient is less than 18 years of age, their parent or legal guardian must agree to ensure compliance with all conditions. If pregnancy does occur during treatment, immediately discontinue thalidomide. Prescribers are encouraged to report all cases of suspected fetal exposure to Celgene Corporation in the U.S. at 1-(888)-423-5436 or to the FDA MedWatch program at 1-(800)-332-1088. Refer the patient to an obstetrician/gynecologist experienced in reproductive toxicity for further evaluation and counseling.

    Blood donation

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

    Contraception requirements, male-mediated teratogenicity, menstrual irregularity, pregnancy testing, reproductive risk

    Counsel patients about the reproductive risk of thalidomide and discuss contraception requirements with both men and females of childbearing potential. Thalidomide may cause severe birth defects or fetal death; defects may occur with even 1 dose to a pregnant female. Thalidomide therapy should not be initiated in females of reproductive potential until negative results from 2 pregnancy tests are confirmed. The first test should be done within 10 to 14 days and the second test within 24 hours prior to prescribing thalidomide. Once treatment is started, pregnancy testing should occur weekly during the first month of treatment, then every month in females with regular menstrual cycles. If the female patient's menstrual cycles are irregular, pregnancy testing should occur every 2 weeks. If any woman of reproductive potential experiences menstrual irregularity or misses her period while receiving thalidomide, treatment must be discontinued and pregnancy testing and counseling should be performed. Effective contraception must be used by all females of reproductive potential for at least 4 weeks before beginning treatment, during therapy and dosage interruptions, and for 4 weeks following discontinuation of therapy. Women must commit to abstain from heterosexual intercourse or to use 2 methods of reliable birth control, including at least 1 highly effective method (e.g., intrauterine devices (IUD), hormonal contraception, tubal ligation, or partner's vasectomy) and 1 additional effective method (e.g., latex condom, diaphragm, or cervical cap). These contraceptive measures should be taken even in patients with a history of infertility, unless a hysterectomy has been performed. Women requiring medications that may interfere with the effectiveness of hormonal contraception (e.g., HIV-protease inhibitors, griseofulvin, modafinil, penicillins, rifampin, rifabutin, phenytoin, carbamazepine, or certain herbal supplements such as St. John’s Wort) must use 2 other effective or highly effective methods of contraception. Some contraceptive methods such as IUD or contraceptive implants may increase the risk for infection or bleeding either at insertion, removal, or during use. Additionally, estrogen-containing contraceptives may increase the risk of blood clot formation. Consider these risks when choosing contraceptive measures. Thalidomide is passed into the semen and there is a potential for male-mediated teratogenicity. Therefore, a male patient must use barrier contraception (latex condom) during sexual intercourse with a woman of reproductive potential while on therapy and for 4 weeks after discontinuing thalidomide therapy, even if he has undergone successful vasectomy. Male patients should not donate sperm while taking thalidomide and for 4 weeks after stopping therapy. If the patient is less than 18 years of age, their parent or legal guardian must agree to ensure compliance with these conditions.

    Breast-feeding

    Due to a potential for serious adverse reactions in breast fed infants, nursing women should not breast feed during thalidomide therapy. It is not known whether thalidomide is excreted in human milk. A decision should be made whether to discontinue breast-feeding or to discontinue the drug, taking into account the importance of the drug to the mother.

    ADVERSE REACTIONS

    Severe

    thrombosis / Delayed / 13.0-22.5
    thromboembolism / Delayed / 0-22.5
    dyspnea / Early / 13.0-13.0
    hypocalcemia / Delayed / 11.0-11.0
    neutropenia / Delayed / 3.0-10.0
    peripheral neuropathy / Delayed / 3.0-8.0
    constipation / Delayed / 3.0-8.0
    pulmonary embolism / Delayed / 7.0-7.0
    leukopenia / Delayed / 0-6.0
    edema / Delayed / 6.0-6.0
    asthenia / Delayed / 5.0-5.0
    nausea / Early / 5.0-5.0
    anorexia / Delayed / 4.0-4.0
    rash (unspecified) / Early / 4.0-4.0
    hypokalemia / Delayed / 3.0-3.0
    stroke / Early / 2.6-2.6
    hyperbilirubinemia / Delayed / 2.0-2.0
    myocardial infarction / Delayed / 1.3-1.3
    xerostomia / Early / 1.0-1.0
    teratogenesis / Delayed / 10.0
    peptic ulcer / Delayed / Incidence not known
    angioedema / Rapid / Incidence not known
    exfoliative dermatitis / Delayed / Incidence not known
    Stevens-Johnson syndrome / Delayed / Incidence not known
    toxic epidermal necrolysis / Delayed / Incidence not known
    aplastic anemia / Delayed / Incidence not known
    megaloblastic anemia / Delayed / Incidence not known
    GI bleeding / Delayed / Incidence not known
    pancytopenia / Delayed / Incidence not known
    atrial fibrillation / Early / Incidence not known
    bradycardia / Rapid / Incidence not known
    seizures / Delayed / Incidence not known
    hyperkalemia / Delayed / Incidence not known
    tumor lysis syndrome (TLS) / Delayed / Incidence not known
    hepatic failure / Delayed / Incidence not known

    Moderate

    peripheral edema / Delayed / 34.0-34.0
    confusion / Early / 28.0-28.0
    anemia / Delayed / 0-12.5
    lymphadenopathy / Delayed / 0-12.5
    depression / Delayed / 10.0-10.0
    orthostatic hypotension / Delayed / 3.0
    hypothyroidism / Delayed / 10.0
    hypotension / Rapid / Incidence not known
    sinus tachycardia / Rapid / Incidence not known
    bullous rash / Early / Incidence not known
    bleeding / Early / Incidence not known
    thrombocytopenia / Delayed / Incidence not known
    lymphopenia / Delayed / Incidence not known
    eosinophilia / Delayed / Incidence not known
    splenomegaly / Delayed / Incidence not known
    hyperuricemia / Delayed / Incidence not known
    hyperphosphatemia / Delayed / Incidence not known
    jaundice / Delayed / Incidence not known
    cholestasis / Delayed / Incidence not known
    cholangitis / Delayed / Incidence not known
    elevated hepatic enzymes / Delayed / Incidence not known
    hepatitis / Delayed / Incidence not known
    galactorrhea / Delayed / Incidence not known

    Mild

    weakness / Early / 40.0-40.0
    tremor / Early / 26.0-26.0
    anxiety / Delayed / 12.0-26.0
    fever / Early / 24.0-24.0
    weight loss / Delayed / 23.0-23.0
    dizziness / Early / 23.0-23.0
    weight gain / Delayed / 22.0-22.0
    fatigue / Early / 21.0-21.0
    xerosis / Delayed / 21.0-21.0
    paresthesias / Delayed / 12.0-12.0
    dyspepsia / Early / 11.0-11.0
    syncope / Early / 3.0-3.0
    drowsiness / Early / 10.0
    vomiting / Early / 3.0
    muscle cramps / Delayed / Incidence not known
    pruritus / Rapid / Incidence not known
    maculopapular rash / Early / Incidence not known
    urticaria / Rapid / Incidence not known
    purpura / Delayed / Incidence not known
    epistaxis / Delayed / Incidence not known
    petechiae / Delayed / Incidence not known
    leukocytosis / Delayed / Incidence not known
    headache / Early / Incidence not known
    oligomenorrhea / Delayed / Incidence not known
    amenorrhea / Delayed / Incidence not known
    gynecomastia / Delayed / Incidence not known

    DRUG INTERACTIONS

    Acebutolol: Thalidomide and other agents that slow cardiac conduction such as beta-blockers should be used cautiously due to the potential for additive bradycardia.
    Acetaminophen; Dichloralphenazone; Isometheptene: Thalidomide frequently causes drowsiness and somnolence and may enhance the sedative activity of dichloralphenazone.
    Acetaminophen; Pentazocine: Avoid the concomitant use of thalidomide with other central nervous system depressants such as pentazocine due to the potential for additive sedative effects.
    Acetaminophen; Tramadol: Avoid the concomitant use of thalidomide with other central nervous system depressants such as tramadol due to the potential for additive sedative effects.
    Aliskiren; Amlodipine: Thalidomide and other agents that slow cardiac conduction such as calcium-channel blockers should be used cautiously due to the potential for additive bradycardia.
    Aliskiren; Amlodipine; Hydrochlorothiazide, HCTZ: Thalidomide and other agents that slow cardiac conduction such as calcium-channel blockers should be used cautiously due to the potential for additive bradycardia.
    Alpha-blockers: Thalidomide and other agents that slow cardiac conduction such as alpha-blockers should be used cautiously due to the potential for additive bradycardia.
    Amiodarone: Thalidomide and other agents that cause peripheral neuropathy such as amiodarone should be used cautiously due to the potential for additive effects.
    Amitriptyline: Avoid the concomitant use of thalidomide with other central nervous system depressants such as tricyclic antidepressants (TCAs) due to the potential for additive sedative effects. Additionally, co-administration of thalidomide and other agents that slow cardiac conduction such as TCAs may increase the potential for additive bradycardia.
    Amitriptyline; Chlordiazepoxide: Avoid the concomitant use of thalidomide with other central nervous system depressants such as tricyclic antidepressants (TCAs) due to the potential for additive sedative effects. Additionally, co-administration of thalidomide and other agents that slow cardiac conduction such as TCAs may increase the potential for additive bradycardia.
    Amlodipine: Thalidomide and other agents that slow cardiac conduction such as calcium-channel blockers should be used cautiously due to the potential for additive bradycardia.
    Amlodipine; Atorvastatin: Thalidomide and other agents that slow cardiac conduction such as calcium-channel blockers should be used cautiously due to the potential for additive bradycardia.
    Amlodipine; Benazepril: Thalidomide and other agents that slow cardiac conduction such as calcium-channel blockers should be used cautiously due to the potential for additive bradycardia.
    Amlodipine; Hydrochlorothiazide, HCTZ; Olmesartan: Thalidomide and other agents that slow cardiac conduction such as calcium-channel blockers should be used cautiously due to the potential for additive bradycardia.
    Amlodipine; Hydrochlorothiazide, HCTZ; Valsartan: Thalidomide and other agents that slow cardiac conduction such as calcium-channel blockers should be used cautiously due to the potential for additive bradycardia.
    Amlodipine; Olmesartan: Thalidomide and other agents that slow cardiac conduction such as calcium-channel blockers should be used cautiously due to the potential for additive bradycardia.
    Amlodipine; Telmisartan: Thalidomide and other agents that slow cardiac conduction such as calcium-channel blockers should be used cautiously due to the potential for additive bradycardia.
    Amlodipine; Valsartan: Thalidomide and other agents that slow cardiac conduction such as calcium-channel blockers should be used cautiously due to the potential for additive bradycardia.
    Anxiolytics; Sedatives; and Hypnotics: Avoid the concomitant use of thalidomide with anxiolytics, sedatives, and hypnotics due to the potential for additive sedative effects.
    Atenolol: Thalidomide and other agents that slow cardiac conduction such as beta-blockers should be used cautiously due to the potential for additive bradycardia.
    Atenolol; Chlorthalidone: Thalidomide and other agents that slow cardiac conduction such as beta-blockers should be used cautiously due to the potential for additive bradycardia.
    Atracurium: Thalidomide and other agents that slow cardiac conduction such as neuromuscular blockers should be used cautiously due to the potential for additive bradycardia.
    Azelastine: Avoid the concomitant use of thalidomide with opiate agonists; antihistamines; antipsychotics; anxiolytics, sedatives, and hypnotics; and other central nervous system depressants due to the potential for additive sedative effects.
    Azelastine; Fluticasone: Avoid the concomitant use of thalidomide with opiate agonists; antihistamines; antipsychotics; anxiolytics, sedatives, and hypnotics; and other central nervous system depressants due to the potential for additive sedative effects.
    Barbiturates: Thalidomide frequently causes drowsiness and somnolence and may enhance the sedative activity of barbiturates.
    Bendroflumethiazide; Nadolol: Thalidomide and other agents that slow cardiac conduction such as beta-blockers should be used cautiously due to the potential for additive bradycardia.
    Benzodiazepines: Thalidomide frequently causes drowsiness and somnolence and may enhance the sedative activity of benzodiazepines.
    Beta-blockers: Thalidomide and other agents that slow cardiac conduction such as beta-blockers should be used cautiously due to the potential for additive bradycardia.
    Betaxolol: Thalidomide and other agents that slow cardiac conduction such as beta-blockers should be used cautiously due to the potential for additive bradycardia.
    Bismuth Subcitrate Potassium; Metronidazole; Tetracycline: Thalidomide and other agents that cause peripheral neuropathy such as metronidazole should be used cautiously due to the potential for additive effects.
    Bismuth Subsalicylate; Metronidazole; Tetracycline: Thalidomide and other agents that cause peripheral neuropathy such as metronidazole should be used cautiously due to the potential for additive effects.
    Bisoprolol: Thalidomide and other agents that slow cardiac conduction such as beta-blockers should be used cautiously due to the potential for additive bradycardia.
    Bisoprolol; Hydrochlorothiazide, HCTZ: Thalidomide and other agents that slow cardiac conduction such as beta-blockers should be used cautiously due to the potential for additive bradycardia.
    Bortezomib: Monitor patients for the development of peripheral neuropathy when receiving bortezomib in combination with other drugs that can cause peripheral neuropathy like thalidomide; the risk of peripheral neuropathy may be additive.
    Brimonidine; Timolol: Thalidomide and other agents that slow cardiac conduction such as beta-blockers should be used cautiously due to the potential for additive bradycardia.
    Buspirone: Avoid the concomitant use of thalidomide with anxiolytics, sedatives, and hypnotics due to the potential for additive sedative effects.
    Butorphanol: Avoid the concomitant use of thalidomide with other central nervous system depressants such as butorphanol due to the potential for additive sedative effects.
    Butyrophenone: Avoid the concomitant use of thalidomide with antipsychotics due to the potential for additive sedative effects.
    Calcium-channel blockers: Thalidomide and other agents that slow cardiac conduction such as calcium-channel blockers should be used cautiously due to the potential for additive bradycardia.
    Carbidopa; Levodopa; Entacapone: Avoid the concomitant use of thalidomide with other central nervous system depressants such as tolcapone due to the potential for additive sedative effects.
    Carteolol: Thalidomide and other agents that slow cardiac conduction such as beta-blockers should be used cautiously due to the potential for additive bradycardia.
    Carvedilol: Thalidomide and other agents that slow cardiac conduction such as beta-blockers should be used cautiously due to the potential for additive bradycardia.
    Cetirizine: Avoid the concomitant use of thalidomide with opiate agonists; antihistamines; antipsychotics; anxiolytics, sedatives, and hypnotics; and other central nervous system depressants due to the potential for additive sedative effects.
    Cetirizine; Pseudoephedrine: Avoid the concomitant use of thalidomide with opiate agonists; antihistamines; antipsychotics; anxiolytics, sedatives, and hypnotics; and other central nervous system depressants due to the potential for additive sedative effects.
    Cimetidine: Thalidomide and other agents that slow cardiac conduction such as H2-blockers should be used cautiously due to the potential for additive bradycardia.
    Cisatracurium: Thalidomide and other agents that slow cardiac conduction such as neuromuscular blockers should be used cautiously due to the potential for additive bradycardia.
    Cisplatin: Thalidomide and other agents that cause peripheral neuropathy such as cisplatin should be used cautiously due to the potential for additive effects.
    Clevidipine: Thalidomide and other agents that slow cardiac conduction such as calcium-channel blockers should be used cautiously due to the potential for additive bradycardia.
    Clomipramine: Avoid the concomitant use of thalidomide with other central nervous system depressants such as tricyclic antidepressants (TCAs) due to the potential for additive sedative effects. Additionally, co-administration of thalidomide and other agents that slow cardiac conduction such as TCAs may increase the potential for additive bradycardia.
    Clozapine: It is unclear if concurrent use of other drugs known to cause neutropenia (e.g., antineoplastic agents) increases the risk or severity of clozapine-induced neutropenia. Because there is no strong rationale for avoiding clozapine in patients treated with these drugs, consider increased absolute neutrophil count (ANC) monitoring and consult the treating oncologist.
    Codeine; Phenylephrine; Promethazine: Thalidomide frequently causes drowsiness and somnolence and may enhance the sedative activity of phenothiazines.
    Codeine; Promethazine: Thalidomide frequently causes drowsiness and somnolence and may enhance the sedative activity of phenothiazines.
    COMT inhibitors: Avoid the concomitant use of thalidomide with other central nervous system depressants such as tolcapone due to the potential for additive sedative effects.
    Darbepoetin Alfa: Thalidomide and darbepoetin alfa should be used cautiously due an increased risk of thromboembolism.
    Denosumab: The safety and efficacy of denosumab use in patients with immunosuppression have not been evaluated. Patients receiving immunosuppressives along with denosumab may be at a greater risk of developing an infection and/or osteonecrosis of the jaw, a rare condition that has been reported during denosumab therapy.
    Desipramine: Avoid the concomitant use of thalidomide with other central nervous system depressants such as tricyclic antidepressants (TCAs) due to the potential for additive sedative effects. Additionally, co-administration of thalidomide and other agents that slow cardiac conduction such as TCAs may increase the potential for additive bradycardia.
    Dexamethasone: Coadministration of dexamethasone with thalidomide should be employed cautiously, as toxic epidermal necrolysis has been reported with concomitant use.
    Dextromethorphan; Promethazine: Thalidomide frequently causes drowsiness and somnolence and may enhance the sedative activity of phenothiazines.
    Dienogest; Estradiol valerate: Thalidomide and hormone contraceptives should be used cautiously due an increased risk of thromboembolism. The pharmacokinetic parameters of norethindrone/estradiol were not affected when a single dose of norethindrone 1 mg/estradiol 75 micrograms was administered in 10 healthy women who were receiving thalidomide 200 mg/day (at steady state levels).
    Digoxin: Thalidomide and digoxin should be used cautiously due to the potential for additive bradycardia. The pharmacokinetic parameters of thalidomide and digoxin were not affected when a single dose of digoxin 0.5 mg was administered in 16 healthy men who were receiving thalidomide 200 mg/day (at steady state levels).
    Diltiazem: Thalidomide and other agents that slow cardiac conduction such as calcium-channel blockers should be used cautiously due to the potential for additive bradycardia.
    Disulfiram: Thalidomide and other agents that cause peripheral neuropathy such as disulfiram should be used cautiously due to the potential for additive effects.
    Docetaxel: Thalidomide and other agents that cause peripheral neuropathy such as docetaxel should be used cautiously due to the potential for additive effects.
    Dorzolamide; Timolol: Thalidomide and other agents that slow cardiac conduction such as beta-blockers should be used cautiously due to the potential for additive bradycardia.
    Doxacurium: Thalidomide and other agents that slow cardiac conduction such as neuromuscular blockers should be used cautiously due to the potential for additive bradycardia.
    Doxazosin: Thalidomide and other agents that slow cardiac conduction such as alpha-blockers should be used cautiously due to the potential for additive bradycardia.
    Doxepin: Avoid the concomitant use of thalidomide with other central nervous system depressants such as tricyclic antidepressants (TCAs) due to the potential for additive sedative effects. Additionally, co-administration of thalidomide and other agents that slow cardiac conduction such as TCAs may increase the potential for additive bradycardia.
    Drospirenone; Estradiol: Thalidomide and hormone contraceptives should be used cautiously due an increased risk of thromboembolism. The pharmacokinetic parameters of norethindrone/estradiol were not affected when a single dose of norethindrone 1 mg/estradiol 75 micrograms was administered in 10 healthy women who were receiving thalidomide 200 mg/day (at steady state levels).
    Drospirenone; Ethinyl Estradiol: Thalidomide and hormone contraceptives should be used cautiously due an increased risk of thromboembolism. The pharmacokinetic parameters of norethindrone/estradiol were not affected when a single dose of norethindrone 1 mg/estradiol 75 micrograms was administered in 10 healthy women who were receiving thalidomide 200 mg/day (at steady state levels).
    Drospirenone; Ethinyl Estradiol; Levomefolate: Thalidomide and hormone contraceptives should be used cautiously due an increased risk of thromboembolism. The pharmacokinetic parameters of norethindrone/estradiol were not affected when a single dose of norethindrone 1 mg/estradiol 75 micrograms was administered in 10 healthy women who were receiving thalidomide 200 mg/day (at steady state levels).
    Enalapril; Felodipine: Thalidomide and other agents that slow cardiac conduction such as calcium-channel blockers should be used cautiously due to the potential for additive bradycardia.
    Entacapone: Avoid the concomitant use of thalidomide with other central nervous system depressants such as tolcapone due to the potential for additive sedative effects.
    Epoetin Alfa: Thalidomide and epoetin alfa should be used cautiously due an increased risk of thromboembolism.
    Esmolol: Thalidomide and other agents that slow cardiac conduction such as beta-blockers should be used cautiously due to the potential for additive bradycardia.
    Estradiol; Levonorgestrel: Thalidomide and hormone contraceptives should be used cautiously due an increased risk of thromboembolism. The pharmacokinetic parameters of norethindrone/estradiol were not affected when a single dose of norethindrone 1 mg/estradiol 75 micrograms was administered in 10 healthy women who were receiving thalidomide 200 mg/day (at steady state levels).
    Estradiol; Norethindrone: Thalidomide and hormone contraceptives should be used cautiously due an increased risk of thromboembolism. The pharmacokinetic parameters of norethindrone/estradiol were not affected when a single dose of norethindrone 1 mg/estradiol 75 micrograms was administered in 10 healthy women who were receiving thalidomide 200 mg/day (at steady state levels).
    Estradiol; Norgestimate: Thalidomide and hormone contraceptives should be used cautiously due an increased risk of thromboembolism. The pharmacokinetic parameters of norethindrone/estradiol were not affected when a single dose of norethindrone 1 mg/estradiol 75 micrograms was administered in 10 healthy women who were receiving thalidomide 200 mg/day (at steady state levels).
    Ethanol: Avoid the concomitant use of thalidomide with alcohol (ethanol) due to the potential for additive sedative effects. Additionally, using thalidomide and alcohol together may potentiate the adverse effect of peripheral neuropathy.
    Ethinyl Estradiol: Thalidomide and hormone contraceptives should be used cautiously due an increased risk of thromboembolism. The pharmacokinetic parameters of norethindrone/estradiol were not affected when a single dose of norethindrone 1 mg/estradiol 75 micrograms was administered in 10 healthy women who were receiving thalidomide 200 mg/day (at steady state levels).
    Ethinyl Estradiol; Desogestrel: Thalidomide and hormone contraceptives should be used cautiously due an increased risk of thromboembolism. The pharmacokinetic parameters of norethindrone/estradiol were not affected when a single dose of norethindrone 1 mg/estradiol 75 micrograms was administered in 10 healthy women who were receiving thalidomide 200 mg/day (at steady state levels).
    Ethinyl Estradiol; Ethynodiol Diacetate: Thalidomide and hormone contraceptives should be used cautiously due an increased risk of thromboembolism. The pharmacokinetic parameters of norethindrone/estradiol were not affected when a single dose of norethindrone 1 mg/estradiol 75 micrograms was administered in 10 healthy women who were receiving thalidomide 200 mg/day (at steady state levels).
    Ethinyl Estradiol; Etonogestrel: Thalidomide and hormone contraceptives should be used cautiously due an increased risk of thromboembolism. The pharmacokinetic parameters of norethindrone/estradiol were not affected when a single dose of norethindrone 1 mg/estradiol 75 micrograms was administered in 10 healthy women who were receiving thalidomide 200 mg/day (at steady state levels).
    Ethinyl Estradiol; Levonorgestrel: Thalidomide and hormone contraceptives should be used cautiously due an increased risk of thromboembolism. The pharmacokinetic parameters of norethindrone/estradiol were not affected when a single dose of norethindrone 1 mg/estradiol 75 micrograms was administered in 10 healthy women who were receiving thalidomide 200 mg/day (at steady state levels).
    Ethinyl Estradiol; Levonorgestrel; Folic Acid; Levomefolate: Thalidomide and hormone contraceptives should be used cautiously due an increased risk of thromboembolism. The pharmacokinetic parameters of norethindrone/estradiol were not affected when a single dose of norethindrone 1 mg/estradiol 75 micrograms was administered in 10 healthy women who were receiving thalidomide 200 mg/day (at steady state levels).
    Ethinyl Estradiol; Norelgestromin: Thalidomide and hormone contraceptives should be used cautiously due an increased risk of thromboembolism. The pharmacokinetic parameters of norethindrone/estradiol were not affected when a single dose of norethindrone 1 mg/estradiol 75 micrograms was administered in 10 healthy women who were receiving thalidomide 200 mg/day (at steady state levels).
    Ethinyl Estradiol; Norethindrone Acetate: Thalidomide and hormone contraceptives should be used cautiously due an increased risk of thromboembolism. The pharmacokinetic parameters of norethindrone/estradiol were not affected when a single dose of norethindrone 1 mg/estradiol 75 micrograms was administered in 10 healthy women who were receiving thalidomide 200 mg/day (at steady state levels).
    Ethinyl Estradiol; Norethindrone Acetate; Ferrous fumarate: Thalidomide and hormone contraceptives should be used cautiously due an increased risk of thromboembolism. The pharmacokinetic parameters of norethindrone/estradiol were not affected when a single dose of norethindrone 1 mg/estradiol 75 micrograms was administered in 10 healthy women who were receiving thalidomide 200 mg/day (at steady state levels).
    Ethinyl Estradiol; Norethindrone: Thalidomide and hormone contraceptives should be used cautiously due an increased risk of thromboembolism. The pharmacokinetic parameters of norethindrone/estradiol were not affected when a single dose of norethindrone 1 mg/estradiol 75 micrograms was administered in 10 healthy women who were receiving thalidomide 200 mg/day (at steady state levels).
    Ethinyl Estradiol; Norethindrone; Ferrous fumarate: Thalidomide and hormone contraceptives should be used cautiously due an increased risk of thromboembolism. The pharmacokinetic parameters of norethindrone/estradiol were not affected when a single dose of norethindrone 1 mg/estradiol 75 micrograms was administered in 10 healthy women who were receiving thalidomide 200 mg/day (at steady state levels).
    Ethinyl Estradiol; Norgestimate: Thalidomide and hormone contraceptives should be used cautiously due an increased risk of thromboembolism. The pharmacokinetic parameters of norethindrone/estradiol were not affected when a single dose of norethindrone 1 mg/estradiol 75 micrograms was administered in 10 healthy women who were receiving thalidomide 200 mg/day (at steady state levels).
    Ethinyl Estradiol; Norgestrel: Thalidomide and hormone contraceptives should be used cautiously due an increased risk of thromboembolism. The pharmacokinetic parameters of norethindrone/estradiol were not affected when a single dose of norethindrone 1 mg/estradiol 75 micrograms was administered in 10 healthy women who were receiving thalidomide 200 mg/day (at steady state levels).
    Etonogestrel: Thalidomide and hormone contraceptives should be used cautiously due an increased risk of thromboembolism. The pharmacokinetic parameters of norethindrone/estradiol were not affected when a single dose of norethindrone 1 mg/estradiol 75 micrograms was administered in 10 healthy women who were receiving thalidomide 200 mg/day (at steady state levels).
    Famotidine: Thalidomide and other agents that slow cardiac conduction such as H2-blockers should be used cautiously due to the potential for additive bradycardia.
    Famotidine; Ibuprofen: Thalidomide and other agents that slow cardiac conduction such as H2-blockers should be used cautiously due to the potential for additive bradycardia.
    Febuxostat: Coadministration of febuxostat and cytotoxic antineoplastic agents has not been studied. After antineoplastic therapy, tumor cell breakdown may greatly increase the rate of purine metabolism to uric acid. Febuxostat inhibits uric acid formation, but does not affect xanthine and hypoxanthine formation. An increased renal load of these two uric acid precursors can occur and result in xanthine nephropathy and calculi.
    Felodipine: Thalidomide and other agents that slow cardiac conduction such as calcium-channel blockers should be used cautiously due to the potential for additive bradycardia.
    Fenofibric Acid: At therapeutic concentrations, fenofibric acid is a weak inhibitor of CYP2C19. Concomitant use of fenofibric acid with CYP2C19 substrates, such as thalidomide, has not been formally studied. Fenofibric acid may theoretically increase plasma concentrations of CYP2C19 substrates and could lead to toxicity for drugs that have a narrow therapeutic range. Monitor the therapeutic effect of thalidomide during coadministration with fenofibric acid.
    Fexofenadine: Avoid the concomitant use of thalidomide with opiate agonists; antihistamines; antipsychotics; anxiolytics, sedatives, and hypnotics; and other central nervous system depressants due to the potential for additive sedative effects.
    Fexofenadine; Pseudoephedrine: Avoid the concomitant use of thalidomide with opiate agonists; antihistamines; antipsychotics; anxiolytics, sedatives, and hypnotics; and other central nervous system depressants due to the potential for additive sedative effects.
    Fosphenytoin: Avoid the concomitant use of thalidomide with other central nervous system depressants such as phenytoin or fosphenytoin due to the potential for additive sedative effects. Additionally, co-administration of thalidomide and agents that cause peripheral neuropathy such as phenytoin may increase the potential for additive neuropathy.
    H2-blockers: Thalidomide and other agents that slow cardiac conduction such as H2-blockers should be used cautiously due to the potential for additive bradycardia.
    Heterocyclic antidepressants: Avoid the concomitant use of thalidomide with other central nervous system depressants such as trazodone due to the potential for additive sedative effects.
    Hydrochlorothiazide, HCTZ; Metoprolol: Thalidomide and other agents that slow cardiac conduction such as beta-blockers should be used cautiously due to the potential for additive bradycardia.
    Hydrochlorothiazide, HCTZ; Propranolol: Thalidomide and other agents that slow cardiac conduction such as beta-blockers should be used cautiously due to the potential for additive bradycardia.
    Imipramine: Avoid the concomitant use of thalidomide with other central nervous system depressants such as tricyclic antidepressants (TCAs) due to the potential for additive sedative effects. Additionally, co-administration of thalidomide and other agents that slow cardiac conduction such as TCAs may increase the potential for additive bradycardia.
    Isradipine: Thalidomide and other agents that slow cardiac conduction such as calcium-channel blockers should be used cautiously due to the potential for additive bradycardia.
    Labetalol: Thalidomide and other agents that slow cardiac conduction such as beta-blockers should be used cautiously due to the potential for additive bradycardia.
    Leuprolide; Norethindrone: Thalidomide and hormone contraceptives should be used cautiously due an increased risk of thromboembolism. The pharmacokinetic parameters of norethindrone/estradiol were not affected when a single dose of norethindrone 1 mg/estradiol 75 micrograms was administered in 10 healthy women who were receiving thalidomide 200 mg/day (at steady state levels).
    Levobetaxolol: Thalidomide and other agents that slow cardiac conduction such as beta-blockers should be used cautiously due to the potential for additive bradycardia.
    Levobunolol: Thalidomide and other agents that slow cardiac conduction such as beta-blockers should be used cautiously due to the potential for additive bradycardia.
    Levocetirizine: Avoid the concomitant use of thalidomide with opiate agonists; antihistamines; antipsychotics; anxiolytics, sedatives, and hypnotics; and other central nervous system depressants due to the potential for additive sedative effects.
    Levonorgestrel: Thalidomide and hormone contraceptives should be used cautiously due an increased risk of thromboembolism. The pharmacokinetic parameters of norethindrone/estradiol were not affected when a single dose of norethindrone 1 mg/estradiol 75 micrograms was administered in 10 healthy women who were receiving thalidomide 200 mg/day (at steady state levels).
    Lithium: Avoid the concomitant use of thalidomide with other central nervous system depressants such as lithium due to the potential for additive sedative effects. Additionally, co-administration of thalidomide and other agents that slow cardiac conduction such as lithium may increase the potential for additive bradycardia.
    Live Vaccines: No data are available on the response to vaccination with live vaccines or on the secondary transmission of infection by live vaccines in patients receiving thalidomide. Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
    Loratadine: Avoid the concomitant use of thalidomide with opiate agonists; antihistamines; antipsychotics; anxiolytics, sedatives, and hypnotics; and other central nervous system depressants due to the potential for additive sedative effects.
    Loratadine; Pseudoephedrine: Avoid the concomitant use of thalidomide with opiate agonists; antihistamines; antipsychotics; anxiolytics, sedatives, and hypnotics; and other central nervous system depressants due to the potential for additive sedative effects.
    Loxapine: Avoid the concomitant use of thalidomide with antipsychotics due to the potential for additive sedative effects.
    Lurasidone: Avoid the concomitant use of thalidomide with antipsychotics due to the potential for additive sedative effects.
    Meperidine; Promethazine: Thalidomide frequently causes drowsiness and somnolence and may enhance the sedative activity of phenothiazines.
    Mestranol; Norethindrone: Thalidomide and hormone contraceptives should be used cautiously due an increased risk of thromboembolism. The pharmacokinetic parameters of norethindrone/estradiol were not affected when a single dose of norethindrone 1 mg/estradiol 75 micrograms was administered in 10 healthy women who were receiving thalidomide 200 mg/day (at steady state levels).
    Methocarbamol: Thalidomide frequently causes drowsiness and somnolence and may enhance the sedative activity of methocarbamol.
    Metoprolol: Thalidomide and other agents that slow cardiac conduction such as beta-blockers should be used cautiously due to the potential for additive bradycardia.
    Metronidazole: Thalidomide and other agents that cause peripheral neuropathy such as metronidazole should be used cautiously due to the potential for additive effects.
    Mivacurium: Thalidomide and other agents that slow cardiac conduction such as neuromuscular blockers should be used cautiously due to the potential for additive bradycardia.
    Molindone: Avoid the concomitant use of thalidomide with antipsychotics due to the potential for additive sedative effects.
    Nadolol: Thalidomide and other agents that slow cardiac conduction such as beta-blockers should be used cautiously due to the potential for additive bradycardia.
    Nalbuphine: Avoid the concomitant use of thalidomide with other central nervous system depressants such as nalbuphine due to the potential for additive sedative effects.
    Nebivolol: Thalidomide and other agents that slow cardiac conduction such as beta-blockers should be used cautiously due to the potential for additive bradycardia.
    Nebivolol; Valsartan: Thalidomide and other agents that slow cardiac conduction such as beta-blockers should be used cautiously due to the potential for additive bradycardia.
    Nefazodone: Avoid the concomitant use of thalidomide with other central nervous system depressants such as nefazodone due to the potential for additive sedative effects.
    Neuromuscular blockers: Thalidomide and other agents that slow cardiac conduction such as neuromuscular blockers should be used cautiously due to the potential for additive bradycardia.
    Nicardipine: Thalidomide and other agents that slow cardiac conduction such as calcium-channel blockers should be used cautiously due to the potential for additive bradycardia.
    Nifedipine: Thalidomide and other agents that slow cardiac conduction such as calcium-channel blockers should be used cautiously due to the potential for additive bradycardia.
    Nimodipine: Thalidomide and other agents that slow cardiac conduction such as calcium-channel blockers should be used cautiously due to the potential for additive bradycardia.
    Nisoldipine: Thalidomide and other agents that slow cardiac conduction such as calcium-channel blockers should be used cautiously due to the potential for additive bradycardia.
    Nizatidine: Thalidomide and other agents that slow cardiac conduction such as H2-blockers should be used cautiously due to the potential for additive bradycardia.
    Non-oral combination contraceptives: Thalidomide and hormone contraceptives should be used cautiously due an increased risk of thromboembolism. The pharmacokinetic parameters of norethindrone/estradiol were not affected when a single dose of norethindrone 1 mg/estradiol 75 micrograms was administered in 10 healthy women who were receiving thalidomide 200 mg/day (at steady state levels).
    Norethindrone: Thalidomide and hormone contraceptives should be used cautiously due an increased risk of thromboembolism. The pharmacokinetic parameters of norethindrone/estradiol were not affected when a single dose of norethindrone 1 mg/estradiol 75 micrograms was administered in 10 healthy women who were receiving thalidomide 200 mg/day (at steady state levels).
    Norgestrel: Thalidomide and hormone contraceptives should be used cautiously due an increased risk of thromboembolism. The pharmacokinetic parameters of norethindrone/estradiol were not affected when a single dose of norethindrone 1 mg/estradiol 75 micrograms was administered in 10 healthy women who were receiving thalidomide 200 mg/day (at steady state levels).
    Nortriptyline: Avoid the concomitant use of thalidomide with other central nervous system depressants such as tricyclic antidepressants (TCAs) due to the potential for additive sedative effects. Additionally, co-administration of thalidomide and other agents that slow cardiac conduction such as TCAs may increase the potential for additive bradycardia.
    Opiate Agonists: Avoid the concomitant use of thalidomide with opiate agonists; antihistamines; antipsychotics; anxiolytics, sedatives, and hypnotics; and other central nervous system depressants due to the potential for additive sedative effects.
    Oral Contraceptives: Thalidomide and hormone contraceptives should be used cautiously due an increased risk of thromboembolism. The pharmacokinetic parameters of norethindrone/estradiol were not affected when a single dose of norethindrone 1 mg/estradiol 75 micrograms was administered in 10 healthy women who were receiving thalidomide 200 mg/day (at steady state levels).
    Oritavancin: Thalidomide is metabolized by CYP2C19; oritavancin is a weak CYP2C19 inhibitor. Coadministration may result in elevated thalidomide plasma concentrations. If these drugs are administered concurrently, monitor patients for signs of thalidomide toxicity, such as increased fatigue, drowsiness, or neuropathy.
    Paclitaxel: Thalidomide and other agents that cause peripheral neuropathy such as paclitaxel should be used cautiously due to the potential for additive effects.
    Pamidronate: In patients with multiple myeloma, the risk of renal dysfunction may be higher in patients taking both pamidronate and thalidomide.
    Pancuronium: Thalidomide and other agents that slow cardiac conduction such as neuromuscular blockers should be used cautiously due to the potential for additive bradycardia.
    Penbutolol: Thalidomide and other agents that slow cardiac conduction such as beta-blockers should be used cautiously due to the potential for additive bradycardia.
    Pentazocine: Avoid the concomitant use of thalidomide with other central nervous system depressants such as pentazocine due to the potential for additive sedative effects.
    Pentazocine; Naloxone: Avoid the concomitant use of thalidomide with other central nervous system depressants such as pentazocine due to the potential for additive sedative effects.
    Perindopril; Amlodipine: Thalidomide and other agents that slow cardiac conduction such as calcium-channel blockers should be used cautiously due to the potential for additive bradycardia.
    Perphenazine; Amitriptyline: Avoid the concomitant use of thalidomide with other central nervous system depressants such as tricyclic antidepressants (TCAs) due to the potential for additive sedative effects. Additionally, co-administration of thalidomide and other agents that slow cardiac conduction such as TCAs may increase the potential for additive bradycardia.
    Phenothiazines: Avoid the concomitant use of thalidomide with opiate agonists; antihistamines; antipsychotics; anxiolytics, sedatives, and hypnotics; and other central nervous system depressants due to the potential for additive sedative effects.
    Phenoxybenzamine: Thalidomide and other agents that slow cardiac conduction such as alpha-blockers should be used cautiously due to the potential for additive bradycardia.
    Phentolamine: Thalidomide and other agents that slow cardiac conduction such as alpha-blockers should be used cautiously due to the potential for additive bradycardia.
    Phenylephrine; Promethazine: Thalidomide frequently causes drowsiness and somnolence and may enhance the sedative activity of phenothiazines.
    Phenytoin: Avoid the concomitant use of thalidomide with other central nervous system depressants such as phenytoin due to the potential for additive sedative effects. Additionally, co-administration of thalidomide and agents that cause peripheral neuropathy such as phenytoin may increase the potential for additive neuropathy.
    Pimozide: Avoid the concomitant use of thalidomide with antipsychotics due to the potential for additive sedative effects.
    Pindolol: Thalidomide and other agents that slow cardiac conduction such as beta-blockers should be used cautiously due to the potential for additive bradycardia.
    Pramipexole: Avoid the concomitant use of thalidomide with other central nervous system depressants such as pramipexole due to the potential for additive sedative effects.
    Prazosin: Thalidomide and other agents that slow cardiac conduction such as alpha-blockers should be used cautiously due to the potential for additive bradycardia.
    Promethazine: Thalidomide frequently causes drowsiness and somnolence and may enhance the sedative activity of phenothiazines.
    Propranolol: Thalidomide and other agents that slow cardiac conduction such as beta-blockers should be used cautiously due to the potential for additive bradycardia.
    Protriptyline: Avoid the concomitant use of thalidomide with other central nervous system depressants such as tricyclic antidepressants (TCAs) due to the potential for additive sedative effects. Additionally, co-administration of thalidomide and other agents that slow cardiac conduction such as TCAs may increase the potential for additive bradycardia.
    Ramelteon: Avoid the concomitant use of thalidomide with anxiolytics, sedatives, and hypnotics due to the potential for additive sedative effects.
    Ranitidine: Thalidomide and other agents that slow cardiac conduction such as H2-blockers should be used cautiously due to the potential for additive bradycardia.
    Rapacuronium: Thalidomide and other agents that slow cardiac conduction such as neuromuscular blockers should be used cautiously due to the potential for additive bradycardia.
    Reserpine: Avoid the concomitant use of thalidomide with other central nervous system depressants such as reserpine due to the potential for additive sedative effects.
    Rocuronium: Thalidomide and other agents that slow cardiac conduction such as neuromuscular blockers should be used cautiously due to the potential for additive bradycardia.
    Ropinirole: Avoid the concomitant use of thalidomide with other central nervous system depressants such as ropinirole due to the potential for additive sedative effects.
    Sedating H1-blockers: Avoid the concomitant use of thalidomide with opiate agonists; antihistamines; antipsychotics; anxiolytics, sedatives, and hypnotics; and other central nervous system depressants due to the potential for additive sedative effects.
    Skeletal Muscle Relaxants: Avoid the concomitant use of thalidomide with other central nervous system depressants such as skeletal muscle relaxants due to the potential for additive sedative effects.
    Sotalol: Thalidomide and other agents that slow cardiac conduction such as beta-blockers should be used cautiously due to the potential for additive bradycardia.
    Succinylcholine: Thalidomide and other agents that slow cardiac conduction such as neuromuscular blockers should be used cautiously due to the potential for additive bradycardia.
    Terazosin: Thalidomide and other agents that slow cardiac conduction such as alpha-blockers should be used cautiously due to the potential for additive bradycardia.
    Thiothixene: Avoid the concomitant use of thalidomide with antipsychotics due to the potential for additive sedative effects.
    Timolol: Thalidomide and other agents that slow cardiac conduction such as beta-blockers should be used cautiously due to the potential for additive bradycardia.
    Tizanidine: Thalidomide frequently causes drowsiness and somnolence and may enhance the sedative activity of tizanidine.
    Tolcapone: Avoid the concomitant use of thalidomide with other central nervous system depressants such as tolcapone due to the potential for additive sedative effects.
    Tramadol: Avoid the concomitant use of thalidomide with other central nervous system depressants such as tramadol due to the potential for additive sedative effects.
    Trandolapril; Verapamil: Thalidomide and other agents that slow cardiac conduction such as calcium-channel blockers should be used cautiously due to the potential for additive bradycardia.
    Trimipramine: Avoid the concomitant use of thalidomide with other central nervous system depressants such as tricyclic antidepressants (TCAs) due to the potential for additive sedative effects. Additionally, co-administration of thalidomide and other agents that slow cardiac conduction such as TCAs may increase the potential for additive bradycardia.
    Tubocurarine: Thalidomide and other agents that slow cardiac conduction such as neuromuscular blockers should be used cautiously due to the potential for additive bradycardia.
    Vecuronium: Thalidomide and other agents that slow cardiac conduction such as neuromuscular blockers should be used cautiously due to the potential for additive bradycardia.
    Verapamil: Thalidomide and other agents that slow cardiac conduction such as calcium-channel blockers should be used cautiously due to the potential for additive bradycardia.
    Vincristine Liposomal: Thalidomide and other agents that cause peripheral neuropathy such as vincristine should be used cautiously due to the potential for additive effects.
    Vincristine: Thalidomide and other agents that cause peripheral neuropathy such as vincristine should be used cautiously due to the potential for additive effects.
    Zoledronic Acid: In multiple myeloma patients, the risk of renal dysfunction may be increased when zoledronic acid is used in combination with thalidomide.

    PREGNANCY AND LACTATION

    Pregnancy

    Counsel patients about the reproductive risk of thalidomide and discuss contraception requirements with both men and females of childbearing potential. Thalidomide may cause severe birth defects or fetal death; defects may occur with even 1 dose to a pregnant female. Thalidomide therapy should not be initiated in females of reproductive potential until negative results from 2 pregnancy tests are confirmed. The first test should be done within 10 to 14 days and the second test within 24 hours prior to prescribing thalidomide. Once treatment is started, pregnancy testing should occur weekly during the first month of treatment, then every month in females with regular menstrual cycles. If the female patient's menstrual cycles are irregular, pregnancy testing should occur every 2 weeks. If any woman of reproductive potential experiences menstrual irregularity or misses her period while receiving thalidomide, treatment must be discontinued and pregnancy testing and counseling should be performed. Effective contraception must be used by all females of reproductive potential for at least 4 weeks before beginning treatment, during therapy and dosage interruptions, and for 4 weeks following discontinuation of therapy. Women must commit to abstain from heterosexual intercourse or to use 2 methods of reliable birth control, including at least 1 highly effective method (e.g., intrauterine devices (IUD), hormonal contraception, tubal ligation, or partner's vasectomy) and 1 additional effective method (e.g., latex condom, diaphragm, or cervical cap). These contraceptive measures should be taken even in patients with a history of infertility, unless a hysterectomy has been performed. Women requiring medications that may interfere with the effectiveness of hormonal contraception (e.g., HIV-protease inhibitors, griseofulvin, modafinil, penicillins, rifampin, rifabutin, phenytoin, carbamazepine, or certain herbal supplements such as St. John’s Wort) must use 2 other effective or highly effective methods of contraception. Some contraceptive methods such as IUD or contraceptive implants may increase the risk for infection or bleeding either at insertion, removal, or during use. Additionally, estrogen-containing contraceptives may increase the risk of blood clot formation. Consider these risks when choosing contraceptive measures. Thalidomide is passed into the semen and there is a potential for male-mediated teratogenicity. Therefore, a male patient must use barrier contraception (latex condom) during sexual intercourse with a woman of reproductive potential while on therapy and for 4 weeks after discontinuing thalidomide therapy, even if he has undergone successful vasectomy. Male patients should not donate sperm while taking thalidomide and for 4 weeks after stopping therapy. If the patient is less than 18 years of age, their parent or legal guardian must agree to ensure compliance with these conditions.

    MECHANISM OF ACTION

    The complete mechanism of action of thalidomide is not completely understood. In vitro and in vivo studies show that thalidomide selectively reduces levels of tumor necrosis factor alpha (TNF-alpha) by accelerating the degradation of TNF-alpha messenger RNA (mRNA) encoding protein. Thalidomide reduces the half-life of the TNF-alpha mRNA encoding protein from 30 minutes to about 17 minutes. Thalidomide does not affect mRNA levels of interleukin (IL)—1 or IL—6. TNF-alpha has been associated with the pathology and symptoms of many different diseases including ENL, AIDS, cancers, graft-versus-host disease, tuberculosis and malaria. Symptoms associated with TNF-alpha include fever, weight loss and characteristics of septic shock resulting in endothelial damage, disturbances of lipid metabolism and release of IL—1. The mechanism of thalidomide is different from the proposed mechanism of pentoxifylline or corticosteroids, which suppress lipopolysaccharide-induced TNF-alpha RNA transcription and translation, respectively. Thalidomide also increases levels of IL—2 and interferon-gamma, augment NK-like activity, and inhibit IL—12 production. Recently, thalidomide has been recognized as an inhibitor of angiogenesis due to inhibition of basic fibroblast growth factor (bFGF). bFGF has been shown to stimulate limb growth and its inhibition may be the basis for the limb defects associated with thalidomide.

    PHARMACOKINETICS

    Thalidomide is administered orally. It is 55—66% protein bound. Thalidomide appears to undergo non-enzymatic hydrolysis in the plasma followed by urinary excretion. Approximately 94% of the radioactivity was recovered at day 8 following a single 400-mg oral dose of 14C-thalidomide; most of the radioactivity was excreted within 48 hours. About 92% of the radioactive dose was excreted in the urine, primarily as hydrolytic metabolites; less than 3.5% of the dose was excreted as unchanged thalidomide. Fecal excretion accounted for less than 2% of the radioactive dose. The half-life ranged from 5.5—7.3 hours in healthy subjects (n = 14) and patients with Hansen's disease (n = 6) who received a single dose of thalidomide (50—400 mg).
     
    Affected cytochrome P450 isoenzymes: none at therapeutic concentrations
    Thalidomide undergoes insignificant metabolism by human CYP450 isoenzymes at therapeutic concentrations. Therefore, clinically important interactions with other CYP450 substrates, inhibitors, or inducers are not expected.

    Oral Route

    Thalidomide is slowly absorbed from the GI tract. The exact bioavailability has not been determined due to the poor aqueous solubility of thalidomide. Following a single dose of thalidomide 50 mg, 200 mg, or 400 mg, the AUC values ranged from 4.9—36.4 micrograms (mcg) X hr/mL in 14 healthy subjects; the AUC value was 46.4 mcg X hr/mL in 6 patients with Hansen's disease (leprosy) who received a single 400-mg dose of thalidomide. Additionally, the Cmax and Tmax values ranged from 0.62—2.82 mcg/mL and 2.9—4.3 hours, respectively, in healthy subjects; the Cmax and Tmax values were 3.44 mcg/mL and 5.7 hours, respectively, in patients with Hansen's disease. Administering thalidomide with a high-fat meal increased the Tmax to about 6 hours; however, the AUC and Cmax values changed by less than 10%.