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  • CLASSES

    Agents for Leprosy
    Immunomodulators, Angiogenesis Inhibitors

    BOXED WARNING

    Myocardial infarction, stroke, thromboembolism

    Venous (e.g., pulmonary embolism, deep vein thrombosis) and arterial (e.g., stroke, myocardial infarction (MI)) thromboembolism 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.

    Intrauterine fetal death, pregnancy

    Thalidomide is contraindicated for use during pregnancy. Thalidomide is a known human teratogen and even a single dose taken by a pregnant woman may cause severe birth defects. 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. It may cause birth defects or intrauterine fetal death if administered during pregnancy. In order to prevent fetal exposure, 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 pregnancy does occur during treatment, immediately discontinue thalidomide. Prescribers are encouraged to report all cases of suspected fetal exposure to Celgene Corporation 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.[60079]

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

    Counsel patients about the reproductive risk and contraception requirements during thalidomide treatment. Do not initiate therapy in females of reproductive potential until pregnancy testing is performed twice with confirmed negative results. Administer the first test within 10 to 14 days and the second test 24 hours prior to prescribing thalidomide. Once treatment is started, continue pregnancy testing weekly during the first 4 weeks of treatment, then every 4 weeks in females with regular menstrual cycles and every 2 weeks in females with irregular menstrual cycles. Effective contraception must be used by all females of reproductive potential for at least 4 weeks before beginning treatment, during therapy and dosage interruptions, and for 4 weeks following discontinuation of therapy. Women must commit to abstain continuously from heterosexual sexual intercourse or use 2 methods of reliable birth control, including at least 1 highly effective method (e.g., intrauterine device (IUD), hormonal contraception, tubal ligation, or partner's vasectomy) and 1 additional effective method (e.g., latex condom, diaphragm, or cervical cap). Follow these contraceptive requirements even in patients with a history of fertility problems, unless a hysterectomy has been performed. Discontinue treatment, test for pregnancy, and counsel any woman of reproductive potential who experiences menstrual irregularity (e.g., dysfunctional uterine bleeding) or misses her period. Advise patients that if her doctor is not available, she can call 1-888-423-5436 for information. Thalidomide passes into semen and there is potential for male-mediated teratogenicity. Male patients must use barrier contraception (latex condom) during sexual intercourse with a woman of reproductive potential while on therapy, during interruptions, and for 4 weeks after discontinuing therapy, even if he has undergone a successful vasectomy. Male patients should be warned against sperm donation during thalidomide therapy and for 4 weeks after stopping therapy. Infertility may occur in males based on data from animal studies.[60079]

    DEA CLASS

    Rx

    DESCRIPTION

    Biologic response modifier with immunomodulatory, antiangiogenic, and antitumor properties
    Used for patients with erythema nodosum leprosum; also used in combination with dexamethasone for the treatment of patients with newly diagnosed multiple myeloma
    Known teratogen that may cause birth defects or embryo-fetal death; routine testing required; prescribers, pharmacies, and patients must register in the THALOMID REMS program (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 to 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 greater than 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 to 4 repeated monthly (median time to max response, 4 months; duration of therapy range, 4 to 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 to 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 to 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 to 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 to 14 and 100 mg/day on days 15 to 28) plus bortezomib 1.3 mg/m2 IV on days 1, 4, 8, and 11 and dexamethasone 40 mg on days 1 to 4 and 9 to 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 newly diagnosed multiple myeloma as induction and consolidation therapy in patients who are eligible for autologous stem-cell transplant, in combination with daratumumab, bortezomib, and dexamethasone†.
    Oral dosage
    Adults 65 years and younger

    100 mg orally daily as continuous therapy in combination with daratumumab, bortezomib, and dexamethasone was evaluated in a multicenter, randomized, phase 3 trial (n = 1,085; the CASSIOPEIA trial). In this trial, thalidomide was administered with up to four 28-day induction therapy cycles and two 28-day consolidation therapy cycles of daratumumab (16 mg/kg IV weekly in induction cycles 1 and 2; 16 mg/kg IV every 2 weeks in induction cycles 3 and 4 and for both consolidation cycles), bortezomib (1.3 mg/m2 subcutaneously on days 1, 4, 8, and 11 in each induction and consolidation cycle), and dexamethasone (40 mg PO/IV on days 1, 2, 8, 9, 15, 16, 22, and 23 in induction cycles 1 and 2; 40 mg PO/IV on days 1 and 2 and 20 mg PO/IV on days 8, 9, 15, and 16 in induction cycles 3 and 4; and 20 mg PO/IV on days 1, 2, 8, 9, 15, and 16 for both consolidation cycles). Consolidation therapy was begun after hematopoietic reconstitution but not earlier than 30 days after transplant.

    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 to 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 to 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 to 600 mg/day PO. In patients with HIV-related aphthous ulcers, more than 90% of patients experienced healing of ulcers, decreased pain, improved appetite and increased sense of well-being following 7 to 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 4 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 less than 67 kg), gradually increased to a target dose of 3 mg/kg PO 4 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 escalated by 200 mg/day every 2 weeks as tolerated to a maximum of 1,000 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 to 1,200 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 to 1,200 mg PO per day was given with carmustine 200 mg/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 to 700 mg/m2 (depending on anti-epileptic regimen). Additionally, temozolomide 150 to 200 mg/m2/day PO on days 1 to 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 to 200 mg PO per day every 7 to 14 days to a maximum dose of 1,200 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 to 400 mg/day PO until clinical response is achieved have been given. Doses are gradually tapered and maintained at 25 to 100 mg PO once daily. Retreatment for relapse with thalidomide 25 to 100 mg/day PO is usually effective.

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

    Thalidomide 100 to 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 to 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 refractory Crohn's disease†.
    NOTE: Thalidomide has been designated an orphan drug by the FDA for this indication.
    Oral dosage
    Adults

    Safety and efficacy not established. Various treatment regimens have been described in the literature, in the range of 50 mg to 300 mg/day PO. Reserve for induction therapy in patients refractory to guideline recommended therapies. Due to side effects and teratogenic potential, as well as lack of evidence for maintenance of remission, thalidomide is not included in current guidelines for the induction or maintenance management of Crohn's disease in adults.

    For the treatment of peripheral T-cell lymphoma (PTCL)†.
    For the first-line treatment of PTCL in combination with gemcitabine, cisplatin, and prednisone†.
    Oral dosage
    Adults and Adolescents 14 years and older

    200 mg orally daily in combination with gemcitabine (800 mg/m2 IV over 30 minutes on days 1 and 8), cisplatin (25 mg/m2 IV on days 1, 2, and 3), and prednisone (60 mg/m2 PO on days 1, 2, 3, 4, and 5) was evaluated in patients with previously untreated PTCL in a randomized trial. Cycles of therapy were repeated every 21 days until disease progression or for up to 6 cycles. Thalidomide was initiated at 50 mg/day and increased in 50-mg increments daily until 200 mg/day. Patients received aspirin 100 mg/day PO during thalidomide therapy. The use of granulocyte colony-stimulation factor was permitted as indicated.

    †Indicates off-label use

    MAXIMUM DOSAGE

    Adults

    Multiple myeloma: 200 mg/day PO.Erythema nodosum leprosum: 400 mg/day PO.

    Geriatric

    Multiple myeloma: 200 mg/day PO.Erythema nodosum leprosum: 400 mg/day PO.

    Adolescents

    Erythema nodosum leprosum: 400 mg/day PO.

    Children

    12 years of age: Erythema nodosum leprosum, 400 mg/day PO.
    1 to 11 years: Safety and efficacy not 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.
    Hazardous Drugs Classification
    NIOSH 2016 List: Group 2
    NIOSH (Draft) 2020 List: Table 1
    Observe and exercise appropriate precautions for handling, preparation, administration, and disposal of hazardous drugs.
    Use gloves to handle. Cutting, crushing, or otherwise manipulating tablets/capsules will increase exposure.
    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.
    Emetic Risk
    Minimal/Low
    Administer prn antiemetics as necessary.

    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 between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F

    CONTRAINDICATIONS / PRECAUTIONS

    Serious rash, thalidomide hypersensitivity

    Use of thalidomide is contraindicated in patients with a history of thalidomide hypersensitivity or hypersensitivity to any component of the product. Hypersensitivity reactions (e.g., angioedema and anaphylactic reactions) have been reported with thalidomide therapy. Hold therapy if a severe reaction occurs; discontinue thalidomide if the reaction recurs after resuming therapy. Do not resume therapy in patients who develop angioedema or anaphylaxis. Serious rash including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug reaction with eosinophilia and systemic symptoms (DRESS) has been reported; some cases were fatal. Hold or consider discontinuing therapy in patients who develop a grade 2 or 3 skin rash. Discontinue therapy in patients who develop a grade 4 skin rash, exfoliative or bullous rash, or other severe cutaneous toxicity (e.g., SJS, TEN, or DRESS); do not resume therapy in these patients.[60079]

    Myocardial infarction, stroke, thromboembolism

    Venous (e.g., pulmonary embolism, deep vein thrombosis) and arterial (e.g., stroke, myocardial infarction (MI)) thromboembolism 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

    Severe and irreversible peripheral neuropathy may occur with thalidomide therapy. Symptoms may occur during therapy or after treatment is discontinued; the correlation of neuropathy with cumulative dose is unclear. Use thalidomide and other medications associated with neuropathy together with caution due to the risk of additive toxicity. Examine patients for signs of neuropathy monthly for the first 3 months and then periodically thereafter. Consider electrophysiologic testing consisting of measurement of sensory nerve action potential (SNAP) amplitudes at baseline and then every 6 months to detect asymptomatic neuropathies. In patients with multiple myeloma who develop peripheral neuropathy, consider therapy interruption or a dose reduction. Therapy interruption, a dose reduction, or therapy discontinuation may be necessary in any patient who develops grade 3 or 4 peripheral neuropathy.[60079]

    Driving or operating machinery, ethanol ingestion

    Thalidomide may cause drowsiness and somnolence. Therefore, advise patients about the risks of driving or operating machinery during therapy and to avoid the use of medications or substances (e.g., ethanol ingestion) that may also cause drowsiness. Consider therapy interruption or a dose reduction in patients with multiple myeloma who develop somnolence.[60079]

    Orthostatic hypotension

    Thalidomide may cause dizziness and orthostatic hypotension; advise patients to sit upright for a few minutes before standing up from a lying or seated position to lower the risk of these side effects.[60079]

    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.

    Human immunodeficiency virus (HIV) infection

    Thalidomide use 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.[60079]

    Seizure disorder, seizures

    Seizures have been reported in patients who received thalidomide; most patients had disorders that predisposed them to seizure activity. It is unknown whether thalidomide has any epileptogenic influence. Closely monitor patients with a history of seizure disorder or with risk factors for developing seizures for clinical changes that could precipitate acute seizure activity.[60079]

    Accidental exposure

    Females of reproductive potential should avoid contact with thalidomide capsules; however, there is no specific data available regarding the reproductive risks of accidental exposure (e.g., cutaneous absorption or inhalation of thalidomide). Healthcare providers or other caregivers who are exposed to body fluids from patients receiving thalidomide should wash the affected area with soap and water. Advise anyone administering thalidomide capsules to take appropriate precautions (e.g., wear gloves) to avoid cutaneous exposure.[60079]

    Blood donation

    Advise male and female patients to avoid blood donation during thalidomide therapy, including during therapy interruption, and for 4 weeks after the last thalidomide dose due to the risk of fetal exposure and birth defects if a pregnant woman is administered donated blood.[60079]

    Treatment outside of a clinical trial

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

    Tumor lysis syndrome (TLS)

    Monitor patients at risk for tumor lysis syndrome (TLS) (e.g., high tumor burden prior to treatment). Take precautionary measures (e.g., hydration, uric acid lowering therapy) as appropriate in these patients.[60079]

    Bradycardia

    Bradycardia has been reported with thalidomide use. Use thalidomide and other medications that decrease heart rate together with caution as concomitant use may result in an additive risk for bradycardia. Monitor all patients for signs and symptoms of bradycardia and syncope. Therapy interruption or discontinuation may be necessary in patients who develop bradycardia.[60079]

    Geriatric

    Adverse events including atrial fibrillation, constipation, fatigue, nausea, hypokalemia, deep venous thrombosis, hyperglycemia, pulmonary embolism, and asthenia occurred more often in geriatric patients 65 years and older with multiple myeloma who received thalidomide compared with younger patients in a clinical study.

    Intrauterine fetal death, pregnancy

    Thalidomide is contraindicated for use during pregnancy. Thalidomide is a known human teratogen and even a single dose taken by a pregnant woman may cause severe birth defects. 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. It may cause birth defects or intrauterine fetal death if administered during pregnancy. In order to prevent fetal exposure, 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 pregnancy does occur during treatment, immediately discontinue thalidomide. Prescribers are encouraged to report all cases of suspected fetal exposure to Celgene Corporation 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.[60079]

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

    Counsel patients about the reproductive risk and contraception requirements during thalidomide treatment. Do not initiate therapy in females of reproductive potential until pregnancy testing is performed twice with confirmed negative results. Administer the first test within 10 to 14 days and the second test 24 hours prior to prescribing thalidomide. Once treatment is started, continue pregnancy testing weekly during the first 4 weeks of treatment, then every 4 weeks in females with regular menstrual cycles and every 2 weeks in females with irregular menstrual cycles. Effective contraception must be used by all females of reproductive potential for at least 4 weeks before beginning treatment, during therapy and dosage interruptions, and for 4 weeks following discontinuation of therapy. Women must commit to abstain continuously from heterosexual sexual intercourse or use 2 methods of reliable birth control, including at least 1 highly effective method (e.g., intrauterine device (IUD), hormonal contraception, tubal ligation, or partner's vasectomy) and 1 additional effective method (e.g., latex condom, diaphragm, or cervical cap). Follow these contraceptive requirements even in patients with a history of fertility problems, unless a hysterectomy has been performed. Discontinue treatment, test for pregnancy, and counsel any woman of reproductive potential who experiences menstrual irregularity (e.g., dysfunctional uterine bleeding) or misses her period. Advise patients that if her doctor is not available, she can call 1-888-423-5436 for information. Thalidomide passes into semen and there is potential for male-mediated teratogenicity. Male patients must use barrier contraception (latex condom) during sexual intercourse with a woman of reproductive potential while on therapy, during interruptions, and for 4 weeks after discontinuing therapy, even if he has undergone a successful vasectomy. Male patients should be warned against sperm donation during thalidomide therapy and for 4 weeks after stopping therapy. Infertility may occur in males based on data from animal studies.[60079]

    Breast-feeding

    It is not known if thalidomide is secreted in human milk or if it has effects on the breast-fed infant or on milk production. Due to the risk of serious adverse reactions in nursing infants, women should discontinue breast-feeding during thalidomide therapy.

    ADVERSE REACTIONS

    Severe

    thrombosis / Delayed / 13.0-22.5
    thromboembolism / Delayed / 0-22.5
    fatigue / Early / 0-17.0
    dyspnea / Early / 0-13.0
    hypocalcemia / Delayed / 0-11.0
    neutropenia / Delayed / 0-10.0
    confusion / Early / 0-9.0
    peripheral neuropathy / Delayed / 3.0-8.0
    constipation / Delayed / 3.0-8.0
    pulmonary embolism / Delayed / 7.0-7.0
    infection / Delayed / 0-7.0
    leukopenia / Delayed / 0-6.0
    edema / Delayed / 0-6.0
    weakness / Early / 0-6.0
    asthenia / Delayed / 0-5.0
    nausea / Early / 0-5.0
    atrial fibrillation / Early / 5.0-5.0
    anorexia / Delayed / 0-4.0
    rash / Early / 0-4.0
    weight loss / Delayed / 0-3.0
    stroke / Early / 2.6-2.6
    tremor / Early / 0-2.0
    hyperbilirubinemia / Delayed / 0-2.0
    anxiety / Delayed / 0-2.0
    vertigo / Early / 0-2.0
    myocardial infarction / Delayed / 1.3-1.3
    fever / Early / 0-1.0
    xerostomia / Early / 0-1.0
    dizziness / Early / 0-1.0
    agitation / Early / 0-1.0
    weight gain / Delayed / 0-1.0
    teratogenesis / Delayed / 10.0
    fetal death / Delayed / Incidence not known
    GI obstruction / Delayed / Incidence not known
    GI perforation / Delayed / Incidence not known
    peptic ulcer / Delayed / Incidence not known
    erythema nodosum / Delayed / Incidence not known
    toxic epidermal necrolysis / Delayed / Incidence not known
    myocarditis / Delayed / Incidence not known
    Stevens-Johnson syndrome / Delayed / Incidence not known
    pericarditis / Delayed / Incidence not known
    skin necrosis / Early / Incidence not known
    erythema multiforme / Delayed / Incidence not known
    Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) / Delayed / Incidence not known
    exfoliative dermatitis / Delayed / Incidence not known
    pancytopenia / Delayed / Incidence not known
    GI bleeding / Delayed / Incidence not known
    seizures / Delayed / Incidence not known
    tumor lysis syndrome (TLS) / Delayed / Incidence not known
    hyperkalemia / Delayed / Incidence not known
    pulmonary hypertension / Delayed / Incidence not known
    progressive multifocal leukoencephalopathy / Delayed / Incidence not known
    hepatitis B exacerbation / Delayed / Incidence not known
    leukemia / Delayed / Incidence not known
    new primary malignancy / Delayed / Incidence not known
    lymphoma / Delayed / Incidence not known
    bradycardia / Rapid / Incidence not known
    suicidal ideation / Delayed / Incidence not known
    pleural effusion / Delayed / Incidence not known
    SIADH / Delayed / Incidence not known
    cyanosis / Early / Incidence not known
    hearing loss / Delayed / Incidence not known
    oliguria / Early / Incidence not known
    renal failure (unspecified) / Delayed / Incidence not known
    organ transplant rejection / Delayed / Incidence not known
    angioedema / Rapid / Incidence not known
    anaphylactoid reactions / Rapid / Incidence not known

    Moderate

    peripheral edema / Delayed / 0-34.0
    hyperglycemia / Delayed / 0-15.0
    depression / Delayed / 0-10.0
    hypokalemia / Delayed / 3.0-3.0
    hyperesthesia / Delayed / Incidence not known
    neuritis / Delayed / Incidence not known
    stomatitis / Delayed / Incidence not known
    hepatitis / Delayed / Incidence not known
    bullous rash / Early / Incidence not known
    lymphadenopathy / Delayed / Incidence not known
    pneumonitis / Delayed / Incidence not known
    anemia / Delayed / Incidence not known
    lymphopenia / Delayed / Incidence not known
    bleeding / Early / Incidence not known
    thrombocytopenia / Delayed / Incidence not known
    eosinophilia / Delayed / Incidence not known
    splenomegaly / Delayed / Incidence not known
    sinus tachycardia / Rapid / Incidence not known
    hypertension / Early / Incidence not known
    peripheral vasodilation / Rapid / Incidence not known
    hypotension / Rapid / Incidence not known
    orthostatic hypotension / Delayed / Incidence not known
    hypomagnesemia / Delayed / Incidence not known
    hyponatremia / Delayed / Incidence not known
    hyperuricemia / Delayed / Incidence not known
    hypophosphatemia / Delayed / Incidence not known
    elevated hepatic enzymes / Delayed / Incidence not known
    hypothyroidism / Delayed / Incidence not known
    impotence (erectile dysfunction) / Delayed / Incidence not known
    galactorrhea / Delayed / Incidence not known
    amnesia / Delayed / Incidence not known
    psychosis / Early / Incidence not known
    euphoria / Early / Incidence not known
    diabetes mellitus / Delayed / Incidence not known
    interstitial lung disease / Delayed / Incidence not known
    hypertonia / Delayed / Incidence not known
    myasthenia / Delayed / Incidence not known
    amblyopia / Delayed / Incidence not known
    nystagmus / Delayed / Incidence not known
    blurred vision / Early / Incidence not known
    pyuria / Delayed / Incidence not known
    hematuria / Delayed / Incidence not known
    proteinuria / Delayed / Incidence not known

    Mild

    xerosis / Delayed / 0-21.0
    myalgia / Early / 0-17.0
    arthralgia / Delayed / 0-13.0
    headache / Early / 12.5-12.5
    paresthesias / Delayed / 0-12.0
    dyspepsia / Early / 0-11.0
    pruritus / Rapid / 0-8.0
    malaise / Early / 0-8.0
    chills / Rapid / 0-4.0
    abdominal pain / Early / 0-4.0
    diarrhea / Early / 0-4.0
    maculopapular rash / Early / 0-4.0
    rhinitis / Early / 0-4.0
    sinusitis / Delayed / 0-4.0
    pharyngitis / Delayed / 0-4.0
    back pain / Delayed / 0-4.0
    syncope / Early / 3.0-3.0
    hypoesthesia / Delayed / Incidence not known
    vomiting / Early / Incidence not known
    eructation / Early / Incidence not known
    flatulence / Early / Incidence not known
    alopecia / Delayed / Incidence not known
    hyperhidrosis / Delayed / Incidence not known
    purpura / Delayed / Incidence not known
    seborrhea / Delayed / Incidence not known
    acne vulgaris / Delayed / Incidence not known
    ichthyosis / Delayed / Incidence not known
    leukocytosis / Delayed / Incidence not known
    petechiae / Delayed / Incidence not known
    epistaxis / Delayed / Incidence not known
    carpal tunnel syndrome / Delayed / Incidence not known
    gynecomastia / Delayed / Incidence not known
    amenorrhea / Delayed / Incidence not known
    insomnia / Early / Incidence not known
    cough / Delayed / Incidence not known
    muscle cramps / Delayed / Incidence not known
    photosensitivity / Delayed / Incidence not known
    ocular pain / Early / Incidence not known
    diplopia / Early / Incidence not known
    xerophthalmia / Early / Incidence not known
    tinnitus / Delayed / Incidence not known
    increased urinary frequency / Early / Incidence not known
    urticaria / Rapid / Incidence not known

    DRUG INTERACTIONS

    Acebutolol: (Moderate) 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: (Moderate) Thalidomide frequently causes drowsiness and somnolence and may enhance the sedative activity of dichloralphenazone.
    Acetaminophen; Pentazocine: (Major) Avoid the concomitant use of thalidomide with other central nervous system depressants such as pentazocine due to the potential for additive sedative effects.
    Aliskiren; Amlodipine: (Moderate) 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: (Moderate) 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: (Moderate) Thalidomide and other agents that slow cardiac conduction such as alpha-blockers should be used cautiously due to the potential for additive bradycardia.
    Amiodarone: (Moderate) Thalidomide and other agents that cause peripheral neuropathy such as amiodarone should be used cautiously due to the potential for additive effects.
    Amitriptyline: (Major) 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: (Moderate) 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: (Moderate) 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: (Moderate) 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; Celecoxib: (Moderate) 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: (Moderate) 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: (Moderate) 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; Hydrochlorothiazide, HCTZ: (Moderate) 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: (Major) The use of anxiolytics, sedatives, or hypnotics concomitantly with thalidomide may cause an additive sedative effect and should be avoided. Thalidomide frequently causes drowsiness and somnolence. Dose reductions may be required. Patients should be instructed to avoid situations where drowsiness may be a problem and not to take other medications that may cause drowsiness without adequate medical advice. Advise patients as to the possible impairment of mental and/or physical abilities required for the performance of hazardous tasks, such as driving a car or operating other complex or dangerous machinery.
    Atenolol: (Moderate) 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: (Moderate) Thalidomide and other agents that slow cardiac conduction such as beta-blockers should be used cautiously due to the potential for additive bradycardia.
    Azelastine: (Major) 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: (Major) 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: (Major) The use of barbiturate anxiolytics, sedatives, or hypnotics with thalidomide may cause an additive sedative effect and should be avoided. Thalidomide frequently causes drowsiness and somnolence. Dose reductions may be required. Patients should be instructed to avoid situations where drowsiness may be a problem and not to take other medications that may cause drowsiness without adequate medical advice. Advise patients as to the possible impairment of mental and/or physical abilities required for the performance of hazardous tasks, such as driving a car or operating other complex or dangerous machinery.
    Bendroflumethiazide; Nadolol: (Moderate) Thalidomide and other agents that slow cardiac conduction such as beta-blockers should be used cautiously due to the potential for additive bradycardia.
    Benzodiazepines: (Major) The use of benzodiazepine anxiolytics, sedatives, or hypnotics with thalidomide may cause an additive sedative effect and should be avoided. Thalidomide frequently causes drowsiness and somnolence. Dose reductions may be required. Patients should be instructed to avoid situations where drowsiness may be a problem and not to take other medications that may cause drowsiness without adequate medical advice. Advise patients as to the possible impairment of mental and/or physical abilities required for the performance of hazardous tasks, such as driving a car or operating other complex or dangerous machinery.
    Beta-blockers: (Moderate) Thalidomide and other agents that slow cardiac conduction such as beta-blockers should be used cautiously due to the potential for additive bradycardia.
    Betaxolol: (Moderate) 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: (Moderate) 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: (Moderate) Thalidomide and other agents that cause peripheral neuropathy such as metronidazole should be used cautiously due to the potential for additive effects.
    Bisoprolol: (Moderate) 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: (Moderate) Thalidomide and other agents that slow cardiac conduction such as beta-blockers should be used cautiously due to the potential for additive bradycardia.
    Bortezomib: (Moderate) 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: (Moderate) Thalidomide and other agents that slow cardiac conduction such as beta-blockers should be used cautiously due to the potential for additive bradycardia.
    Buspirone: (Major) Avoid the concomitant use of thalidomide with anxiolytics, sedatives, and hypnotics due to the potential for additive sedative effects.
    Butorphanol: (Major) Avoid the concomitant use of thalidomide with other central nervous system depressants such as butorphanol due to the potential for additive sedative effects.
    Butyrophenone: (Major) Avoid the concomitant use of thalidomide with antipsychotics due to the potential for additive sedative effects.
    Calcium Carbonate; Famotidine; Magnesium Hydroxide: (Moderate) Thalidomide and other agents that slow cardiac conduction such as H2-blockers should be used cautiously due to the potential for additive bradycardia.
    Calcium-channel blockers: (Moderate) Thalidomide and other agents that slow cardiac conduction such as calcium-channel blockers should be used cautiously due to the potential for additive bradycardia.
    Cannabidiol: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and thalidomide. CNS depressants can potentiate the effects of cannabidiol.
    Carbidopa; Levodopa; Entacapone: (Major) The use of thalidomide and COMT inhibitors may cause an additive sedative effect and should be avoided if possible. If concurrent treatment is needed, prescribers should monitor patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment. Patients should be advised to avoid driving or other tasks requiring mental alertness until they know how the combination affects them.
    Carteolol: (Moderate) Thalidomide and other agents that slow cardiac conduction such as beta-blockers should be used cautiously due to the potential for additive bradycardia.
    Carvedilol: (Moderate) Thalidomide and other agents that slow cardiac conduction such as beta-blockers should be used cautiously due to the potential for additive bradycardia.
    Cenobamate: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cenobamate and thalidomide. Concurrent use may result in additive CNS depression.
    Cetirizine: (Moderate) Concurrent use of cetirizine/levocetirizine with thalidomide should generally be avoided. Coadministration may increase the risk of CNS depressant-related side effects. If concurrent use is necessary, monitor for excessive sedation and somnolence.
    Cetirizine; Pseudoephedrine: (Moderate) Concurrent use of cetirizine/levocetirizine with thalidomide should generally be avoided. Coadministration may increase the risk of CNS depressant-related side effects. If concurrent use is necessary, monitor for excessive sedation and somnolence.
    Chlordiazepoxide; Amitriptyline: (Major) 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.
    Cimetidine: (Moderate) Thalidomide and other agents that slow cardiac conduction such as H2-blockers should be used cautiously due to the potential for additive bradycardia.
    Cisplatin: (Moderate) Monitor for peripheral neuropathy if coadministration of thalidomide and cisplatin is necessary. Both drugs can cause peripheral neuropathy, which may be additive.
    Clevidipine: (Moderate) 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: (Major) 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: (Major) It is unclear if concurrent use of other drugs known to cause neutropenia (e.g., antineoplastic agents) increases the risk or severity of clozapine-induced neutropenia. Because there is no strong rationale for avoiding clozapine in patients treated with these drugs, consider increased absolute neutrophil count (ANC) monitoring and consult the treating oncologist.
    COMT inhibitors: (Major) The use of thalidomide and COMT inhibitors may cause an additive sedative effect and should be avoided if possible. If concurrent treatment is needed, prescribers should monitor patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment. Patients should be advised to avoid driving or other tasks requiring mental alertness until they know how the combination affects them.
    Darbepoetin Alfa: (Moderate) Thalidomide and darbepoetin alfa should be used cautiously due an increased risk of thromboembolism.
    Denosumab: (Moderate) The safety and efficacy of denosumab use in patients with immunosuppression have not been evaluated. Patients receiving immunosuppressives along with denosumab may be at a greater risk of developing an infection and/or osteonecrosis of the jaw, a rare condition that has been reported during denosumab therapy.
    Desipramine: (Major) 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.
    Desogestrel; Ethinyl Estradiol: (Moderate) 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).
    Deutetrabenazine: (Moderate) Concurrent use of deutetrabenazine and drugs that can cause CNS depression, such as thalidomide, may have additive effects and worsen drowsiness or sedation. Advise patients about worsened somnolence and not to drive or perform other tasks requiring mental alertness until they know how deutetrabenazine affects them.
    Dexamethasone: (Moderate) Coadministration of dexamethasone with thalidomide should be employed cautiously, as toxic epidermal necrolysis has been reported with concomitant use.
    Dienogest; Estradiol valerate: (Moderate) 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).
    Difelikefalin: (Moderate) Monitor for dizziness, somnolence, mental status changes, and gait disturbances if concomitant use of difelikefalin with CNS depressants is necessary. Concomitant use may increase the risk for these adverse reactions.
    Digoxin: (Moderate) 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: (Moderate) 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: (Moderate) Thalidomide and other agents that cause peripheral neuropathy such as disulfiram should be used cautiously due to the potential for additive effects.
    Docetaxel: (Moderate) Thalidomide and other agents that cause peripheral neuropathy such as docetaxel should be used cautiously due to the potential for additive effects.
    Dorzolamide; Timolol: (Moderate) Thalidomide and other agents that slow cardiac conduction such as beta-blockers should be used cautiously due to the potential for additive bradycardia.
    Doxazosin: (Moderate) Thalidomide and other agents that slow cardiac conduction such as alpha-blockers should be used cautiously due to the potential for additive bradycardia.
    Doxepin: (Major) 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: (Moderate) 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; Estetrol: (Moderate) 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; Estradiol: (Moderate) 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: (Moderate) 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: (Moderate) 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).
    Elagolix; Estradiol; Norethindrone acetate: (Moderate) 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: (Moderate) 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: (Major) The use of thalidomide and COMT inhibitors may cause an additive sedative effect and should be avoided if possible. If concurrent treatment is needed, prescribers should monitor patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment. Patients should be advised to avoid driving or other tasks requiring mental alertness until they know how the combination affects them.
    Epoetin Alfa: (Moderate) Thalidomide and epoetin alfa should be used cautiously due an increased risk of thromboembolism.
    Esketamine: (Major) Closely monitor patients receiving esketamine and thalidomide for sedation and other CNS depressant effects. Instruct patients who receive a dose of esketamine not to drive or engage in other activities requiring alertness until the next day after a restful sleep.
    Esmolol: (Moderate) 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: (Moderate) 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: (Moderate) 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: (Moderate) 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: (Major) Avoid the concomitant use of thalidomide with alcohol due to the potential for additive sedative effects. Additionally, using thalidomide and alcohol together may potentiate the adverse effect of peripheral neuropathy. (Moderate) Avoid the concomitant use of thalidomide with alcohol due to the potential for additive sedative effects. Additionally, using thalidomide and alcohol together may potentiate the adverse effect of peripheral neuropathy.
    Ethinyl Estradiol: (Moderate) 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: (Moderate) 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: (Moderate) 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: (Moderate) 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: (Moderate) 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).
    Ethynodiol Diacetate; Ethinyl Estradiol: (Moderate) 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: (Moderate) 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; Ethinyl Estradiol: (Moderate) 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: (Moderate) Thalidomide and other agents that slow cardiac conduction such as H2-blockers should be used cautiously due to the potential for additive bradycardia.
    Felodipine: (Moderate) Thalidomide and other agents that slow cardiac conduction such as calcium-channel blockers should be used cautiously due to the potential for additive bradycardia.
    Fenfluramine: (Major) Avoid coadministration of fenfluramine with thalidomide due to the risk of additive CNS depression.
    Fenofibric Acid: (Minor) 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.
    Food: (Major) Advise patients to avoid cannabis use while taking CNS depressants due to the risk for additive CNS depression and potential for other cognitive adverse reactions.
    Fosphenytoin: (Major) 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.
    Gabapentin: (Major) Avoid coadministration of thalidomide with gabapentin because of the risk of additive CNS depression. If concurrent use cannot be avoided, initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration. Educate patients about the risks and symptoms of excessive CNS depression.
    H2-blockers: (Moderate) Thalidomide and other agents that slow cardiac conduction such as H2-blockers should be used cautiously due to the potential for additive bradycardia.
    Ibuprofen; Famotidine: (Moderate) Thalidomide and other agents that slow cardiac conduction such as H2-blockers should be used cautiously due to the potential for additive bradycardia.
    Imipramine: (Major) 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: (Moderate) 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: (Moderate) Thalidomide and other agents that slow cardiac conduction such as beta-blockers should be used cautiously due to the potential for additive bradycardia.
    Lasmiditan: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and thalidomide. Concurrent use may result in additive CNS depression.
    Lemborexant: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and thalidomide. Dosage adjustments of lemborexant and thalidomide may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants.
    Leuprolide; Norethindrone: (Moderate) 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).
    Levamlodipine: (Moderate) Thalidomide and other agents that slow cardiac conduction such as calcium-channel blockers should be used cautiously due to the potential for additive bradycardia.
    Levobetaxolol: (Moderate) Thalidomide and other agents that slow cardiac conduction such as beta-blockers should be used cautiously due to the potential for additive bradycardia.
    Levobunolol: (Moderate) Thalidomide and other agents that slow cardiac conduction such as beta-blockers should be used cautiously due to the potential for additive bradycardia.
    Levocetirizine: (Moderate) Concurrent use of cetirizine/levocetirizine with thalidomide should generally be avoided. Coadministration may increase the risk of CNS depressant-related side effects. If concurrent use is necessary, monitor for excessive sedation and somnolence.
    Levonorgestrel: (Moderate) 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).
    Levonorgestrel; Ethinyl Estradiol: (Moderate) 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).
    Levonorgestrel; Ethinyl Estradiol; Ferrous Bisglycinate: (Moderate) 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: (Major) 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.
    Lofexidine: (Moderate) Monitor for additive hypotension, bradycardia, and sedation during coadministration of lofexidine and thalidomide. Lofexidine can potentiate the effects of CNS depressants. Patients should be advised to avoid driving or performing any other tasks requiring mental alertness until the effects of the combination are known.
    Loxapine: (Major) Avoid the concomitant use of thalidomide with antipsychotics due to the potential for additive sedative effects.
    Lumateperone: (Moderate) Avoid the concurrent use of thalidomide and lumateperone if possible due to the potential for additive CNS depression. If coadministration is required, monitor for excessive sedation and somnolence.
    Lurasidone: (Major) Avoid the concomitant use of thalidomide with antipsychotics due to the potential for additive sedative effects.
    Mestranol; Norethindrone: (Moderate) 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: (Moderate) Thalidomide frequently causes drowsiness and somnolence and may enhance the sedative activity of methocarbamol.
    Metoprolol: (Moderate) Thalidomide and other agents that slow cardiac conduction such as beta-blockers should be used cautiously due to the potential for additive bradycardia.
    Metoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Thalidomide and other agents that slow cardiac conduction such as beta-blockers should be used cautiously due to the potential for additive bradycardia.
    Metronidazole: (Moderate) Thalidomide and other agents that cause peripheral neuropathy such as metronidazole should be used cautiously due to the potential for additive effects.
    Molindone: (Major) Avoid the concomitant use of thalidomide with antipsychotics due to the potential for additive sedative effects.
    Nabilone: (Major) The use of CNS depressants concomitantly with thalidomide may cause an additive sedative effect and should be avoided.
    Nadolol: (Moderate) Thalidomide and other agents that slow cardiac conduction such as beta-blockers should be used cautiously due to the potential for additive bradycardia.
    Nalbuphine: (Major) Avoid the concomitant use of thalidomide with other central nervous system depressants such as nalbuphine due to the potential for additive sedative effects.
    Nebivolol: (Moderate) 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: (Moderate) Thalidomide and other agents that slow cardiac conduction such as beta-blockers should be used cautiously due to the potential for additive bradycardia.
    Nefazodone: (Major) Avoid the concomitant use of thalidomide with other central nervous system depressants such as nefazodone due to the potential for additive sedative effects.
    Nicardipine: (Moderate) 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: (Moderate) 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: (Moderate) 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: (Moderate) 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: (Moderate) 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: (Moderate) 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 Acetate; Ethinyl Estradiol; Ferrous fumarate: (Moderate) 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: (Moderate) 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; Ethinyl Estradiol: (Moderate) 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; Ethinyl Estradiol; Ferrous fumarate: (Moderate) 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).
    Norgestimate; Ethinyl Estradiol: (Moderate) 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: (Moderate) 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: (Major) 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.
    Olmesartan; Amlodipine; Hydrochlorothiazide, HCTZ: (Moderate) Thalidomide and other agents that slow cardiac conduction such as calcium-channel blockers should be used cautiously due to the potential for additive bradycardia.
    Opiate Agonists: (Major) Avoid coadministration of opioid agonists with thalidomide due to the risk of additive CNS depression.
    Opicapone: (Major) The use of thalidomide and COMT inhibitors may cause an additive sedative effect and should be avoided if possible. If concurrent treatment is needed, prescribers should monitor patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment. Patients should be advised to avoid driving or other tasks requiring mental alertness until they know how the combination affects them.
    Oral Contraceptives: (Moderate) 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: (Moderate) 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: (Moderate) Thalidomide and other agents that cause peripheral neuropathy such as paclitaxel should be used cautiously due to the potential for additive effects.
    Pamidronate: (Moderate) In patients with multiple myeloma, the risk of renal dysfunction may be higher in patients taking both pamidronate and thalidomide.
    Penbutolol: (Moderate) Thalidomide and other agents that slow cardiac conduction such as beta-blockers should be used cautiously due to the potential for additive bradycardia.
    Pentazocine: (Major) 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: (Major) 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: (Moderate) 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: (Major) 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: (Major) 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: (Moderate) Thalidomide and other agents that slow cardiac conduction such as alpha-blockers should be used cautiously due to the potential for additive bradycardia.
    Phentolamine: (Moderate) Thalidomide and other agents that slow cardiac conduction such as alpha-blockers should be used cautiously due to the potential for additive bradycardia.
    Phenytoin: (Moderate) 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: (Major) Avoid the concomitant use of thalidomide with antipsychotics due to the potential for additive sedative effects.
    Pindolol: (Moderate) Thalidomide and other agents that slow cardiac conduction such as beta-blockers should be used cautiously due to the potential for additive bradycardia.
    Pramipexole: (Major) Avoid the concomitant use of thalidomide with other central nervous system depressants such as pramipexole due to the potential for additive sedative effects.
    Prazosin: (Moderate) Thalidomide and other agents that slow cardiac conduction such as alpha-blockers should be used cautiously due to the potential for additive bradycardia.
    Pregabalin: (Major) Avoid coadministration of thalidomide with pregabalin because of the risk of additive CNS depression. If concurrent use cannot be avoided, initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration. Educate patients about the risks and symptoms of excessive CNS depression.
    Propranolol: (Moderate) Thalidomide and other agents that slow cardiac conduction such as beta-blockers should be used cautiously due to the potential for additive bradycardia.
    Propranolol; Hydrochlorothiazide, HCTZ: (Moderate) Thalidomide and other agents that slow cardiac conduction such as beta-blockers should be used cautiously due to the potential for additive bradycardia.
    Protriptyline: (Major) 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: (Major) Avoid the concomitant use of thalidomide with anxiolytics, sedatives, and hypnotics due to the potential for additive sedative effects.
    Ranitidine: (Moderate) Thalidomide and other agents that slow cardiac conduction such as H2-blockers should be used cautiously due to the potential for additive bradycardia.
    Relugolix; Estradiol; Norethindrone acetate: (Moderate) 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).
    Reserpine: (Major) Avoid the concomitant use of thalidomide with other central nervous system depressants such as reserpine due to the potential for additive sedative effects.
    Ropinirole: (Major) 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: (Major) 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.
    Segesterone Acetate; Ethinyl Estradiol: (Moderate) 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).
    Skeletal Muscle Relaxants: (Major) 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: (Moderate) Thalidomide and other agents that slow cardiac conduction such as beta-blockers should be used cautiously due to the potential for additive bradycardia.
    Succinylcholine: (Moderate) Use succinylcholine with caution in patients taking thalidomide due the risk of additive bradycardia.
    Telmisartan; Amlodipine: (Moderate) Thalidomide and other agents that slow cardiac conduction such as calcium-channel blockers should be used cautiously due to the potential for additive bradycardia.
    Terazosin: (Moderate) Thalidomide and other agents that slow cardiac conduction such as alpha-blockers should be used cautiously due to the potential for additive bradycardia.
    Thiothixene: (Major) Avoid the concomitant use of thalidomide with antipsychotics due to the potential for additive sedative effects.
    Timolol: (Moderate) Thalidomide and other agents that slow cardiac conduction such as beta-blockers should be used cautiously due to the potential for additive bradycardia.
    Tizanidine: (Moderate) Thalidomide frequently causes drowsiness and somnolence and may enhance the sedative activity of tizanidine.
    Tolcapone: (Major) The use of thalidomide and COMT inhibitors may cause an additive sedative effect and should be avoided if possible. If concurrent treatment is needed, prescribers should monitor patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment. Patients should be advised to avoid driving or other tasks requiring mental alertness until they know how the combination affects them.
    Trandolapril; Verapamil: (Moderate) Thalidomide and other agents that slow cardiac conduction such as calcium-channel blockers should be used cautiously due to the potential for additive bradycardia.
    Trazodone: (Major) The use of CNS depressants, such as trazodone, concomitantly with thalidomide may cause an additive sedative effect and should be avoided. Thalidomide frequently causes drowsiness and somnolence. Dose reductions may be required. Patients should be instructed to avoid situations where drowsiness may be a problem and not to take other medications that may cause drowsiness without adequate medical advice. Advise patients as to the possible impairment of mental and/or physical abilities required for the performance of hazardous tasks, such as driving a car or operating other complex or dangerous machinery.
    Trimipramine: (Major) 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.
    Verapamil: (Moderate) 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: (Moderate) Thalidomide and other agents that cause peripheral neuropathy such as vincristine should be used cautiously due to the potential for additive effects.
    Vincristine: (Moderate) Thalidomide and other agents that cause peripheral neuropathy such as vincristine should be used cautiously due to the potential for additive effects.
    Zoledronic Acid: (Moderate) 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

    It is not known if thalidomide is secreted in human milk or if it has effects on the breast-fed infant or on milk production. Due to the risk of serious adverse reactions in nursing infants, women should discontinue breast-feeding during thalidomide therapy.

    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%.