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ALERT: U.S. Boxed Warning
The FDA-approved labeling includes a boxed warning. See Warnings/Precautions section for a concise summary of this information. For verbatim wording of the boxed warning, consult the product labeling or www.fda.gov.
Pronunciation
(tha LI doe mide)
Generic Available (U.S.)
No
Medication Guide
An FDA-approved patient medication guide, which is available with the product information and at http://www.fda.gov/downloads/Drugs/DrugSafety/UCM222363.pdf, must be dispensed with this medication.
REMS Components
Elements to Assure Safe Use; Implementation System; Medication Guide
Prescribing and Access Restrictions
U.S.: As a requirement of the REMS program, access to this medication is restricted. Thalidomide is approved for marketing only under a special distribution program. This program, called the "System for Thalidomide Education and Prescribing Safety" (STEPS® 1-888-423-5436), has been approved by the FDA. Prescribers and pharmacists must be registered with the program. No more than a 4-week supply should be dispensed. Blister packs should be dispensed intact (do not repackage capsules). Prescriptions must be filled within 7 days. Subsequent prescriptions may be filled only if fewer than 7 days of therapy remain on the previous prescription. A new prescription is required for further dispensing (a telephone prescription may not be accepted.) Pregnancy testing is required for females of childbearing potential.
Canada: Access to thalidomide is restricted through a controlled distribution program called RevAid®. Only physicians and pharmacists enrolled in this program are authorized to prescribe or dispense thalidomide. Patients must be enrolled in the program by their physicians. Further information is available by calling 1-888-738-2431.
Brand Names: U.S.
Brand Names: Canada
Pharmacologic Category
Pharmacologic Category Synonyms
Use: Labeled Indications
Treatment of newly-diagnosed multiple myeloma; treatment and maintenance of cutaneous manifestations of erythema nodosum leprosum (ENL)
Use: Unlabeled
Treatment of refractory Crohn's disease; treatment of chronic graft-versus-host disease (GVHD) in hematopoietic stem cell transplantation; AIDS-related aphthous stomatitis; Waldenström's macroglobulinemia; maintenance therapy of multiple myeloma (following autologous stem cell transplant)
Pregnancy Risk Factor
X
Pregnancy Considerations
[U.S. Boxed Warning]: Thalidomide is a known teratogen; either abstinence or 2 forms of effective contraception must be used for at least 4 weeks before initiating therapy, during therapy, and for 4 weeks following discontinuation of thalidomide for women of childbearing potential. Distribution is restricted; physicians, pharmacists, and patients must be registered with the S.T.E.P.S.® program. Women of childbearing potential should be treated only if they are able to comply with the conditions of the S.T.E.P.S.® program. Embryotoxic with limb defects noted from the 27th to 40th gestational day of exposure; all cases of phocomelia occur from the 27th to 42nd gestational day; fetal cardiac, gastrointestinal, bone, external ear, eye, and genitourinary tract abnormalities have also been described. Mortality at or shortly after birth has also been reported. A negative pregnancy test (sensitivity of at least 50 mIU/mL) within 24 hours prior to beginning therapy, weekly during the first 4 weeks, and every 4 weeks (every 2 weeks for women with irregular menstrual cycles) thereafter is required for women of childbearing potential. Males (even those vasectomized) must use a latex condom during any sexual contact with women of childbearing age. Risk to the fetus from semen of male patients is unknown. The parent or legal guardian for patients between 12 and 18 years of age must agree to ensure compliance with the required guidelines. Thalidomide must be immediately discontinued and the patient referred to a reproductive toxicity specialist if pregnancy occurs during treatment. Any suspected fetal exposure to thalidomide must be reported to the FDA via the MedWatch program (1-800-FDA-1088) and to Celgene Corporation (1-888-423-5436). In Canada, thalidomide is available only through a restricted-distribution program called RevAid® (1-888-738-2431).
Lactation
Excretion in breast milk unknown/not recommended
Breast-Feeding Considerations
Due to the potential for serious adverse reactions in the infant, a decision should be made to discontinue nursing or discontinue treatment with thalidomide. Use in breast-feeding women is contraindicated in the Canadian labeling.
Contraindications
Hypersensitivity to thalidomide or any component of the formulation; patient unable to comply with STEPS® program (including males); women of childbearing potential unless alternative therapies are inappropriate and adequate precautions are taken to avoid pregnancy; pregnancy
Canadian labeling: Additional contraindications (not in U.S. labeling): Hypersensitivity to lenalidomide; breast-feeding
Warnings/Precautions
Boxed warnings:
• Appropriate use: See “Other warnings/precautions” below.
• Pregnancy: See “Special populations” below.
• Thromboembolic events: See “Concerns related to adverse effects” below.
Special handling:
• Hazardous agent: Use appropriate precautions for handling and disposal.
Concerns related to adverse effects:
• Bradycardia: May cause bradycardia; use with caution in patients with cardiovascular disease.
• Hypersensitivity/skin reactions: Hypersensitivity, Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) have been reported; withhold therapy and evaluate with skin rashes; permanently discontinue if rash is exfoliative, purpuric, bullous or if SJS or TEN is suspected.
• Neutropenia: May cause neutropenia; avoid initiating therapy if ANC <750/mm3; interruption or discontinuation of therapy may be necessary if ANC <750/mm3 during therapy.
• Orthostatic hypotension: May cause orthostatic hypotension; use with caution in patients who would not tolerate transient hypotensive episodes.
• Peripheral neuropathy: Use has been associated with the development of peripheral neuropathy, which may be irreversible; generally occurs following chronic use (over months), but may occur with short-term use. Use caution with other medications which may cause peripheral neuropathy. Consider immediate discontinuation (if clinically appropriate) in patients who develop neuropathy.
• Sedation: May cause sedation; patients must be warned to use caution when performing tasks which require alertness.
• Seizures: May cause seizures; use caution in patients with a history of seizures, concurrent therapy with drugs which alter seizure threshold, or conditions which predispose to seizures.
• Thromboembolic events: [U.S. Boxed Warning]: Thrombotic events have been reported, generally in patients with other risk factors for thrombosis (neoplastic disease, inflammatory disease, or concurrent therapy with combination chemotherapy). Use in combination with dexamethasone is associated with increased risk for deep vein thrombosis (DVT) and pulmonary embolism (PE). Monitor for signs and symptoms of thromboembolism; patients at risk may benefit from prophylactic anticoagulation or aspirin. The NCCN multiple myeloma guidelines (v.1.2011) recommend anticoagulant prophylaxis with thalidomide-based therapy. Anticoagulant prophylaxis should be individualized and selected based on the venous thromboembolism risk of the combination treatment regimen, using the safest and easiest to administer (Palumbo, 2008). The Canadian labeling recommends anticoagulant prophylaxis for at least the first 5 months of thalidomide-based therapy.
Disease-related concerns:
• Cardiovascular disease: Use with caution in patients with cardiovascular disease.
• Constipation: Use with caution in patients with constipation.
• Neurological disorders: Use with caution in patients with neurological disorders, including seizure disorder.
Concurrent drug therapy issues:
• Contraceptives: Use with caution with drugs which may decrease the efficacy of hormonal contraceptives.
Special populations:
• HIV infected patients: Use with caution in patients with HIV infection; has been associated with increased viral loads.
• Pregnancy: [U.S. Boxed Warning]: Thalidomide is a known teratogen; either abstinence or 2 effective forms of contraception must be used for at least 4 weeks before initiating therapy, during therapy, and for 4 weeks following discontinuation of thalidomide for women of childbearing potential.
Other warnings/precautions:
• Appropriate use: [U.S. Boxed Warning]: Thalidomide should only be prescribed to patients (male and female) who can understand and comply with the conditions of the S.T.E.P.S.® program. Distribution is restricted; physicians, pharmacists, and patients must be registered with the S.T.E.P.S.® program.
Adverse Reactions
>10%:
Cardiovascular: Edema (57%), thrombosis/embolism (23%; grade 3: 13%, grade 4: 9%), hypotension (16%)
Central nervous system: Fatigue (79%; grade 3: 14%, grade 4: 3%), somnolence (36% to 38%), dizziness (4% to 20%), sensory neuropathy (54%), confusion (28%), anxiety/agitation (9% to 26%), fever (19% to 23%), motor neuropathy (22%), headache (13% to 19%)
Dermatologic: Rash/desquamation (21% to 30%; grade 3: 4%), dry skin (21%), maculopapular rash (4% to 19%), acne (3% to 11%)
Endocrine & metabolic: Hypocalcemia (72%)
Gastrointestinal: Constipation (3% to 55%), nausea (4% to 28%), anorexia (3% to 28%), weight loss (23%), weight gain (22%), diarrhea (4% to 19%), oral moniliasis (4% to 11%)
Hematologic: Leukopenia (17% to 35%), neutropenia (31%), anemia (6% to 13%), lymphadenopathy (6% to 13%)
Hepatic: AST increased (3% to 25%), bilirubin increased (14%)
Neuromuscular & skeletal: Muscle weakness (40%), tremor (4% to 26%), weakness (6% to 22%), myalgia (17%), paresthesia (6% to 16%), arthralgia (13%)
Renal: Hematuria (11%)
Respiratory: Dyspnea (42%)
Miscellaneous: Diaphoresis (13%)
1% to 10%:
Cardiovascular: Peripheral edema (3% to 8%), facial edema (4%)
Central nervous system: Insomnia (9%), nervousness (3% to 9%), malaise (8%), vertigo (8%), pain (3% to 8%)
Dermatologic: Dermatitis (fungal 4% to 9%), pruritus (3% to 8%), nail disorder (3% to 4%)
Endocrine & metabolic: Hyperlipemia (6% to 9%)
Gastrointestinal: Xerostomia (8% to 9%), flatulence (8%), tooth pain (4%)
Genitourinary: Impotence (3% to 8%)
Hepatic: LFTs abnormal (9%)
Neuromuscular & skeletal: Neuropathy (8%), back pain (4% to 6%), neck pain (4%), neck rigidity (4%)
Renal: Albuminuria (3% to 8%)
Respiratory: Pharyngitis (4% to 8%), rhinitis (4%), sinusitis (3% to 8%)
Miscellaneous: Infection (6% to 8%)
Postmarketing and/or case reports (limited to important or life-threatening): Acute renal failure, alkaline phosphatase increased, ALT increased, amenorrhea, aphthous stomatitis, arrhythmia, atrial fibrillation, bile duct obstruction, bradycardia, BUN increased, CML, creatinine clearance decreased, creatinine increased, deafness, depression, diplopia, dysesthesia, ECG abnormalities, enuresis, eosinophilia, epistaxis, erythema multiforme, erythema nodosum, erythroleukemia, exfoliative dermatitis, febrile neutropenia, foot drop, galactorrhea, granulocytopenia, gynecomastia, hepatomegaly, Hodgkin's disease, hypercalcemia, hyper-/hypokalemia, hypersensitivity, hypertension, hyper-/hypothyroidism, hyperuricemia, hypomagnesemia, hyponatremia, hypoproteinemia, intestinal obstruction, intestinal perforation, interstitial pneumonitis, LDH increased, lethargy, leukocytosis, lymphedema, lymphopenia, mental status changes, metrorrhagia, myxedema, nystagmus, oliguria, orthostatic hypotension, pancytopenia, paresthesia, petechiae, peripheral neuritis, photosensitivity, pleural effusion, prothrombin time changes, psychosis, pulmonary embolus, pulmonary hypertension, purpura, Raynaud's syndrome, seizure, status epilepticus, Stevens-Johnson syndrome, stomach ulcer, stupor, suicide attempt, syncope, tachycardia, thrombocytopenia, toxic epidermal necrolysis, tumor lysis syndrome
Metabolism/Transport Effects
None known.
Drug Interactions
Abatacept: Anti-TNF Agents may enhance the adverse/toxic effect of Abatacept. An increased risk of serious infection during concomitant use has been reported. Risk X: Avoid combination
Alcohol (Ethyl): CNS Depressants may enhance the CNS depressant effect of Alcohol (Ethyl). Risk C: Monitor therapy
Anakinra: Anti-TNF Agents may enhance the adverse/toxic effect of Anakinra. An increased risk of serious infection during concomitant use has been reported. Risk X: Avoid combination
BCG: Immunosuppressants may diminish the therapeutic effect of BCG. Risk X: Avoid combination
Canakinumab: Anti-TNF Agents may enhance the adverse/toxic effect of Canakinumab. Specifically, the risk for serious infections and/or neutropenia may be increased. Risk X: Avoid combination
Certolizumab Pegol: Anti-TNF Agents may enhance the immunosuppressive effect of Certolizumab Pegol. Risk X: Avoid combination
CloZAPine: Myelosuppressive Agents may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk for agranulocytosis may be increased. Risk X: Avoid combination
CNS Depressants: May enhance the adverse/toxic effect of other CNS Depressants. Exceptions: Levocabastine (Nasal). Risk C: Monitor therapy
Coccidioidin Skin Test: Immunosuppressants may diminish the diagnostic effect of Coccidioidin Skin Test. Risk C: Monitor therapy
Denosumab: May enhance the adverse/toxic effect of Immunosuppressants. Specifically, the risk for serious infections may be increased. Risk C: Monitor therapy
Dexamethasone: May enhance the dermatologic adverse effect of Thalidomide. Dexamethasone may enhance the thrombogenic effect of Thalidomide. Risk D: Consider therapy modification
Dexamethasone (Systemic): May enhance the dermatologic adverse effect of Thalidomide. Dexamethasone (Systemic) may enhance the thrombogenic effect of Thalidomide. Risk D: Consider therapy modification
Droperidol: May enhance the CNS depressant effect of CNS Depressants. Management: Consider dose reductions of droperidol or of other CNS agents (e.g., opioids, barbiturates) with concomitant use. Risk D: Consider therapy modification
Echinacea: May diminish the therapeutic effect of Immunosuppressants. Risk D: Consider therapy modification
HydrOXYzine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Leflunomide: Immunosuppressants may enhance the adverse/toxic effect of Leflunomide. Specifically, the risk for hematologic toxicity such as pancytopenia, agranulocytosis, and/or thrombocytopenia may be increased. Management: Consider not using a leflunomide loading dose in patients receiving other immunosuppressants. Patients receiving both leflunomide and another immunosuppressant should be monitored for bone marrow suppression at least monthly. Risk D: Consider therapy modification
Methotrimeprazine: CNS Depressants may enhance the CNS depressant effect of Methotrimeprazine. Methotrimeprazine may enhance the CNS depressant effect of CNS Depressants. Management: Reduce adult dose of CNS depressant agents by 50% with initiation of concomitant methotrimeprazine therapy. Further CNS depressant dosage adjustments should be initiated only after clinically effective methotrimeprazine dose is established. Risk D: Consider therapy modification
Natalizumab: Immunosuppressants may enhance the adverse/toxic effect of Natalizumab. Specifically, the risk of concurrent infection may be increased. Risk X: Avoid combination
Pamidronate: Thalidomide may enhance the nephrotoxic effect of Pamidronate. Risk C: Monitor therapy
Pimecrolimus: May enhance the adverse/toxic effect of Immunosuppressants. Risk X: Avoid combination
Rilonacept: Anti-TNF Agents may enhance the adverse/toxic effect of Rilonacept. Risk X: Avoid combination
Roflumilast: May enhance the immunosuppressive effect of Immunosuppressants. Risk D: Consider therapy modification
Selective Serotonin Reuptake Inhibitors: CNS Depressants may enhance the adverse/toxic effect of Selective Serotonin Reuptake Inhibitors. Specifically, the risk of psychomotor impairment may be enhanced. Risk C: Monitor therapy
Sipuleucel-T: Immunosuppressants may diminish the therapeutic effect of Sipuleucel-T. Risk C: Monitor therapy
Tacrolimus (Topical): May enhance the adverse/toxic effect of Immunosuppressants. Risk X: Avoid combination
Trastuzumab: May enhance the neutropenic effect of Immunosuppressants. Risk C: Monitor therapy
Vaccines (Inactivated): Immunosuppressants may diminish the therapeutic effect of Vaccines (Inactivated). Risk C: Monitor therapy
Vaccines (Live): Immunosuppressants may enhance the adverse/toxic effect of Vaccines (Live). Vaccinial infections may develop. Immunosuppressants may diminish the therapeutic effect of Vaccines (Live). Management: Avoid use of live organism vaccines with immunosuppressants; live-attenuated vaccines should not be given for at least 3 months after immunosuppressants. Risk X: Avoid combination
Zoledronic Acid: Thalidomide may enhance the adverse/toxic effect of Zoledronic Acid. Risk C: Monitor therapy
Ethanol/Nutrition/Herb Interactions
Ethanol: May increase CNS depression; monitor for increased effects with coadministration. Caution patients about effects.
Herb/Nutraceutical: Avoid cat's claw and echinacea (have immunostimulant properties; consider therapy modifications).
Storage
Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). Protect from light. Keep in original package.
Mechanism of Action
Immunomodulatory and antiangiogenic characteristics; immunologic effects may vary based on conditions; may suppress excessive tumor necrosis factor-alpha production in patients with ENL, yet may increase plasma tumor necrosis factor-alpha levels in HIV-positive patients. In multiple myeloma, thalidomide is associated with an increase in natural killer cells and increased levels of interleukin-2 and interferon gamma. Other proposed mechanisms of action include suppression of angiogenesis, prevention of free-radical-mediated DNA damage, increased cell mediated cytotoxic effects, and altered expression of cellular adhesion molecules.
Pharmacodynamics/Kinetics
Protein binding: 55% to 66%
Metabolism: Nonenzymatic hydrolysis in plasma; forms multiple metabolites
Bioavailability: Capsule: 90%
Half-life elimination: 5-7 hours
Time to peak, plasma: 3-6 hours
Excretion: Urine (<1% as unchanged drug)
Dosage
Oral:
Children ≥3 years: Chronic graft-versus-host disease (refractory), treatment (unlabeled second-line use; limited data): 3 mg/kg 4 times/day (dose adjusted to goal thalidomide concentration of ≥5 mcg/mL 2 hours postdose) (Vogelsang, 1992) or Initial: 3-6 mg/kg/day in 2-4 divided doses; target dose 12 mg/kg/day; Maximum daily dose: 800 mg (Rovelli, 1998)
Children ≥12 years and Adults: Cutaneous ENL: Initial: 100-300 mg once daily
Adjustments to initial dose:
Patients weighing <50 kg: Initiate at lower end of the dosing range
Severe cutaneous reaction or patients previously requiring high dose may be initiated at 400 mg/day; doses may be divided, but taken 1 hour after meals
Duration and tapering/maintenance:
Maintenance: Dosing should continue until active reaction subsides (usually at least 2 weeks), then tapered in 50 mg decrements every 2-4 weeks
Patients who flare during tapering or with a history of requiring prolonged maintenance should be maintained on the minimum dosage necessary to control the reaction. Efforts to taper should be repeated every 3-6 months, in decrements of 50 mg every 2-4 weeks.
Adults:
Multiple myeloma: Note: Details concerning dosing for multiple myeloma with combination regimens should also be consulted.
200 mg once daily at bedtime (in combination with dexamethasone 40 mg daily on days 1-4, 9-12, and 17-20 of a 28-day treatment cycle)
In combination with melphalan and prednisone (unlabeled combination in U.S.): 200-400 mg once daily (Facon, 2007) or 100 mg once daily (Palumbo, 2008)
Canadian labeling: Adults ≥65 years: 200 mg once daily (in combination with melphalan and prednisone)
AIDS-related aphthous stomatitis (unlabeled use): 200 mg once daily at bedtime for up to 8 weeks, if no response, then 200 mg twice daily for 4 weeks (Jacobson, 1997)
Chronic graft-versus-host disease (refractory), treatment (unlabeled second-line use; optimum dose not determined): Initial: 100 mg at bedtime, with dose escalation up to 400 mg/day in 3-4 divided doses (Wolff, 2010) or Initial: 50-100 mg 3 times/day; maximum dose: 600-1200 mg/day (Kulkarni, 2003) or 200 mg 4 times/day (dose adjusted to goal thalidomide concentration of ≥5 mcg/mL 2 hours postdose) (Vogelsang, 1992) or 100-300 mg 4 times/day (Parker, 1995)
Crohn's disease, refractory (unlabeled use): 50-100 mg/day at bedtime (Vasiliauskas, 1999) or 200-300 mg/day at bedtime (Ehrenpreis, 1999)
Multiple myeloma, maintenance (following autologous stem cell transplant; unlabeled use): 200 mg/day starting 3-6 months after transplant; continue until disease progression or unacceptable toxicity (Brinker, 2006) or 100 mg/day starting 42-60 days following transplant; increase to 200 mg/day after 2 weeks if tolerated; continue for up to 12 months (in combination with prednisolone) (Spencer, 2009)
Waldenström's macroglobulinemia (unlabeled use): 200 mg/day for up to 52 weeks (in combination with rituximab) (Treon, 2008)
Dosing adjustment for toxicity:
ANC ≤750/mm3: Withhold treatment if clinically appropriate
Multiple myeloma:
U.S. labeling: Constipation, oversedation, peripheral neuropathy: Temporarily withhold or continue with a reduced dose
Canadian labeling:
ANC <1500/mm3: Withhold melphalan and prednisone for 1 week; resume melphalan and prednisone after 1 week if ANC >1500/mm3 or if ANC 1000-1500/mm3 reduce melphalan dose by 50% or if ANC <1000/mm3 adjust chemotherapy dose based on clinical status of patient.
Constipation, oversedation: Temporarily withhold thalidomide treatment or continue with a reduced dose
Peripheral neuropathy, Grade 1 (paresthesia, weakness and/or loss of reflexes) without loss of function): Evaluate patient and consider dose reduction with worsening of symptoms; symptom improvement may not follow dose reduction, however.
Peripheral neuropathy, Grade 2 (interferes with function but not with daily activities), Grade 3 (interferes with daily activities), or Grade 4 (disabling neuropathy): Discontinue thalidomide treatment
Thromboembolic events: Withhold therapy and initiate standard anticoagulant treatment; may resume thalidomide therapy at original dose following stabilization of patient and resolution of thromboembolic event; maintain anticoagulant treatment for duration of thalidomide therapy
Dosing adjustment in renal impairment: No adjustment is required for patients with renal impairment and on dialysis (per manufacturer). In a study of 6 patients with end-stage renal disease on dialysis, although clearance was increased by dialysis, a supplemental dose was not needed (Eriksson, 2003).
Multiple myeloma: An evaluation of 29 newly-diagnosed myeloma patients with renal failure (serum creatinine ≥2 mg/dL) treated with thalidomide and dexamethasone (some also received cyclophosphamide) found that toxicities and efficacy were similar to patients with normal renal function (Seol, 2010). A study evaluating induction therapy with thalidomide and dexamethasone in 31 newly-diagnosed myeloma patients with renal failure (Clcr <50 mL/minute), including 16 patients with severe renal impairment (Clcr <30 mL/minute) and 7 patients on chronic hemodialysis found that toxicities were similar to patients without renal impairment and that thalidomide and dexamethasone could be administered safely (Tosi, 2009).
Dosing adjustment in hepatic impairment: Thalidomide does not appear to undergo significant hepatic metabolism; the pharmacokinetics of thalidomide have not been studied in patients with liver dysfunction (per manufacturer).
Dosage: Combination Regimens
Multiple myeloma:
Bortezomib-Melphalan-Prednisone-Thalidomide
DTPACE
Melphalan-Prednisone-Thalidomide (Multiple Myeloma)
Thalidomide-Dexamethasone (MM)
Administration: Oral
Administer orally with water, preferably at bedtime once daily on an empty stomach, at least 1 hour after the evening meal. Doses >400 mg/day may be given in 2-3 divided doses. For missed doses, if <12 hours patient may receive dose; if >12 hours wait till next dose due.
Avoid extensive handling of capsules; capsules should remain in blister pack until ingestion. If exposed to the powder content from broken capsules or body fluids from patients receiving thalidomide, the exposed area should be washed with soap and water.
Monitoring Parameters
CBC with differential, platelets; signs of neuropathy monthly for the first 3 months, then periodically during treatment; consider monitoring of sensory nerve application potential amplitudes (at baseline and every 6 months) to detect asymptomatic neuropathy. Monitor for signs and symptoms of thromboembolism (shortness of breath, chest pain, arm/leg swelling). In HIV-seropositive patients: viral load after 1 and 3 months, then every 3 months. Pregnancy testing (sensitivity of at least 50 mIU/mL) is required within 24 hours prior to initiation of therapy, weekly during the first 4 weeks, then every 4 weeks in women with regular menstrual cycles or every 2 weeks in women with irregular menstrual cycles.
Reference Range
Graft-vs-host disease: Therapeutic plasma thalidomide levels are 5-8 mcg/mL, although it has been suggested that lower plasma levels (0.5-1.5 mcg/mL) may be therapeutic; peak serum thalidomide level after a 200 mg dose: 1.8 mcg/mL
Dietary Considerations
Should be taken at least 1 hour after the evening meal.
Patient Education
You will be given oral and written instructions about the necessity of using two methods of contraception and the necessity of keeping return visits for pregnancy testing. Do not donate blood while taking this medicine. Male patients should not donate sperm. Avoid extensive handling of capsules; capsules should remain in blister pack until ingestion. If exposed to the powder content from broken capsules or body fluids from patients receiving thalidomide, the exposed area should be washed with soap and water. Avoid alcohol. You may experience postural hypotension, sleepiness, dizziness, fatigue, fever, headaches, lack of concentration, nausea or vomiting or loss of appetite, constipation or diarrhea, oral thrush (frequent mouth care is necessary), or sexual dysfunction (reversible). Report any of the above if persistent or severe. Report chest pain or palpitations or swelling of extremities; respiratory difficulty; back, neck, muscle pain, muscle weakness, or stiffness; numbness or pain in extremities; significant weight loss or gain; skin rash or eruptions; or increased nervousness, anxiety, confusion, or insomnia.
Dental Health: Effects on Dental Treatment
Key adverse event(s) related to dental treatment: Oral moniliasis (HIV-seropositive patients), toothache, xerostomia (normal salivary flow resumes upon discontinuation), and aphthous stomatitis.
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Mental Health: Effects on Mental Status
Sedation is common; may cause dizziness, nervousness, insomnia, agitation, abnormal thinking, amnesia, anxiety, confusion, depression, euphoria, and psychosis
Mental Health: Effects on Psychiatric Treatment
May cause leukopenia; use caution with clozapine and carbamazepine; concurrent use with other psychotropics may produce additive sedation
Nursing: Physical Assessment/Monitoring
Patient must be capable of complying with STEPS® program. Instruct patient on risks of pregnancy, appropriate contraceptive measures, and necessity for frequent pregnancy testing (schedule pregnancy testing at time of dispensing and give patient schedule in writing). Monitor for signs of fluid retention, weight gain, and hypotension. Monitor closely for signs of neuropathy, neutropenia, and CNS depression.
Oncology: Emetic Potential
Low (10% to 30%)
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, oral:
Thalomid®: 50 mg, 100 mg, 150 mg, 200 mg
Extemporaneously Prepared
Hazardous agent: Use appropriate precautions for handling and disposal.
A 20 mg/mL oral suspension may be prepared with capsules and a 1:1 mixture of Ora-Sweet® and Ora-Plus®. Empty the contents of twelve 100 mg capsules into a glass mortar. Add small portions of the vehicle and mix to a uniform paste; mix while adding the vehicle in incremental proportions to almost 60 mL; transfer to an amber calibrated bottle, rinse mortar with vehicle, and add quantity of vehicle sufficient to make 60 mL. Label “shake well,” “protect from light,” and “refrigerate”. Stable for 35 days refrigerated.
Kraft S, Johnson CE, and Tyler RP, "Stability of an Extemporaneously Prepared Thalidomide Suspension," Am J Health Syst Pharm, 2011, 69(1):56-8.
References
Antonioli E, Nozzoli C, Gianfaldoni G, et al, “Pulmonary Hypertension Related to Thalidomide Therapy in Refractory Multiple Myeloma,” Ann Oncol, 2005, 16(11):1849-50.
Brinker BT, Walker EK, Leong T, et al, “Maintenance Therapy With Thalidomide Improves Overall Survival After Autologous Hematopoietic Progenitor Cell Transplantation for Multiple Myeloma,” Cancer, 2006, 106(10):2171-80.
Browne PV, Weisdorf DJ, DeFor T, et al, “Response to Thalidomide Therapy in Refractory Chronic Graft-Versus-Host Disease,” Bone Marrow Transplant, 2000, 26(8):865-9.
Cavo M, Tacchetti P, Patriarca F, et al, “Bortezomib With Thalidomide Plus Dexamethasone Compared With Thalidomide Plus Dexamethasone as Induction Therapy Before, and Consolidation Therapy After, Double Autologous Stem-Cell Transplantation in Newly Diagnosed Multiple Myeloma: A Randomised Phase 3 Study,” Lancet, 2010, 376(9758):2075-85.
Dimopoulos MA, Terpos E, Chanan-Khan A, et al, “Renal Impairment in Patients With Multiple Myeloma: A Consensus Statement on Behalf of the International Myeloma Working Group,” J Clin Oncol, 2010, 28(33):4976-84.
Ehrenpreis ED, Kane SV, Cohen LB, et al, “Thalidomide Therapy for Patients With Refractory Crohn's Disease: An Open-Label Trial,” Gastroenterology, 1999, 117(6):1271-7.
Eriksson T, Höglund P, Turesson I, et al, “Pharmacokinetics of Thalidomide in Patients With Impaired Renal Function and While On and Off Dialysis,” J Pharm Pharmacol, 2003, 55(12):1701-6.
Facon T, Mary JY, Hulin C, et al, "Melphalan and Prednisone Plus Thalidomide Versus Melphalan and Prednisone Alone or Reduced-Intensity Autologous Stem Cell Transplantation in Elderly Patients With Multiple Myeloma (IFM 99-06): A Randomised Trial," Lancet, 2007, 370(9594):1209-18.
Hamuryudan V, Mat C, Saip S, et al, “Thalidomide in the Treatment of the Mucocutaneous Lesions of the Behçet Syndrome. A Randomized, Double-Blind, Placebo-Controlled Trial,” Ann Intern Med, 1998, 128(6):443-50.
Hulin C, Facon T, Rodon P, et al, “Efficacy of Melphalan and Prednisone Plus Thalidomide in Patients Older Than 75 Years With Newly Diagnosed Multiple Myeloma: IFM 01/01 Trial,” J Clin Oncol, 2009, 27(22):3664-70.
Jacobson JM, Greenspan JS, Spritzler J, et al, “Thalidomide for the Treatment of Oral Aphthous Ulcers in Patients With Human Immunodeficiency Virus Infection. National Institute of Allergy and Infectious Diseases AIDS Clinical Trials Group,” N Engl J Med, 1997, 336(21):1487-93.
Kulkarni S, Powles R, Sirohi B, et al, “Thalidomide After Allogeneic Haematopoietic Stem Cell Transplantation: Activity in Chronic But Not in Acute Graft-Versus-Host Disease,” Bone Marrow Transplant, 2003, 32(2):165-70.
Kyle RA and Rajkumar SV, “Multiple Myeloma,” N Engl J Med, 2004, 351(18): 1860-73.
Lokhorst HM, van der Holt B, Zweegman S, et al, “A Randomized Phase 3 Study on the Effect of Thalidomide Combined With Adriamycin, Dexamethasone, and High-Dose Melphalan, Followed by Thalidomide Maintenance in Patients With Multiple Myeloma,” Blood, 2010, 115(6):1113-20.
National Comprehensive Cancer Network® (NCCN), “Clinical Practice Guidelines in Oncology™: Multiple Myeloma,” Version 1.2011. Available at http://www.nccn.org/professionals/physician_gls/PDF/myeloma.pdf
Onozawa M, Hashino S, Sogabe S, et al, “Side Effects and Good Effects from New Chemotherapeutic Agents. Case 2. Thalidomide-Induced Interstitial Pneumonitis,” J Clin Oncol, 2005, 23(10):2425-6.
Palumbo A, Bringhen S, Liberati AM, et al, "Oral Melphalan, Prednisone, and Thalidomide in Elderly Patients With Multiple Myeloma: Updated Results of a Randomized Controlled Trial," Blood, 2008, 112(8):3107-14.
Palumbo A, Bringhen S, Rossi D, et al, “Bortezomib-Melphalan-Prednisone-Thalidomide Followed by Maintenance With Bortezomib-Thalidomide Compared With Bortezomib-Melphalan-Prednisone for Initial Treatment of Multiple Myeloma: a Randomized Controlled Trial,” J Clin Oncol, 2010, 28(34):5101-9.
Palumbo A, Rajkumar SV, Dimopoulos MA, et al, “Prevention of Thalidomide- and Lenalidomide-Associated Thrombosis in Myeloma,” Leukemia, 2008, 22(2): 414-23.
Parker PM, Chao N, Nademanee A, et al, “ Thalidomide as Salvage Therapy for Chronic Graft-Versus-Host Disease,” Blood, 1995, 86(9):3604-9.
Rajkumar SV, Blood E, Vesole D, et al, “Phase III Clinical Trial of Thalidomide Plus Dexamethasone Compared With Dexamethasone Alone in Newly Diagnosed Multiple Myeloma: A Clinical Trial Coordinated by the Eastern Cooperative Oncology Group,” J Clin Oncol, 2006, 24(3):431-6.
Rovelli A, Arrigo C, Nesi F, et al, “The Role of Thalidomide in the Treatment of Refractory Chronic Graft-Versus-Host Disease Following Bone Marrow Transplantation in Children,” Bone Marrow Transplant, 1998, 21(6):577-81.
Seol Y, Chung J, Kwon B, et al, “Treatment for Patients With Multiple Myeloma Complicated by Renal Failure by Thalidomide-Based Regimens,” J Clin Oncol, 2010, 28(suppl):e13093 [abstract e13093 from 2010 ASCO Annual Meeting].
Spencer A, Prince HM, Roberts AW, et al, “Consolidation Therapy With Low-Dose Thalidomide and Prednisolone Prolongs the Survival of Multiple Myeloma Patients Undergoing a Single Autologous Stem-Cell Transplantation Procedure,” J Clin Oncol, 2009, 27(11):1788-93.
Tosi P, Zamagni E, Tacchetti P, et al, “Thalidomide-Dexamethasone as Induction Therapy Prior to Autologous Stem-Cell Transplantation in Patients With Newly Diagnosed Multiple Myeloma and Renal Failure,” Blood, 2009, 114(22):4934 [abstract 4934 from 2009 ASH Annual Meeting].
Treon SP, Soumerai JD, Branagan AR, et al, “Thalidomide and Rituximab in Waldenstrom Macroglobulinemia,” Blood, 2008, 112(12):4552-7.
Uhl K, Cox E, Rogan R, et al, “Thalidomide Use in the US: Experience With Pregnancy Testing in the S.T.E.P.S.® Programme,” Drug Saf, 2006, 29(4):231-9.
Vasiliauskas EA, Kam LY, Abreu-Martin MT, et al, “An Open-Label Pilot Study of Low-Dose Thalidomide in Chronically Active, Steroid-Dependent Crohn's Disease,” Gastroenterology, 1999, 117(6):1278-87.
Vogelsang GB, Farmer ER, Hess AD, et al, “Thalidomide for the Treatment of Chronic Graft-Versus-Host Disease,” N Engl J Med, 1992, 326(16):1055-8.
Wijermans P, Schaafsma M, Termorshuizen F, et al, “Phase III Study of the Value of Thalidomide Added to Melphalan Plus Prednisone in Elderly Patients With Newly Diagnosed Multiple Myeloma: the HOVON 49 Study,” J Clin Oncol, 2010, 28(19):3160-6.
Wolff D, Schleuning M, von Harsdorf S, et al, “Consensus Conference on Clinical Practice in Chronic GVHD: Second-Line Treatment of Chronic Graft-versus-Host Disease,” Biol Blood Marrow Transplant, 2010, 17(1):1-17.
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