Thalomid (thalidomide)

Temporary interruption of therapy, dosage reduction, and/or permanent discontinuance of thalidomide may be necessary in patients experiencing grade 3 or 4 adverse effects. If constipation, somnolence, or peripheral neuropathy occurs, temporarily interrupt thalidomide therapy and consider dosage reduction upon resumption of therapy.

If angioedema, anaphylaxis, grade 4 rash, skin exfoliation, bullae, or any other severe dermatologic reaction (e.g., grade 4 rash, skin exfoliation, bullae) occurs, thalidomide therapy should be permanently discontinued.

Thalidomide is administered orally. Because administration with a high-fat meal substantially delays the time to peak plasma concentrations of thalidomide, the drug should be administered with water at least 1 hour after a meal.

When thalidomide is given as a single daily dose, the manufacturer recommends that the dose preferably be given at bedtime (to minimize the sedative effects of the drug) with water and at least 1 hour after the evening meal. When high daily dosage of thalidomide is necessary (e.g., 400 mg daily), the daily dose may be given as a single dose at bedtime or, alternatively, in divided doses given with water at least 1 hour after meals.

No dosing information is available for this tab.

In vitro, thalidomide does not inhibit or induce cytochrome P-450 (CYP) isoenzymes at clinically relevant concentrations. Thalidomide is not a substrate of CYP isoenzymes.

Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

Selected Immunosuppressive Agents/Live Vaccines; Live Bcg

SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

MECHANISM OF ACTION: A variety of disease modifying agents suppress the immune system. Immunocompromised patients may be at increased risk for uninhibited replication after administration of live, attenuated vaccines or intravesicular BCG. Immune response to vaccines may be decreased during periods of immunocompromise.(1)

CLINICAL EFFECTS: The expected serum antibody response may not be obtained and/or the vaccine may result in illness.(1) After instillation of intravesicular BCG, immunosuppression may interfere with local immune response, or increase the severity of mycobacterial infection following inadvertent systemic exposure.(2)

PREDISPOSING FACTORS: Immunosuppressive diseases (e.g. hematologic malignancies, HIV disease), treatments (e.g. radiation) and drugs may all increase the magnitude of immunodeficiency.

PATIENT MANAGEMENT: The Centers for Disease Control(CDC) Advisory Committee on Immunization Practices (ACIP) states that live-virus and live, attenuated vaccines should not be administered to patients who are immunocompromised. The magnitude of immunocompromise and associated risks should be determined by a physician.(1) For patients scheduled to receive chemotherapy, vaccination should ideally precede the initiation of chemotherapy by 14 days. Patients vaccinated while on immunosuppressive therapy or in the 2 weeks prior to starting therapy should be considered unimmunized and should be revaccinated at least 3 months after discontinuation of therapy.(1) Patients who receive anti-B cell therapies should not receive live vaccines for at least 6 months after such therapies due to a prolonged duration of immunosuppression. An exception is the Zoster vaccine, which can be given at least 1 month after receipt of anti-B cell therapies.(1) The US manufacturer of abatacept states live vaccines should not be given during or for up to 3 months after discontinuation of abatacept.(2) The US manufacturer of live BCG for intravesicular treatment of bladder cancer states use is contraindicated in immunosuppressed patients.(3) The US manufacturer of daclizumab states live vaccines are not recommended during and for up to 4 months after discontinuation of treatment.(4) The US manufacturer of guselkumab states that live vaccines should be avoided during treatment with guselkumab.(5) The US manufacturer of inebilizumab-cdon states that live vaccines are not recommended during treatment and after discontinuation until B-cell repletion. Administer all live vaccinations at least 4 weeks prior to initiation of inebilizumab-cdon.(6) The US manufacturer of ocrelizumab states that live vaccines are not recommended during treatment and until B-cell repletion occurs after discontinuation of therapy. Administer all live vaccines at least 4 weeks prior to initiation of ocrelizumab.(7) The US manufacturer of ozanimod states that live vaccines should be avoided during and for up to 3 months after discontinuation of ozanimod.(8) The US manufacturer of siponimod states that live vaccines are not recommended during treatment and for up to 4 weeks after discontinuation of treatment.(9) The US manufacturer of ustekinumab states BCG vaccines should not be given in the year prior to, during, or the year after ustekinumab therapy.(10) The US manufacturer of satralizumab-mwge states that live vaccines are not recommended during treatment and should be administered at least four weeks prior to initiation of satralizumab-mwge.(11) The US manufacturer of ublituximab-xiiy states that live vaccines are not recommended during treatment and until B-cell recovery. Live vaccines should be administered at least 4 weeks prior to initiation of ublituximab-xiiy.(12) The US manufacturer of etrasimod states that live vaccines should be avoided during and for 5 weeks after treatment. Live vaccines should be administered at least 4 weeks prior to initiation of etrasimod.(13) The US manufacturer of emapalumab-lzsg states that live vaccines should not be administered to patients receiving emapalumab-lzsg and for at least 4 weeks after the last dose of emapalumab-lzsg. The safety of immunization with live vaccines during or following emapalumab-lzsg therapy has not been studied.(14) The US manufacturer of sibeprenlimab-szsi states live vaccines should not be given within 30 days prior to initiation or during treatment with sibeprenlimab-szsi.(15)

DISCUSSION: Killed or inactivated vaccines do not pose a danger to immunocompromised patients.(1) Patients with a history of leukemia who are in remission and have not received chemotherapy for at least 3 months are not considered to be immunocompromised.(1)

Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

Thalidomide Analogues/Estrogen-Containing Contraceptives

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: Both the thalidomide analogues and estrogen-containing contraceptives are associated with an increased risk of thromboembolic disorders.(1-9) The US manufacturer of thalidomide states that it is unknown if these risks are additive.(1)

CLINICAL EFFECTS: Use of iberdomide, lenalidomide, pomalidomide, or thalidomide in patients taking estrogen-containing hormonal contraceptives may increase the risk of venous or arterial thromboembolism, including deep vein thrombosis (DVT), pulmonary embolism (PE), myocardial infarction (MI), and stroke.(1-10)

PREDISPOSING FACTORS: Previous history of thromboembolic events or concomitant administration of erythropoietic agents may increase the thrombotic risk. Modifiable risk factors (e.g., diabetes, hyperlipidemia, hypertension, smoking) should be minimized.(1-9)

PATIENT MANAGEMENT: The Canadian manufacturer of the thalidomide analogues states that use of hormonal contraceptives is not recommended.(2-4) The UK manufacturer of the thalidomide analogues states that concurrent combined hormonal contraceptives is not recommended and that patients should be switched to a progesterone-only or non-hormonal contraceptive (e.g., progestin-only pills, progestin implant or intrauterine device, depot medroxyprogesterone acetate, tubal sterilization).(5-7) The US manufacturer of the thalidomide analogues does not recommend against use of hormonal contraceptives but instead includes them as an option for highly effective contraception. Estrogen-containing therapies should be used with caution after assessment of their risks and benefits.(1,8-9) The risk of venous thromboembolism continues for 4-6 weeks after discontinuing combined oral contraception.(5-7) If the estrogen-containing contraceptive is not used, two other simultaneous, effective methods of contraception are still required in the US and Canada.(1-4,8,9) In the UK, at least one effective method of contraception is required.(5-7)

DISCUSSION: Iberdomide, lenalidomide, pomalidomide, and thalidomide can all cause thromboembolism. Concurrent use of other agents that may increase the risk of thrombosis, like estrogen-containing therapies, may result in an increased risk of thrombosis.

Thalidomide Analogues/Pd-1 And Pd-L1 Blocking Antibodies

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: The mechanism of this interaction is not known.

CLINICAL EFFECTS: Concurrent use of a thalidomide analogue with dexamethasone and a PD-1 or PD-L1 blocking antibody may increase the risk of mortality.

PREDISPOSING FACTORS: Concurrent use of dexamethasone may increase the risk of venous thromboembolism (VTE), ischemic heart disease including myocardial infarction, and stroke.

PATIENT MANAGEMENT: Concurrent administration of a thalidomide analogue plus dexamethasone with a PD-1 or PD-L1 blocking antibody is not recommended outside of controlled clinical trials.

DISCUSSION: Two randomized clinical trials in multiple myeloma patients showed an increase in mortality associated with the concurrent use of pembrolizumab, a thalidomide analogue, and dexamethasone. In the first clinical trial, patients were randomized to receive pomalidomide, dexamethasone, and pembrolizumab. In this trial, the relative risk of death was increased by more than 50% in the experimental arm containing pembrolizumab and the hazard ratio for overall survival was 1.61. Causes of death in the experimental arm included myocarditis, Stevens-Johnson syndrome, myocardial infarction, pericardial hemorrhage, cardiac failure, respiratory tract infection, neutropenia sepsis, sepsis, multiple organ dysfunction, and respiratory failure. In the second clinical trial, patients were randomized to receive lenalidomide, dexamethasone, and pembrolizumab. In this trial, the relative risk of death was increased by more than 100% in the experimental arm containing pembrolizumab and the hazard ratio for overall survival was 2.06. Causes of death in the experimental arm included intestinal ischemia, cardio-respiratory arrest, pulmonary embolism, cardiac arrest, pneumonia, sudden death, myocarditis, large intestinal perforation, and cardiac failure. PD-1 and PD-L1 blocking antibodies linked to this monograph include atezolizumab, avelumab, cemiplimab, cosibelimab, dostarlimab, durvalumab, ivonescimab, nivolumab, pembrolizumab, penpulimab, retifanlimab, sintilimab, sugemalimab, and toripalimab.

Moderate Interaction: Assess the risk to the patient and take action as needed.

Anti-Angiogenic Agents/Erlotinib

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: The exact mechanism is unknown.

CLINICAL EFFECTS: Concurrent use of anti-angiogenic agents may increase the risk of gastrointestinal perforation in patients receiving erlotinib. Fatalities have been reported.(1)

PREDISPOSING FACTORS: Patients with a history of peptic ulceration or diverticular disease or who are receiving concomitant corticosteroids, NSAIDs, and/or taxane-based chemotherapy may be an increased risk of gastrointestinal perforation.(1)

PATIENT MANAGEMENT: Monitor patients receiving concurrent therapy for signs of gastrointestinal perforation. Discontinue erlotinib in patients who develop gastrointestinal perforation.(1)

DISCUSSION: In a phase II trial of concurrent bevacizumab plus erlotinib, 2 of 13 patients suffered fatal gastrointestinal perforations.(2) In another phase II trial of concurrent bevacizumab with erlotinib, 1 of 104 patients died of gastrointestinal perforation.(3)

Thalidomide Analogues/Dexamethasone

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: The mechanism of this interaction is unknown.

CLINICAL EFFECTS: Concurrent use of dexamethasone with iberdomide, lenalidomide, pomalidomide or thalidomide may increase the risk of venous thromboembolism (VTE), ischemic heart disease including myocardial infarction, and stroke.(1,2)

PREDISPOSING FACTORS: The effects of the interaction are greater with high-dose dexamethasone (480 mg/month or more).(3) Erythropoietic agents may also increase the risk.(1,2)

PATIENT MANAGEMENT: The US manufacturer of lenalidomide states the risk of deep vein thrombosis (DVT) and pulmonary embolism (PE) is significantly increased when lenalidomide and dexamethasone are given concurrently in patients with multiple myeloma and recommends thromboprophylaxis and the regimen should be selected based on the patient's underlying risks. Observe patients for signs and symptoms of venous thromboembolism (VTE) and instruct patients to see medical care if they develop symptoms such as shortness of breath, chest pain, or arm or leg swelling.(1) The US manufacturer of thalidomide states the risk of VTE increases significantly when thalidomide is used with concurrent therapy with standard chemotherapeutic agents including dexamethasone therapy and recommends considering thromboprophylaxis based on an assessment of individual patients' underlying risk factors. Observe patients closely for signs and symptoms of VTE and instruct patients to see medical care if they develop symptoms such as shortness of breath, chest pain, or arm or leg swelling.(2) The National Comprehensive Cancer Network (NCCN) Guidelines recommend VTE chemoprophylaxis with low-molecular weight heparin (LMWH) with a dose equivalent to enoxaparin 40 mg once daily or full-dose warfarin with a dose to maintain a target international normalized ratio (INR) 2-3.(3)

DISCUSSION: The National Comprehensive Cancer Network (NCCN) Guidelines include lenalidomide/thalidomide plus high-dose dexamethasone as a treatment-related venous thromboembolism (VTE) risk factor for cancer patients. High-dose dexamethasone is defined by NCCN as >/= 480 mg per month. The NCCN Guidelines recommend VTE chemoprophylaxis with low-molecular weight heparin (LMWH) at a dose equivalent to enoxaparin 40 mg once daily or full-dose warfarin with a dose to maintain a target international normalized ratio (INR) 2-3.(3) The US manufacturer states the standard dosing for multiple myeloma includes lenalidomide (25 mg daily) on days 1-21 of the 28-day cycle and dexamethasone (40 mg daily) on days 1, 8, 15, and 22 of the 28-day cycle.(1) The dexamethasone dose is adjusted for patients >75 years old to 20 mg daily on days 1, 8, 15, and 22 of the 28-day cycle.(1) In 2 studies of 703 patients who received at least one dose of lenalidomide/dexamethasone or placebo/dexamethasone, the incidence of DVT was 9.3% and 4.3%, respectively. In the same population, the incidence of grade 3/4 adverse reactions the incidence of DVT was 8.2% and 3.4%, respectively, and the incidence of serious adverse reactions of DVT was 7.4% and 3.1%, respectively. The US manufacturer states the standard dosing for multiple myeloma includes combination therapy with thalidomide (200 mg daily) and dexamethasone (40 mg daily on days 1-4, 9-12, and 17-20) in a 28-day treatment cycle.(2) The overall rate of adverse reactions in clinical trials for multiple myeloma resulting in treatment discontinuation were 30% in the thalidomide/dexamethasone group and 16% in the dexamethasone monotherapy group.(2) In a safety study of 466 subjects, the incidence of DVT was higher in the thalidomide/dexamethasone arm than in the placebo/dexamethasone arm with 13% versus 2%, respectively.(2) In a safety study of Grade 3/4 adverse drug reactions, the thalidomide/dexamethasone arm had a 12% incidence of DVT compared to a 2% incidence in the placebo/dexamethasone arm.(2) A summary article discusses the incidence of VTE in patients receiving treatment for multiple myeloma. The use of thalidomide as a single agent does not significantly increase the risk of VTE in both new diagnoses and relapsed/refractory patients with a VTE incidence of 3-4% and 2-4%, respectively. The addition of dexamethasone to thalidomide increased the risk of VTE in newly diagnosed patients with an incidence of 14-26%. Similarly, the use of lenalidomide as a single agent does not increase the risk of VTE. Lenalidomide with dexamethasone increased the incidence of VTE in newly diagnosed patients as well as relapsed/refractory patients to 75% and 17%, respectively. Concurrent therapy with lenalidomide and dexamethasone showed a difference in the incidence of VTE based on the dexamethasone dose (high dose defined as 480 mg/month and low dose defined as 160 mg/month) with higher doses associated with an increase risk (26% versus 12% incidence, respectively). The incidence of VTE in studies with thalidomide alone range from 1.5-4.6% versus studies with thalidomide/dexamethasone at 7-26%.(4) Several studies have evaluated the optimal VTE prophylaxis agent with lenalidomide-treated patients. Patients receiving lenalidomide/dexamethasone and no chemoprophylaxis had a VTE incidence of 11-75%, 26% with the use of aspirin, 17% with the use of aspirin/LMWH/warfarin combination therapy, and 2-15% with the use of LMWH. (5) Several studies have evaluated the optimal VTE prophylaxis agent in thalidomide-treated patients. Patients receiving thalidomide/dexamethasone and no chemoprophylaxis had a VTE incidence of 26%, 10% with the use of low-dose warfarin and 0% with the use of therapeutic warfarin/LMWH.(5) Lenalidomide/dexamethasone compared to placebo/dexamethasone increased the rate of myocardial infarction (1.7% versus 0.6%, respectively) and stroke (2.3% versus 0.9%, respectively).(1) Thalidomide/dexamethasone compared to placebo/dexamethasone increased the rate of ischemic heart disease (11.1% versus 4.7%, respectively), including myocardial infarction (1.3% versus 1.7%, respectively), and stroke (2.6% versus 0.9%, respectively).(2)

*Thalidomide is contraindicated in females who are pregnant.

*Thalidomide is contraindicated in patients with known hypersensitivity (e.g., angioedema, anaphylaxis) to the drug or any ingredient in the formulation.

• Lactation
• Pregnancy

• Bradycardia
• Cerebrovascular accident
• Deep venous thrombosis
• Myocardial ischemia
• Neutropenic disorder
• Peripheral neuropathy
• Pulmonary thromboembolism
• Thromboembolic disorder

• Acute myeloid leukemia
• HIV infection
• Lower seizure threshold
• Myelodysplastic syndrome
• Orthostatic hypotension
• Seizure disorder
• Thrombocytopenic disorder

Adverse effects reported in at least 20% of patients with multiple myeloma receiving thalidomide include fatigue, hypocalcemia, edema, constipation, sensory or motor neuropathy, dyspnea, muscle weakness, leukopenia, neutropenia, rash/desquamation, confusion, anorexia, nausea, anxiety/agitation, asthenia, tremor, fever, weight loss, thromboembolism, weight gain, dizziness, and dry skin.

Adverse effects reported in at least 10% of patients with erythema nodosum leprosum (ENL) receiving thalidomide include somnolence, rash, and headache.

More Frequent

• Dyspnea
• Hypocalcemia
• Leukopenia
• Peripheral motor neuropathy
• Peripheral neuropathy
• Thromboembolic disorder

Less Frequent

• Acute abdominal pain
• Hyperbilirubinemia
• Infection
• Oral candidiasis

Rare or Very Rare

• Abnormal ECG
• Acute myocardial infarction
• Anaphylaxis
• Angioedema
• Apnea
• Arterial thrombosis
• Biliary obstruction
• Bradycardia
• Cardiac arrhythmia
• Cerebrovascular accident
• Chronic myelocytic leukemia
• Cytomegalovirus disease
• Deep venous thrombosis
• DRESS syndrome
• Erythema multiforme
• Erythema nodosum
• Exfoliative dermatitis
• Gastrointestinal hemorrhage
• Gastrointestinal obstruction
• Gastrointestinal perforation
• Hearing loss
• Herpes zoster
• Hypersensitivity drug reaction
• Hypotension
• Hypothyroidism
• Lymphopenia
• Neutropenic disorder
• Pancytopenia
• Pleural effusions
• Posterior reversible encephalopathy syndrome
• Progressive multifocal leukoencephalopathy
• Pulmonary hypertension
• Pulmonary thromboembolism
• Reactivation of hepatitis B
• Renal failure
• Seizure disorder
• Septic shock
• Sick sinus syndrome
• Stevens-johnson syndrome
• Suicidal
• Syncope
• Thrombocytopenic disorder
• Toxic epidermal necrolysis
• Transient cerebral ischemia
• Tumor lysis syndrome

More Frequent

• Acute cognitive impairment
• Constipation
• Dizziness
• Drowsy
• Dry skin
• Edema
• Fatigue
• Fever
• General weakness
• Headache disorder
• Muscle weakness
• Nausea
• Peripheral edema
• Skin rash
• Symptoms of anxiety
• Tremor
• Weight gain
• Weight loss

Less Frequent

• Agitation
• Anorexia
• Arthralgia
• Diarrhea
• Increased appetite
• Mood changes
• Myalgia
• Orthostatic hypotension
• Xerostomia

Rare or Very Rare

• Amenorrhea
• Aphthous stomatitis
• Blurred vision
• Conjunctivitis
• Cramps in legs
• Depression
• Diplopia
• Dysgeusia
• Flu-like symptoms
• Galactorrhea not associated with childbirth
• Lymphedema
• Nail disorders
• Nystagmus
• Oliguria
• Raynaud's phenomenon
• Sedation hangover effect
• Urinary incontinence
• Urticaria

No enhanced messaging available.

Although safety and efficacy of thalidomide in pediatric patients younger than 12 years of age have not been established, the drug has been used in a limited number of children 6 months to 12 years of age+. When thalidomide was used for the treatment of graft-versus-host disease in a limited number of bone marrow transplant recipients 1.5-17 years of age+, adverse effects of the drug included somnolence (which required discontinuance of the drug in at least one child), constipation, and a syndrome of rash, eosinophilia, and pancreatitis (which resolved after the drug was discontinued).

When thalidomide was used for the treatment of Crohn disease in a limited number of children and adolescents 2-18 years of age+, the most frequent severe adverse effect was peripheral neuropathy.

Thalidomide is a human teratogen and is contraindicated for use during pregnancy.

It is not known whether thalidomide is distributed into human milk. Because many drugs are distributed into milk, and because of the potential for serious thalidomide-related adverse effects in nursing infants, a decision should be made whether to discontinue nursing or the drug, taking into account the importance of the drug to the mother.

The manufacturer makes no specific dosage recommendations for geriatric patients.

In clinical trials evaluating thalidomide in combination with dexamethasone, 52% of patients were 65 years of age or older and 15% were 75 years of age or older. Atrial fibrillation, constipation, fatigue, nausea, hypokalemia, thromboembolism, hyperglycemia, and asthenia occurred at a higher incidence compared with younger adults.