Thalidomide is a drug that was originally developed and marketed in the late 1950s and early 1960s as a sedative and anti-nausea medication.

It was widely prescribed to pregnant women, particularly in Europe, as a treatment for morning sickness.

However, the drug's use during pregnancy led to a tragic and notorious public health disaster.

Thalidomide was found to cause severe birth defects in babies born to mothers who had taken the drug during pregnancy.

These birth defects included limb deformities, where babies were born with shortened or missing limbs.

This crisis brought significant attention to the need for rigorous drug testing and safety regulations.

Thalidomide (Thalomid) is a chemotherapeutic medicine used in the treatment of multiple myeloma and other plasma cell dyscrasias.

In the mid-19th century, it was used to relieve nausea associated with pregnancy.

However, it led to severe fetal malformations including absent limbs. Currently, it is recommended for only a few diseases because of its potent anti-angiogenic properties.

Indications of Thalidomide:

• Erythema nodosum leprosum:

  • It is used for the acute treatment of moderate to severe cutaneous manifestations of erythema nodosum leprosum.
  • It is also used for the maintenance treatment for suppression and prevention of recurrence of cutaneous manifestations of erythema nodosum leprosum.
  • Limitation of use: Thalidomide is not indicated as monotherapy for erythema nodosum leprosum treatment in the presence of moderate to severe neuritis.

• Multiple myeloma:

  • It is indicated for the treatment of newly diagnosed multiple myeloma (in combination with dexamethasone).

• Off-Label Use of Thalidomide in Adults:

  • AIDS-related aphthous stomatitis;
  • refractory Chronic graft-versus-host disease;
  • Multiple myeloma, maintenance therapy;
  • Multiple myeloma, salvage therapy;
  • Systemic light chain amyloidosis;
  • Refractory Uremic pruritus;
  • Waldenström macroglobulinemia
  • Beta Thalassemia Major

Thalidomide (Thalomid) dose in Adults

Thalidomide (Thalomid) dose in the treatment of acute cutaneous erythema nodosum leprosum:

• Standard Starting Dose:
  • Begin with 100 to 300 mg taken orally at bedtime.
  • Continue until symptoms get better (usually around 2 weeks).
  • Afterward, reduce the dose by 50 mg every 2 to 4 weeks.
• If the Patient Weighs Less than 50 kg:
  • Start with a dose closer to the 100 mg end of the range.
• Severe Skin Reaction or Patients Needing High Doses in the Past:
  • Start with up to 400 mg. This can be taken all at bedtime or split into smaller doses throughout the day.
• When Neuritis is Moderate to Severe:
  • Use corticosteroids alongside thalidomide.
  • As neuritis gets better, reduce and eventually stop corticosteroid use.

Thalidomide Maintenance Dose for Erythema Nodosum Leprosum:

• Goal: Keep the dose as low as needed to control the condition.
• Tapering Attempts: Try to reduce the dose every 3 to 6 months.
• Tapering Method: Decrease the dose by 50 mg every 2 to 4 weeks during tapering attempts.

Thalidomide (Thalomid) dose in the treatment of newly diagnosed multiple myeloma:

• Dose: 200 mg taken orally at bedtime.
• Usage: Use in combination with dexamethasone.

Thalidomide (Thalomid) dose in the treatment of multiple myeloma (off-label dosing or combinations):

In Combination with Bortezomib and Dexamethasone (Off-label combination):

• Induction Therapy:
  • Start with 100 mg once daily for the first 14 days.
  • Then, 200 mg once daily for three 21-day cycles (Based on Cavo 2010).
  • Alternatively, 100 mg once daily for up to eight 21-day cycles (Based on Kaufman 2010).

In Combination with Melphalan and Prednisone (Off-label combination):

• Options based on different studies:
  • 200 to 400 mg once daily (Facon 2007).
  • 100 mg once daily (Palumbo 2008).
  • 50 to 100 mg once daily, adjusted according to the patient's tolerance(Hulin 2009).

Thalidomide (Thalomid) dose in the maintenance treatment of multiple myeloma (following autologous stem cell transplant; off-label):

Based on Brinker 2006:

• Dose: 200 mg taken orally once daily.
• Start: 3 to 6 months after the transplant.
• Duration: Continue until there's disease progression or unacceptable side effects.

Based on Spencer 2009 (Used with Prednisolone):

• Initial Dose: 100 mg taken orally once daily.
• Start: 42 to 60 days after the transplant.
• Dose Increase: If well-tolerated, increase to 200 mg once daily after 2 weeks.
• Duration: Continue for up to 12 months.

Thalidomide (Thalomid) dose in the treatment of Multiple myeloma as salvage therapy:

Based on Singhal 1999:

• Initial Dose: 200 mg taken orally once daily at bedtime.
• Dose Increase: If tolerated, increase daily dose by 200 mg every 2 weeks for 6 weeks.
• Maximum Dose: Up to 800 mg taken orally once daily at bedtime.

Based on Palumbo 2001 (Used with Dexamethasone):

• Dose: 100 mg taken orally once daily.

Based on Garderet 2012 (Used with Bortezomib and Dexamethasone):

• Dose: 200 mg taken orally once daily.
• Duration: Continue for 1 year.

Based on Lee 2003 (Used with Dexamethasone, Cisplatin, Doxorubicin, Cyclophosphamide, and Etoposide):

• Dose: 400 mg taken orally once daily at bedtime.

Thalidomide (Thalomid) dose in the treatment of AIDS-related aphthous stomatitis (off-label):

Based on Jacobson 1997:

• Initial Dose: 200 mg taken orally once daily at bedtime.
• Duration: Up to 8 weeks.
• If No Response: Increase to 200 mg taken orally twice daily.
• Duration for Increased Dose: Continue for 4 weeks.

Thalidomide (Thalomid) dose in the treatment of refractory chronic graft-versus-host disease (as off-label second-line treatment; optimum dose not determined):

Based on Wolff 2010:

• Initial Dose: 100 mg taken orally once daily at bedtime.
• Dose Escalation: Can be increased to a total of 400 mg daily, divided into 3 to 4 doses.

Based on Kulkarni 2003:

• Initial Dose: Between 50 to 100 mg taken orally three times daily.
• Maximum Dose: Ranges from 600 to 1,200 mg daily.

Based on Vogelsang 1992:

• Dose: 200 mg taken orally four times daily.
• Adjustment Criterion: Dose is adjusted to achieve a thalidomide concentration of ≥5 mcg/mL 2 hours after taking the dose.

Based on Parker 1995:

• Dose: Between 100 to 300 mg taken orally four times daily.

Thalidomide (Thalomid) dose in the treatment of systemic light-chain amyloidosis (off-label):

Based on Wechalekar 2007:

• Starting Dose: 50 to 100 mg taken orally once daily.
• Titration: Increase the dose at 4-week intervals.
• Typical Dose: 200 mg taken orally once daily.
• Usage: Use in combination with cyclophosphamide and dexamethasone.

Thalidomide (Thalomid) dose in the treatment of refractory uremic pruritus (off-label):

Based on Silva 1994:

• Dose: 100 mg taken orally once daily at bedtime.

Note: More research is needed to clarify the role of thalidomide in treating this condition. There are several other treatments available with safer side effect profiles.

Thalidomide (Thalomid) dose in the treatment of Waldenström macroglobulinemia (off-label):

Based on Treon 2008:

• Dose: Up to 200 mg taken orally once daily.
• Duration: For up to 52 weeks.
• Usage: Use in combination with rituximab.

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Thalidomide (Thalomid) dose in Children

Thalidomide (Thaled) dose in the treatment of AIDS-related aphthous stomatitis:

Limited Data Based on Jacobson 1997:

• Age Group: Adolescents aged 13 years and older.
• Starting Dose: 200 mg taken orally once daily at bedtime.
• Duration: For 4 weeks or until symptoms resolve.
• Dose Increase: If there's no improvement after 4 weeks, the dose may be increased to 200 mg taken orally twice daily.

Study Details: This dosing is based on a double-blind, placebo-controlled trial conducted by the AIDS Clinical Trials Group. In the study, which included 57 participants aged 13 years and older, 55% of the patients in the thalidomide treatment group experienced healing, compared to only 7% in the placebo group.

Thalidomide (Thalomid) dose in the treatment of refractory chronic graft-versus-host disease:

Limited Data Available:

• Age Group: Children aged 2 years and older, and Adolescents.
• Starting Dose:
  • 3 to 6 mg/kg/day.
  • The maximum starting dose should not exceed 100 mg/day.
  • Can be taken at bedtime or divided into 2 to 4 doses before meals.
• Dose Adjustments:
  • The dose can be adjusted at intervals of 2 weeks or more, based on patient response.
  • The dose can be increased up to 12 mg/kg/day, split into 3 to 4 doses.
  • The maximum daily dose should not exceed 800 mg/day.

Study Details:

• Dosing is based on research by Browne 2000, Rovelli 1998, and Wolff 2011.
• Another trial, as cited from Vogelsang 1992, used initial doses of 3 mg/kg every 6 hours. The dosage was adjusted to achieve a thalidomide concentration of at least 5 mcg/mL 2 hours after taking the dose.

Thalidomide (Thalomid) dose in the treatment of refractory Crohn's disease and ulcerative colitis:

Limited Data Available:

• Age Group: Children aged 1 year and older, and Adolescents.
• Starting Dose:
  • 0.5 to 3 mg/kg/day.
  • The dose is usually taken once daily in the evening.
  • The maximum daily dose should not exceed 300 mg/day.
• Post-Remission: Once remission is achieved, titrate down to the lowest effective dose.

Study References:

• The dosing guidelines are based on research from Facchini 2001, Lazzerini 2007, Martelossi 2004, and Zheng 2011.

Thalidomide (Thalomid) dose in the treatment of erythema nodosum leprosum (ENL): 

Age Group: Children aged 12 years and older, and Adolescents.

• Acute Treatment:
  • Starting Dose: 100 to 300 mg taken orally once daily at bedtime.
  • Duration: Continue until symptoms subside, typically around 2 weeks.
  • Dose Reduction: Afterward, reduce the dose by 50 mg every 2 to 4 weeks.
  • Severe Cases with Neuritis: For moderate to severe neuritis, corticosteroids can be started alongside thalidomide. Once neuritis improves, taper and discontinue corticosteroids.
  • Patients Weighing <50 kg: Start with a dose closer to the 100 mg end of the range.
  • Severe Skin Reaction or Prior High Dose Requirement: The dose can be started or increased to 400 mg/day. This can be taken all at bedtime or divided throughout the day.
• Maintenance Treatment:
  • Goal: Use the lowest possible dose to manage the condition.
  • Tapering Attempts: Try to reduce the dose every 3 to 6 months.
  • Dose Reduction Method: Decrease the dose by 50 mg every 2 to 4 weeks during tapering attempts.

Thalidomide (Thalomid) dose in the treatment of Systemic juvenile idiopathic arthritis (SJIA):

Limited Data Available:

• Age Group: Children aged 3 years and older, and Adolescents.
• Starting Dose:
  • 2 mg/kg/day taken orally.
• Dose Adjustment:
  • If necessary, the dose can be increased at 2-week intervals to 3 to 5 mg/kg/day.

Study Details:

• This dosing is based on a multicenter, open-labeled prospective study by Lehman in 2004.
• The study involved 13 participants aged between 3 to 23 years.
• Within 4 weeks, 11 out of the 13 patients showed:
  • Improvement in JRA (Juvenile Rheumatoid Arthritis) scores.
  • Significant decrease in ESR (Erythrocyte Sedimentation Rate).
  • Significant increase in hemoglobin levels.

Thalidomide Dose in Patients with Beta Thalassemia Major:

Thalidomide has been found to reduce the requirements for blood transfusions in children and adults with Beta-thalassemia Major.

It has been found to be more effective than Hydroxyurea in reducing transfusion requirements. 

Thalidomide increases the gene expression of the Gamma chain, hence increasing the levels of fetal hemoglobin. 

• Thalidomide dose in beta thalassemia:
  • 100 mg once daily after the evening meals.
  • In young children, the dose is 2 -5 mg/ kg/ day.

Dosing adjustment for toxicity:

Dosing Adjustment for Toxicity in Children and Adolescents:

• ANC (Absolute Neutrophil Count) ≤750/mm³:
  • Withhold treatment if it's clinically appropriate.
• For Other Observed Toxicities (based on adult patients with multiple myeloma):
  • Constipation, Oversedation:
    • Temporarily withhold the drug or continue at a reduced dose.
  • Peripheral Neuropathy:
    • Manufacturer's Recommendation: Temporarily withhold or continue with a reduced dose.
    • Additional Adjustments (based on Richardson 2012):
      • Grade 1: Reduce the dose by 50%.
      • Grade 2: Temporarily stop the therapy. Once the symptoms reduce to Grade 1 or lower, resume therapy at a 50% reduced dose (only if it's clinically appropriate).
      • Grade 3 or Higher: Discontinue the therapy completely.

Thalidomide Pregnancy Risk Category: X

[US Boxed Warning]

• Thalidomide can cause severe birth defects or death to the fetus.
• Do not take if pregnant or if there's a chance of getting pregnant.
• Even one dose can cause severe birth defects.
• To prevent misuse, thalidomide is only available through a special program called Thalomid REMS.
• Animal studies and data from pregnant women show harmful effects on the fetus.
• Birth defects observed: missing limbs, bone issues, facial paralysis, heart defects, urinary and genital abnormalities, and others.
• About 40% of infants may die at or shortly after birth.
• Women who can become pregnant:
  • Avoid pregnancy 4 weeks before, during, and 4 weeks after stopping thalidomide.
  • Use two reliable birth control methods or don't have sex.
  • Need a negative pregnancy test before starting and then regularly.
  • If there's a missed period, abnormal pregnancy test, or unexpected bleeding, stop thalidomide immediately.
• Women (including health workers) should avoid touching thalidomide capsules.
• Thalidomide can be present in semen.
  • Men (even if vasectomized) should use condoms during sex and not donate sperm.
• For patients aged 12-18, a parent/guardian must ensure they follow the guidelines.
• If someone gets pregnant while on thalidomide:
  • Stop the drug immediately.

Use of thalidomide during lactation

• It's unclear if thalidomide passes into breast milk.
• Because of possible severe side effects in the breastfed baby, the maker of the drug advises against breastfeeding while on thalidomide.

Thalidomide (Thalomid) Dose adjustment in renal disease:

• For patients with renal impairment or those on dialysis, no dosage adjustment is typically necessary, as per the manufacturer's recommendations.
• A study involving patients with renal failure who were treated with thalidomide and dexamethasone for multiple myeloma found that toxicities and efficacy were similar to those with normal kidney function (Seol 2010).
• Another study that looked at induction therapy with thalidomide and dexamethasone in newly diagnosed myeloma patients with renal failure, including those on chronic hemodialysis, found that toxicities were similar to patients without renal impairment. This suggests that thalidomide and dexamethasone can be safely administered to these patients (Tosi 2009).
• The International Myeloma Working Group (IMWG) also suggests that thalidomide can be safely given to patients with renal impairment, including those on dialysis. They recommend using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) or the Modification of Diet in Renal Disease (MDRD) formulas to assess renal function in multiple myeloma patients with stable serum creatinine levels (Dimopoulos 2016).

Thalidomide (Thalomid) Dose adjustment in liver disease:

• The manufacturer doesn't provide any dosage adjustments for patients with liver impairment, as it hasn't been specifically studied.
• Thalidomide doesn't seem to be majorly metabolized by the liver.

Common Side Effects of Thalidomide (Thalomid):

• Central nervous system:
  • Drowsiness
  • Headache
  • Peripheral neuropathy

Rare Side Effects of Thalidomide (Thalomid):

• Cardiovascular:
  • Facial Edema
  • Peripheral Edema
• Central Nervous System:
  • Malaise
  • Pain
  • Vertigo
  • Dizziness
• Dermatologic:
  • Pruritus
  • Fungal Dermatitis
  • Maculopapular Rash
  • Nail Disease
• Gastrointestinal:
  • Constipation
  • Nausea
  • Oral Candidiasis
  • Toothache
• Genitourinary:
  • Impotence
• Neuromuscular & Skeletal:
  • Weakness
  • Back Pain
  • Neck Pain
  • Neck Stiffness
  • Tremor
• Miscellaneous:
  • Accidental Injury

Contraindications to Thalidomide (Thalomid):

US Labeling:

• Allergic reactions to thalidomide or any ingredient in the drug.
• Pregnancy.

Canadian Labeling (includes the above and some additional contraindications not found in US labeling):

• Allergic reactions to lenalidomide or pomalidomide.
• Females who might become pregnant and male patients who can't follow or adhere to specific conditions for use (refer to manufacturer's instructions).
• Breastfeeding.

Thalomid Precautions and Warnings

Suppression of bone marrow

• It can lead to leukopenia (low white blood cell count) and neutropenia (low neutrophil count).
• Therapy should not be initiated if the absolute neutrophil count (ANC) is less than 750/mm³.
• Persistent neutropenia might require a temporary interruption of treatment.
• Thalidomide can also cause thrombocytopenia (low platelet count), including severe cases (grades 3 and 4). This might necessitate a dose reduction, treatment delay, or discontinuation.
• Monitoring for signs of bleeding is crucial, such as petechiae (small red or purple spots on the skin), nosebleeds (epistaxis), and gastrointestinal bleeding. This is especially important if other medications being taken increase the risk of bleeding.
• Regular monitoring of complete blood count (CBC) with differential and platelet levels is recommended.
• Anemia (low red blood cell count) has also been reported as an adverse effect.

Bradycardia

• Thalidomide can lead to bradycardia (slow heart rate).
• Caution is needed when giving thalidomide with other drugs that can also slow down the heart rate.
• Depending on the severity and the patient's overall health, a reduction in the thalidomide dose or discontinuation of the medication might be necessary.

CNS effects

• Thalidomide can lead to dizziness, drowsiness, and somnolence (feeling very sleepy).
• Patients should be cautioned about engaging in activities that require mental alertness, such as operating machinery or driving, especially when experiencing these effects.
• Avoiding alcohol (ethanol) and medications that could worsen these symptoms is important.
• If drowsiness or somnolence becomes excessive, dose reductions might be necessary.

Constipation

• Constipation is a common side effect of thalidomide.
• Depending on the severity, treatment might need to be paused or the dosage reduced.

Dermatologic reactions

• Severe skin reactions, including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug reactions with eosinophilia and systemic symptoms (DRESS) have been reported. These reactions can be fatal.
• For a grade 2 or 3 rash, consider withholding the drug or discontinuing the treatment.
• If the rash is grade 4 or presents as exfoliative, bullous, or especially severe (like SJS, TEN, DRESS), then permanently discontinue the drug.

Hepatotoxicity

• There have been reports of abnormal liver function tests, hepatitis, and cholestatic jaundice after using thalidomide.
• Hepatotoxicity (liver damage), which can be due to hepatocellular (affecting liver cells) or cholestatic (affecting bile flow) injury, is rare but has been observed.
• These liver-related side effects usually develop around 46 days on average after starting the drug, based on case reports (Vilas-Boas 2012).
• Most of these adverse events resolved after discontinuing thalidomide.

Hypersensitivity

• Hypersensitivity reactions, including angioedema (swelling under the skin), anaphylactic reactions (severe allergic reactions), and erythematous macular rash (red, flat rash) have been reported.
• These reactions might be accompanied by symptoms like fever, tachycardia (fast heart rate), and hypotension (low blood pressure).
• For angioedema or anaphylaxis, treatment should be permanently discontinued.
• Other severe hypersensitivity reactions may necessitate a treatment interruption and should be discontinued if they happen again when the drug is restarted.

Orthostatic hypotension

• Thalidomide can lead to orthostatic hypotension, which is a sudden drop in blood pressure when standing up from sitting or lying down.
• Use the drug with caution in patients who might be at risk or adversely affected by short-lived episodes of low blood pressure.
• To help prevent this, patients should be advised to sit up for a few moments before standing up when getting up from a lying position.

Peripheral neuropathy

• Thalidomide is commonly linked to peripheral neuropathy, which is a condition affecting the nerves outside of the brain and spinal cord.
• Peripheral neuropathy might be irreversible, and it can develop with chronic use (over months) or even with short-term use. The onset can also be delayed.
• Be cautious when using thalidomide alongside other medications that can also cause peripheral neuropathy.
• Monitoring for signs and symptoms of neuropathy is crucial, especially during the first 3 months of therapy and regularly thereafter.
• Electrophysiological testing may be considered at the beginning and every 6 months to detect asymptomatic neuropathy.
• To limit further damage, the drug should be immediately discontinued if neuropathy develops, if it's clinically appropriate. Treatment can only be restarted if the neuropathy returns to baseline, and this might require a dosage reduction or permanent discontinuation.

Secondary malignancy

• An increased occurrence of second primary malignancies (SPMs) has been seen in previously untreated multiple myeloma patients taking thalidomide combined with melphalan and prednisone.
• The observed secondary malignancies include acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS).
• Beyond AML and MDS, solid tumors have also been reported in those on thalidomide maintenance treatment for multiple myeloma, as noted in a study by Usmani in 2012.
• It's essential to thoroughly evaluate patients for SPMs before starting and during the treatment. Any discovered malignancies should be addressed and managed based on clinical guidelines.

Seizures

• Seizures, including serious ones like grand mal convulsions, have been reported in data collected after the drug's release to the market.
• Patients with a history of seizures, those on medications that can affect the seizure threshold, or those with conditions that make them more susceptible to seizures should be monitored closely for signs pointing to potential seizure activity.

Thromboembolic Events: [US Boxed Warning]

• Thalidomide, especially when used for treating multiple myeloma, comes with an increased risk of venous thromboembolism (VTE), which includes deep vein thrombosis (DVT) and pulmonary embolism (PE). This risk is even higher when thalidomide is combined with standard chemotherapy drugs like dexamethasone.
• In a controlled study, the incidence of VTE was much higher (22.5%) in patients receiving thalidomide with dexamethasone compared to those on dexamethasone alone (4.9%).
• Therefore, patients should be closely monitored for signs and symptoms of thromboembolism, such as shortness of breath, chest pain, or arm/leg swelling. If these symptoms develop, patients should seek immediate medical attention.
• Depending on individual risk factors, thromboprophylaxis (measures to prevent blood clots) should be considered. The American Society of Clinical Oncology guidelines recommend different approaches based on the level of risk.
• Thalidomide treatment, especially in combination with chemotherapy and dexamethasone, is associated with a higher risk of ischemic heart disease, including heart attacks (MI) and strokes. Therefore, individual risk factors should be assessed, and thromboprophylaxis should be considered accordingly.
• Thalidomide users should be closely monitored for signs and symptoms of thromboembolism, and they should be advised to seek immediate medical care if such symptoms occur.
• When using other medications known to be associated with thromboembolism, caution should be exercised.

Tumor lysis syndrome

• Tumor lysis syndrome (TLS) is a condition where there's a rapid release of cell contents into the bloodstream, usually after the treatment of certain cancers. It can lead to dangerous levels of potassium, phosphate, and uric acid in the blood.
• Patients with a high tumor burden, meaning they have a large number of cancer cells, might be at risk for TLS when treated with thalidomide.
• Such patients should be closely monitored. Specifically, the level of uric acid in the blood can become elevated, which can lead to complications like kidney stones and kidney failure.
• For patients at risk or those showing signs of TLS, appropriate measures to manage hyperuricemia (elevated uric acid levels) should be instituted. This might include hydration and medications like allopurinol or rasburicase to lower uric acid levels.

Heart Failure:

• According to a scientific statement from the American Heart Association (AHA), thalidomide is identified as an agent that has the potential to worsen underlying heart muscle (myocardial) dysfunction.
• The magnitude of this effect is considered to be minor.
• Therefore, patients with existing heart conditions, especially those with heart failure, should be closely monitored when taking thalidomide, and any changes in their cardiac symptoms or function should be promptly addressed (AHA [Page 2016]).

Multiple myeloma

• In two clinical studies involving patients with multiple myeloma, an increase in mortality was observed in those who received pembrolizumab in combination with a thalidomide analogue and dexamethasone.
• Causes of death in the group receiving this experimental combination (pembrolizumab, dexamethasone, and a thalidomide analogue such as pomalidomide or lenalidomide) included various serious conditions like myocarditis (inflammation of the heart muscle), Stevens-Johnson syndrome (SJS), heart attacks (MI), and other cardiac, respiratory, and infectious complications.
• Importantly, the use of pembrolizumab for treating multiple myeloma in combination with a thalidomide analogue and dexamethasone is not approved because multiple myeloma is not an authorized indication for PD-1 or PD-L1 blocking antibodies like pembrolizumab. This combination should only be considered within the context of a clinical trial.

Thalidomide: Drug Interaction

Risk Factor C (Monitor therapy)
Alfuzosin	May enhance the hypotensive effect of Blood Pressure Lowering Agents.
Alizapride	May enhance the CNS depressant effect of CNS Depressants.
Bisphosphonate Derivatives	Angiogenesis Inhibitors (Systemic) may enhance the adverse/toxic effect of Bisphosphonate Derivatives. Specifically, the risk for osteonecrosis of the jaw may be increased.
Blood Pressure Lowering Agents	May enhance the hypotensive effect of HypotensionAssociated Agents.
Brimonidine (Topical)	May enhance the CNS depressant effect of CNS Depressants.
Brimonidine (Topical)	May enhance the hypotensive effect of Blood Pressure Lowering Agents.
Bromopride	May enhance the CNS depressant effect of CNS Depressants.
Cannabidiol	May enhance the CNS depressant effect of CNS Depressants.
Cannabis	May enhance the CNS depressant effect of CNS Depressants.
Chloramphenicol (Ophthalmic)	May enhance the adverse/toxic effect of Myelosuppressive Agents.
Chlorphenesin Carbamate	May enhance the adverse/toxic effect of CNS Depressants.
Coccidioides immitis Skin Test	Immunosuppressants may diminish the diagnostic effect of Coccidioides immitis Skin Test.
Denosumab	May enhance the adverse/toxic effect of Immunosuppressants. Specifically, the risk for serious infections may be increased.
Diazoxide	May enhance the hypotensive effect of Blood Pressure Lowering Agents.
Dimethindene (Topical)	May enhance the CNS depressant effect of CNS Depressants.
Dronabinol	May enhance the CNS depressant effect of CNS Depressants.
DULoxetine	Blood Pressure Lowering Agents may enhance the hypotensive effect of DULoxetine.
Erythropoiesis-Stimulating Agents	May enhance the thrombogenic effect of Thalidomide.
Estrogen Derivatives	May enhance the thrombogenic effect of Thalidomide.
Estrogen Derivatives (Contraceptive)	May enhance the thrombogenic effect of Thalidomide.
Herbs (Hypotensive Properties)	May enhance the hypotensive effect of Blood Pressure Lowering Agents.
Hypotension-Associated Agents	Blood Pressure Lowering Agents may enhance the hypotensive effect of Hypotension-Associated Agents.
Kava Kava	May enhance the adverse/toxic effect of CNS Depressants.
Levodopa-Containing Products	Blood Pressure Lowering Agents may enhance the hypotensive effect of Levodopa-Containing Products.
Lofexidine	May enhance the CNS depressant effect of CNS Depressants. Management: Drugs listed as exceptions to this monograph are discussed in further detail in separate drug interaction monographs.
Magnesium Sulfate	May enhance the CNS depressant effect of CNS Depressants.
Mesalamine	May enhance the myelosuppressive effect of Myelosuppressive Agents.
MetyroSINE	CNS Depressants may enhance the sedative effect of MetyroSINE.
Minocycline	May enhance the CNS depressant effect of CNS Depressants.
Molsidomine	May enhance the hypotensive effect of Blood Pressure Lowering Agents.
Nabilone	May enhance the CNS depressant effect of CNS Depressants.
Naftopidil	May enhance the hypotensive effect of Blood Pressure Lowering Agents.
Nicergoline	May enhance the hypotensive effect of Blood Pressure Lowering Agents.
Nicorandil	May enhance the hypotensive effect of Blood Pressure Lowering Agents.
Nitroprusside	Blood Pressure Lowering Agents may enhance the hypotensive effect of Nitroprusside.
Ocrelizumab	May enhance the immunosuppressive effect of Immunosuppressants.
Pamidronate	Thalidomide may enhance the nephrotoxic effect of Pamidronate.
Pentoxifylline	May enhance the hypotensive effect of Blood Pressure Lowering Agents.
Phosphodiesterase 5 Inhibitors	May enhance the hypotensive effect of Blood Pressure Lowering Agents.
Pidotimod	Immunosuppressants may diminish the therapeutic effect of Pidotimod.
Piribedil	CNS Depressants may enhance the CNS depressant effect of Piribedil.
Pramipexole	CNS Depressants may enhance the sedative effect of Pramipexole.
Progestins (Contraceptive)	May enhance the thrombogenic effect of Thalidomide.
Prostacyclin Analogues	May enhance the hypotensive effect of Blood Pressure Lowering Agents.
Quinagolide	May enhance the hypotensive effect of Blood Pressure Lowering Agents.
ROPINIRole	CNS Depressants may enhance the sedative effect of ROPINIRole.
Rotigotine	CNS Depressants may enhance the sedative effect of Rotigotine.
Rufinamide	May enhance the adverse/toxic effect of CNS Depressants. Specifically, sleepiness and dizziness may be enhanced.
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.
Siponimod	Immunosuppressants may enhance the immunosuppressive effect of Siponimod.
Tertomotide	Immunosuppressants may diminish the therapeutic effect of Tertomotide.
Tetrahydrocannabinol	May enhance the CNS depressant effect of CNS Depressants.
Tetrahydrocannabinol and Cannabidiol	May enhance the CNS depressant effect of CNS Depressants.
Trastuzumab	May enhance the neutropenic effect of Immunosuppressants.
Zoledronic Acid	Thalidomide may enhance the adverse/toxic effect of Zoledronic Acid.
Risk Factor D (Consider therapy modification)
Amifostine	Blood Pressure Lowering Agents may enhance the hypotensive effect of Amifostine. Management: When amifostine is used at chemotherapy doses, blood pressure-lowering medications should be withheld for 24 hours prior to amifostine administration. If blood pressure-lowering therapy cannot be withheld, amifostine should not be administered.
Baricitinib	Immunosuppressants may enhance the immunosuppressive effect of Baricitinib. Management: Use of baricitinib in combination with potent immunosuppressants such as azathioprine or cyclosporine is not recommended. Concurrent use with antirheumatic doses of methotrexate or nonbiologic disease-modifying antirheumatic drugs (DMARDs) is permitted.
Deferiprone	Myelosuppressive Agents may enhance the neutropenic effect of Deferiprone. Management: Avoid the concomitant use of deferiprone and myelosuppressive agents whenever possible. If this combination cannot be avoided, monitor the absolute neutrophil count more closely.
Dexamethasone (Systemic)	May enhance the dermatologic adverse effect of Thalidomide. Dexamethasone (Systemic) may enhance the thrombogenic effect of Thalidomide.
Echinacea	May diminish the therapeutic effect of Immunosuppressants.
Fingolimod	Immunosuppressants may enhance the immunosuppressive effect of Fingolimod. Management: Avoid the concomitant use of fingolimod and other immunosuppressants when possible. If combined, monitor patients closely for additive immunosuppressant effects (eg, infections).
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.
Nivolumab	Immunosuppressants may diminish the therapeutic effect of Nivolumab.
Obinutuzumab	May enhance the hypotensive effect of Blood Pressure Lowering Agents. Management: Consider temporarily withholding blood pressure-lowering medications beginning 12 hours prior to obinutuzumab infusion and continuing until 1 hour after the end of the infusion.
Roflumilast	May enhance the immunosuppressive effect of Immunosuppressants.
Sipuleucel-T	Immunosuppressants may diminish the therapeutic effect of Sipuleucel-T. Management: Evaluate patients to see if it is medically appropriate to reduce or discontinue therapy with immunosuppressants prior to initiating sipuleucel-T therapy.
Tofacitinib	Immunosuppressants may enhance the immunosuppressive effect of Tofacitinib. Management: Concurrent use with antirheumatic doses of methotrexate or nonbiologic disease-modifying antirheumatic drugs (DMARDs) is permitted, and this warning seems particularly focused on more potent immunosuppressants.
Vaccines (Inactivated)	Immunosuppressants may diminish the therapeutic effect of Vaccines (Inactivated). Management: Vaccine efficacy may be reduced. Complete all age-appropriate vaccinations at least 2 weeks prior to starting an immunosuppressant. If vaccinated during immunosuppressant therapy, revaccinate at least 3 months after immunosuppressant discontinuation.
Risk Factor X (Avoid combination)
Abatacept	Anti-TNF Agents may enhance the adverse/toxic effect of Abatacept. An increased risk of serious infection during concomitant use has been reported.
Anakinra	Anti-TNF Agents may enhance the adverse/toxic effect of Anakinra. An increased risk of serious infection during concomitant use has been reported.
Azelastine (Nasal)	CNS Depressants may enhance the CNS depressant effect of Azelastine (Nasal).
BCG (Intravesical)	Immunosuppressants may diminish the therapeutic effect of BCG (Intravesical).
BCG (Intravesical)	Myelosuppressive Agents may diminish the therapeutic effect of BCG (Intravesical).
Bromperidol	Blood Pressure Lowering Agents may enhance the hypotensive effect of Bromperidol. Bromperidol may diminish the hypotensive effect of Blood Pressure pressure-lowering agents.
Bromperidol	May enhance the CNS depressant effect of CNS Depressants.
Canakinumab	Anti-TNF Agents may enhance the adverse/toxic effect of Canakinumab. Specifically, the risk for serious infections and/or neutropenia may be increased.
Certolizumab Pegol	Anti-TNF Agents may enhance the immunosuppressive effect of Certolizumab Pegol.
Cladribine	May enhance the immunosuppressive effect of Immunosuppressants.
Cladribine	May enhance the myelosuppressive effect of Myelosuppressive Agents.
CNS Depressants	May enhance the CNS depressant effect of Thalidomide.
Dipyrone	May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased
Natalizumab	Immunosuppressants may enhance the adverse/toxic effect of Natalizumab. Specifically, the risk of concurrent infection may be increased.
Orphenadrine	CNS Depressants may enhance the CNS depressant effect of Orphenadrine.
Oxomemazine	May enhance the CNS depressant effect of CNS Depressants.
Paraldehyde	CNS Depressants may enhance the CNS depressant effect of Paraldehyde.
Pembrolizumab	May enhance the adverse/toxic effect of Thalidomide Analogues. Specifically, mortality may be increased when this combination is used for the treatment of refractory multiple myeloma.
Pimecrolimus	May enhance the adverse/toxic effect of Immunosuppressants.
Rilonacept	Anti-TNF Agents may enhance the adverse/toxic effect of Rilonacept.
Tacrolimus (Topical)	May enhance the adverse/toxic effect of Immunosuppressants.
Tocilizumab	May enhance the immunosuppressive effect of anti-TNF agents.
Vaccines (Live)	Immunosuppressants may enhance the adverse/toxic effects of Vaccines (Live). Immunosuppressants may diminish the therapeutic effect of Vaccines (Live). Management: Avoid the use of live organism vaccines with immunosuppressants; live-attenuated vaccines should not be given for at least 3 months after immunosuppressants.
Vedolizumab	Anti-TNF Agents may enhance the adverse/toxic effect of Vedolizumab.

Monitoring parameters:

Blood Tests:

• Complete Blood Count (CBC): Check blood cell counts, including white blood cells, red blood cells, and platelets.
• Thyroid Function:
  • Test TSH at the beginning and then every 2 to 3 months.
• Liver Function:
  • Periodic tests, are especially important if there are pre-existing liver issues or if taking other medications known for liver toxicity.

For HIV-Positive Patients:

• Check the viral load after 1 and 3 months, then every 3 months after.

Pregnancy Monitoring:

• Pregnancy tests (with a sensitivity of at least 50 milliunits/mL) are needed:
  • 10 to 14 days before therapy starts.
  • Within 24 hours before starting the treatment.
  • Weekly for the first month.
  • Every 4 weeks if menstrual cycles are regular.
  • Every 2 weeks if menstrual cycles are irregular.

Neuropathy (Nerve Damage):

• Check for signs of neuropathy (like numbness or tingling) monthly for the first 3 months, then periodically.
• Consider testing nerve function (sensory nerve application potential amplitudes) at the beginning and every 6 months to catch any hidden neuropathy.

Symptoms to Watch For:

• Thromboembolism: Symptoms like shortness of breath, chest pain, and swelling in the arm or leg.
• Tumor Lysis Syndrome: A rapid release of cell contents into the blood, usually after cancer treatment.
• Heart Issues: Monitor for slow heart rate (bradycardia) and fainting spells (syncope).
• Seizure: Especially in patients with a history of seizures, watch for signs that might indicate a potential seizure.

General:

• It's essential to ensure that the patient is taking the medication as prescribed, so monitor adherence to the regimen.

How to administer Thalidomide (Thalomid)?

• When to Take:
  • Take orally, ideally at bedtime, once daily.
  • Ensure it's at least 1 hour after the evening meal.
• Dosage:
  • If the prescribed dose is more than 400 mg/day, it can be split and taken in divided doses. Always wait at least 1 hour after meals before taking the medication.
• Method:
  • Capsules should be swallowed whole with water.
  • Don't open or crush the capsules.
• Handling:
  • Keep capsules in their blister pack until it's time to take them.
  • If the powder from inside a broken capsule, or body fluids from someone taking thalidomide, comes into contact with the skin, wash the area immediately and thoroughly using soap and water.
• Missed Doses:
  • If you forget a dose and realize it within 12 hours, you can still take it.
  • If it's been more than 12 hours, skip the missed dose and wait for the next scheduled dose.

Mechanism of action of Thalidomide (Thalomid):

• Thalidomide helps adjust the immune system and can stop the formation of new blood vessels.
• In some conditions, it can control the production of a protein called tumor necrosis factor-alpha.
• For patients with a disease called erythema nodosum leprosum, it reduces this protein.
• But in patients with HIV, it increases it.
• In another disease called multiple myeloma, thalidomide boosts certain cells in the immune system and raises the levels of some protective substances in the body.
• It's also believed to protect DNA from damage, enhance the body's ability to kill harmful cells, and change how certain cells stick together.

Absorption:

• Slow
• Good absorption into the body

Distribution:

• Volume of Distribution (V): 1.1 L/kg
• It spreads well throughout the body

Protein Binding:

• 55% to 66% of the drug binds to proteins in the blood
• This affects how the drug is distributed and used in the body

Metabolism:

• Minimal metabolism occurs
• The drug mostly remains unchanged as it circulates in the body

Half-life elimination:

• 5.5 to 7.3 hours
• The time it takes for half of the drug to be removed from the body

Time to peak, plasma:

• Approximately 2 to 5 hours
• The time it takes for the drug to reach its highest concentration in the blood

Excretion:

• Mainly excreted in urine (about 92%)
• Less than 4% of the dose is excreted as an unchanged drug
• A small portion is eliminated in feces (less than 2%)

International Brands of Thalidomide:

• Bescamin
• Inmunoprin
• Midothal
• Myrin
• Talidex
• Talizer
• Thado
• Thaled
• Thalix
• Thaloma
• Thalomid

Thalidomide Brand Names in Pakistan:

Thalidomide 50 mg Capsules
Thalido	Atco Laboratories Limited

Thalidomide 100 mg Capsules
Thalido	Atco Laboratories Limited