Drug Safety-related Labeling Changes (SrLC)

Get Email Alerts | Guide

THALOMID (NDA-020785)

(THALIDOMIDE)

Safety-related Labeling Changes Approved by FDA Center for Drug Evaluation and Research (CDER)

Download Data

Expand all

02/25/2021 (SUPPL-69)

Approved Drug Label (PDF)

6 Adverse Reactions

6.2 Postmarketing Experience

(Additions and/or revisions underlined)

The following additional adverse reactions have been identified during post approval use of THALOMID and are not already included in Clinical Trials Experience [see Adverse Reactions (6.1)]. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Blood and Lymphatic: Decreased white blood cell counts including febrile neutropenia, changes in prothrombin time, pancytopenia, chronic myelogenous leukemia, nodular sclerosing Hodgkin’s disease, erythroleukemia, lymphedema, lymphopenia.

Body as a Whole: Hangover effect

Cardiovascular System: Sick sinus syndrome, EKG abnormalities, pulmonary hypertension.

Digestive System: Intestinal perforation, gastrointestinal perforations, bile duct obstruction, stomach ulcer, aphthous, stomatitis.

Ear and Labyrinthine Disorders: Hearing impairment.

Immune System Disorders: Hypersensitivity including anaphylaxis, solid organ transplant rejection.

Infections and infestations: Severe infections (e.g., fatal sepsis including septic shock), viral infections (including varicella zoster virus, cytomegalovirus, and hepatitis B virus reactivation) and progressive multifocal leukoencephalopathy (PML).

Metabolic and Endocrine: Electrolyte imbalance including hypercalcemia, hyponatremia and hypomagnesemia, hypothyroidism, increased alkaline phosphatase, tumor lysis syndrome, myxedema.

Nervous System: Changes in mental status or mood including suicide attempts, disturbances in consciousness including lethargy, loss of consciousness or stupor, seizures including grand mal convulsions and status epilepticus, Parkinson’s disease, stroke, carpal tunnel, Raynaud’s syndrome, migraine, foot drop.

Renal and Urinary Disorders: Renal failure, acute renal failure, oliguria, enuresis.

Reproductive System and Breast Disorders: amenorrhea, sexual dysfunction, galactorrhea, gynecomastia, metrorrhagia.

Respiratory System: Pleural effusion, interstitial lung disease.

Skin and Appendages: Erythema multiforme, erythema nodosum, toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), purpura, petechiae.

Special Senses: Diplopia, nystagmus

06/07/2019 (SUPPL-67)

Approved Drug Label (PDF)

Boxed Warning

THALOMID replaces Thalidomide throughout the first and last paragraphs of the Box Warning.

4 Contraindications

4.1 Pregnancy

Newly added information:

THALOMID is contraindicated in females who are pregnant.

THALOMID replaces Thalidomide throughout subsection.

5 Warnings and Precautions

THALOMID replaces Thalidomide throughout subsections.

Additions and/or revisions underlined:

5.6 Peripheral Neuropathy

…  patients with ENL treated with THALOMID.

5.12 Severe Cutaneous Reactions

Severe cutaneous reactions including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug reaction with eosinophilia and systemic symptoms (DRESS) have been reported with THALOMID use. DRESS may present with a cutaneous reaction (such as rash or exfoliative dermatitis), eosinophilia, fever, and/or lymphadenopathy with systemic complications such as hepatitis, nephritis, pneumonitis, myocarditis, and/or pericarditis. These events can be fatal. THALOMID interruption or discontinuation should be considered for Grade 2-3 skin rash.

Discontinue THALOMID for Grade 4 rash, exfoliative or bullous rash, or for other severe cutaneous reactions such as SJS, TEN, or DRESS, and do not resume therapy

5.16 Hypersensitivity

Hypersensitivity, including angioedema and anaphylactic reactions to THALOMID has been reported. Signs and symptoms have included the occurrence of erythematous macular rash, possibly associated with fever, tachycardia, and hypotension, and if severe, may necessitate interruption of therapy. If the reaction recurs when dosing is resumed, THALOMID should be discontinued. Do not resume THALOMID treatment after angioedema and anaphylaxis.

6 Adverse Reactions

‘Clinically significant’ added prior to adverse reactions described in detail.

‘Severe Cutaneous Reactions’ replaces Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis in bulleted line listing.

6.1 Clinical Trials Experience

Section has been revised; please refer to label for complete information.

6.2 Postmarketing Experience

Additions and/or revisions underlined:

Immune System Disorders: Hypersensitivity including anaphylaxis, solid organ transplant rejection.

Skin and Appendages: Erythema multiforme, erythema nodosum, toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), purpura, petechiae.

8 Use in Specific Populations

8.1 Pregnancy

Additions and/or revisions underlined:

The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. The estimated background risk in the U.S. general population of major birth defects is 2%-4% …

17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)

MEDICATION GUIDE

Additions and/or revisions underlined:

Tell your healthcare provider about all the medicines you take …

Certain medicines can affect the way that birth control pills, injections, transdermal systems (patches), or implants work.

What are the possible side effects of THALOMID? THALOMID can cause serious side effects, including:

• Severe skin reactions and severe allergic reactions. Severe skin reactions and severe allergic reactions can happen with THALOMID and may cause death.

  Newly added information:

  Call your healthcare provider right away if you develop any of the following signs or symptoms during treatment with THALOMID:

• a red, itchy, skin rash

• peeling of your skin or blisters

• severe itching

• fever

Get emergency medical help right away if you develop any of the following signs or symptoms during treatment with THALOMID:

• swelling of your lips, mouth, tongue, or throat

• trouble breathing or swallowing

• raised red areas on your skin (hives)

• a very fast heartbeat

• you feel dizzy or faint

The most common side effects of THALOMID for treatment of multiple myeloma include:

• skin rash or peeling. See “Severe skin reactions and severe allergic reactions” above.

PATIENT COUNSELING INFORMATION

Additions and/or revisions underlined:

Severe Cutaneous Reactions Inform patients of the potential risk for severe skin reactions such as SJS, TEN and DRESS and report any signs and symptoms associated with these events to their healthcare provider for evaluation.

Hypersensitivity

Inform patients of the potential for severe hypersensitivity reactions such as angioedema and anaphylaxis to THALOMID. Instruct patients to contact their healthcare provider right away for signs of a skin reaction. Advise patients to seek emergency medical attention for signs or symptoms of severe hypersensitivity reactions.

12/29/2017 (SUPPL-65)

Approved Drug Label (PDF)

5 Warnings and Precautions

5.4 Increased Mortality in Patients with MM When Pembrolizumab Is Added to a Thalidomide Analogue and Dexamethasone

(Subsection title has been revised)

6 Adverse Reactions

(Additions and/or revisions are underlined)

The following adverse reactions are described in detail in other labeling sections:

• Increased Mortality in Patients with MM When Pembrolizumab Is Added to a Thalidomide Analogue and Dexamethasone

11/30/2017 (SUPPL-64)

Approved Drug Label (PDF)

5 Warnings and Precautions

5.4 Increased Mortality in MM When Pembrolizumab Is Added to Dexamethasone and a Thalidomide Analogue

(Newly added subsection)

In two randomized clinical trials in patients with MM, the addition of pembrolizumab to a thalidomide analogue plus dexamethasone resulted in increased mortality, a use for which no PD-1 or PD-L1 blocking antibody is indicated. Treatment of patients with MM with a PD-1 or PD-L1 blocking antibody in combination with a thalidomide analogue plus dexamethasone is not recommended outside of controlled clinical trials.

6 Adverse Reactions

(Additions and/or revisions are underlined)

The following adverse reactions are described in detail in other labeling sections:

…

• Increased Mortality in MM When Pembrolizumab Is Added to Dexamethasone and a Thalidomide Analogue

17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)

17 PATIENT COUNSELING INFORMATION

(Additions and/or revisions are underlined)

…

Increased Mortality in MM Patients When Pembrolizumab Was Added to Dexamethasone and a Thalidomide Analogue Regimen

Inform patients of potential for increased risk of death in people with MM when a PD-1 blocking antibody was added to a dexamethasone and thalidomide analogue treatment regimen.

MEDICATION GUIDE

(Additions and/or revisions are underlined)

What are the possible side effects of THALOMID?

THALOMID can cause serious side effects, including:

…

• Increased risk of death in people with MM when used with pembrolizumab. An increased risk of death has been observed in people with MM when pembrolizumab was added to a dexamethasone and thalidomide analogue treatment regimen. The use of these drugs together for treating MM is not recommended outside of controlled clinical trials.

01/27/2017 (SUPPL-61)

Approved Drug Label (PDF)

6 Adverse Reactions

6.2 Postmarketing Experience

(Additions and/or revisions are underlined)

The following additional adverse reactions have been identified during post approval use of THALOMID and are not already included in Clinical Trials Experience. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Cardiovascular System: Sick sinus syndrome, EKG abnormalities, pulmonary hypertension.

Infections and infestations: Severe infections (e.g., fatal sepsis including septic shock) and viral infections (including varicella zoster virus, cytomegalovirus, and hepatitis B virus reactivation).

8 Use in Specific Populations

8.1 Pregnancy

(Pregnancy and Lactation Labeling Rule (PLLR) Conversion; Additions and/or revisions are underlined)

Pregnancy Exposure Registry

There is a pregnancy exposure registry that monitors pregnancy outcomes in females exposed to THALOMID during pregnancy as well as female partners of male patients who are exposed to THALOMID. This registry is also used to understand the root cause for the pregnancy. Report any suspected fetal exposure to THALOMID to the FDA via the MedWatch program at 1-800-FDA-1088 and to Celgene Corporation at 1-888-423-5436.

 

Risk Summary

Based on the mechanism of action, human and animal data, THALOMID can cause embryo-fetal harm when administered to a pregnant female and is contraindicated during pregnancy

 

Thalidomide crossed the placenta after administration to pregnant hamsters.

The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. The estimated background risk in the U.S. general population of major birth defects is 2%-4% and of miscarriage is 15%-20% of clinically recognized pregnancies.

 

Data

Animal data

In a study conducted in pregnant rabbits, thalidomide levels in fetal plasma were approximately 11% to 73% of the maternal Cmax. In a study conducted with 14C-thalidomide (150 mg/kg orally) in pregnant hamsters, radioactivity was detected in the embryo, and the relative concentrations of radioactivity in the embryo and maternal plasma were about the same at 4, 12 and 24 hours after dosing. Based on the radioactivity data, thalidomide crossed the placental barrier, and the fetal levels of drug-related material were approximately similar to those of maternal levels.

8.2 Lactation

(Pregnancy and Lactation Labeling Rule (PLLR) Conversion; Additions and/or revisions are underlined)

Risk Summary

There is no information regarding the presence of thalidomide in human milk, the effects of THALOMID on the breastfed infant, or the effects of THALOMID on milk production…Because many drugs are excreted in human milk and because of the potential for adverse reactions in breastfed infants from THALOMID, advise women not to breastfeed during treatment with THALOMID.

 

Data

Animal Data

In lactating female rabbits at an oral dose of 150 mg/kg/day, the average thalidomide concentrations in milk ranged from 22 to 36 mcg per mL. In the study of lactating female rabbits, high concentrations of thalidomide (7741 – 71425 ng per mL) were noted in milk during four weeks of pre-weaning period. Milk concentrations were 1.16 - 2.11, 1.05 – 2.43, and 0.64 – 3.63 times that of plasma at 30, 150 and 500 mg/kg thalidomide doses, respectively; thalidomide, as a lipophilic compound, distributed into milk, with concentrations attained similar to or slightly higher than those of systemic concentrations.

8.3 Females and Males of Reproductive Potential

(Pregnancy and Lactation Labeling Rule (PLLR) Conversion; Additions and/or revisions are underlined)

Pregnancy Testing

…Verify the pregnancy status of females of reproductive potential prior to initiating THALOMID therapy and during therapy. Advise females of reproductive potential that they must avoid pregnancy 4 weeks before therapy, while taking THALOMID, during dose interruptions and for at least 4 weeks after completing therapy.

 

Infertility

Based on findings in animals, male fertility may be compromised by treatment with THALOMID.

17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)

17 PATIENT COUNSELING INFORMATION

(Additions and/or revisions are underlined)

Embryo-Fetal Toxicity

Advise patient that if her healthcare provider is not available, she should call Celgene Customer Care Center at 1-888-423-5436.

 

Pregnancy Exposure Registry

Inform females there is a Pregnancy Exposure Registry that monitors pregnancy outcomes in females exposed to THALOMID during pregnancy and that they can contact the Pregnancy Exposure Registry by calling 1-888-423-5436.

 

Venous and Arterial Thromboembolism

Inform patients of the potential risk of developing venous thromboembolism (such as DVT and PE)…

MEDICATION GUIDE

(Additions and/or revisions are underlined)

What is the most important information I should know about THALOMID?

Before prescribing THALOMID, your healthcare provider will explain the THALOMID REMS program to you and have you sign the Patient-Physician Agreement Form.

THALOMID can cause serious side effects including:

• Severe and life-threatening human birth defects (deformed babies) or death of an unborn baby. Females who are pregnant or who plan to become pregnant must not take THALOMID.

  Females who can become pregnant:

  • Talk with your healthcare provider to find out about options for acceptable forms of birth control that you may use to prevent pregnancy before, during, and after treatment with THALOMID.

  • Stop taking THALOMID and call your healthcare provider right away if you have unprotected sex or if you think your birth control has failed.

If you become pregnant while taking THALOMID, stop taking it right away and call your healthcare provider. If your healthcare provider is not available, you should call Celgene Customer Care Center at 1-888-423-5436.

There is a pregnancy exposure registry that monitors the outcomes of females who take THALOMID during pregnancy, or if their male partner takes THALOMID and they are exposed during pregnancy. You can enroll in this registry by calling Celgene Corporation at the phone number listed above.

 THALOMID can pass into human semen:

• Males, including those who have had a vasectomy, must always use a latex or synthetic condom during any sexual contact with a pregnant female or a female that can become pregnant while taking THALOMID, during any breaks (interruptions) in your treatment with THALOMID, and for up to 4 weeks after stopping THALOMID.

What is THALOMID?

THALOMID is a prescription medicine used

• as maintenance treatment to prevent and keep the skin lesions of leprosy from coming back (recurring). It is not known if THALOMID is safe and effective in children under 12 years of age.

Talk with your healthcare provider before taking any new medicines.

How should I take THALOMID?

• Do not open or crush THALOMID capsules or handle them any more than needed.

  • If powder from the THALOMID capsule comes in contact with your skin, wash the skin right away with soap and water.

  • If powder from the THALOMID capsule comes in contact with the inside of your eyes, nose, and mouth, flush well with water.

 

What should I avoid while taking THALOMID?

• Do not donate blood while you take THALOMID, during any breaks (interruptions) in your treatment, and for 4 weeks after stopping THALOMID. If someone who is pregnant gets your donated blood, her baby may be exposed to THALOMID and may be born with birth defects.

• THALOMID can cause drowsiness and sleepiness.

What are the possible side effects of THALOMID? THALOMID can cause serious side effects, including:…

 

Your healthcare provider may tell you to decrease your dose, temporarily stop or permanently stop taking THALOMID if you develop certain serious side effects during treatment with THALOMID.

 

The most common side effects of THALOMID for treatment of multiple myeloma include:

• shortness of breath

• muscle weakness

• blood clots