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Guide
Drug Safety-related Labeling Changes (SrLC) Database
| ANDA | Abbreviated New Drug Application |
| BLA | Biologics License Application |
| CDER | Center for Drug Evaluation and Research |
| MG | Medication Guide |
| NDA | New Drug Application |
| PCI | Patient Counseling Information |
| PI | Patient Information |
| PLR | Physician Labeling Rule |
| PLLR | Pregnancy and Lactation Labeling Rule |
| Italics | For the most part, italics indicate an FDA comment such as:
Additions and/or revisions underlined These italics usually appear at the beginning of the section. In some cases, italics may be an inherent part of the label, and will most often appear in the body of the section. |
| Underlines | Any text that is underlined indicates text that has been added or revised. There are exceptions where underlining occurs in a section subtitle or heading. This is the case when there is just one word underlined in the body of the text. |
Sections
| BW | Box Warning |
| WP | Warnings and Precautions all in one section (PLR-format) Warnings as one section (pre-PLR format) Precautions as one section (pre-PLR format) |
| AR | Adverse Reactions (in pre-PLR format, this may be a subheading under precautions). |
| DI | Drug Interactions (in pre-PLR format, this may be a subheading under precautions). |
| USP | Use in Specific Populations (Inclusive on one or more of the following: Pregnancy; Lactation (PLLR- format); Nursing Mothers (pre-PLLR format); Females and Males of Reproductive Potential (PLLR format only); Pediatric Use, Geriatric Use, Renal Impairment, Hepatic Impairment, Sex, Race (these last six may be a subheading of precautions if label in pre-PLLR format. |
| PCI/PI/MG | Patient Counseling Information (PLR format only) - summarizes the information that a health care provider should convey to a patient (or caregiver when applicable) when a counseling discussion is taking place (e.g., a physician prescribing a drug during an office visit, a nurse providing discharge instructions at a hospital, or a pharmacist conveying information at a pharmacy). Patient Information - FDA approved patient labeling. Medication Guide - paper handouts that come with many prescription medicines. The guides address issues that are specific to particular drugs and drug classes, and they contain FDA-approved information that can help patients avoid serious adverse events. |
Only NDAs and CDER regulated BLAs are included in this database. ANDAs are not included.
Applications that remain active, even if the product has been discontinued, undergo safety-related labeling changes.
PROMACTA (NDA-022291)
(ELTROMBOPAG OLAMINE)
Safety-related Labeling Changes Approved by FDA Center for Drug Evaluation and Research (CDER)
06/06/2025 (SUPPL-41)
5 Warnings and Precautions
5.6 Laboratory Test Interference
Newly added section:
Eltrombopag (PROMACTA) is highly colored and can cause patient sample discoloration, which can interfere with some clinical laboratory tests. Inaccurate test results that are inconsistent with clinical observations may occur for multiple clinical chemistry tests including bilirubin and creatinine. In addition, other lab tests may be impacted, including but not limited to total protein and albumin, and incorrect test results may be generated if there is eltrombopag in the patient’s specimen. Communicate to the lab conducting the testing if your patient is taking PROMACTA. Re-testing using other methods may also help in determining the validity of the test results [see Drug Interactions (7.5)].
7 Drug Interactions
7.5 Interference with Clinical Laboratory Tests
Newly added section:
Eltrombopag (PROMACTA) is highly colored and can cause patient sample discoloration, which is reported to interfere with some clinical laboratory tests, including, but not limited to bilirubin and creatinine.
Bilirubin Testing: Eltrombopag can cause both positive and negative interference with bilirubin assays. If the laboratory results for bilirubin are inconsistent with clinical observations, further evaluation of liver function should be performed to clarify the clinical status of the patient. Evaluating contemporaneous aminotransferase values (AST, ALT) may help determine the validity of normal total bilirubin levels in the presence of clinical jaundice.
Creatinine Testing: Eltrombopag can cause positive interference with creatinine measurements, leading to falsely elevated creatinine levels. In the event of an unexpected serum creatinine test result, further evaluation of renal function should be performed. Blood urea should be evaluated if serum creatinine is unexpectedly high.
Communicate to the lab conducting testing if the patient is taking PROMACTA. Re-testing using other methods may also help in determining the validity of the test results.
03/31/2022 (SUPPL-33)
8 Use in Specific Populations
8.7 EthnicityAdditions underlined
Reduce the initial dose of PROMACTA for patients of East-/Southeast-Asian ancestry with ITP (adult and pediatric patients 6 years and older only) or severe aplastic anemia [see Dosage and Administration (2.1, 2.3), Clinical Pharmacology (12.3)]. No reduction in the initial dose of PROMACTA is recommended in patients of East-/Southeast-Asian ethnicity with chronic hepatitis C [see Clinical Pharmacology (12.3)].
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
MEDICATION GUIDEAdditions underlined
…
Before you take PROMACTA, tell your healthcare provider about all of your medical conditions, including if you:
…
are of East-/Southeast-Asian ancestry. You may need a lower dose of PROMACTA.
…
02/03/2021 (SUPPL-31)
5 Warnings and Precautions
5.5 Cataracts(Additions and/or revisions underlined)
In the three controlled clinical trials in adults with persistent or chronic ITP, cataracts developed or worsened in 15 (7%) patients who received 50 mg of PROMACTA daily and 8 (7%) placebo-group patients. In the extension trial, cataracts developed or worsened in 11% of patients who underwent ocular examination prior to therapy with PROMACTA.
6 Adverse Reactions
6.1 Clnical Trials Experience(Addition of the indication of Persistent Immune Thrombocytopenia (ITP) to information pertaining to Chronic ITP)
8 Use in Specific Populations
8.1 Pregnancy(Addition of the indication of Persistent Immune Thrombocytopenia (ITP) to information pertaining to Chronic ITP)
(Addition of the indication of Persistent Immune Thrombocytopenia (ITP) to information pertaining to Chronic ITP)
(Addition of the indication of Persistent Immune Thrombocytopenia (ITP) to information pertaining to Chronic ITP)
(Additions and/or revisions underlined)
Reduce the initial dose of PROMACTA for patients of Asian ancestry (such as Chinese, Japanese, Taiwanese, Korean, or Thai) with ITP (adult and pediatric patients 6 years and older only) or severe aplastic anemia [see Dosage and Administration (2.1, 2.3), Clinical Pharmacology (12.3)].
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
Medication Guide(Addition of the indication of Persistent Immune Thrombocytopenia (ITP) to information pertaining to Chronic ITP)
(Additions and/or revisions underlined)
Before you take PROMACTA, tell your healthcare provider about all of your medical conditions, including if you:
• are of Asian ancestry (such as Chinese, Japanese, Taiwanese, Korean, or Thai).
(Addition of the indication of Persistent Immune Thrombocytopenia (ITP) to information pertaining to Chronic ITP)
04/29/2020 (SUPPL-27)
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
MEDICATION GUIDE(additions underlined)
…
How should I take PROMACTA?
…
Take Promacta without a meal or with a meal low in calcium (50 mg or less) and at least 2 hours before or 4 hours after eating calcium-rich foods such as dairy products, calcium-fortified juices, and certain fruits and vegetables.
…
(additions underlined)
…
Drug Interactions
Advise patients to take PROMACTA at least 2 hours before or 4 hours after calcium-rich foods, mineral supplements, and antacids which contain polyvalent cations such as iron, calcium, aluminum, magnesium, selenium, and zinc.
…
Administration of PROMACTA
…
Advise patients to take PROMACTA without a meal or with a meal low in calcium (less than or equal to 50 mg) and at least 2 hours before or 4 hours after other medications (e.g., antacids) and calcium-rich foods.
…
11/16/2018 (SUPPL-21)
5 Warnings and Precautions
5.2 Hepatotoxicity(subsection revised, additions and revisions underlined)
PROMACTA may increase the risk of severe and potentially life-threatening hepatotoxicity.One patient (<1%) with chronic ITP treated with PROMACTA in clinical trials experienced drug-induced liver injury. Eleven patients (1%) with chronic hepatitis C treated with PROMACTA in clinical trials experienced drug-induced liver injury.
Treatment of ITP, Chronic Hepatitis C-associated Thrombocytopenia, and Refractory Severe Aplastic Anemia
…
First-Line Treatment of Severe Aplastic Anemia
Measure ALT, AST, and bilirubin prior to initiation of PROMACTA, every other day while hospitalized for h- ATG therapy, and then every 2 weeks during treatment. During treatment, manage increases in ALT or AST levels as recommended in Table 6.
6 Adverse Reactions
6.1 Clinical Trials Experience(extensive additions, please refer to label)
8 Use in Specific Populations
8.4 Pediatric Use(subsection revised, additions underlined)
The safety and efficacy of PROMACTA have been established in pediatric patients 1 year and older with chronic ITP and in pediatric patients 2 years and older with definitive immunosuppressive therapy (IST)-naïve severe aplastic anemia (in combination with horse antithymocyte globulin [h-ATG] and cyclosporine). Safety and efficacy in pediatric patients below the age of 1 year with ITP have not been established. Safety and efficacy in pediatric patients with thrombocytopenia associated with chronic hepatitis C and refractory severe aplastic anemia have not been established.
…
The safety and efficacy of PROMACTA in combination with h-ATG and cyclosporine for the first-line treatment of severe aplastic anemia in pediatric patients 2 years and older were evaluated in a single-arm, open- label trial. A total of 26 pediatric patients (ages 2 to <17 years) were evaluated; 12 children (aged 2 to <12 years) and 14 adolescents (aged 12 to <17). See Dosage and Administration (2.3) for dosing recommendations for pediatric patients 2 years and older. The safety and efficacy of PROMACTA in combination with h-ATG and cyclosporine in pediatric patients younger than 2 years for the first-line treatment of severe aplastic anemia have not yet been established. In patients 2 to 16 years of age, 69% of patients experienced serious adverse events compared to 42% in patients 17 years and older. Among the 12 patients who were 2 to 11 years of age in the PROMACTA D1 – M6 cohort and reached the 6-month assessment or withdrew earlier, the complete response rate at Month 6 was 8% versus 46% in patients age 12 to 16 years and 50% in patients 17 years of age and older.
(additions underlined)
Of the 106 patients in two randomized clinical trials of PROMACTA 50 mg in chronic ITP, 22% were 65 years of age and over, while 9% were 75 years of age and over. Of the 1439 patients in two randomized clinical trials of PROMACTA in patients with chronic hepatitis C and thrombocytopenia, 7% were 65 years of age and over, while < 1% were 75 years of age and over. Of the 196 patients who received PROMACTAfor the treatment of severe aplastic anemia, 18% were 65 years of age and over, while 3% were 75 years of age and over. No overall differences in safety or effectiveness were observed between these patients and younger patients.
(additions underlined)
Patients with Chronic ITP and Severe Aplastic Anemia
Reduce the initial dose of PROMACTA in patients with chronic ITP (adult and pediatric patients 6 years and older only) or refractory severe aplastic anemia who also have hepatic impairment (Child-Pugh Class A, B, C).
In a clinical trial in patients with severe aplastic anemia who had not received prior definitive immunosuppressive therapy, patients with baseline ALT or AST > 5 x ULN were ineligible to participate. If a patient with hepatic impairment (Child-Pugh Class A, B, C) initiates therapy with PROMACTA for the first- line treatment of severe aplastic anemia, reduce the initial dose.
Patients with Chronic Hepatitis C
No dosage adjustment is recommended in patients with chronic hepatitis C and hepatic impairment.
07/24/2018 (SUPPL-20)
5 Warnings and Precautions
Newly added subsection:
5.3 Increased Risk of Death and Progression of Myelodysplastic Syndromes (MDS) to Acute Myeloid Leukemia (AML)
A randomized, double-blind, placebo-controlled, multicenter trial in patients with International Prognostic Scoring System (IPSS) intermediate-1, intermediate-2 or high risk MDS with thrombocytopenia, receiving azacitidine in combination with either PROMACTA (n equals 179) or placebo (n equals 177) was terminated due to lack of efficacy and safety reasons, including increased progression to AML. Patients received PROMACTA or placebo at a starting dose of 200 mg once daily, up to a maximum of 300 mg once daily, in combination with azacitidine for at least six cycles. The incidence of death (overall survival) was 32% (57/179) in the PROMACTA arm versus 29% (51/177) in the placebo arm (HR [95% CI] equals 1.42 [0.97, 2.08], showing an increased relative risk of death in this trial by 42% in the PROMACTA arm). The incidence of progression to AML was 12% (21/179) in the PROMACTA arm versus 6% (10/177) in the placebo arm (HR [95% CI] equals 2.66 [1.31, 5.41], showing an increased relative risk of progression to AML in this trial by 166% in the PROMACTA arm).
6 Adverse Reactions
Addition of the following to the bulleted line listing:
Increased Risk of Death and Progression of Myelodysplastic Syndromes to Acute Myeloid Leukemia
10/04/2017 (SUPPL-19)
5 Warnings and Precautions
Newly added subsection:
5.3 Increased Risk of Death and Progression of Myelodysplastic Syndromes (MDS) to Acute Myeloid Leukemia (AML)
A randomized, double-blind, placebo-controlled, multicenter trial in patients with International Prognostic Scoring System (IPSS) intermediate-1, intermediate-2 or high risk MDS with thrombocytopenia, receiving azacitidine in combination with either PROMACTA (n equals 179) or placebo (n equals 177) was terminated due to lack of efficacy and safety reasons, including increased progression to AML. Patients received PROMACTA or placebo at a starting dose of 200 mg once daily, up to a maximum of 300 mg once daily, in combination with azacitidine for at least six cycles. The incidence of death (overall survival) was 32% (57/179) in the PROMACTA arm versus 29% (51/177) in the placebo arm (HR [95% CI] equals 1.42 [0.97, 2.08], showing an increased relative risk of death in this trial by 42% in the PROMACTA arm). The incidence of progression to AML was 12% (21/179) in the PROMACTA arm versus 6% (10/177) in the placebo arm (HR [95% CI] equals 2.66 [1.31, 5.41], showing an increased relative risk of progression to AML in this trial by 166% in the PROMACTA arm).
6 Adverse Reactions
The following serious adverse reactions associated with PROMACTA are described in other sections.
Addition of the following:
Increased Risk of Death and Progression of Myelodysplastic Syndromes to Acute Myeloid Leukemia
07/05/2017 (SUPPL-18)
6 Adverse Reactions
6.1 Clinical Trials Experience(Additions and/or revisions are underlined)
Chronic Immune (Idiopathic) Thrombocytopenia: Adults:…
In the three controlled chronic ITP trials, cataracts developed or worsened in 7% of patients treated with PROMACTA and 7% of patients in the placebo group. All patients had documented, preexisting risk factors for cataractogenesis including corticosteroid use. In the extension trial, cataracts developed or worsened in 11% of patients who underwent ocular examination prior to therapy with PROMACTA. Seventy-two percent of patients had preexisting risk factors, including corticosteroid use.
Pediatric Patients: …
In the two controlled clinical chronic ITP trials, cataracts developed or worsened in 2 (1%) patients treated with PROMACTA. Both patients had received chronic oral corticosteroids, a risk factor for cataractogenesis.
Chronic Hepatitis C-associated Thrombocytopenia: …
In the two controlled clinical trials in patients with chronic hepatitis C, cataracts developed or worsened in 8% of patients treated with PROMACTA and 5% of patients treated with placebo.
Severe Aplastic Anemia:…
Rash was reported in 7% of patients; cataract was reported in 2% of patients.
03/09/2017 (SUPPL-17)
6 Adverse Reactions
6.1 Clinical Trials Experience(additions underlined)
Chronic Hepatitis C-associated Thrombocytopenia: In the two placebo-controlled trials, 955 patients with chronic hepatitis C-associated thrombocytopenia received PROMACTA….
Rash was reported in 9% and 7% of patients receiving PROMACTA and placebo, respectively.
In the two controlled clinical trials in patients with chronic hepatitis C, hyperbilirubinemia was reported in 8%
of patients receiving PROMACTA compared with 3% for placebo. Total bilirubin greater than or equal to
1.5 x ULN was reported in 76% and 50% of patients receiving PROMACTA and placebo, respectively. ALT or AST greater than or equal to 3 x ULN was reported in 34% and 38% of patients for PROMACTA and placebo, respectively.
…
Severe Aplastic Anemia: In the single-arm, open-label trial, 43 patients with severe aplastic anemia received PROMACTA. Eleven patients (26%) were treated for greater than 6 months and 7 patients (16%) were treated for greater than 1 year. The most common adverse reactions (greater than or equal to 20%) were nausea, fatigue, cough, diarrhea, and headache.
Rash was reported in 7% of patients.
In this trial, patients had bone marrow aspirates evaluated for cytogenetic abnormalities. Eight patients had a new cytogenetic abnormality reported on therapy, including 5 patients who had complex changes in chromosome 7.
(addition underline)
The following adverse reactions have been identified during post approval use of PROMACTA. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate the frequency or establish a causal relationship to drug exposure.
Vascular Disorders: Thrombotic microangiopathy with acute renal failure.
Skin and Subcutaneous Tissue Disorders: Skin discoloration including hyperpigmentation and skin yellowing.
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
Medication Guide(additions and revisions; please refer to label)
10/12/2016 (SUPPL-16)
Boxed Warning
CHRONIC HEPATITIS C (addition underlined)PROMACTA may increase the risk of severe and potentially life-threatening hepatotoxicity. Monitor hepatic function and discontinue dosing as recommended.
5 Warnings and Precautions
5.2 Hepatotoxicity (addition underlined)PROMACTA may increase the risk of severe and potentially life-threatening hepatotoxicity.
Isolated cases of severe liver injury were identified in clinical trials. The elevation of liver laboratory values occurred approximately three months after initiation of PROMACTA. In all cases, the event resolved following PROMACTA discontinuation.
Thrombotic/thromboembolic complications may result from increases in platelet counts with PROMACTA. Reported thrombotic/thromboembolic complications included both venous and arterial events and were observed at low and at normal platelet counts.
… In the extension trial, cataracts developed or worsened in 11% of patients who underwent ocular examination prior to therapy with PROMACTA.
6 Adverse Reactions
6.1 Clinical Trials Experience (revision underlined)Chronic Immune (Idiopathic) Thrombocytopenia:
…The data described below reflect exposure of PROMACTA to patients with chronic ITP aged 18 to 85 years, of whom 66% were female, in three placebo-controlled trials and one open-label extension trial. PROMACTA was administered to 330 patients for at least 6 months and 218 patients for at least 1 year.
Among 302 patients with chronic ITP who received PROMACTA in the single-arm extension trial, the adverse reactions occurred in a pattern similar to that seen in the placebo-controlled trials.
Seventeen of the patients treated with PROMACTA in the controlled trials with hepatobiliary laboratory abnormalities were re-exposed to PROMACTA in the extension trial. Eight of these patients again experienced liver test abnormalities (less than or equal to Grade 3) resulting in discontinuation of PROMACTA in one patient. In the extension chronic ITP trial, six additional patients had PROMACTA discontinued due to liver test abnormalities (less than or equal to Grade 3).
In clinical trials in patients with chronic ITP, one patient treated with PROMACTA (less than1%) experienced drug- induced liver injury.
Pediatric Patients: The data described below reflect median exposure to PROMACTA of 91 days for 107 pediatric patients (aged 1 to 17 years) with chronic ITP, of whom 53% were female, across the randomized phase of two placebo-controlled trials.
Table 6 presents the most common adverse drug reactions (experienced by greater than or equal to 3% of pediatric patients 1 year and older receiving PROMACTA) across the two placebo-controlled trials, with a higher incidence for PROMACTA versus placebo.
Table 6. Adverse Reactions (greater than or equal to 3%) with a Higher Incidence for PROMACTA versus Placebo from Two Placebo-controlled Trials in Pediatric Patients 1 Year and Older with Chronic Immune (Idiopathic) Thrombocytopenia (please refer to label)
Chronic Hepatitis C-associated Thrombocytopenia:
In clinical trials in patients with chronic hepatitis C, 11 patients treated with PROMACTA (1%) experienced drug-induced liver injury.
7 Drug Interactions
7.1 Polyvalent Cations (Chelation) (addition underlined)Take PROMACTA at least 2 hours before or 4 hours after any medications or products containing polyvalent cations such as antacids, dairy products, and mineral supplements to avoid significant reduction in absorption of PROMACTA due to chelation.
8 Use in Specific Populations
8.4 Pediatric Use (revisions underlined)The safety and efficacy of PROMACTA in pediatric patients 1 year and older with chronic ITP were evaluated in two double-blind, placebo-controlled trials. The pharmacokinetics of eltrombopag have been evaluated in 168 pediatric patients 1 year and older with ITP dosed once daily. The safety and efficacy of PROMACTA in pediatric patients younger than 1 year with ITP have not yet been established.
Patients of East Asian ethnicity (i.e., Japanese, Chinese, Taiwanese, and Korean) exhibit higher eltrombopag exposures. A reduction in the initial dose of PROMACTA is recommended for patients of East Asian ancestry with ITP (adult and pediatric patients 6 years and older only) or severe aplastic anemia. No dose reduction is needed in patients of East Asian ethnicity with chronic hepatitis.
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
17 PATIENT COUNSELING INFORMATION (revised)Please refer to label.