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The following serious adverse reactions associated with PROMACTA are described in other sections.
- Hepatic Decompensation in Patients with Chronic Hepatitis C [see WARNINGS AND PRECAUTIONS]
- Hepatotoxicity [see WARNINGS AND PRECAUTIONS]
- Thrombotic/Thromboembolic Complications [see WARNINGS AND PRECAUTIONS]
- Cataracts [see WARNINGS AND PRECAUTIONS]
Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared with rates in the clinical trials of another drug and may not reflect the rates observed in practice.
Chronic Immune (Idiopathic) Thrombocytopenia
In clinical trials, hemorrhage was the most common serious adverse reaction and most hemorrhagic reactions followed discontinuation of PROMACTA. Other serious adverse reactions included thrombotic/thromboembolic complications [see WARNINGS AND PRECAUTIONS]. 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 [see Clinical Studies]. PROMACTA was administered to 330 patients for at least 6 months and 218 patients for at least 1 year.
Table 4 presents the most common adverse drug reactions (experienced by greater than or equal to 3% of patients receiving PROMACTA) from the three placebo-controlled trials, with a higher incidence in PROMACTA versus placebo.
Table 4:Adverse Reactions (≥3%) from Three Placebo-controlled Trials in Adults with Chronic Immune (Idiopathic) Thrombocytopenia
|Adverse Reaction||PROMACTA 50 mg
n = 241
n = 128
|Upper respiratory tract infection||7||6|
|Urinary tract infection||5||3|
In the three controlled clinical chronic ITP trials, alopecia, musculoskeletal pain, blood alkaline phosphatase increased, and dry mouth were the adverse reactions reported in 2% of patients treated with PROMACTA and in no patients who received placebo.
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. Table 5 presents the most common treatment-related adverse reactions (experienced by greater than or equal to 3% of patients receiving PROMACTA) from the extension trial.
Table 5. Treatment-related Adverse Reactions (≥3%) from Extension Trial in Adults with Chronic Immune (Idiopathic) Thrombocytopenia
|Adverse Reaction||PROMACTA 50 mg
n = 302
|Blood bilirubin increased||4|
In the three controlled chronic ITP trials, serum liver test abnormalities (predominantly Grade 2 or less in severity) were reported in 11% and 7% of patients for PROMACTA and placebo, respectively. Four patients (1%) treated with PROMACTA and three patients in the placebo group (2%) discontinued treatment due to hepatobiliary laboratory abnormalities. 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 (<1%) experienced drug-induced liver injury [see WARNINGS AND PRECAUTIONS].
In a placebo-controlled trial of PROMACTA in patients with chronic liver disease and thrombocytopenia not related to ITP, six patients treated with PROMACTA and one patient in the placebo group developed portal vein thromboses [see WARNINGS AND PRECAUTIONS].
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 (≥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
n = 107
n = 50
|Upper respiratory tract infection||17||6|
|a Includes adverse reactions or laboratory abnormalities >3 x ULN.|
Chronic Hepatitis C-Associated Thrombocytopenia
In the two placebo-controlled trials, 955 patients with chronic hepatitis C-associated thrombocytopenia received PROMACTA. Table 7 presents the most common adverse drug reactions (experienced by greater than or equal to 10% of patients receiving PROMACTA compared with placebo).
Table 7. Adverse Reactions (≥10% and Greater than Placebo) from Two Placebo-controlled Trials in Adults with Chronic Hepatitis C
|Adverse Reaction||PROMACTA + Peginterferon/Ribavirin
n = 955
|Placebo + Peginterferon/Ribavirin
n = 484
|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.
In clinical trials in patients with chronic hepatitis C, 11 patients treated with PROMACTA (1%) experienced drug-induced liver injury [see WARNINGS AND PRECAUTIONS].
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.
Table 8. Adverse Reactions (≥10%) from One Open-label Trial in Adults with Severe Aplastic Anemia
(n = 43)
|Pain in extremity||19|
|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.
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.
Skin And Subcutaneous Tissue Disorders
Skin discoloration including hyperpigmentation and skin yellowing.
Read the Promacta (eltrombopag tablets) Side Effects Center for a complete guide to possible side effects
Polyvalent Cations (Chelation)
Eltrombopag chelates polyvalent cations (such as iron, calcium, aluminum, magnesium, selenium, and zinc) in foods, mineral supplements, and antacids. In a clinical trial, administration of PROMACTA with a polyvalent cation-containing antacid decreased plasma eltrombopag systemic exposure by approximately 70% [see CLINICAL PHARMACOLOGY].
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 [see DOSAGE AND ADMINISTRATION, CLINICAL PHARMACOLOGY].
Coadministration of PROMACTA with the OATP1B1 and breast cancer resistance protein (BCRP) substrate, rosuvastatin, to healthy adult subjects increased plasma rosuvastatin AUC 0-INF by 55% and Cmax by 103% [see CLINICAL PHARMACOLOGY].
Use caution when concomitantly administering PROMACTA and drugs that are substrates of OATP1B1 (e.g., atorvastatin, bosentan, ezetimibe, fluvastatin, glyburide, olmesartan, pitavastatin, pravastatin, rosuvastatin, repaglinide, rifampin, simvastatin acid, SN-38 [active metabolite of irinotecan], valsartan) or BCRP (e.g., imatinib, irinotecan, lapatinib, methotrexate, mitoxantrone, rosuvastatin, sulfasalazine, topotecan). Monitor patients closely for signs and symptoms of excessive exposure to the drugs that are substrates of OATP1B1 or BCRP and consider reduction of the dose of these drugs, if appropriate. In clinical trials with PROMACTA, a dose reduction of rosuvastatin by 50% was recommended.
HIV Protease Inhibitors
In a drug interaction trial, coadministration of PROMACTA with lopinavir/ritonavir (LPV/RTV) decreased plasma eltrombopag exposure by 17% [see CLINICAL PHARMACOLOGY]. No dose adjustment is recommended when PROMACTA is coadministered with LPV/RTV. Drug interactions with other HIV protease inhibitors have not been evaluated.
Hepatitis C Virus (HCV) Protease Inhibitors
Coadministration of PROMACTA with either boceprevir or telaprevir did not affect eltrombopag or protease inhibitor exposure significantly [see CLINICAL PHARMACOLOGY]. No dose adjustments are recommended. Drug interactions with other HCV protease inhibitors have not been evaluated.
Peginterferon Alfa-2a/b Therapy
Coadministration of peginterferon alfa-2a (PEGASYS®) or -2b (PEGINTRON®) did not affect eltrombopag exposure in two randomized, double-blind, placebo-controlled trials with adult patients with chronic hepatitis C [see CLINICAL PHARMACOLOGY].
Read the Promacta Drug Interactions Center for a complete guide to possible interactions
Last reviewed on RxList: 3/24/2017
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