"The Centers for Disease Control and Prevention has identified a cluster of newborns in Tennessee with late vitamin K deficiency bleeding (VKDB). VKDB is a serious, but preventable bleeding disorder that can cause bleeding in the brain. In each"...
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 to 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 446 patients with chronic ITP aged 18 to 85, of whom 65% were female across the ITP clinical development program including 3 placebo-controlled trials. PROMACTA was administered to 277 patients for at least 6 months and 202 patients for at least 1 year.
Table 3 presents the most common adverse drug reactions (experienced by ≥ 3% of patients receiving PROMACTA) from the 3 placebo-controlled trials, with a higher incidence in PROMACTA versus placebo.
Table 3: Adverse Reactions ( ≥ 3%) from Three
Placebo-Controlled Trials in Adults With Chronic Immune (Idiopathic)
|Adverse Reaction||PROMACTA 50 mg
n = 241 (%)
n = 128 (%)
|Upper respiratory tract infection||7||6|
|Urinary tract infection||5||3|
In the 3 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 299 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 placebocontrolled trials. Table 4 presents the most common treatment-related adverse reactions (experienced by ≥ 3% of patients receiving PROMACTA) from the extension trial.
Table 4: Treatment-Related Adverse Reactions ( ≥ 3%)
from Extension Trial in Adults With Chronic Immune (Idiopathic)
|Adverse Reaction||PROMACTA 50 mg
n = 299 (%)
In the 3 controlled chronic ITP trials, serum liver test abnormalities (predominantly Grade 2 or less in severity) were reported in 11% and 7% of the PROMACTA and placebo groups, respectively. Four patients (1%) treated with PROMACTA and three patients in the placebo group (2%) discontinued treatment due to hepatobiliary laboratory abnormalities. Seven of the patients treated with PROMACTA in the controlled trials with hepatobiliary laboratory abnormalities were re-exposed to PROMACTA in the extension trial. Six of these patients again experienced liver test abnormalities (predominantly Grade 1) resulting in discontinuation of PROMACTA in one patient. In the extension chronic ITP trial, one additional patient had PROMACTA discontinued due to liver test abnormalities ( ≤ Grade 3).
In a placebo-controlled trial of PROMACTA in non-ITP thrombocytopenic patients with chronic liver disease, six patients in the PROMACTA group and one patient in the placebo group developed portal vein thromboses [see WARNINGS AND PRECAUTIONS].
Chronic Hepatitis C-Associated Thrombocytopenia
In the 2 placebo-controlled trials, 955 patients with chronic hepatitis C-associated thrombocytopenia received PROMACTA. Table 5 presents the most common adverse drug reactions (experienced by ≥ 10% of patients receiving PROMACTA compared to placebo).
Table 5: Adverse Reactions ( ≥ 10% and Greater
than Placebo) from Two Placebo-Controlled Trials in Adults With Chronic
|Adverse Reaction||PROMACTA + Peginterferon/ Ribavirin
n = 955 (%)
|Placebo + Peginterferon/ Ribavirin
n = 484 (%)
In the 2 controlled clinical trials in patients with chronic hepatitis C, hyperbilirubinemia was reported in 8% of patients receiving PROMACTA compared to 3% for placebo. Total bilirubin ≥ 1.5 X ULN was reported in 76% and 50% of patients receiving PROMACTA and placebo, respectively. ALT or AST ≥ 3X ULN was reported in 34% and 38% of the PROMACTA and placebo groups, respectively.
Read the Promacta (eltrombopag tablets) Side Effects Center for a complete guide to possible side effects
In vitro, CYP1A2, CYP2C8, UDP-glucuronosyltransferase (UGT)1A1 and UGT1A3 are involved in the metabolism of eltrombopag. In vitro, eltrombopag inhibits the following metabolic or transporter systems: CYP2C8, CYP2C9, UGT1A1, UGT1A3, UGT1A4, UGT1A6, UGT1A9, UGT2B7, UGT2B15, OATP1B1 and breast cancer resistance protein (BCRP) [see CLINICAL PHARMACOLOGY].
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].
PROMACTA must not be taken within 4 hours of any medications or products containing polyvalent cations such as antacids, dairy products, and mineral supplements to avoid significant reduction in PROMACTA absorption due to chelation [see DOSAGE AND ADMINISTRATION].
Co-administration of PROMACTA with the OATP1B1 and BCRP substrate, rosuvastatin, to healthy adult subjects increased plasma rosuvastatin AUC0-∞ 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, co-administration 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
Co-administration of peginterferon alfa 2a (PEGASYS®) or 2b (PEGINTRON®) did not affect eltrombopag exposure in 2 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: 7/10/2014
This monograph has been modified to include the generic and brand name in many instances.
Additional Promacta Information
Report Problems to the Food and Drug Administration
You are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.
Find out what women really need.