The following serious adverse reactions associated with PROMACTA are described in other sections.

• Hepatotoxicity [see WARNINGS AND PRECAUTIONS]
• Hepatic Decompensation in Patients With Chronic Hepatitis C [see WARNINGS AND PRECAUTIONS]
• Bone Marrow Reticulin Formation and Risk for Bone Marrow Fibrosis [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) Thrombocytopenic

In clinical studies, hemorrhage was the most common serious adverse reaction and most hemorrhagic reactions followed discontinuation of PROMACTA. Other serious adverse reactions included liver test abnormalities and 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 studies. 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 studies, with a higher incidence in PROMACTA versus placebo.

Table 3: Adverse Reactions ( ≥ 3%) from Three Placebo-Controlled Studies in Adults With Chronic Immune (Idiopathic) Thrombocytopenia

In the 3 controlled clinical chronic ITP studies, 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 studies. 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) Thrombocytopenia

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 Studies in Adults With Chronic Hepatitis C

In the 2 controlled clinical studies in patients with chronic hepatitis C, hyperbilirubinemia was also reported (8% for PROMACTA versus 3% for placebo).

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].

Transporters

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.

Lopinavir/ritonavir

In a drug interaction study, 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 co-administered with LPV/RTV. Drug interactions with other HIV 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.

Last reviewed on RxList: 12/5/2012
This monograph has been modified to include the generic and brand name in many instances.