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) Thrombocytopenia
|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) Thrombocytopenia
|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 Hepatitis C
|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.