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 | ||
persistent or chronic ITP trial , six additional patients had PROMACTA discontinued due to liver | ||
test abnormalities ( less than or equal to Grade 3 ). | ||
In the three controlled persistent or 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 cortico steroid 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 . | ||
The safety of PROMACTA was also assessed in all patients treated in 7 adult persistent or chronic ITP | ||
clinical trials ( N = 763 PROMACTA-treated patients and 179 placebo-treated patients ). Thromboembolic | ||
events were reported in 6 % of PROMACTA-treated patients versus 0 % of placebo-treated patients and | ||
thrombotic microangiopathy with acute renal failure was reported in < 1 % of PROMACTA-treated | ||
patients versus 0 % of placebo-treated patients . | ||
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 ( 5.4 )]. | ||
Pediatric Patients : The data described below reflect median exposure to PROMACTA of 91 days for | ||
107 pediatric patients ( aged 1 to 17 years ) with persistent or chronic ITP , of whom 53 % were female , | ||
across the randomized phase of two placebo-controlled trials . | ||
Table 10 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 10 . Adverse Reactions ( ≥ 3 %) With a Higher Incidence for PROMACTA Versus Placebo From | ||
Two Placebo-controlled Trials in Pediatric Patients 1 Year and Older With Persistent or Chronic | ||
Immune Thrombocytopenia | ||
PROMACTA |
Placebo |
|
n = 107 |
n = 50 |
|
Adverse Reaction |
(%) |
(%) |
Upper respiratory tract infection |
17 |
6 |
Nasopharyngitis |
12 |
4 |
Cough |
9 |
0 |
Diarrhea |
9 |
2 |
Pyrexia |
9 |
8 |
Abdominal pain |
8 |
4 |
Oropharyngeal pain |
8 |
2 |
Toothache |
6 |
0 |
ALT increased a
|
6 |
0 |
Rash |
5 |
2 |
AST increased |
4 |
0 |
Rhinorrhea |
4 |
0 |
Abbreviations : ALT , alanine aminotransferase ; AST , aspartate aminotransferase . | ||
a
Includes adverse reactions or laboratory abnormalities > 3 x ULN .
| ||
In the two controlled clinical persistent or 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 placebo-controlled trials , 955 patients | ||
with chronic hepatitis C-associated thrombocytopenia received PROMACTA . Table 11 presents the most | ||
common adverse drug reactions ( experienced by greater than or equal to 10 % of patients receiving | ||
PROMACTA compared with placebo ). | ||
Table 11 . Adverse Reactions ( ≥ 10 % and Greater Than Placebo ) From Two Placebo-controlled Trials | ||
in Adults With Chronic Hepatitis C | ||
PROMACTA |
Placebo |
|
+ Peginterferon / Ribavirin |
+ Peginterferon / Ribavirin |
|
n = 955 |
n = 484 |
|
Adverse Reaction |
(%) |
(%) |
Anemia |
40 |
35 |
Pyrexia |
30 |
24 |
Fatigue |
28 |
23 |
Headache |
21 |
20 |
Nausea |
19 |
14 |
Diarrhea |
19 |
11 |
Decreased appetite |
18 |
14 |
Influenza-like illness |
18 |
16 |
Insomnia a
|
16 |
15 |
Asthenia |
16 |
13 |
Cough |
15 |
12 |
Pruritus |
15 |
13 |
Chills |
14 |
9 |
Myalgia |
12 |
10 |
Alopecia |
10 |
6 |
Peripheral edema |
10 |
5 |
a
Includes PTs of Insomnia , Initial insomnia , and Poor quality sleep .
| ||
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 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 . | ||
The safety of PROMACTA was also assessed in all patients treated with PROMACTA in the two controlled | ||
trials , including patients who initially received PROMACTA in the pre-antiviral treatment phase of the | ||
trial and were later randomized to the placebo arm ( N = 1520 PROMACTA-treated patients ). Hepatic | ||
failure was reported in 0.8 % of PROMACTA-treated patients and 0.4 % of placebo-treated patients . |