in patients receiving CAPRELSA after data cut-off. Causes of discontinuation in CAPRELSA-treated patients in >1 patient included asthenia, fatigue rash, arthralgia, diarrhea, hypertension, prolonged QT interval, increase in creatinine and pyrexia. Serious adverse events in CAPRELSA-treated patients in >2% of patients included diarrhea, pneumonia, and hypertension. Clinically important uncommon adverse drug reactions in patients who received CAPRELSA versus patients who received placebo included pancreatitis (0.4% vs. 0%) and heart failure (0.9% vs. 0%). In the integrated summary of safety database, the most common cause of death in patients who received CAPRELSA was pneumonia.
The incidence of Grade 1-2 bleeding events was 14% in patients receiving CAPRELSA compared with 7% on placebo in the randomized portion of the medullary thyroid cancer (MTC) study. The incidence was similar in the 300 mg monotherapy safety program with a 13% incidence.
Blurred vision was more common in patients who received CAPRELSA versus patients who received placebo for medullary thyroid cancer (9% vs. 1%, respectively). Scheduled slit lamp examinations have revealed corneal opacities (vortex keratopathies) in treated patients, which can lead to halos and decreased visual acuity. It is unknown if this will improve after discontinuation. Ophthalmologic examination, including slit lamp, is recommended in patients who report visual changes. If a patient has blurred vision, do not drive or operate machinery.
Table 2 provides the frequency and severity of laboratory abnormalities reported for patients with medullary thyroid cancer receiving randomized treatment with CAPRELSA or placebo.
Table 2 - Laboratory Abnormalities in Patients with MTC Laboratory Parameter CAPRELSA 300 mg Placebo N=99
All Grades
Grade 3–4 All Grades Grade 3–4
|
Chemistries
|
|
|
Calcium Decreased
|
132 (57%)
|
13 (6%)
|
25 (25%)
|
3 (3%)
|
|
ALT Increased
|
118 (51%)
|
4 (2%)
|
19 (19%)
|
0
|
|
Glucose Decreased
|
55 (24%)
|
0
|
7 (7%)
|
1 (1%)
|
|
Creatinine Increased
|
38 (16%)
|
0
|
1 (1%)
|
0
|
|
Bilirubin Increased
|
29 (13%)
|
0
|
17 (17%)
|
0
|
|
Magnesium Decreased
|
17 (17%)
|
1 (<1%)
|
2 (2%)
|
0
|
|
Calcium Increased
|
16 (7%)
|
2 (1%)
|
9 (9%)
|
1 (1%)
|
|
Potassium Decreased
|
15 (6%)
|
1 (<1%)
|
3 (3%)
|
0
|
|
