ADVERSE REACTIONS
The most common adverse events for FOSRENOL® were gastrointestinal events, such as nausea and vomiting and they generally abated over time with continued dosing.
In double-blind, placebo-controlled studies where a total of 180 and 95 ESRD patients were randomized to FOSRENOL® and placebo, respectively, for 4-6 weeks of treatment, the most common events that were more frequent (≥5% difference) in the FOSRENOL® group were nausea, vomiting, dialysis graft occlusion, and abdominal pain (Table 1).
Table 1. Adverse Events That Were More Common on FOSRENOL® in Placebo-Controlled, Double-Blind Studies with Treatment Periods of 4-6 Weeks. | FOSRENOL®
%
(N=180) | Placebo
%
(N=95) |
|---|
|
Nausea
|
11
|
5
|
|
Vomiting
|
9
|
4
|
|
Dialysis graft occlusion
|
8
|
1
|
|
Abdominal pain
|
5
|
0
|
The safety of FOSRENOL® was studied in two long-term clinical trials that included 1215 patients treated with FOSRENOL® and 943 with alternative therapy. Fourteen percent (14%) of patients in these comparative, open-label studies discontinued in the FOSRENOL®-treated group due to adverse events. Gastrointestinal adverse events, such as nausea, diarrhea and vomiting, were the most common type of event leading to discontinuation.
The most common adverse events (≥ 5% in either treatment group) in both the long-term (2 year), open-label, active controlled, study of FOSRENOL® vs. alternative therapy (Study A) and the 6-month, comparative study of FOSRENOL® vs. calcium carbonate (Study B) are shown in Table 2. In Table 2, Study A events have been adjusted for mean exposure differences between treatment groups (with a mean exposure of 0.9 years on lanthanum and 1.3 years on alternative therapy). The adjustment for mean exposure was achieved by multiplying the observed adverse event rates in the alternative therapy group by 0.71.
Table 2. Incidence of Treatment-Emergent Adverse Events that Occurred in ≥ 5% of Patients (in Either Treatment Group) and in Both Comparative Studies A and B | Study A
% | Study B
% |
|---|
|
FOSRENOL®
(N = 682) | Alternative
Therapy Adjusted
Rates
(N=676) |
FOSRENOL®
(N=533) | Calcium
Carbonate
(N=267) |
|---|
|
Nausea
|
36
|
28
|
16
|
13
|
|
Vomiting
|
26
|
21
|
18
|
11
|
|
Dialysis graft complication
|
26
|
25
|
3
|
5
|
|
Diarrhea
|
23
|
22
|
13
|
10
|
|
Headache
|
21
|
20
|
5
|
6
|
|
Dialysis graft occlusion
|
21
|
20
|
4
|
6
|
|
Abdominal pain
|
17
|
17
|
5
|
3
|
|
Hypotension
|
16
|
17
|
8
|
9
|
|
Constipation
|
14
|
13
|
6
|
7
|
|
Bronchitis
|
5
|
6
|
5
|
6
|
|
Rhinitis
|
5
|
7
|
7
|
6
|
|
Hypercalcemia
|
4
|
8
|
0
|
20
|
|
