ADVERSE REACTIONS
Pre-marketing experiences
Pre-marketing safety data on Ventavis were obtained from 215 patients with pulmonary arterial hypertension receiving iloprost in two 12-week clinical trials and two long-term extensions. Patients received inhaled Ventavis for periods of from 1 day to more than 3 years. The median number of weeks of exposure was 15 weeks. Forty patients completed 12 months of open-label treatment with iloprost.
The following table shows adverse events reported by at least 4 iloprost patients and reported at least 3% more frequently for iloprost patients than placebo patients in the 12-week placebo-controlled study.
Table 3: Adverse Events in Phase 3 Clinical Trial Adverse
Event | Iloprost
n=101 | Placebo
n=102 | Placebo subtracted
% |
|---|
|
Vasodilation (flushing)
|
27
|
9
|
18
|
|
Cough increased
|
39
|
26
|
13
|
|
Headache
|
30
|
20
|
10
|
|
Trismus
|
12
|
3
|
9
|
|
Insomnia
|
8
|
2
|
6
|
|
Nausea
|
13
|
8
|
5
|
|
Hypotension
|
11
|
6
|
5
|
|
Vomiting
|
7
|
2
|
5
|
|
Alk phos increased
|
6
|
1
|
5
|
|
Flu syndrome
|
14
|
10
|
4
|
|
Back pain
|
7
|
3
|
4
|
|
Abnormal lab test
|
7
|
3
|
4
|
|
Tongue pain
|
4
|
0
|
4
|
|
Palpitations
|
7
|
4
|
3
|
|
Syncope
|
8
|
5
|
3
|
|
GGT increased
|
6
|
3
|
3
|
|
Muscle cramps
|
6
|
3
|
3
|
|
Hemoptysis
|
5
|
2
|
3
|
|
Pneumonia
|
4
|
1
|
3
|
Pre-marketing serious adverse events reported with the use of inhaled iloprost and not shown in Table 3 include congestive heart failure, chest pain, supraventricular tachycardia, dyspnea, peripheral edema, and kidney failure.
In a small clinical trial (the STEP trial, see CLINICAL TRIALS), safety trends in patients receiving concomitant bosentan and iloprost were consistent with those observed in the larger experience of the Phase 3 study in patients receiving only iloprost.
Adverse events with higher doses
In a study in healthy volunteers (n=160), inhaled doses of iloprost solution were given every 2 hours, beginning with 5 mcg and increasing up to 20 mcg for a total of 6 dose inhalations (total cumulative dose of 70 mcg) or up to the highest dose tolerated in a subgroup of 40 volunteers. There were 13 subjects (32%) who failed to reach the highest scheduled dose (20 mcg). Five were unable to increase the dose because of (mild to moderate) transient chest pain/discomfort/tightness, usually accompanied by headache, nausea, and dizziness. The remaining 8 subjects discontinued for other reasons.
POSTMARKETING EXPERIENCE
The following adverse reactions have been identified during the postapproval use of Ventavis. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Cases of epistaxis and gingival bleeding have been reported within one month of starting iloprost treatment.
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