Pressure and Heart Rate Assessed at MWT
Sessions from Baseline through Week 12: Mean (95% CI)*
Placebo SUNOSI
37.5 mg
SUNOSI
75 mg
SUNOSI
150 mg
SUNOSI
300 mg**
Narcolepsy
n
SBP
52
3.5 (0.7, 6.4) - 51
3.1 (0.1, 6.0)
49
4.9 (1.7, 8.2)
53
6.8 (3.2, 10.3)
n
DBP
23
1.8 (-1.8, 5.5) - 47
2.2 (0.2, 4.1)
49
4.2 (2.0, 6.5)
53
4.2 (1.5, 6.9) STUDY 1
n
HR
48
2.3 (-0.1, 4.7) - 26
3.7 (0.4, 6.9)
49
4.9 (2.3, 7.6)
53
6.5 (3.9, 9.0)
OSA
n
SBP
35
1.7 (-1.4, 4.9)
17
4.6 (-1.1, 10.2)
54
3.8 (1.2, 6.4)
103
2.4 (0.4, 4.4)
35
4.5 (1.1, 7.9)
n
DBP
99
1.4 (-0.1, 2.9)
17
1.9 (-2.3, 6.0)
17
3.2 (-0.9, 7.3)
107
1.8 (0.4, 3.2)
91
STUDY 2 3.3 (1.8, 4.8)
n
HR
106
1.7 (0.1, 3.3)
17
1.9 (-1.9, 5.7)
51
3.3 (0.6, 6.0)
102
2.9 (1.4, 4.4)
91
4.5 (3.0, 6.0)
SBP = systolic blood pressure; DBP = diastolic blood pressure; HR = heart rate
* For study weeks 1, 4, and 12, SDP, DBP, and HR were assessed pre-dose and every 1-2 hours for 10 hours after test drug administration. For alltime points at all visits, the mean change from baseline was calculated, by indication and dose, for all patients with a valid assessment. The tableshows, by indication and dose, the mean changes from baseline for the week and time point with the maximal change in SDP, DBP, and HR.
** The maximum recommended daily dose is 150 mg. Dosages above 150 mg daily do not confer increased effectiveness sufficient to outweighdose-related adverse reactions.
Table 5: Blood Pressure and Heart Rate by 24-hour Ambulatory Monitoring: Mean
Change (95% CI) from Baseline at Week 8
Placebo SUNOSI
37.5 mg
SUNOSI
75 mg
SUNOSI
150 mg
SUNOSI
300 mg**
Narcolepsy
n* 46 44 44 40
SBP -0.4 (-3.1, 2.4) - 1.6 (-0.4, 3.5) -0.5 (-2.1, 1.1) 2.4 (0.5, 4.3)
STUDY 1 DBP -0.2 (-1.9, 1.6) - 1.0 (-0.4, 2.5) 0.8 (-0.4, 2.0) 3.0 (1.4, 4.5)
HR 0.0 (-1.9, 2.0) - 0.2 (-2.1, 2.4) 1.0 (-1.2, 3.2) 4.8 (2.3, 7.2)
OSA
STUDY 2
n* 92 43 49 96 84
SBP -0.2 (-1.8, 1.4) 1.8 (-1.1, 4.6) 2.6 (0.02, 5.3) -0.2 (-2.0, 1.6) 2.8 (-0.1, 5.8)
DBP 0.2 (-0.9, 1.3) 1.4 (-0.4, 3.2) 1.5 (-0.04, 3.1) -0.1 (-1.1, 1.0) 2.4 (0.5, 4.4)
HR -0.4 (-1.7, 0.9) 0.4 (-1.4, 2.2) 1.0 (-0.9, 2.81) 1.7 (0.5, 2.9) 1.6 (0.3, 2.9)
SBP = systolic blood pressure; DBP = diastolic blood pressure; HR = heart rate
* Number of patients who had at least 50% valid ABPM readings.
**The maximum recommended daily dose is 150 mg. Dosages above 150 mg daily do not confer increased effectiveness sufficient tooutweigh dose-related adverse reactions.
7 DRUG INTERACTIONS
7.1 Monoamine Oxidase (MAO) Inhibitors
Do not administer SUNOSI concomitantly with MAOIs or within 14 days after discontinuing MAOItreatment. Concomitant use of MAO inhibitors and noradrenergic drugs may increase the risk of ahypertensive reaction. Potential outcomes include death, stroke, myocardial infarction, aorticdissection, ophthalmological complications, eclampsia, pulmonary edema, and renal failure [seeContraindications (4)].
7.2 Drugs that Increase Blood Pressure and/or Heart Rate
Concomitant use of SUNOSI with other drugs that increase blood pressure and/or heart rate hasnot been eva luated, and such combinations should be used with caution [see Warnings andPrecautions (5.1)].
7.3 Dopaminergic Drugs
Dopaminergic drugs that increase levels of dopamine or that bind directly to dopa |
