A1,
A2,
B,
C1,
C2,
D,
E,
F,
G-H,
I-K,
L,
M,
N,
O,
P1,
P2,
Q-R,
S,
T,
U-V,
W-Z
Xenical Side Effects, and Drug Interactions - Orlistat
Xenical Side Effects, and Drug Interactions - Orlistat
SIDE EFFECTS
Commonly Observed (based on first year and second
year data — XENICAL 120 mg three times a day versus placebo):
Gastrointestinal (GI) symptoms were the most commonly observed
treatment-emergent adverse events associated with the use of XENICAL
in double-blind, placebo-controlled clinical
trials and are primarily a manifestation
of the mechanism of
action. (Commonly observed is defined as an incidence
of ³5% and an incidence
in the XENICAL 120 mg group
that is at least twice that of placebo.)
Table 7. Commonly Observed Adverse Events
|
Adverse Event
|
Year
1 |
Year
2 |
|
XENICAL*
% of Patients
(N=1913)
|
Placebo*
% of Patients
(N=1466)
|
XENICAL*
% of Patients
(N=613)
|
Placebo*
% of Patients
(N=524)
|
| Oily Spotting |
26.6
|
1.3
|
4.4
|
0.2
|
| Flatus with Discharge |
23.9
|
1.4
|
2.1
|
0.2
|
| Fecal Urgency |
22.1
|
6.7
|
2.8
|
1.7
|
| Fatty/Oily Stool |
20.0
|
2.9
|
5.5
|
0.6
|
| Oily Evacuation |
11.9
|
0.8
|
2.3
|
0.2
|
| Increased Defecation |
10.8
|
4.1
|
2.6
|
0.8
|
| Fecal Incontinence |
7.7
|
0.9
|
1.8
|
0.2
|
*Treatment designates XENICAL three times a day plus diet
or placebo plus diet.
These and other commonly observed adverse reactions were generally
mild and transient, and they decreased during the second year of
treatment. In general, the
first occurrence of these events was within 3 months of starting
therapy. Overall, approximately 50% of all episodes of GI
adverse events associated with orlistat treatment lasted for less
than 1 week, and a majority lasted for no
more than 4 weeks. However, GI
adverse events may occur in some individuals over a period of 6
months or longer.
Discontinuation of Treatment: In controlled clinical
trials, 8.8% of patients treated with XENICAL discontinued treatment
due to adverse events, compared with 5.0% of placebo-treated patients.
For XENICAL, the most common adverse events resulting in discontinuation
of treatment were
gastrointestinal.
Incidence in Controlled Clinical Trials: The following
table lists other treatment-emergent
adverse events from seven multicenter, double-blind, placebo-controlled
clinical trials that occurred at a frequency
of ³ 2% among patients treated with XENICAL 120 mg
three times a day and with an incidence
that was greater than placebo
during year 1 and year 2, regardless of relationship to study medication.
Table 8. Other Treatment-Emergent Adverse Events
From Seven Placebo-Controlled Clinical Trials
|
Body System/Adverse Event
|
Year 1
|
Year 2
|
|
XENICAL*
% Patients
(N=1913)
|
Placebo*
% Patients
(N=1466)
|
XENICAL*
% Patients
(N=613)
|
Placebo*
% Patients
(N=524)
|
- Gastrointestinal System
Abdominal Pain/Discomfort
Nausea
Infectious Diarrhea
Rectal Pain/Discomfort
Tooth Disorder
Gingival Disorder
Vomiting
|
25.5
8.1
5.3
5.2
4.3
4.1
3.8
|
21.4
7.3
4.4
4.0
3.1
2.9
3.5
|
-
3.6
-
3.3
2.9
2.0
-
|
-
2.7
-
1.9
2.3
1.5
-
|
- Respiratory System
Influenza
Upper Respiratory Infection
Lower Respiratory Infection
Ear, Nose & Throat Symptoms
|
39.7
38.1
7.8
2.0
|
36.2
32.8
6.6- 1.6
|
-- 26.1
- -
- -
|
-- 25.8
- -
- -
|
- Musculoskeletal System
- Back Pain
- Pain Lower Extremities
- Arthritis
- Myalgia
- Joint Disorder
- Tendonitis
|
13.9- -
- 5.4
- 4.2
- 2.3
- -
|
12.1- -
- 4.8
- 3.3
- 2.2
- -
|
-- 10.8
- -
- -
- -
- 2.0
|
-- 10.3
- -
- -
- -
- 1.9
|
- Central Nervous System
- Headache
- Dizziness
|
30.6- 5.2
|
27.6- 5.0
|
-- -
|
-- -
|
- Body as a Whole
- Fatigue
- Sleep Disorder
|
7.2- 3.9
|
6.4- 3.3
|
3.1- -
|
1.7- -
|
- Skin & Appendages
- Rash
- Dr.
Skin
|
4.3- 2.1
|
4.0- 1.4
|
-- -
|
-- -
|
- Reproductive, Female
- Menstrual Irregularity
- Vaginitis
|
9.8- 3.8
|
7.5- 3.6
|
-- 2.6
|
-- 1.9
|
- Urinary System
- Urinary Tract Infection
|
7.5
|
7.3
|
5.9
|
4.8
|
- Psychiatric Disorder
- Psychiatric Anxiety
- Depression
|
4.7- -
|
2.9- -
|
2.8- 3.4
|
2.1- 2.5
|
- Hearing & Vestibular Disorders
- Otitis
|
4.3
|
3.4
|
2.9
|
2.5
|
- Cardiovascular Disorders
- Pedal Edema
|
-
|
-
|
2.8
|
1.9
|
*Treatment designates XENICAL 120 mg
three times a day plus diet or placebo
plus diet
-None reported at a frequency
³2% and greater than placebo.
DRUG INTERACTIONS
Alcohol: In a multiple-dose study in 30 normal
weight subjects, coadministration
of XENICAL and 40 grams of alcohol
(e.g., approximately 3 glasses
of wine) did not result in alteration of alcohol
pharmacokinetics,
orlistat pharmacodynamics
(fecal fat excretion), or systemic
exposure to orlistat.
Cyclosporine: No drug interaction studies have been
conducted with XENICAL and cyclosporine. Since changes in cyclosporine
absorption have been
reported with variations in dietary
intake, caution is advised in the concomitant
use of XENICAL plus diet
in patients receiving cyclosporine
therapy.
Digoxin: In 12 normal-weight subjects receiving XENICAL
120 mg three times a day
for 6 days, XENICAL did not alter the pharmacokinetics
of a single dose of digoxin.
Fat-soluble Vitamin Supplements and Analogues: A
pharmacokinetic interaction study showed a 30% reduction in beta-carotene
supplement absorption
when concomitantly administered with XENICAL. XENICAL inhibited
absorption of a vitamin
E acetate supplement
by approximately 60%. The effect
of orlistat on the absorption
of supplemental vitamin D, vitamin
A, and nutritionally-derived vitamin
K is not known at this time.
Glyburide: In 12 normal-weight subjects receiving
orlistat 80 mg three times
a day for 5 days, orlistat did not alter the pharmacokinetics
or pharmacodynamics
(blood glucose-lowering) of glyburide.
Nifedipine (extended-release tablets): In 17 normal-weight
subjects receiving XENICAL 120 mg
three times a day for 6 days, XENICAL did not alter the bioavailability
of nifedipine (extended-release tablets).
Oral Contraceptives: In 20 normal-weight female
subjects, the treatment
of XENICAL 120 mg three times a day for 23 days resulted in no
changes in the ovulation-suppressing action of oral
contraceptives.
Phenytoin: In 12 normal-weight subjects receiving
XENICAL 120 mg three times
a day for 7 days, XENICAL did not alter the pharmacokinetics
of a single 300-mg dose of phenytoin.
Pravastatin: In a parallel study of 24 normal-weight,
mildly hypercholesterolemic subjects receiving XENICAL 120 mg
three times a day for 10 days, the effect
of XENICAL was additive
to the lipid-lowering effect
of pravastatin. Modest increases (approximately 30%) in pravastatin
plasma concentrations
were observed during coadministration
with XENICAL.
Warfarin: In 12 normal-weight subjects, administration
of XENICAL 120 mg three times
a day for 16 days did not result in any change in either warfarin
pharmacokinetics
(both R- and S-enantiomers) or pharmacodynamics
(prothrombin time and serum
Factor VII). Although undercarboxylated osteocalcin, a marker
of vitamin K nutritional
status, was unaltered with XENICAL administration, vitamin
K levels tended to decline
in subjects taking XENICAL. Therefore, as vitamin
K absorption may be decreased with XENICAL, patients on chronic
stable doses of warfarin
who are prescribed XENICAL should be monitored closely for changes
in coagulation parameters.
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