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 Warnings, Precautions, Pregnancy, Nursing, Abuse - Orlistat
Xenical Warnings, Precautions, Pregnancy, Nursing, Abuse - Orlistat
WARNINGS
Miscellaneous: Organic causes of obesity
(e.g., hypothyroidism) should be excluded before prescribing XENICAL.
PRECAUTIONS
General
Patients should be advised to adhere to dietary
guidelines (see DOSAGE AND ADMINISTRATION).
Gastrointestinal events (see ADVERSE
REACTIONS) may increase when XENICAL is taken with a diet
high in fat (>30% total
daily calories from fat). The daily intake
of fat should be distributed
over three main meals. If XENICAL is taken with any one meal
very high in fat, the possibility of gastrointestinal
effects increases.
Patients should be counseled to take
a multivitamin supplement that contains fat-soluble vitamins to
ensure adequate nutrition
because XENICAL has been shown to reduce
the absorption of some fat-soluble vitamins and beta-carotene. In
addition, the levels of vitamin
D and beta-carotene may be low in obese
patients compared with non-obese subjects. The supplement should
be taken once a day at least 2 hours before or after the administration
of XENICAL, such as at bedtime.
Table 6 illustrates the percentage of patients on XENICAL and placebo
who developed a low vitamin level on two or more consecutive visits
during 1 and 2 years of therapy in studies in which patients were
not previously receiving vitamin
supplementation.
|
Table 6. Incidence of Low Vitamin Values on Two or More
Consecutive Visits (Nonsupplemented Patients With Normal
Baseline Values — First and Second Year)
|
| |
Placebo*
|
XENICAL*
|
| Vitamin
A |
1.0%
|
2.2%
|
| Vitamin
D |
6.6%
|
12.0%
|
| Vitamin
E |
1.0%
|
5.8%
|
| Beta-carotene |
1.7%
|
6.1%
|
|
* Treatment designates placebo
plus diet or XENICAL
plus diet.
|
Some patients may develop increased levels of urinary
oxalate following treatment
with XENICAL. Caution should be exercised when prescribing XENICAL
to patients with a history of hyperoxaluria
or calcium oxalate
nephrolithiasis.
Weight-loss induction
by XENICAL may be accompanied by improved metabolic control
in diabetics, which might require a reduction
in dose of oral
hypoglycemic medication (e.g., sulfonylureas, metformin) or insulin
(see CLINICAL STUDIES).
Misuse Potential
As with any weight-loss agent,
the potential exists
for misuse of XENICAL in inappropriate patient
populations (e.g., patients with anorexia
nervosa or bulimia). See INDICATIONS
AND USAGE for recommended prescribing guidelines.
Information for Patients
Patients should read the Patient Information before starting treatment
with XENICAL and each time
their prescription
is renewed.
Drug Interactions
See DRUG INTERACTIONS section.
Carcinogenesis, Mutagenesis, Impairment of Fertility
Carcinogenicity studies in rats and mice did not show
a carcinogenic
potential for orlistat
at doses up to 1000 mg/kg/day and 1500 mg/kg/day, respectively.
For mice and rats, these doses are 38 and 46 times the daily human
dose calculated on an area
under concentration vs time
curve basis
of total drug-related material.
Orlistat had no detectable
mutagenic or genotoxic
activity as determined
by the Ames test, a mammalian forward mutation
assay (V79/HPRT), an in
vitro clastogenesis assay
in peripheral human lymphocytes, an unscheduled DNA
synthesis assay
(UDS) in rat hepatocytes
in culture, and an in vivo mouse
micronucleus test.
When given to rats at a dose of 400 mg/kg/day in a fertility
and reproduction
study, orlistat had no observable adverse effects. This dose
is 12 times the daily human
dose calculated on a body
surface area
(mg/m2) basis.
Pregnancy
Teratogenic Effects: Pregnancy Category B. Teratogenicity
studies were conducted in rats and rabbits at doses up to 800 mg/kg/day.
Neither study showed embryotoxicity or teratogenicity. This dose
is 23 and 47 times the daily human
dose calculated on a body
surface area
(mg/m2) basis
for rats and rabbits, respectively.
The incidence of
dilated cerebral ventricles was increased in the mid- and high-dose
groups of the rat teratology
study. These doses were 6 and 23 times the daily human
dose calculated on a body
surface area
(mg/m2) basis for the mid- and high-dose levels, respectively.
This finding was not reproduced in two additional rat
teratology studies
at similar doses.
There are no adequate and
well-controlled studies of XENICAL in pregnant
women. Because animal
reproductive studies are not always predictive of human
response, XENICAL is not recommended for use during pregnancy.
Nursing Mothers
It is not known if orlistat is secreted in human
milk. Therefore, XENICAL should not be taken by nursing
women.
Pediatric Use
The safety and efficacy
of XENICAL in pediatric
patients have not been established.
Geriatric Use
Clinical studies of XENICAL did not include sufficient numbers
of patients aged 65 years and older to determine whether they respond
differently from younger patients.
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