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
Evista Side Effects, and Drug Interactions - Raloxifene
Evista Side Effects, and Drug Interactions - Raloxifene
SIDE EFFECTS
The safety of raloxifene has been assessed primarily in 12 Phase
2 and Phase 3 studies with placebo,
estrogen, and estrogen-progestin
replacement therapy (HRT) control
groups. The duration
of treatment ranged
from 2 to 30 months and 2036 women were exposed to raloxifene (371
patients received 10 to 50 mg/day, 828 received 60 mg/day, and 837
received from 120 to 600 mg/day).
The majority of adverse events occurring during clinical
trials were mild and generally did not require discontinuation of
therapy.
Therapy was discontinued due to an adverse event in 11.4% of 581
EVISTA-treated women and 12.2% of 584 placebo-treated women. Common
adverse events considered to be drug-related were hot
flashes and leg cramps (see
Table 4). The first occurrence of hot
flashes was most commonly reported during the first 6 months of
treatment.
Discontinuation rates due to hot
flashes did not differ significantly between EVISTA and placebo
groups (1.7% and 2.2%, respectively).
Adverse Events in Placebo-controlled Clinical Trials
Table 4 lists adverse events occurring in the placebo-controlled
clinical trial database at a frequency
³2.0% in either group
and in more EVISTA-treated women than in placebo-treated women.
Adverse events are shown without attribution of causality.
Table 4.
|
Adverse events occurring in placebo-controlled
clinical trials at a frequency
³ 2.0% and in more EVISTA-treated
(60 mg once daily)
women than placebo-treated women
|
| Body
System |
EVISTA
N= 581
%
|
Placebo
N= 584
%
|
| Body as a Whole
|
| Infection |
15.1
|
14.6
|
| Flu Syndrome |
14.6
|
13.5
|
| Leg Cramps |
5. 9
|
1. 9
|
| Chest Pain |
4. 0
|
3. 6
|
| Fever |
3. 1
|
2. 6
|
| Cardiovascular
|
| Hot Flashes |
24.6
|
18.3
|
| Migraine |
2. 4
|
2. 1
|
| Digestive |
| Nausea |
8. 8
|
8. 6
|
| Dyspepsia |
5. 9
|
5. 8
|
| Vomiting |
3. 4
|
3. 3
|
| Flatulence |
3. 1
|
2. 4
|
| Gastrointestinal
Disorder |
3. 3
|
2. 1
|
| Gastroenteritis |
2.6
|
2.1
|
| Metabolic and
Nutritional |
| Weight Gain |
8. 8
|
6. 8
|
| Peripheral Edema
|
3. 3
|
1. 9
|
| Musculoskeletal
|
| Arthralgia |
10.7
|
10.1
|
| Myalgia |
7. 7
|
6. 2
|
| Arthritis |
4. 0
|
3. 6
|
| Nervous |
| Depression |
6. 4
|
6. 0
|
| Insomnia |
5. 5
|
4. 3
|
| Respiratory |
| Sinusitis |
10.3
|
6.5
|
| Pharyngitis |
7. 6
|
7. 2
|
| Cough Increased |
6.0
|
5.7
|
| Pneumonia |
2. 6
|
1. 5
|
| Laryngitis |
2. 2
|
1. 4
|
| Skin and Appendages
|
| Rash |
5. 5
|
3. 8
|
| Sweating |
3. 1
|
1. 7
|
| Urogenital |
| Vaginitis |
4. 3
|
3. 6
|
| Urinary Tract Infection
|
4. 0
|
3. 9
|
| Cystitis |
3. 3
|
3. 1
|
| Leukorrhea |
3.3
|
1.7
|
| Endometrial Disorder
a |
3.1
|
1.9
|
a Treatment-emergent uterine-related adverse
event, including only patients with an intact uterus: EVISTA, n=
354, Placebo, n= 364.
Comparison of EVISTA and Hormone Replacement Therapy Adverse
Events
EVISTA was compared with estrogen-progestin replacement
therapy (HRT) in 3 clinical
trials. Table 5 shows adverse events occurring more frequently in
one treatment group
and at an incidence
³2.0% in any group. Adverse events
are shown without attribution of causality.
|
Adverse events reported in clinical
trials with EVISTA (60 mg once daily) and continuous combined
or cyclic estrogen plus progestin (HRT) at an incidence
³ 2.0% in any treatment
group a
|
| Adverse
Event |
HRT-Continuous
|
|
EVISTA
(N= 317)
%
|
Combined
(N= 96)
%
|
HRT-Cyclic
(N= 219)
%
|
| Urogenital |
| Breast Pain |
4.4
|
37.5
|
29.7
|
| Vaginal Bleeding
b |
6.2
|
64.2
|
88.5
|
| Digestive |
| Flatulence |
1. 6
|
12.5
|
6.4
|
| Cardiovascular
|
| Hot flashes |
28.7
|
3.1
|
5.9
|
| Body as a Whole
|
| Infection |
11.0
|
0
|
6.8
|
| Abdominal Pain |
6. 6
|
10.4
|
18.7
|
| Chest Pain |
2. 8
|
0
|
0. 5
|
aThese data are from both blinded
and open-label studies.
bTreatment-emergent uterine-related adverse
event, including only patients with an intact uterus: EVISTA, n=
290, HRT-Continuous Combined, n= 67, HRT-Cyclic, n= 217.
Continuous Combined HRT = 0.625 mg
conjugated estrogens plus 2.5 mg
medroxyprogesterone acetate.
Cyclic HRT = 0.625 mg
conjugated estrogens for 28 days with concomitant
5 mg medroxyprogesterone
acetate or 0.15 mg
norgestrel on days 1 through 14 or 17 through 28.
Laboratory Changes
The following changes in analyte
concentrations are commonly observed during EVISTA therapy: increased
apolipoprotein
A1; and reduced serum
total cholesterol, LDL cholesterol,
fibrinogen, apolipoprotein
B, and lipoprotein (a). EVISTA modestly increases hormone-binding
globulin concentrations,
including sex steroid-binding
globulin, thyroxine-binding globulin, and corticosteroid-binding
globulin with corresponding
increases in measured total hormone
concentrations. There is no
evidence that these
changes in hormone-binding globulin
concentrations affect
concentrations of the corresponding free hormones.
There were small decreases in serum
total calcium, inorganic
phosphate, total protein,
and albumin which were
generally of lesser magnitude
than decreases observed during ERT/HRT. Platelet count
was also decreased slightly and was not different from ERT.
Additional Safety INFORMATION
Incidences of estrogen-dependent carcinoma
of the endometrium
and breast are being evaluated across all completed and ongoing
clinical trials involving
12,802 patients, of which approximately 8300 women have received
at least one dose of raloxifene.
The duration of exposure
has been up to 39 months.
Endometrium: Compared to placebo,
raloxifene did not increase the risk
of endometrial cancer.
Breast: Compared to placebo,
raloxifene did not increase the risk
of breast cancer.
DRUG INTERACTIONS
Cholestyramine: Cholestyramine causes a 60% reduction
in the absorption
and enterohepatic
cycling of raloxifene and should not be coadministered with EVISTA.
Warfarin: The coadministration
of EVISTA and warfarin has not been assessed under chronic
conditions. However, 10% decreases in prothrombin
time have been observed
in single-dose studies. If EVISTA is given concurrently with warfarin,
prothrombin time
should be monitored.
Other Highly Protein-Bound Drugs: Raloxifene is more
than 95% bound to plasma
proteins. In vitro, raloxifene
did not affect the binding
of warfarin, phenytoin, or tamoxifen. Caution should be used when
EVISTA is coadministered with other highly protein-bound drugs,
such as clofibrate, indomethacin,
naproxen, ibuprofen, diazepam, and diazoxide.
See also CLINICAL PHARMACOLOGY,
Drug-Drug Interactions
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