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
Flomax Side Effects, and Drug Interactions - Tamsulosin
Flomax Side Effects, and Drug Interactions - Tamsulosin
SIDE EFFECTS
The incidence of
treatment-emergent adverse events has been ascertained from six
short-term U. S. and European placebo-controlled clinical
trials in which daily doses of 0.1 to 0.8 mg
FLOMAX capsules were used. These studies evaluated safety in 1783
patients treated with FLOMAX capsules and 798 patients administered
placebo. Table 3 summarizes the treatment- emergent adverse events
that occurred in ³2% of patients
receiving either FLOMAX capsules 0.4 mg, or 0.8 mg
and at an incidence numerically higher than that in the placebo
group during two 13-week
U. S. trials (US92-03A and US93-01) conducted in 1487 men.
TABLE 3: TREATMENT EMERGENT1 ADVERSE
EVENTS OCCURRING IN ³2%
OF FLOMAX CAPSULES
OR PLACEBO PATIENTS IN TWO U. S. SHORT-TERM
PLACEBO-CONTROLLED CLINICAL STUDIES
|
BODY SYSTEM / ADVERSE EVENT
|
FLOMAX CAPSULES GROUPS
|
PLACEBO
|
|
0.4 mg
n= 502
|
0.8 mg
n= 492
|
n= 493
|
| BODY AS
WHOLE |
| Headache |
97 (19.3%)
|
104 (21.1%)
|
99 (20.1%)
|
| Infection |
45 (9.0%)
|
53 (10.8%)
|
37 (7.5%)
|
| Asthenia |
39 (7.8%)
|
42 (8.5%)
|
27 (5.5%)
|
| Back Pain |
35 (7.0%)
|
41 (8.3%)
|
27 (5.5%)
|
| Chest Pain |
20 (4.0%)
|
20 (4.1%)
|
18 (3.7%)
|
| NERVOUS SYSTEM |
| Dizziness |
75 (14.9%)
|
84 (17.1%)
|
50 (10.1%)
|
| Somnolence |
15 (3.0%)
|
21 ( 4.3%)
|
8 (1.6%)
|
| Insomnia |
12 (2.4%)
|
7 (1.4%)
|
3 (0.6%)
|
| Libido Decreased
|
5 (1.0%)
|
10 (2.0%)
|
6 (1.6%)
|
| RESPIRATORY SYSTEM
|
| Rhinitis |
66 (13.1%)
|
88 (17.9%)
|
41 (8.3%)
|
| Pharyngitis |
29 (5.8%)
|
25 (5.1%)
|
23 (4.7%)
|
| Cough Increased |
17 (3.4%)
|
22 (4.5%)
|
12 (2.4%)
|
| Sinusitis |
11 (2.2%)
|
18 (3.7%)
|
8 (1.6%)
|
| DIGESTIVE SYSTEM |
| Diarrhea |
31 (6.2%)
|
21 (4.3%)
|
22 (4.5%)
|
| Nausea |
13 (2.6%)
|
19 (3.9%)
|
16 (3.2%)
|
| Tooth Disorder |
6 (1.2%)
|
10 (2.0%)
|
7 (1.4%)
|
| UROGENITAL SYSTEM |
| Abnormal Ejaculation
|
42 (8.4%)
|
89 (18.1%)
|
1 (0.2%)
|
| SPECIAL SENSES |
| Amblyopia |
1 (0.2%)
|
10 (2.0%)
|
2 (0.4%)
|
1-A treatment-emergent adverse event was defined
as any event satisfying one of the following criteria:
•The adverse event occurred for the first time
after initial dosing with double-blind study medication.
•The adverse event was present
prior to or at the time of initial
dosing with double-blind study medication
and subsequently increased in severity during double-blind treatment;
or
•The adverse event was present
prior to or at the time of initial
dosing with double-blind study medication,
disappeared completely, and then reappeared during double-blind
treatment.
Signs and Symptoms of Orthostasis
In the two U. S. studies, symptomatic
postural hypotension
was reported by 0.2% of patients (1 of 502) in the 0.4-mg group,
0.4% of patients (2 of 492) in the 0.8-mg group, and by no
patients in the placebo
group. Syncope was reported by 0.2% of patients (1 of 502) in the
0.4-mg group, 0.4% of patients (2 of 492) in the 0.8-mg group
and 0.6% of patients (3 of 493) in the placebo
group. Dizziness was reported by 15% of patients (75 of 502) in
the 0.4-mg group, 17% of patients (84 of 492) in the 0.8-mg group,
and 10% of patients (50 of 493) in the placebo
group. Vertigo was reported by 0.6% of patients (3 of 502) in the
0.4-mg group, 1 % of patients (5 of 492) in the 0.8 mg
group and by 0.6% of patients
(3 of 493) in the placebo group.
Multiple testing for orthostatic
hypotension was
conducted in a number of studies. Such a test
was considered positive
if it met one or more of the following criteria: (1) a decrease
in systolic blood
pressure of 20 mmHg
upon standing from the supine
position during the
orthostatic tests;
(2) a decrease in diastolic
blood pressure
l0mmHg upon standing, with the standing diastolic
blood pressure
<65 mmHg during the orthostatic
test; (3) an increase in pulse
rate of 20bpm upon standing
with a standing pulse rate < 100bpm during the orthostatic
test; and (4) the presence of clinical symptoms (faintness, lightheadedness/
lightheaded, dizziness,
spinning sensation, vertigo, or postural
hypotension) upon standing during the orthostatic test.
Following the first dose
of double- blind medication
in Study 1, a positive orthostatic test
result at 4 hours post-dose was observed in 7% of patients (37 of
498) who received FLOMAX capsules 0.4 mg
once daily and in 3% of the patients (8 of 253) who received placebo.
At 8 hours post-dose, a positive
orthostatic test result
was observed for 6% of the patients (31 of 498) who received FLOMAX
capsules 0.4 mg once daily
and 4% (9 of 250) who received placebo (Note: patients in the 0.8-mg
group received 0.4 mg
once daily for the first week of Study 1).
In Studies 1 and 2, at least one positive
orthostatic test
result was observed during the course of these studies for 81 of
the 502 patients (16%) in the FLOMAX capsules 0.4-mg once daily
group, 92 of the 491 patients (19%) in the FLOMAX capsules 0.8-mg
once daily group and 54
of the 493 patients (11 %) in the placebo
group.
Because orthostasis was detected more frequently in FLOMAX capsule-treated
patients than in placebo
recipients, there is a potential
risk of syncope (see WARNINGS).
Abnormal Ejaculation
Abnormal ejaculation
includes ejaculation
failure, ejaculation
disorder, retrograde ejaculation
and ejaculation
decrease. As shown in Table
3, abnormal ejaculation was associated with FLOMAX capsules administration
and was dose-related in the U.S. studies. Withdrawal from these
clinical studies of
FLOMAX capsules because of abnormal
ejaculation was
also dose-dependent with 8 of 492 patients (1.6%) in the 0.8-mg
group, and no patients in
the 0.4-mg or placebo
groups discontinuing treatment
due to abnormal ejaculation.
Post-Marketing Experience
Allergic-type reactions such
as skin rash,
pruritus, angioedema
of tongue, lips and face
and urticaria have
been reported with positive
rechallenge in some cases.
DRUG INTERACTIONS
Nifedipine, Atenolol, Enalapril: In
three studies in hypertensive subjects (age range
47- 79 years) whose blood
pressure was controlled
with stable doses of Procardia XL®, atenolot, or enalapril
for at least three months, FLOMAX capsules 0.4 mg
for seven days followed by FLOMAX capsules 0.8 mg
for another seven days (n= 8 per
study) resulted in no clinically significant
effects on blood pressure
and pulse rate
compared to placebo
(n= 4 per study). Therefore,
dosage adjustments are
not necessary when FLOMAX capsules are administered concomitantly
with Procardia XL®, atenolol, or enalapril.
Warfarin: A definitive
drug-drug interaction study between tamsulosin HCl and warfarin
was not conducted. Results from limited in vitro and in
vivo studies are inconclusive. Therefore, caution should be
exercised with concomitant
administration
of warfarin and FLOMAX capsules.
Digoxin and Theophylline: In
two studies in healthy
volunteers (n= 10 per study;
age range
19-39 years) receiving FLOMAX capsules 0.4 mg/ day for two days,
followed by FLOMAX capsules 0.8 mg/day for five to eight days, single
intravenous doses
of digoxin 0.5 mg
or theophylline 5 mg/kg resulted in no
change in the pharmacokinetics
of digoxin or theophylline.
Therefore, dosage adjustments
are not necessary when a FLOMAX capsule
is administered concomitantly with digoxin
or theophylline.
Furosemide: The pharmacokinetic and pharmacodynamic interaction
between FLOMAX capsules 0.8 mg/day (steady-state) and furosemide
20 mg intravenously (single dose) was evaluated in ten healthy
volunteers (age range 21-40 years). FLOMAX capsules had no
effect on the pharmacodynamics
(excretion of electrolytes) of furosemide. While furosemide
produced an 11% to 12% reduction
in tamsulosin HCl Cmax and A.C.
these changes are expected to be clinically insignificant and do
not require adjustment
of the FLOMAX capsules dosage.
Cimetidine: The effects of cimetidine
at the highest recommended dose (400 mg
every six hours for six days) on the pharmacokinetics
of a single FLOMAX capsule
0.4 mg dose
was investigated in ten healthy
volunteers (age range
21-38 years). Treatment with cimetidine
resulted in a significant decrease (26%) in the clearance
of tamsulosin HCl which resulted in a moderate increase in tamsulosin
HCl AUC (44%). Therefore,
FLOMAX capsules should be used with caution in combination with
cimetidine, particularly at doses higher than 0.4 mg.
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