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
Nilandron Side Effects, and Drug Interactions - Nilutamide
Nilandron Side Effects, and Drug Interactions - Nilutamide
SIDE EFFECTS
The following adverse experiences were reported during a multicenter
clinical trial comparing
NILANDRON + surgical
castration versus placebo
+ surgical castration.
The most frequently reported (greater than 5%) adverse experiences
during treatment with
NILANDRON tablets in combination with surgical
castration are listed
below. For comparison, adverse experiences seen with surgical
castration and placebo
are also listed.
| Adverse Experience |
NILANDRON
+
surgical castration
(N=225)
% All
|
Placebo
+
surgical castration
(N=232)
% All
|
|
Cardiovascular System
|
| Hypertension |
5.3
|
2.6
|
|
Digestive System
|
| Nausea |
9.8
|
6.0
|
| Constipation |
7.1
|
3.9
|
|
Endocrine System
|
| Hot flushes |
28.4
|
22.4
|
|
Metabolic and Nutritional
System
|
| Increased AST |
8.0
|
3.9
|
| Increased ALT |
7.6
|
4.3
|
|
Nervous System
|
| Dizziness |
7.1
|
3.4
|
|
Respiratory System
|
| Dyspnea |
6.2
|
7.3
|
|
Special Senses
|
| Impaired adaptation
to dark |
12.9
|
1.3
|
| Abnormal vision |
6.7
|
1.7
|
|
Urogenital System
|
| Urinary tract
infection |
8.0
|
9.1
|
The overall incidence
of adverse experiences was 86% (194/225) for the NILANDRON group
and 81% (188/232) for the placebo group.
The following adverse experiences were reported during a multicenter
clinical trial comparing
NILANDRON + leuprolide versus placebo + leuprolide. The most frequently
reported (greater than 5%) adverse experiences during treatment
with NILANDRON tablets in combination with leuprolide are listed
below. For comparison, adverse experiences seen with leuprolide
and placebo are also
listed.
| Adverse Experience |
NILANDRON
+
leuprolide
(N=209)
% All
|
Placebo
+
leuprolide
(N=202)
% All
|
|
Body as a Whole
|
| Pain |
26.8
|
27.7
|
| Headache |
13.9
|
10.4
|
| Asthenia |
19.1
|
20.8
|
| Back pain |
11.5
|
16.8
|
| Abdominal pain |
10.0
|
5.4
|
| Chest pain |
7.2
|
4.5
|
| Flu syndrome |
7.2
|
3.0
|
| Fever |
5.3
|
6.4
|
|
Cardiovascular System
|
| Hypertension |
9.1
|
9.9
|
|
Digestive System
|
| Nausea |
23.9
|
8.4
|
| Constipation |
19.6
|
16.8
|
| Anorexia |
11.0
|
6.4
|
| Dyspepsia |
6.7
|
4.5
|
| Vomiting |
5.7
|
4.0
|
|
Endocrine System
|
| Hot flushes |
66.5
|
59.4
|
| Impotence |
11.0
|
12.9
|
| Libido decreased |
11.0
|
4.5
|
|
Hemic and Lymphatic System
|
| Anemia |
7.2
|
6.4
|
|
Metabolic and Nutritional
System
|
| Increased AST |
12.9
|
13.9
|
| Peripheral edema |
12.4
|
17.3
|
| Increased ALT |
9.1
|
8.9
|
|
Musculo Skeletal System
|
| Bone Pain |
6.2
|
5.0
|
|
Nervous System
|
| Insomnia |
16.3
|
15.8
|
| Dizziness |
10.0
|
11.4
|
| Depression |
8.6
|
7.4
|
| Hypesthesia |
5.3
|
2.0
|
|
Respiratory System
|
| Dyspnea |
10.5
|
7.4
|
| Upper respiratory
infection |
8.1
|
10.9
|
| Pneumonia |
5.3
|
3.5
|
|
Skin and Appendages
|
| Sweating |
6.2
|
3.0
|
| Body hair
loss |
5.7
|
0.5
|
| Dry skin |
5.3
|
2.5
|
| Rash |
5.3
|
4.0
|
|
Special Senses
|
| Impaired adaptation
to dark |
56.9
|
5.4
|
| Chromatopsia |
8.6
|
0.0
|
| Impaired adaptation
to light |
7.7
|
1.0
|
| Abnormal vision |
6.2
|
4.5
|
|
Urogenital System
|
| Testicular atrophy |
16.3
|
12.4
|
| Gynecomastia |
10.5
|
11.9
|
| Urinary tract
infection |
8.6
|
21.3
|
| Hematuria |
8.1
|
7.9
|
| Urinary tract
disorder |
7.2
|
10.4
|
| Nocturia |
6.7
|
6.4
|
The overall incidence
of adverse experiences is 99.5% (208/209) for the NILANDRON group
and 98.5% (199/202) for the placebo group.
Some frequently occurring adverse experiences, for example hot
flushes, impotence, and decreased libido,
are known to be associated with low serum androgen levels and known
to occur with medical
or surgical castration
alone. Notable was the higher incidence
of visual disturbances
(variously described as impaired adaptation
to darkness, abnormal
vision, and colored vision), which led to treatment
discontinuation in 1% to 2% of patients.
Interstitial pneumonitis
occurred in one (<1%) patient
receiving NILANDRON in combination with surgical
castration and in
seven patients (3%) receiving NILANDRON in combination with leuprolide
and one patient receiving
placebo in combination with leuprolide. Overall, it has been reported
in 2% of patients receiving NILANDRON. This included a report
of interstitial
pneumonitis in 8 of 47 patients (17%) in a small study performed
in Japan.
In addition, the following adverse experiences were reported in
2 to 5% of patients treated with NILANDRON in combination with leuprolide
or orchiectomy.
Body as a Whole: Malaise (2%).
Cardiovascular System: Angina (2%), heart
failure (3%), syncope
(2%).
Digestive System: Diarrhea (2%), gastrointestinal
disorder (2%), gastrointestinal
hemorrhage (2%),
melena (2%).
Metabolic and Nutritional System: Alcohol intolerance
(5%), edema (2%), weight
loss (2%).
Musculoskeletal System: Arthritis (2%).
Nervous System: Dr.
mouth (2%), nervousness
(2%), paresthesia
(3%).
Respiratory System: Cough increased (2%), interstitial
lung disease (2%), lung
disorder (4%), rhinitis
(2%).
Skin and Appendages: Pruritus (2%).
Special Senses: Cataract (2%), photophobia
(2%).
Laboratory Values: Haptoglobin increased (2%), leukopenia
(3%), alkaline phosphatase
increased (3%), BUN increased
(2%), creatinine
increased (2%), hyperglycemia
(4%).
DRUG INTERACTIONS
In vitro, nilutamide has been shown to inhibit the activity
of liver cytochrome
P-450 isoenzymes and therefore,
may reduce the metabolism
of compounds requiring these systems.
Consequently, drugs with a low therapeutic
margin, such as vitamin
K antagonists, phenytoin, and theophylline, could have a delayed
elimination and
increases in their serum
half-life leading
to a toxic level. The
dosage of these drugs
or others with a similar metabolism
may need to be modified
if they are administered concomitantly with nilutamide. For example,
when vitamin K antagonists are administered concomitantly with nilutamide,
prothrombin time should be carefully monitored and
if necessary, the dosage
of vitamin K antagonists should be reduced.
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