SIDE EFFECTS
The safety of DOSTINEX Tablets has been evaluated in
more than 900 patients with hyperprolactinemic disorders.
Most adverse events were mild or moderate in severity.
In a 4-week, double-blind, placebo-controlled study, treatment
consisted of placebo or cabergoline at fixed doses of 0.
125, 0.5, 0.75, or 1.0 mg twice weekly. Doses were halved
during the first week. Since a possible dose-related effect
was observed for nausea only, the four cabergoline treatment
groups have been combined. The incidence of the most common
adverse events during the placebo-controlled study is presented
in the following table.
Incidence
of Reported Adverse Events During the 4-Week, Double-Blind,
Placebo-Controlled Trial |
|
Adverse Event* |
Cabergoline
(n= 168)
0. 125 to 1 mg two
times a week |
Placebo
(n=20) |
|
Number (percent) |
| Gastrointestinal |
| Nausea |
45 (27) |
4 (20) |
| Constipation |
16 (10) |
0 |
| Abdominal pain | 9 (5) |
1 (5) |
| Dyspepsia |
4 (2) |
0 |
| Vomiting |
4 (2) |
0 |
| Central and Peripheral
Nervous System |
| Headache |
43 (26) |
5 (25) |
| Dizziness |
5 (15) |
1 (5) |
| Paresthesia |
2 (1) |
0 |
| Vertigo |
2 (1) |
0 |
| Body As a Whole |
| Asthenia |
15 (9) |
2 (10) |
| Fatigue |
12 (7) |
0 |
| Hot flashes |
2 (1) |
1 (5) |
| Psychiatric |
| Somnolence |
9 (5) |
1 (5) |
| Depression |
5 (3) |
1 (5) |
| Nervousness |
4 (2) |
0 |
| Autonomic Nervous System |
| Postural hypotension |
6 (4) |
0 |
| Reproductive - Female |
| Breast pain | 2 (1) |
0 |
| Dysmenorrhea |
2 (1) |
0 |
| Vision |
| Abnormal vision |
2 (1) |
0 |
*Reported at ³1 % for
cabergoline
In the 8-week, double-blind period of the comparative trial
with bromocriptine, DOSTINEX (at a dose of 0.5 mg twice
weekly) was discontinued because of an adverse event in
4 of 221 patients (2%) while bromocriptine (at a dose of
2.5 mg two times a day) was discontinued in 14 of 231 patients
(6%). The most common reasons for discontinuation from DOSTINEX
were headache, nausea and vomiting (3,2 and 2 patients respectively);
the most common reasons for discontinuation from bromocriptine
were nausea, vomiting, headache, and dizziness or vertigo
(10,3,3, and 3 patients respectively). The incidence of
the most common adverse events during the double-blind portion
of the comparative trial with bromocriptine is presented
in the following table.
Incidence Of Reported
Adverse Events During the 8-Week, Double-Blind
Period of the Comparative Trial With Bromocriptine |
|
Adverse Event* |
Cabergoline
(n= 221)
|
Bromocriptine
(n = 231) |
|
Number (percent) |
| Gastrointestinal |
| Nausea |
63( 29) |
100 (43) |
| Constipation |
15 (7) |
21 (9) |
| Abdominal Pain |
12 (5) |
19 (8) |
| Dyspepsia |
11 (5) |
16 (7) |
| Vomiting |
9 (4) |
16 (7) |
| Dry Mouth |
5 (2) |
2 (1) |
| Diarrhea |
4 (2) |
7 (3) |
| Flatulence |
4 (2) |
3 (1) |
| Throat Irritation |
2 (1) |
0 |
| Toothache |
2 (1) |
0 |
| Central, and Peripheral
Nervous System |
| Headache |
58 (26) |
62 (27) |
| Dizziness |
38 (17) |
42 (18) |
| Vertigo |
9 (4) |
10 (4) |
| Paresthesia |
5 (2) |
6 (3) |
| Body As
a Whole |
| Asthenia |
13 (6) |
15 (6) |
| Fatigue |
10 (5) |
18 (8) |
| Syncope |
3 ( 1) |
3 (1) |
| Influenza Like Symptoms |
2 (1) |
0 |
| Malaise |
2 (1) |
0 |
| Periorbital Edema |
2 (1) |
2 (1) |
| Peripheral Edema |
2 (1) |
1 |
| Psychiatric |
| Depression |
7 (3) |
5 (2) |
| Somnolence |
5 (2) |
5 (2) |
| Anorexia |
3 (1) |
3 (1) |
| Anxiety |
3 (1) |
3 (1) |
| Insomnia |
3 (1) |
2 (1) |
| Impaired Concentration |
2 (1) |
1 |
| Nervousness |
2 (1) |
5 (2) |
| Cardiovascular |
| Hot Flashes |
6 (3) |
3 (1) |
| Hypotension |
3 (1) |
4 (2) |
| Dependent Edema |
2 (1) |
1 |
| Palpitation |
2 (1) |
5 (2) |
| Reproductive - Female |
| Breast Pain |
5
(2) |
8
(3) |
| Dysmenorrhea |
2
(1) |
1 |
| Skin and Appendages |
| Acne |
3 (1) |
0 |
| Pruritus |
2 (1) |
1 |
| Musculoskeletal |
| Pain |
4(2) |
6 (3) |
| Arthralgia |
2 (1) |
0 |
| Respirator |
| Rhinitis |
2 (1) |
9 (4) |
| Vision |
| Abnormal Vision |
2 (1) |
2 (1) |
*Reported at ³1% for cabergoline
Other adverse events that were reported at an incidence
of <1.0% in the overall clinical studies follow.
Body As a Whole: facial edema, influenza-like
symptoms: malaise
Cardiovascular System: hypotension,
syncope, palpitations
Digestive System: dry mouth, flatulence,
diarrhea, anorexia
Metabolic and Nutritional System: weight
loss, weight gain
Nervous System: somnolence, nervousness,
paresthesia, insomnia, anxiety
Respiratory System: nasal stuffiness,
epistaxis
Skin and Appendages: acne, pruritus
Special Senses: abnormal vision
Urogenital System: dysmenorrhea, increased
libido
The safety of cabergoline has been evaluated in approximately
1,200 patients with Parkinson's disease in controlled
and uncontrolled studies at dosages of up to 11.5 mg/day
which greatly exceeds the maximum recommended dosage of
cabergoline for hyperprolactinemic disorders. In addition
to the adverse events that occurred in the patients with
hyperprolactinemic disorders, the most common adverse
events in patients with Parkinson's disease were dyskinesia,
hallucinations, confusion, and Peripheral edema. Heart
failure, pleural effusion, pulmonary fibrosis, and gastric
or duodenal ulcer occurred rarely. One case of constrictive
pericarditis has been reported.
DRUG INTERACTIONS
DOSTINEX should not be administered concurrently with
D2-antagonists, such as phenothiazines, butyrophenones,
thioxanthines, or metoclopramide.
|
|
