ADVERSE REACTIONS
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 EventReported at ≥1% for cabergoline | 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 | 25 (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 |
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 EventReported at ≥1% for cabergoline | 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 |
| Respiratory | | |
| Rhinitis | 2 (1) | 9 (4) |
| Vision | | |
| Abnormal vision | 2 (1) | 2 (1) |
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.
Post-marketing Surveillance data
The following events have been reported in association with cabergoline: valvulopathy and fibrosis, (See WARNINGS, Valvulopathy and PRECAUTIONS, Fibrosis).
Others events have been reported in association with cabergoline: hypersexuality, increased libido, pathological gambling (See PRECAUTIONS, Psychiatric). In addition, during post-marketing surveillance, cases of alopecia, aggression and psychotic disorder have been reported in patients taking DOSTINEX. Some of these reports have been in patients who have had prior adverse reactions to dopamine agonist products.
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