Cabergoline (Cabergoline) - Side Effects and Adverse Reactions

ADVERSE REACTIONS

The safety of cabergoline 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

*Reported at ≥ 1% for cabergoline
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	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, cabergoline (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 cabergoline 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

*Reported at ≥ 1% for cabergoline
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
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.

Postmarketing Surveillance data:

The following events have been reported in association with cabergoline: cardiac valvulopathy and extracardiac fibrotic reactions (See WARNINGS, Cardiac Valvulopathy and Extracardiac Fibrotic Reactions).

Others events have been reported in association with cabergoline: hypersexuality, increased libido, pathological gambling (See PRECAUTIONS, Psychiatric). In addition, cases of alopecia, aggression and psychotic disorder have been reported in patients taking cabergoline. Some of these reports have been in patients who have had prior adverse reactions to dopamine agonist products.

REPORTS OF SUSPECTED CABERGOLINE SIDE EFFECTS / ADVERSE REACTIONS

Possible Cabergoline side effects / adverse reactions in 46 year old male

Reported by a physician from Denmark on 2011-10-10

Patient: 46 year old male

Reactions: Pulmonary Arterial Pressure Increased, Pathological Gambling, Pulmonary Embolism

Adverse event resulted in: hospitalization

Suspect drug(s):
Cabergoline
    Dosage: 2-8 mg daily
    Administration route: Oral
    Indication: Parkinson's Disease
    Start date: 1997-12-19
    End date: 2009-01-01

Ropinirole
    Dosage: 16 mg + 8 mg
    Administration route: Oral
    Indication: Parkinson's Disease
    Start date: 2009-05-28

Other drugs received by patient: Madopar; Stalevo 100

Possible Cabergoline side effects / adverse reactions in 50 year old male

Reported by a health professional (non-physician/pharmacist) from United States on 2011-10-10

Patient: 50 year old male

Reactions: Neoplasm Progression, Skin Hyperpigmentation, Headache, Death, Fatigue, Aspiration, Eye Movement Disorder, Back Pain, Pupillary Reflex Impaired, Dysphagia, Hyperglycaemia, Muscular Weakness, Hypoaesthesia, Hemianopia, Blood Corticotrophin Increased, Areflexia, Cortisol Free Urine Increased, Memory Impairment, Anosmia, Metastases TO Bone

Adverse event resulted in: death, hospitalization

Suspect drug(s):
Octreotide Acetate
    Dosage: 300 ug, tid

Cabergoline
    Dosage: 0.5 mg, twice a week
    Administration route: Oral

Metyrapone
    Dosage: 250 mg, bid
    Administration route: Oral

Octreotide Acetate
    Dosage: 300 ug, tid
    Indication: Blood Corticotrophin Increased

Other drugs received by patient: Rosiglitazone; Capecitabine; Cisplatin; Temozolomide; Etoposide

Possible Cabergoline side effects / adverse reactions in 50 year old male

Reported by a health professional (non-physician/pharmacist) from United States on 2011-10-10

Patient: 50 year old male

Reactions: Neoplasm Progression, Skin Hyperpigmentation, Headache, Death, Fatigue, Aspiration, Eye Movement Disorder, Pupillary Reflex Impaired, Back Pain, Dysphagia, Hyperglycaemia, Muscular Weakness, Hypoaesthesia, Hemianopia, Blood Corticotrophin Increased, Cortisol Free Urine Increased, Areflexia, Memory Impairment, Anosmia, Metastases TO Bone

Adverse event resulted in: death, hospitalization

Suspect drug(s):
Octreotide Acetate
    Dosage: 300 ug, tid

Octreotide Acetate
    Dosage: 300 ug, tid
    Indication: Blood Corticotrophin Increased

Metyrapone
    Dosage: 250 mg, bid
    Administration route: Oral

Cabergoline
    Dosage: 0.5 mg, twice a week
    Administration route: Oral

Other drugs received by patient: Capecitabine; Temozolomide; Cisplatin; Etoposide; Rosiglitazone