Ergot Derivative

Cabergoline

Approved 29 Dec 2005OralTablet

The FDA lists this product in 9 strengths and forms.

Indications

Cabergoline Tablets, USP are indicated for the treatment of hyperprolactinemic disorders, either idiopathic or due to pituitary adenomas

Contraindications

Cabergoline Tablets, USP are contraindicated in patients with Uncontrolled hypertension or known hypersensitivity to ergot derivatives. History of cardiac valvular disorders, as suggested by anatomical evidence of valvulopathy of any valve, determined by pre-treatment evaluation including echocardiographic demonstration of valve leaflet thickening, valve restriction, or mixed valve restriction-stenosis (See WARNINGS ).

History of pulmonary, pericardial, or retroperitoneal fibrotic disorders (See WARNINGS ).

Warnings and precautions

1. Pregnancy : Dopamine agonists in general should not be used in patients with pregnancy-induced hypertension, for example, preeclampsia, eclampsia, and postpartum hypertension, unless the potential benefit is judged to outweigh the possible risk. 2. Fibrotic Complications: a. Cardiac Valvulopathy: All patients should undergo a cardiovascular evaluation, including echocardiogram to assess the potential presence of valvular disease.

If valvular disease is detected, the patient should not be treated with Cabergoline (See CONTRAINDICATIONS ). Post-marketing cases of cardiac valvulopathy have been reported in patients receiving Cabergoline. These cases have generally occurred during administration of high doses of Cabergoline (>2mg/day) used for the treatment of Parkinson's disease. Cases of cardiac valvulopathy have also been reported in patients receiving lower doses for the treatment of hyperprolactinemic disorders.

A multi-country, retrospective cohort study using general practice records and record linkage systems in the UK, Italy and the Netherlands was conducted to assess the association between new use of dopamine agonists including cabergoline (n=27,812) for Parkinson's disease and hyperprolactinemia and cardiac valvular regurgitation (CVR), other fibroses, and other cardiopulmonary events over a maximum of 12 years of follow up.

In this study, the use of cabergoline among persons with Parkinson's disease was associated with an increased risk of CVR when compared to non-ergot-derived dopamine agonists (DAs) and levodopa [Incidence Rate (IR) per 10,000 person years of 68.1 (95% confidence interval (CI): 37.2 to 115.3) for cabergoline vs. 10.0 (95% CI: 5.2 to 19.4) for non-ergot DAs and 11.3 (95% CI: 7.2 to 17.0) for levodopa]. In the study analysis confined to persons with dopamine agonist-treated hyperprolactinemia (n=8,386), when compared to non-use (n=15,147), persons exposed to cabergoline did not have an elevated risk of CVR.

At a glance

Brand name: Cabergoline
Pharmacologic class: Ergot Derivative
Route: Oral
Dosage form: Tablet
Applicant: Strides Pharma Intl
Status: Prescription
FDA approval: 29 Dec 2005
Application: ANDA076310-001

Contraindications

History of pulmonary, pericardial, or retroperitoneal fibrotic disorders (See WARNINGS ).

Warnings and precautions

Adverse reactions

The safety of Cabergoline Tablets, USP 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 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 Constipation Abdominal pain Dyspepsia Vomiting 45 (27) 16 (10) 9 (5) 4 (2) 4 (2) 4 (20) 0 1 (5) 0 0 Central and Peripheral Nervous System Headache Dizziness Paresthesia Vertigo 43 (26) 25 (15) 2 (1) 2 (1) 5 (25) 1 (5) 0 0 Body As a Whole Asthenia Fatigue Hot flashes 15 (9) 12 (7) 2 (1) 2 (10) 0 1 (5) Psychiatric Somnolence Depression Nervousness 9 (5) 5 (3) 4 (2) 1 (5) 1 (5) 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 ≥1% for cabergoline 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 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 Dizziness Vertigo Paresthesia 58 (26) 38 (17) 9 (4) 5 (2) 62 (27) 42 (18) 10 (4) 6 (3) Body As a Whole Asthenia Fatigue Syncope Influenza-like symptoms Malaise Periorbital edema Peripheral edema 13 (6) 10 (5) 3 (1) 2 (1) 2 (1) 2 (1) 2 (1) 15 (6) 18 (8) 3 (1) 0 0 2 (1) 1 Psychiatric Depression Somnolence Anorexia Anxiety Insomnia Impaired concentration Nervousness 7 (3) 5 (2) 3 (1) 3 (1) 3 (1) 2 (1) 2 (1) 5 (2) 5 (2) 3 (1) 3 (1) 2 (1) 1 5 (2) Cardiovascular Hot flashes Hypotension Dependent edema Palpitation 6 (3) 3 (1) 2 (1) 2 (1) 3 (1) 4 (2) 1 5 (2) Reproductive - Female Breast pain Dysmenorrhea 5 (2) 2 (1) 8 (3) 1 Skin and Appendages Acne Pruritus 3 (1) 2 (1) 0 1 Musculoskeletal Pain Arthralgia 4 (2) 2 (1) 6 (3) 0 Respiratory Rhinitis 2 (1) 9 (4) Vision Abnormal vision 2 (1) 2 (1) *Reported at ≥1% 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. Post-marketing 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 ).

Other events have been reported in association with cabergoline: impulse control/ compulsive behavior symptoms, including hypersexuality, increased libido and 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.

To report SUSPECTED ADVERSE REACTIONS, contact Avet Pharmaceuticals Inc. at 1-866-901-DRUG (3784) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Cabergoline

Indications

Contraindications

Warnings and precautions

At a glance

Two medicines in one question?

Cabergoline

Indications

Contraindications

Warnings and precautions

At a glance

Two medicines in one question?

Interactions

Pregnancy and breastfeeding

Adverse reactions

Composition

Strengths and forms

Official product information