Drug Facts
Composition & Profile
Identifiers & Packaging
16 HOW SUPPLIED/STORAGE AND HANDLING CABERGOLINE tablets are white, scored, oblong, with functional score on one side with the letter P and the letter U on either side of the breakline, engraved with the number 700 on the opposite side and they are available in the following configuration: 0.5 mg strength, 8-count bottle, and NDC number 59762-1005-1. Store at controlled room temperature 20°C to 25°C (68°F to 77°F) [see USP]. Store the tablets in the original container.; PRINCIPAL DISPLAY PANEL - 8 Tablet Bottle Label NDC 59762-1005-1 8 Tablets GREENSTONE ® BRAND cabergoline tablets 0.5 mg Rx only PRINCIPAL DISPLAY PANEL - 8 Tablet Bottle Label; PRINCIPAL DISPLAY PANEL - 8 Tablet Bottle Carton NDC 59762-1005-1 8 Tablets GREENSTONE ® BRAND cabergoline tablets 0.5 mg Rx only PRINCIPAL DISPLAY PANEL - 8 Tablet Bottle Carton
- 16 HOW SUPPLIED/STORAGE AND HANDLING CABERGOLINE tablets are white, scored, oblong, with functional score on one side with the letter P and the letter U on either side of the breakline, engraved with the number 700 on the opposite side and they are available in the following configuration: 0.5 mg strength, 8-count bottle, and NDC number 59762-1005-1. Store at controlled room temperature 20°C to 25°C (68°F to 77°F) [see USP]. Store the tablets in the original container.
- PRINCIPAL DISPLAY PANEL - 8 Tablet Bottle Label NDC 59762-1005-1 8 Tablets GREENSTONE ® BRAND cabergoline tablets 0.5 mg Rx only PRINCIPAL DISPLAY PANEL - 8 Tablet Bottle Label
- PRINCIPAL DISPLAY PANEL - 8 Tablet Bottle Carton NDC 59762-1005-1 8 Tablets GREENSTONE ® BRAND cabergoline tablets 0.5 mg Rx only PRINCIPAL DISPLAY PANEL - 8 Tablet Bottle Carton
Overview
Cabergoline is an ergot derivative and dopamine receptor agonist. The chemical name for cabergoline is 1-[(6-allylergolin-8ß-yl)-carbonyl]-1-[3-(dimethylamino) propyl]-3-ethylurea. Its empirical formula is C 26 H 37 N 5 O 2 , and its molecular weight is 451.62. The structural formula is as follows Cabergoline is a white powder soluble in ethyl alcohol, chloroform, and N, N-dimethylformamide (DMF); slightly soluble in 0.1N hydrochloric acid; very slightly soluble in n-hexane; and insoluble in water. CABERGOLINE tablets, for oral administration, contain 0.5 mg of cabergoline and the inactive ingredients of leucine, USP, and lactose, NF. Structural formula
Indications & Usage
CABERGOLINE is an ergot derivative indicated for the treatment of hyperprolactinemic disorders, either idiopathic or due to pituitary adenomas in adults. Limitations of Use Avoid use of CABERGOLINE for the inhibition or suppression of postpartum physiologic lactation because of the risk of serious adverse reactions [see Warnings and Precautions (5.4) ] . CABERGOLINE is an ergot derivative indicated for the treatment of hyperprolactinemic disorders, either idiopathic or due to pituitary adenomas in adults. ( 1 ) Limitations of Use Avoid use of CABERGOLINE for the inhibition or suppression of postpartum physiologic lactation because of the risk of serious adverse reactions. ( 5.4 )
Dosage & Administration
• Before initiating CABERGOLINE evaluate for valvular heart disease, including with an echocardiogram. If valvular disease is detected, do not administer CABERGOLINE. ( 2.1 ) • Recommended starting dosage of CABERGOLINE is 0.25 mg orally twice weekly. ( 2.2 ) • Titrate CABERGOLINE to achieve normal serum prolactin levels by increasing CABERGOLINE by 0.25 mg orally twice weekly at intervals of no less than 4 weeks. ( 2.2 ) • Maximum recommended dosage is 1 mg orally, twice weekly. ( 2.2 ) 2.1 Recommended Evaluation Before Initiating CABERGOLINE Before initiating CABERGOLINE evaluate for valvular heart disease, including with an echocardiogram. If valvular disease is detected, do not administer CABERGOLINE [see Contraindications (4) and Warnings and Precautions (5.1) ] . 2.2 Recommended Dosage The recommended starting dosage of CABERGOLINE is 0.25 mg orally twice weekly. Titrate CABERGOLINE to achieve normal serum prolactin levels by increasing CABERGOLINE by 0.25 mg orally twice weekly at intervals of no less than 4 weeks. The maximum recommended dosage is 1 mg orally, twice weekly [see Warnings and Precautions (5.2) ] . Administer CABERGOLINE with or without food [see Clinical Pharmacology (12.3) ] . If CABERGOLINE is discontinued, monitor the serum prolactin level periodically to determine whether CABERGOLINE should be reinstituted.
Warnings & Precautions
• Cardiac Valvulopathy and Pericardial Fibrosis : Before initiating CABERGOLINE, perform a cardiovascular evaluation, including echocardiogram, to evaluate for valvular disease. During CABERGOLINE treatment, monitor for the development of valvulopathy with a cardiac echocardiogram at intervals of 6 to 12 months or as clinically indicated and monitor for chest pain and signs and symptoms of heart failure (if heart failure occurs, exclude valvular fibrosis and pericarditis). Consider additional clinical and diagnostic monitoring at baseline and as necessary during CABERGOLINE treatment. Use CABERGOLINE in patients treated with other drugs associated with valvulopathy only if the potential benefit of CABERGOLINE outweighs the risk. Discontinue CABERGOLINE if the patient has a new diagnosis of valvular regurgitation, valvular restriction, valve leaflet thickening, or pericarditis. ( 5.1 ) • Pleural, Pulmonary and Retroperitoneal Fibrosis : During CABERGOLINE treatment monitor for signs and symptoms of progressive fibrosis, (e.g., pleuro-pulmonary disease, renal impairment, ureteral/abdominal vascular obstruction). Consider clinical and diagnostic monitoring for pleural, pulmonary, and retroperitoneal fibrosis at baseline and as necessary during CABERGOLINE treatment. If pleural, pericardial, retroperitoneal, or pulmonary fibrosis occur, discontinue CABERGOLINE. ( 5.2 ) • Orthostatic Hypotension : Check blood pressure at baseline and during treatment with CABERGOLINE and monitor for orthostatic hypotension. ( 5.3 ) • Risks with Use of CABERGOLINE for Postpartum Lactation Inhibition or Suppression : Avoid use of CABERGOLINE for the inhibition or suppression of physiologic lactation. Use of bromocriptine, another dopamine agonist for this unapproved use has been associated with cases of hypertension, stroke, myocardial infarction, seizures, and death. ( 5.4 ) • Impulse Control Disorders and Compulsive Behaviors : Specifically ask patients about the development of new or increased gambling urges, sexual urges, uncontrolled spending, or other urges while being treated with CABERGOLINE. Consider dosage reduction or stopping CABERGOLINE if a patient develops such urges while taking CABERGOLINE. ( 5.5 ) 5.1 Cardiac Valvulopathy and Pericardial Fibrosis Before initiating CABERGOLINE, perform a cardiovascular evaluation, including with an echocardiogram, to evaluate for valvular disease. CABERGOLINE is contraindicated in the presence of valvular disease or pericardial fibrosis [see Contraindications (4) ] . Cases of valvular and pericardial fibrosis have often manifested as heart failure. Following CABERGOLINE treatment initiation, monitor for the development of valvulopathy with a cardiac echocardiogram at intervals of 6 to 12 months or as clinically indicated with new onset edema, cardiac murmur, dyspnea, or heart failure. During CABERGOLINE treatment, monitor for chest pain and signs and symptoms of heart failure and if heart failure occurs, valvular fibrosis and pericarditis should be excluded. Consider clinical and diagnostic monitoring such as erythrocyte sedimentation rate, serum creatinine measurements, chest-x- ray, and other investigations and cardiac imaging at baseline and as necessary while patients are treated with during CABERGOLINE treatment. Use CABERGOLINE in patients treated with other drugs associated with valvulopathy only if the potential benefit of CABERGOLINE outweighs the risk. Discontinue CABERGOLINE if the patient has a new diagnosis of valvular regurgitation, valvular restriction, valve leaflet thickening, or pericarditis. Postmarketing cases of cardiac valvulopathy have been reported in patients who received CABERGOLINE. These cases have generally occurred during administration of high doses of CABERGOLINE (>2 mg/day) for the treatment of Parkinson’s disease (PD) (CABERGOLINE is not approved for the treatment of PD). Cases of cardiac valvulopathy have also been reported in patients who received lower dosages of CABERGOLINE for the treatment of hyperprolactinemic disorders. In a 12-year, multi-country retrospective cohort study, the use of CABERGOLINE for PD was associated with an increased risk of cardiac valvular regurgitation (CVR). Compared to non-ergot-derived dopamine agonists and levodopa, CVR with CABERGOLINE use had an incidence rate per 10,000 person years of 68 (95% CI: 37, 115) versus 10 (95% CI: 5, 19) for non-ergot dopamine agonists and 11 (95% CI: 7, 17) for levodopa. 5.2 Pleural, Pulmonary and Retroperitoneal Fibrosis CABERGOLINE is contraindicated in patients with a history of pleural, pulmonary, or retroperitoneal fibrosis. During CABERGOLINE treatment monitor for signs and symptoms of progressive fibrosis, including: • Pleuro-pulmonary disease (e.g., dyspnea, shortness of breath, persistent cough, chest pain). • Renal impairment or ureteral/abdominal vascular obstruction (e.g., pain in the loin/flank, lower limb edema, abdominal masses or tenderness that may indicate retroperitoneal fibrosis). Consider clinical and diagnostic monitoring for pleural, pulmonary, and retroperitoneal fibrosis such as with erythrocyte sedimentation rate, serum creatinine measurements, chest-x-ray, and other investigations at baseline and as necessary during CABERGOLINE treatment. If pleural, pericardial, retroperitoneal, or pulmonary fibrosis occur, discontinue CABERGOLINE. Postmarketing cases of pleural, pulmonary, and retroperitoneal fibrosis have been reported following CABERGOLINE administration. Some reports were in patients previously treated with other ergotinic dopamine agonists. CABERGOLINE-treated patients who developed a pleural effusion or pulmonary fibrosis and subsequently discontinued CABERGOLINE had improvement of their pulmonary symptoms. 5.3 Orthostatic Hypotension Check blood pressure at baseline and during treatment with CABERGOLINE and monitor for orthostatic hypotension. Warn patients about the risk of orthostatic hypotension and precautions to take when rising from a supine or sitting position. Instruct patients to report dizziness or lightheadedness with changes in position to their healthcare provider. CABERGOLINE can cause orthostatic hypotension [see Adverse Reactions (6.1) ] . In a 4-week, placebo-controlled trial in patients with hyperprolactinemic disorders, the percentage of CABERGOLINE-treated patients and placebo-treated patients who developed orthostatic hypotension was 4% and 0%, respectively [see Adverse Reactions (6.1) ] . The risk of orthostatic hypotension is greater in CABERGOLINE-treated patients when taking concomitant drugs that lower blood pressure. 5.4 Risks with Use of CABERGOLINE for Postpartum Lactation Inhibition or Suppression Avoid use of CABERGOLINE for the inhibition or suppression of postpartum physiologic lactation because of the risk of serious adverse reactions. Use of bromocriptine, another dopamine agonist for this unapproved use has been associated with cases of hypertension, stroke, myocardial infarction seizures, and death. 5.5 Impulse Control Disorders and Compulsive Behaviors Because patients may not recognize impulse control and compulsive behaviors as abnormal, it is important for health care providers to specifically ask patients about the development of new or increased gambling urges, sexual urges, uncontrolled spending, or other urges while being treated with CABERGOLINE. Consider dosage reduction or stopping CABERGOLINE if a patient develops such urges while taking CABERGOLINE. Patients can experience intense urges to gamble or to spend money, increased sexual urges, binge eating, and/or other intense urges, and the inability to control these urges while taking one or more drugs that increase central dopaminergic tone, including CABERGOLINE. In some cases, these urges were reported to have stopped when the dosage was reduced, or the drug was stopped.
Contraindications
CABERGOLINE is contraindicated in patients with: • Uncontrolled hypertension. • 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, or history of pericardial fibrosis [see Warnings and Precautions (5.1) ] . • History of pleural, pulmonary, or retroperitoneal fibrotic disorders [see Warnings and Precautions (5.2) ] . • Uncontrolled hypertension. ( 4 ) • Known hypersensitivity to ergot derivatives. ( 4 ) • History of cardiac valvular disorders, or pericardial fibrosis. ( 5.1 ) • History of pleural, pulmonary, or retroperitoneal fibrotic disorders. ( 5.2 )
Adverse Reactions
The following clinically significant adverse reactions are described elsewhere in the labeling: • Cardiac Valvulopathy and Pericardial Fibrosis [see Warnings and Precautions (5.1) ] . • Pleural, Retroperitoneal, and Pulmonary Fibrosis [see Warnings and Precautions (5.2) ] . • Orthostatic Hypotension [see Warnings and Precautions (5.3) ] . • Impulse Control Disorders and Compulsive Behaviors [see Warnings and Precautions (5.5) ] . The most common adverse reactions (incidence >10%) are nausea, headache, and dizziness. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Greenstone LLC at 1-877-446-3679 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The safety of CABERGOLINE has been evaluated in more than 900 patients with hyperprolactinemic disorders. In a 4-week, double-blind, placebo-controlled trial (CABERGOLINE vs. placebo) [see Clinical Studies (14) ] , the incidence of the most common adverse reactions during the placebo-controlled trial in patients with hyperprolactinemic disorders is presented in Table 1. Table 1. Adverse Reactions (n (%)) Adverse reactions that occurred ≥1% in the CABERGOLINE group and frequency more than that reported in the placebo group. During the 4-Week, Double-Blind, Placebo-Controlled Trial in Hyperprolactinemic Females CABERGOLINE (n=168) Placebo (n=20) Nausea 45 (27%) 4 (20%) Headache 43 (26%) 5 (25%) Dizziness 25 (15%) 1 (5%) Constipation 16 (10%) 0% Fatigue 12 (7%) 0% Postural hypotension 6 (4%) 0% Dyspepsia 4 (2%) 0% Vomiting 4 (2%) 0% Nervousness 4 (2%) 0% Vertigo 2 (1%) 0% Paresthesia 2 (1%) 0% Breast pain 2 (1%) 0% Dysmenorrhea 2 (1%) 0% Abnormal vision 2 (1%) 0% In the 8-week, double-blind period of the comparative trial with bromocriptine, 2% (4/221) of CABERGOLINE-treated patients (0.5 mg twice weekly) discontinued treatment because of an adverse event and 6% (14/231) of bromocriptine-treated patients (at a dose of 2.5 mg twice daily) discontinued treatment because of an adverse event. The most common reasons for CABERGOLINE discontinuation were headache, nausea, and vomiting (3, 2, and 2 patients, respectively). The incidence of the most common adverse events during the double-blind period of the comparative trial with bromocriptine is presented in Table 2. Table 2. Adverse Events Adverse events reported ≥1% in the CABERGOLINE group. Abbreviation: n=number of patients. During the 8-Week, Double-Blind Period of the Comparative Trial in Hyperprolactinemic Females CABERGOLINE (n=221) Bromocriptine (n=231) Nausea 63 (29%) 100 (43%) Headache 58 (26%) 62 (27%) Dizziness 38 (17%) 42 (18%) Constipation 15 (7%) 21 (9%) Asthenia 13 (6%) 15 (6%) Abdominal pain 12 (5%) 19 (8%) Dyspepsia 11 (5%) 16 (7%) Fatigue 10 (5%) 18 (8%) Vertigo 9 (4%) 10 (4%) Vomiting 9 (4%) 16 (7%) Depression 7 (3%) 5 (2%) Hot flashes 6 (3%) 3 (1%) Breast pain 5 (2%) 8 (3%) Dry mouth 5 (2%) 2 (1%) Paresthesia 5 (2%) 6 (3%) Somnolence 5 (2%) 5 (2%) Diarrhea 4 (2%) 7 (3%) Flatulence 4 (2%) 3 (1%) Pain 4 (2%) 6 (3%) Acne 3 (1%) 0% Anorexia 3 (1%) 3 (1%) Anxiety 3 (1%) 3 (1%) Hypotension 3 (1%) 4 (2%) Insomnia 3 (1%) 2 (1%) Syncope 3 (1%) 3 (1%) Abnormal vision 2 (1%) 2 (1%) Arthralgia 2 (1%) 0% Dependent edema 2 (1%) 1 (<1%) Dysmenorrhea 2 (1%) 1 (<1%) Impaired concentration 2 (1%) 1 (<1%) Influenza-like symptoms 2 (1%) 0% Malaise 2 (1%) 0% Nervousness 2 (1%) 5 (2%) Palpitation 2 (1%) 5 (2%) Periorbital edema 2 (1%) 2 (1%) Peripheral edema 2 (1%) 1 (<1%) Pruritus 2 (1%) 1 (<1%) Rhinitis 2 (1%) 9 (4%) Throat irritation 2 (1%) 0% Toothache 2 (1%) 0% Events that were reported at an incidence of <1% in the 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 6.2 Postmarketing Experience The following adverse reactions have been identified during post-approval use of CABERGOLINE. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. • Psychiatric: impulse control disorders and compulsive behaviors including, hypersexuality, increased libido, pathological gambling; psychotic disorder, aggression • Skin and subcutaneous: alopecia
Drug Interactions
CABERGOLINE, a dopamine receptor agonist, is not recommended for concomitant use with D2-antagonists, such as phenothiazines, butyrophenones, thioxanthenes, or metoclopramide. CABERGOLINE, a dopamine receptor agonist, is not recommended for concomitant use with D2-antagonists, such as phenothiazines, butyrophenones, thioxanthenes, or metoclopramide. ( 7 )
Similar Drugs
Related medications based on brand, generic name, substance, active ingredients.