Cabergoline

Cabergoline is used to treat hyperprolactinemia (high levels of prolactin, a natural substance that helps breast-feeding women produce milk but can cause symptoms such as infertility, sexual problems, and bone loss in women who are not breast-feeding or men). Cabergoline is in a class of medications called dopamine receptor agonists. It works by decreasing the amount of prolactin in the body.

Before taking cabergoline,

• tell your doctor and pharmacist if you are allergic to cabergoline, ergot medications such as bromocriptine (Parlodel); dihydroergotamine (D.H.E. 45, Migranal), ergoloid mesylates (Hydergine), ergotamine (in Cafergot, in Ergomar), methylergonovine (Methergine), methysergide (Sansert), and pergolide (Permax); any other medications, or any of the ingredients in cabergoline tablets. Ask your pharmacist for a list of the ingredients.
• tell your doctor and pharmacist what other prescription and nonprescription medications, vitamins, nutritional supplements, and herbal products you are taking or plan to take. Be sure to mention any of the following: antihistamines; ergot medications such as dihydroergotamine (D.H.E. 45, Migranal), ergotamine (in Cafergot, in Ergomar), and methylergonovine (Methergine); haloperidol (Haldol); levodopa (in Parcopa, Sinemet, and Stalevo); medications for high blood pressure, mental illness, or nausea; metoclopramide (Reglan); or thiothixene (Navane). Your doctor may need to change the doses of your medications or monitor you carefully for side effects.
• tell your doctor if you use or have ever used street drugs and if you have or have ever had high blood pressure or any condition that causes thickening or scarring in your lungs, heart, or abdomen. Also tell your doctor if you have or have ever had heart valve disease. Your doctor will examine you and will order tests to see if your heart valves are healthy. Your doctor may tell you not to take cabergoline if you have signs of heart valve disease or any of these conditions.
• tell your doctor if you have or have ever had liver disease.
• tell your doctor if you are pregnant or plan to become pregnant. If you become pregnant while taking cabergoline, call your doctor.
• tell your doctor if you are breast-feeding or plan to breast-feed. Cabergoline may slow or stop the production of breast-milk.
• you should know that cabergoline may cause dizziness, lightheadedness, and fainting when you get up too quickly from a lying position. This is more common when you first start taking cabergoline. To avoid this problem, get out of bed slowly, resting your feet on the floor for a few minutes before standing up.
• you should know that some people treated with cabergoline have developed gambling problems or other intense urges or behaviors that were compulsive or unusual for them, such as increased sexual urges or behaviors. There is not enough information to tell whether the people developed these problems because they took the medication or for other reasons. Call your doctor if you have an urge to gamble that is difficult to control, you have intense urges, or you are unable to control your behavior. Tell your family members about this risk so that they can call the doctor even if you do not realize that your gambling or any other intense urges or unusual behaviors have become a problem.

Take the missed dose as soon as you remember it. However, if it is almost time for the next dose, skip the missed dose and continue your regular dosing schedule. Do not take a double dose to make up for a missed one.

>10%

Nausea (27%)

Headache (26%)

Dizziness (15%)

1-10%

Asthenia (9%)

Fatigue (7%)

Abdominal pain (5%)

Somnolence (5%)

Postural hypotension (4%)

Depression (3%)

Dyspepsia (2%)

Nervousness (2%)

Abnormal vision (1%)

Breast pain (1%)

Dysmenorrhea (1%)

Hot flashes (1%)

Paresthesia (1%)

Constipation (10%)

<1%

Aggression

Fibrosis

Gastric ulcer

Valvulopathy

Gastric ulcer

Pleural effusion

Psychosis

Common side effects of cabergoline include the following:

• constipation
• fatigue
• a drop in blood pressure when standing (postural hypotension)
• dizziness

This is not a complete list of cabergoline side effects. Ask your doctor or pharmacist for more information.

Tell your doctor if you have any side effect that bothers you or that does not go away.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

It is not known if cabergoline crosses into human milk. Because many medications can cross into human milk and because of the possibility for serious adverse reactions in nursing infants with use of this medication, a choice should be made whether to stop nursing or stop the use of this medication. Your doctor and you will decide if the benefits outweigh the risk of using cabergoline.

If you take too much this medication, call your healthcare provider or local Poison Control Center, or seek emergency medical attention right away.

If this medication is administered by a healthcare provider in a medical setting, it is unlikely that an overdose will occur. However, if overdose is suspected, seek emergency medical attention.

• Store at controlled room temperature.
• Keep this and all other medications out of the reach of children.

You should not use this medication if you are allergic to cabergoline, or if you have uncontrolled high blood pressure, pregnancy-related high blood pressure, a history of heart or breathing problems or heart valve disorder, or if you are allergic to any type of ergot medicine such as ergotamine (Ergomar, Cafergot, Migergot), dihydroergotamine (D.H.E. 45, Migranal), ergonovine (Ergotrate), or methylergonovine (Methergine).

Before taking cabergoline, tell your doctor if you have liver disease, heart disease, or a breathing disorder.

Cabergoline is usually taken twice each week for at least 6 months. Do not take this medication every day unless your doctor tells you to.

Tell your doctor about all other medicines you use, especially blood pressure medication.

You may have increased sexual urges, unusual urges to gamble, or other intense urges while taking this medication. Talk with your doctor if you believe you have any intense or unusual urges while taking cabergoline.

To be sure this medication is helping your condition, your blood will need to be tested on a regular basis to measure your prolactin levels. Your doctor may want to continue checking your prolactin levels for several months after you stop taking cabergoline. Visit your doctor regularly.

Usual Adult Dose for Hyperprolactinemia:

Initial dose: 0.25 mg orally twice a week
-Increase dose in increments of 0.25 mg twice a week no more frequently than every 4 weeks according to patient's prolactin level
Maximum dose: 1 mg twice a week

Comments:
-Patients should be maintained on the lowest dose that provides maximal response.
-After maintaining normal serum prolactin levels for 6 months, this drug may be stopped and serum prolactin levels followed to determine whether reinitiating therapy is necessary.

Use: For the treatment of hyperprolactinemic disorders, either idiopathic or due to pituitary adenomas.

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur:

• Bloating or swelling of the face, arms, hands, lower legs, or feet
• burning, crawling, itching, numbness, prickling, "pins and needles", or tingling feelings
• chills
• cold sweats
• confusion
• dizziness, faintness, or lightheadedness when getting up from lying or sitting position
• fast, irregular, pounding, or racing heartbeat or pulse
• general feeling of discomfort or illness
• rapid weight gain
• swelling around the eyes
• tingling of the hands or feet
• unusual tiredness or weakness
• unusual weight gain or loss

• Chest pain or tightness
• continuing loss of appetite
• continuing or severe abdominal or stomach pain
• continuing or severe nausea and vomiting
• cough
• decreased ability to exercise
• fever
• increased frequency of urination
• loss of appetite
• lower abdominal or stomach pain
• lower back pain
• nausea
• shortness of breath
• trouble with breathing
• vomiting
• weakness

Get emergency help immediately if any of the following symptoms of overdose occur:

• Fainting
• seeing, hearing, or feeling things that are not there
• stuffy nose

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Difficulty having a bowel movement (stool)
• dizziness
• excess air or gas in the stomach or intestines
• full feeling
• headache
• lack or loss of strength
• passing gas

• Abdominal or stomach pain
• acid or sour stomach
• anxiety
• belching
• blemishes on the skin
• breast pain
• burning, itching, or stinging of the skin
• changes in vision
• cramps
• depression
• diarrhea
• difficulty with moving
• dry mouth or toothache
• feeling of constant movement of self or surroundings
• feeling of warmth
• gas
• heartburn
• heavy bleeding
• indigestion
• itching skin
• joint pain
• muscle aches and pains
• muscle stiffness
• pimples
• redness of the face, neck, arms, and occasionally, upper chest
• runny nose
• sensation of spinning
• shivering
• sleeplessness
• sleepiness or unusual drowsiness
• sneezing
• sore throat
• stomach discomfort or upset
• sudden sweating
• trouble with sleeping
• unable to sleep
• weight loss

• Bloody nose
• difficulty in concentrating
• increased in sexual ability, desire, drive, or performance
• increased interest in sexual intercourse

• Attack, assault, or force
• feeling that others are watching you or controlling your behavior
• feeling that others can hear your thoughts
• hair loss or thinning of the hair
• pathological gambling
• severe mood or mental changes
• unusual behavior

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Cabergoline tablets contain Cabergoline, a dopamine receptor agonist. The chemical name for Cabergoline is 1-[(6-allylergolin-8ß-yl)-carbonyl]-1-[3-(dimethylamino) propyl]-3-ethylurea. Its molecular formula is C26H37N5O2, and its molecular weight is 451.62. The structural formula is as follows:

The drug substance used in Cabergoline tablet is the amorphous form of Cabergoline. Cabergoline is a cream to 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.

Each tablet, for oral administration, contain 0.5 mg of Cabergoline. Inactive ingredients consist of lactose anhydrous, leucine, and magnesium stearate.

1. Pregnancy

Dopamine agonists in general should not be used in patients with pregnancy-induced hypertension, for example, preeclampsia, eclampsia, and post partum hypertension, unless the potential benefit is judged to outweigh the possible risk.

2. Fibrotic Complications:

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). Postmarketing 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) for the treatment of Parkinson's disease. Cases of cardiac valvulopathy have also been reported in patients receiving lower doses of Cabergoline 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. The findings with respect to the risk of CVR associated with Cabergoline treatment for persons with Parkinson’s disease (increased risk) and those with hyperprolactinemia (no increased risk) are consistent with the findings in other published studies.

Physicians should use the lowest effective dose of Cabergoline for the treatment of hyperprolactinemic disorders and should periodically reassess the need for continuing therapy with Cabergoline. Following treatment initiation, clinical and diagnostic monitoring (for example, chest x-ray, CT scan and cardiac echocardiogram) should be conducted to assess the risk of cardiac valvulopathy. The recommended frequency of routine echocardiographic monitoring is every 6 to 12 months or as clinically indicated with the presence of signs and symptoms such as edema, new cardiac murmur, dyspnea, or congestive heart failure.

Cabergoline should be discontinued if an echocardiogram reveals new valvular regurgitation, valvular restriction or valve leaflet thickening.

Cabergoline should be used with caution in patients exposed to other medications associated with valvulopathy.

Postmarketing cases of pleural, pericardial, and retroperitoneal fibrosis have been reported following administration of Cabergoline. Some reports were in patients previously treated with other ergotinic dopamine agonists. Cabergoline should not be used in patients with a history of cardiac or extracardiac fibrotic disorders.

Fibrotic disorders can have an insidious onset and patients should be monitored for manifestations of progressive fibrosis. Therefore, during treatment, attention should be paid to the signs and symptoms of:

• Pleuro-pulmonary disease such as dyspnea, shortness of breath, persistent cough or chest pain.
• Renal insufficiency or ureteral/abdominal vascular obstruction that may occur with pain in the loin/flank and lower limb edema as well as any possible abdominal masses or tenderness that may indicate retroperitoneal fibrosis.
• Cardiac failure: Cases of valvular and pericardial fibrosis have often manifested as cardiac failure. Therefore, valvular fibrosis (and constrictive pericarditis) should be excluded if such symptoms occur.

Clinical and diagnostic monitoring such as erythrocyte sedimentation rate, chest-x ray, serum creatinine measurements, and other investigations should be considered at baseline and as necessary while patients are treated with Cabergoline.

Following diagnosis of pleural effusion or pulmonary fibrosis, the discontinuance of Cabergoline was reported to result in improvement of signs and symptoms.

The safety of Cabergoline tablets have 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.

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.

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).

Other events have been reported in association with Cabergoline: 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.

APOTEX CORP. NDC 60505-2597-2

Cabergoline Tablets

0.5 mg

Rx only

8 Tablets

Applies to cabergoline: oral tablet

Gastrointestinal

Very common (10% or more): Nausea (up to 29%)
Common (1% to 10%): Constipation, dyspepsia, gastritis, vomiting, abdominal pain, dyspepsia, dry mouth, diarrhea, flatulence, throat irritation, toothache[Ref]

Nervous system

Very common (10% or more): Headache (up to 26%), dizziness (up to 17%)
Common (1% to 10%): Dizziness/vertigo, dyskinesia, paresthesia, somnolence
Uncommon (0.1% to 1%): Hyperkinesia
Frequency not reported: Sudden sleep onset, syncope, tremor[Ref]

Other

Common (1% to 10%): Asthenia
Uncommon (0.1% to 1%): Fatigue, malaise[Ref]

Psychiatric

Common (1% to 10%): Hallucinations sleep disturbance, increased libido, confusion, depression, anxiety, insomnia, nervousness
Uncommon (0.1% to 1%): Delusions, psychotic disorder
Frequency not reported: Aggression, hypersexuality, pathological gambling[Ref]

Cardiovascular

Very common (10% or more): Peripheral edema
Common (1% to 10%): Angina (with concomitant levodopa use), postural hypotension, hot flashes, cardiac valvulopathy, hypotension, dependent edema, palpitation
Uncommon (0.1% to 1%): Erythromelalgia
Rare (less than 0.1%): Syncope, heart failure
Frequency not reported: Constrictive pericarditis, digital vasospasm
Postmarketing reports: Cardiac valvulopathy, pericarditis, pericardial effusion[Ref]

Reports of cardiac valvulopathy have generally been received in patients on higher doses (greater than 2 mg/day); however, there have been cases in patients receiving lower doses for the treatment of hyperprolactinemic disorders. In a multi-country, retrospective cohort study, record review looking for an association between the new use of dopamine agonists (including this drug; n=27,812) and cardiac valvular regurgitation (CVR), other fibrosis, and other cardiopulmonary events found an increased risk of CVR among patients with Parkinson's disease when compared to non-ergot derived dopamine agonists and levodopa. Analysis in patients with hyperprolactinemia treated with this drug (n=8386) found that compared to non-users, exposed persons did not have an elevated risk of CVR. These findings are consistent with other published studies.[Ref]

Musculoskeletal

Frequency not reported: Leg cramps[Ref]

Dermatologic

Uncommon (0.1% to 1%): Rash, acne, pruritus
Frequency not reported: Alopecia[Ref]

Respiratory

Common (1% to 10%): Dyspnea
Uncommon (0.1% to 1%): Pleural effusion, pulmonary fibrosis, rhinitis
Very rare (less than 0.01%): Fibrosis (including pleural fibrosis)
Frequency not reported: Respiratory disorder, respiratory failure, pleuritic, chest pain[Ref]

Ocular

Uncommon (0.1% to 1%): Periorbital edema, abnormal vision[Ref]

Endocrine

Common (1% to 10%): Breast pain
Uncommon (0.1% to 1%): Dysmenorrhea[Ref]

General

Adverse effects are generally dose related. At lower doses, the more commonly reported adverse reactions included nausea, headache, dizziness/vertigo, abdominal pain/dyspepsia/gastritis, asthenia/fatigue; at higher doses, additional events of valvulopathy, dyspnea, dyskinesia, orthostatic hypotension, hallucination, and constipation have been commonly reported.[Ref]

Hepatic

Uncommon (0.1% to 1%): Hepatic function abnormalities
Postmarketing reports: Liver function test abnormal[Ref]

Hypersensitivity

Uncommon (0.1% to 1%): Hypersensitivity reaction[Ref]

Some side effects of cabergoline may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.

No adjustment recommended

Summary of Use during Lactation

Cabergoline is usually not used during breastfeeding because it suppresses lactation. The U.S. Food and Drug Administration considers cabergoline to be not indicated to suppress lactation because the similar drug bromocriptine has caused hypertension, stroke, seizures and psychosis when used for this purpose. Cabergoline's use in other conditions has caused side effects similar to other dopamine agonists, such as bromocriptine. Whether rare cases of severe adverse effects occur with cabergoline as with bromocriptine cannot be determined because of the small number of postpartum patients treated in clinical trials to date. However, limited experience from clinical trials indicates that a single oral dose of 1 mg of cabergoline causes fewer side effects (usually headache, dizziness and nausea) than 14 days of bromocriptine and is at least as effective when used to suppress unwanted lactation. Some experts recommend cabergoline as a safer alternative to bromocriptine for lactation suppression, but others do not.[1][2][3] The disadvantage of cabergoline is that it has a half-life of about 68 hours, which means that any adverse effects will persist for a prolonged period of time. Women treated with cabergoline for pituitary adenomas who become pregnant can breastfed their infants with no apparent risk of recurrence. A treatment scheme has been reported for mothers with hypergalactia that uses low doses of cabergoline to decrease milk supply.[4]

Drug Levels

Maternal Levels. Relevant published information was not found as of the revision date.

Infant Levels. Relevant published information was not found as of the revision date.

Effects in Breastfed Infants

Relevant published information was not found as of the revision date.

Effects on Lactation and Breastmilk

Seventeen women who did not wish to breastfeed received a placebo or a single oral dose of cabergoline 400 mcg or 600 mcg on day 2 or 3 postpartum. Use of other lactation suppressing measures (e.g., breast binding, lack of nipple stimulation) was not mentioned. Blood samples were taken periodically over the next 96 hours. In the 7 women who received 400 mcg, plasma prolactin levels were decreased at 24 and 48 hours, but 4 developed breast engorgement. In the 5 women who received 600 mcg, plasma prolactin levels were decreased by 12 hours and persisted up to 96 hours and none developed breast engorgement. Some women had minor decreases in blood pressure, but no other adverse effects were reported.[5]

Thirty-two women who did not wish to breastfeed were given placebo or cabergoline 400, 600 or 800 mcg within 24 hours after delivery in a double-blind trial. Use of other lactation suppressing measures (e.g., breast binding, lack of nipple stimulation) was not mentioned. Lactation was prevented in 4 of 8 women who received the 400 mcg dose and all women who received the 600 or 800 mcg dose. Only 1 of 8 women receiving placebo had cessation of lactation by day 14 postpartum. Serum prolactin levels collected on days 2, 3 and 4 of treatment were decreased significantly in all women who received cabergoline, but the decreases were not statistically different among the various doses.[6]

A prospective, randomized, double-blinded study compared the effects of a single dose of cabergoline 0.5, 0.75 or 1 mg in 40 women each and to 20 women who received a placebo. The drug was given in the first 24 hours postpartum and use of other lactation suppressing measures (e.g., breast binding, lack of nipple stimulation) was not mentioned. The adequacy of lactation suppression on day 14 postpartum was dose-related, with excellent results in 18 patients who receive 0.5 mg, 28 who received 0.75 mg and 36 who received 1 mg. Serum prolactin levels collected during 13 days of treatment were decreased significantly in all women who received cabergoline, but the decreases were not statistically different among the various doses. Adverse effects included occasional dizziness and headache between days 1 and 3 after the dose.[7]

In a single-blind trial, 36 women were given either a single oral dose of cabergoline 1 mg or oral bromocriptine 2.5 mg twice daily for 14 days, starting about 50 hours after cesarean section. Use of other lactation suppressing measures (e.g., breast binding, lack of nipple stimulation) was not mentioned. Another 13 women who were breastfeeding after cesarean section served as controls. Both cabergoline and bromocriptine suppressed baseline serum prolactin by about 90% compared to baseline and control women within 3 days; this persisted at least through day 7, but somewhat rebounded by day 14. Suppression of lactation as measured by milk secretion, tenderness, and engorgement was equal between the 2 treatment groups. Lactation suppression was complete in 17 of 18 women who received cabergoline and 16 of 18 women who received bromocriptine, although the response was more rapid with cabergoline. Adverse events from cabergoline were fewer in number than with bromocriptine and consisted of occasional headache lasting 2 days, dizziness, and vomiting.[8]

A well-designed and evaluated double-blind study compared oral cabergoline 1 mg in a single dose (n = 136) to oral bromocriptine 2.5 mg twice daily for 14 days (n = 136) in women within 27 hours postpartum. Some women in each group (cabergoline n = 18; bromocriptine n = 16) received an ergot alkaloid or oral contraceptive postpartum. Symptoms of milk production and engorgement were recorded by the women and serum prolactin levels were measured on 3 occasions during the first 2 to 3 weeks postpartum. Cabergoline was at least as effective as bromocriptine, with complete success in 78% of cabergoline patients and 69% of bromocriptine patients. The rate of rebound lactation was much higher in bromocriptine patients (24%) than in cabergoline patients (5%). Serum prolactin was suppressed in both groups, but rebound was more common with bromocriptine on days 15 and 21. Adverse effects were numerically, but not statistically less frequent in cabergoline patients, with the most frequent being dizziness, headache, nausea and epigastric pain.[9]

Cabergoline was evaluated for lactation suppression in a prospective, but nonrandomized, unblinded trial. Women who were within 24 hours postpartum were given a single 1 mg dose (n = 54); those who were beyond 24 hours were given 0.25 mg twice daily for 2 days (n = 46). Only composite results were given for the entire group of 100 women. Mean serum prolactin dropped from 181.4 mcg/L (range 153 to 213 mcg/L) on the first day to 12.5 mcg/L (range 0.9 to 37 mcg/L) on day 4, and 18.2 mcg/L (range 2 to 36.2 mcg/L) on day 14 after the dose. Lactation was completely inhibited in 92% of women; 8 women required a second doses of 1 mg to inhibit lactation. Twenty-six percent of women had side effects such as dizziness, headache, nausea and abdominal pain. In 4% of women, side effects were severe enough to require symptomatic treatment.[7][10]

In a prospective, nonrandomized, unblinded trial, 43 women who underwent a second trimester abortion were given cabergoline 1 mg orally to suppress lactation. A single dose was effective in 88% of women.[11]

A randomized, nonblinded trial compared cabergoline 0.5 mg (n = 80) and 1 mg (n = 80) orally in a single dose given at an unstated time in the early postpartum period. The 1 mg dose was more effective in suppressing lactation than the 0.5 mg dose. Headache and nausea were the most common adverse effects.[12]

A follow-up survey was conducted on 91 women who became pregnant after treatment with cabergoline for hyperprolactinemia from pituitary adenomas. Eighty-eight patient breastfed their infants, 35 for less than 2 months and 56 for 2 to 6 months. No patients were restarted on cabergoline after pregnancy. At 3 and 12 months after pregnancy, serum prolactin was slightly higher than prepregnancy levels, but by 60 months postpartum, prolactin levels were lower than prepregnancy levels. Mothers who nursed for more than 2 months had lower serum prolactin at 60 months after cessation of breastfeeding than those who breastfed for less than 2 months. The authors concluded that breastfeeding does not increase the risk of recurrence of hyperprolactinemia.[13]

Alternate Drugs to Consider

(Hyperprolactinemia) Bromocriptine

References

1. Anon. Inhibiting the onset of lactation: Is cabergoline an alternative to bromocriptine? Prescrire Int. 2015;24:276-7. PMID: 26688910

2. Marcellin L, Chantry AA. [Breast-feeding (part II): Lactation inhibition--Guidelines for clinical practice]. J Gynecol Obstet Biol Reprod (Paris). 2015;44:1080-3. 26527027

3. Snellen M, Power J, Blankley G et al. Pharmacological lactation suppression with D receptor agonists and risk of postpartum psychosis: A systematic review. Aust N Z J Obstet Gynaecol. 2016;56:336-40. PMID: 27297803

4. Eglash A. Treatment of maternal hypergalactia. Breastfeed Med. 2014;9:423-5. PMID: 25361472

5. Melis GB, Gambacciani M et al. Dose-related prolactin inhibitory effect of the new long-acting dopamine receptor agonist cabergoline in normal cycling, puerperal, and hyperprolactinemic women. J Clin Endocrinol Metab. 1987;65:541-5. PMID: 3624413

6. Melis GB, Mais V et al. Prevention of puerperal lactation by a single oral administration of the new prolactin-inhibiting drug, cabergoline. Obstet Gynecol. 1988;71:311-4. PMID: 3279351

7. Caballero-Gordo A, Lopez-Nazareno N et al. Oral cabergoline. Single-dose inhibition of puerperal lactation. J Reprod Med. 1991;36:717-21. PMID: 1683403

8. Giorda G, de Vincentiis S et al. Cabergoline versus bromocriptine in suppression of lactation after cesarean delivery. Gynecol Obstet Investig. 1991;31:93-6. PMID: 2037265

9. European Multicentre Study Group for Cabergoline in Lactation Inhibition. Single dose cabergoline versus bromocriptine in inhibition of puerperal lactation: randomised, double blind, multicentre study. Br Med J. 1991;302:1367-70. PMID: 1676318

10. Bracco PL, Armentano G, Pellegrini A et al. [Cabergoline in the inhibition of lactogenesis and suppression of lactopoiesis]. Minerva Ginecol. 1997;49:469-73. PMID: 9463181

11. Pavlista D, Calda P, Zivny J. [Arrest of lactation after 2nd trimester abortion with a single dose of cabergoline in comparison with 10-day administration of teguride]. Ceska Gynekol. 2003;68:46-50. PMID: 12708116

12. Bravo-Topete EG, Mendoza-Hernandez F et al. [Cabergoline for inhibition of lactation]. Cir Cir. 2004;72:5-9. PMID: 15087045

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Substance Name

Cabergoline

CAS Registry Number

81409-90-7

Drug Class

Antiparkinson Agents

Dopamine Agonists