کابرلین (کابولین)
Cabergoline (Dostinex)
کابرلین (کابولین)

نام ژنریک

Cabergoline

شکل دارویی

اشكال دارويي:


Tablet: 0.5, 1, 2 mg

موارد مصرف

موارد و مقدار مصرف


الف) هايپرپرولاكتينمي


بزرگسالان: شروع با دوز 25/0 ميلي‌گرم خوراكي 2 بار در هفته و افزايش دوز حداقل هر 4 هفته.


ب) بيماري پاركينسون.


بزرگسالان: شروع با دوز 1 ميلي‌گرم روزانه و افزايش 1- 5/0 ميلي‌گرم هر 14- 7 روز حداكثر 6- 2 ميلي‌گرم.


تنظيم سيكل قاعدگي در سندرم تخمدان پلي كيستيك.


بزرگسالان: 5/0 ميلي‌گرم خوراكي هر هفته.


پ) سندرم پاي بي‌قرار.


بزرگسالان: 4- 1 ميلي‌گرم روزانه
مكانيسم اثر
كابرگولين آگونيست طولاني اثر گيرنده‌هاي D2 مي‌باشد. كابرگولين تمايل كمي به گيرنده‌هاي 5-HT2, 5-HT 1, ?2, ?1, D1 دارد.

موارد منع مصرف

تداخل دارويي


در صورت مصرف همزمان با داروهاي كاهنده فشار خون به دليل افزايش بيش از حد فشار خون، دوز داروهاي ضد فشار خون بايد كاهش داده شود.


آثار درماني گابرگولين در صورت مصرف همزمان با آنتاگونيستها‌ي دوپامين كاهش مي‌يابد.


مصرف همزمان با قرص‌هاي ضد بارداري خوراكي، داروهاي منقبض كننده عروقي و پروپرانولول موجب تشديد خطر بروز انقباض‌هاي عروق محيطي مي‌شود.

موارد قابل توجه

-

تداخل دارویی

عوارض جانبي


اعصاب مركزي: سردرد، سرگيجه، خواب آلودگي، پارستزي، افسردگي، عصبانيت، اضطراب، ضعف، خستگي.


قلبي- عروقي: افت فشار خون وضعيتي، كاهش فشار خون، طپش قلب، سنكوپ، ادم محيطي.


چشم، بيني: اختلال ديد، گرفتگي بيني، خونريزي از بيني، ادم دور چشم.


دستگاه گوارش: درد شكم، سوء ‌هاضمه، خشكي دهان، اسهال، نفخ، بي‌اشتهايي.


پوست: آكنه، خارش، حملات گر گرفتگي.


ساير عوارض: ديسمنوره، كاهش يا افزايش وزن، درد پستان، افزايش ميل جنسي.


مسموميت و درمان.


مصرف بيش از حد باعث احتقان بيني، سنكوپ يا توهم مي‌شود. در موارد مسموميت اقدامات حمايتي اوليّه و كنترل فشار خون توصيه مي‌شود.

مکانیزم اثر

عوارض جانبي


اعصاب مركزي: سردرد، سرگيجه، خواب آلودگي، پارستزي، افسردگي، عصبانيت، اضطراب، ضعف، خستگي.


قلبي- عروقي: افت فشار خون وضعيتي، كاهش فشار خون، طپش قلب، سنكوپ، ادم محيطي.


چشم، بيني: اختلال ديد، گرفتگي بيني، خونريزي از بيني، ادم دور چشم.


دستگاه گوارش: درد شكم، سوء ‌هاضمه، خشكي دهان، اسهال، نفخ، بي‌اشتهايي.


پوست: آكنه، خارش، حملات گر گرفتگي.


ساير عوارض: ديسمنوره، كاهش يا افزايش وزن، درد پستان، افزايش ميل جنسي.


مسموميت و درمان.


مصرف بيش از حد باعث احتقان بيني، سنكوپ يا توهم مي‌شود. در موارد مسموميت اقدامات حمايتي اوليّه و كنترل فشار خون توصيه مي‌شود.

فارماكوكینتیك

موارد منع مصرف و احتياط


موارد منع مصرف: سابقه حساسيت به مشتقات ارگوت، فشار خون كنترل نشده، پرفشار خوني بارداري، دوران شيردهي، اكلامپسي و
پره اكلامپسي.


موارد احتياط: اختلال عملكرد كبدي، كودكان، فشار خون بسيار پايين

سایر اطلاعات

طبقه‌بندي فارماكولوژيك: آلكالوئيد ارگوت


طبقه‌بندي درماني: آگونيست گيرنده دوپاميني D2


طبقه‌بندي مصرف در بارداري: رده ‍B


نام‌هاي تجاري: Cabaser, Dostinex





ملاحظات اختصاصي


1- بررسي سطح پرولاكتين سرم ماهيانه بايد اندازه‌گيري شود.


2- شروع دارو درماني با دوز بيش از يك ميلي‌گرم ممكن است باعث افت فشار خون وضعيتي شود.


3- درمان بايد تا 6 ماه پس از طبيعي شدن سطح پرولاكتين ادامه يابد.


4- افزايش دوز دارو بايد هر 4 هفته يكبار انجام شود.


نكات قابل توصيه به بيمار


1- به بيمار توصيه شود جهت جلوگيري از افت فشار خون وضعيتي از تغيير وضعيت ناگهاني خودداري نمايد.


2- در صورت بارداري در طي دوران درمان، بيمار بايد به پزشك اطلاع دهد.




مصرف در شيردهي: ترشح دارو در شير مشخص نيست. با توجه به اهميت تجويز دارو، مزايا و مضرات تجويز بايد در نظر گرفته شود.

Cabergoline (Dostinex)

DOSTINEX®
(cabergoline) Tablets

DRUG DESCRIPTION

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

DOSTINEX® (cabergoline) Structural Formula Illustration

Cabergoline is a white powder soluble in ethyl alcohol, chloroform, and N, Ndimethylformamide (DMF); slightly soluble in 0.1N hydrochloric acid; very slightly soluble in n-hexane; and insoluble in water.

DOSTINEX Tablets, for oral administration, contain 0.5 mg of cabergoline. Inactive ingredients consist of leucine, USP, and lactose, NF.

What are the possible side effects of cabergoline (Dostinex)?

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Stop using cabergoline and call your doctor at once if you have any of these serious side effects:

  • cough or trouble breathing; or
  • feeling light-headed, fainting.

Less serious side effects may include:

  • nausea, vomiting, stomach pain, constipation;
  • headache;
  • dizziness, drowsiness, nervousness;
  • numbness or tingly feeling; or
  • hot...

Read All Potential Side Effects and See Pictures of Dostinex »

What are the precautions when taking cabergoline (Dostinex)?

Before taking cabergoline, tell your doctor or pharmacist if you are allergic to it; or to other ergot medications (such as ergotamine); or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: liver disease, high blood pressure (hypertension), heart valve disease, abnormal scarring/thickening of the lining in the lungs/heart/behind the abdomen (pulmonary/pericardial/retroperitoneal fibrosis).

This drug may make you dizzy. Do not drive, use machinery, or do any activity that requires alertness until you are sure you can perform such activities safely. Limit...

Read All Potential Precautions of Dostinex »

Last reviewed on RxList: 7/28/2011
This monograph has been modified to include the generic and brand name in many instances.

INDICATIONS

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

DOSAGE AND ADMINISTRATION

The recommended dosage of DOSTINEX Tablets for initiation of therapy is 0.25 mg twice a week. Dosage may be increased by 0.25 mg twice weekly up to a dosage of 1 mg twice a week according to the patient's serum prolactin level. Before initiating treatment, cardiovascular evaluation should be performed and echocardiography should be considered to assess for valvular disease.

Dosage increases should not occur more rapidly than every 4 weeks, so that the physician can assess the patient's response to each dosage level. If the patient does not respond adequately, and no additional benefit is observed with higher doses, the lowest dose that achieved maximal response should be used and other therapeutic approaches considered. Patients receiving long term treatment with DOSTINEX should undergo periodic assessment of their cardiac status and echocardiography should be considered.

After a normal serum prolactin level has been maintained for 6 months, DOSTINEX may be discontinued, with periodic monitoring of the serum prolactin level to determine whether or when treatment with DOSTINEX should be reinstituted. The durability of efficacy beyond 24 months of therapy with DOSTINEX has not been established.

HOW SUPPLIED

DOSTINEX Tablets are white, scored, capsule-shaped tablets containing 0.5 mg cabergoline. Each tablet is scored on one side and has the letter P and the letter U on either side of the breakline. The other side of the tablet is engraved with the number 700.

DOSTINEX is available as follows:

Bottles of 8 tablets NDC 0013-7001-12

Storage

Store at controlled room temperature 20°to 25°C (68°to 77°F) [see USP].

Distributed by : Pharmacia & Upjohn Company, Division of Pfizer Inc, NY, NY 10017. Revised July 2011

Last reviewed on RxList: 7/28/2011
This monograph has been modified to include the generic and brand name in many instances.

SIDE EFFECTS

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 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
*Reported at ≥ 1% for cabergoline

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 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)
*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.

Postmarketing Surveillance data

The following events have been reported in association with DOSTINEX: 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 DOSTINEX. Some of these reports have been in patients who have had prior adverse reactions to dopamine agonist products.

Read the Dostinex (cabergoline) Side Effects Center for a complete guide to possible side effects »

DRUG INTERACTIONS

DOSTINEX should not be administered concurrently with D2antagonists, such as phenothiazines, butyrophenones, thioxanthenes, or metoclopramide.

Last reviewed on RxList: 7/28/2011
This monograph has been modified to include the generic and brand name in many instances.

WARNINGS

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.

Fibrotic Complications

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 DOSTINEX. Postmarketing cases of cardiac valvulopathy have been reported in patients receiving DOSTINEX. These cases have generally occurred during administration of high doses of DOSTINEX ( > 2mg/day) for the treatment of Parkinson's disease. Cases of cardiac valvulopathy have also been reported in patients receiving lower doses of Dostinex for the treatment of hyperprolactinemic disorders.

Physicians should use the lowest effective dose of DOSTINEX for the treatment of hyperprolactinemic disorders and should periodically reassess the need for continuing therapy with DOSTINEX. 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.

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

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

Extracardiac Fibrotic Reactions

Postmarketing cases of pleural, pericardial, and retroperitoneal fibrosis have been reported following administration of DOSTINEX. Some reports were in patients previously treated with other ergotinic dopamine agonists. DOSTINEX 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 DOSTINEX.

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

PRECAUTIONS

General

Initial doses higher than 1.0 mg may produce orthostatic hypotension. Care should be exercised when administering DOSTINEX with other medications known to lower blood pressure.

Postpartum Lactation Inhibition or Suppression

DOSTINEX is not indicated for the inhibition or suppression of physiologic lactation. Use of bromocriptine, another dopamine agonist for this purpose, has been associated with cases of hypertension, stroke, and seizures.

Hepatic Impairment

Since cabergoline is extensively metabolized by the liver, caution should be used, and careful monitoring exercised, when administering DOSTINEX to patients with hepatic impairment.

Psychiatric

Pathological gambling, increased libido, and hypersexuality have been reported in patients treated with dopamine agonists including cabergoline. This has been generally reversible upon reduction of the dose or treatment discontinuation (See Postmarketing Surveillance data).

Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenicity studies were conducted in mice and rats with cabergoline given by gavage at doses up to 0.98 mg/kg/day and 0.32 mg/kg/day, respectively. These doses are 7 times and 4 times the maximum recommended human dose calculated on a body surface area basis using total mg/m²/week in rodents and mg/m²/week for a 50 kg human.

There was a slight increase in the incidence of cervical and uterine leiomyomas and uterine leiomyosarcomas in mice. In rats, there was a slight increase in malignant tumors of the cervix and uterus and interstitial cell adenomas. The occurrence of tumors in female rodents may be related to the prolonged suppression of prolactin secretion because prolactin is needed in rodents for the maintenance of the corpus luteum. In the absence of prolactin, the estrogen/progesterone ratio is increased, thereby increasing the risk for uterine tumors. In male rodents, the decrease in serum prolactin levels was associated with an increase in serum luteinizing hormone, which is thought to be a compensatory effect to maintain testicular steroid synthesis. Since these hormonal mechanisms are thought to be species-specific, the relevance of these tumors to humans is not known.

The mutagenic potential of cabergoline was evaluated and found to be negative in a battery of in vitro tests. These tests included the bacterial mutation (Ames) test with Salmonella typhimurium, the gene mutation assay with Schizosaccharomyces pombe P1 and V79 Chinese hamster cells, DNA damage and repair in Saccharomyces cerevisiae D4, and chromosomal aberrations in human lymphocytes. Cabergoline was also negative in the bone marrow micronucleus test in the mouse.

In female rats, a daily dose of 0.003 mg/kg for 2 weeks prior to mating and throughout the mating period inhibited conception. This dose represents approximately 1/28 the maximum recommended human dose calculated on a body surface area basis using total mg/m²/week in rats and mg/m²/week for a 50 kg human.

Pregnancy

Teratogenic Effects - Category B

Reproduction studies have been performed with cabergoline in mice, rats, and rabbits administered by gavage.

(Multiples of the maximum recommended human dose in this section are calculated on a body surface area basis using total mg/m²/week for animals and mg/m²/week for a 50 kg human.)

There were maternotoxic effects but no teratogenic effects in mice given cabergoline at doses up to 8 mg/kg/day (approximately 55 times the maximum recommended human dose) during the period of organogenesis.

A dose of 0.012 mg/kg/day (approximately 1/7 the maximum recommended human dose) during the period of organogenesis in rats caused an increase in post-implantation embryofetal losses. These losses could be due to the prolactin inhibitory properties of cabergoline in rats. At daily doses of 0.5 mg/kg/day (approximately 19 times the maximum recommended human dose) during the period of organogenesis in the rabbit, cabergoline caused maternotoxicity characterized by a loss of body weight and decreased food consumption. Doses of 4 mg/kg/day (approximately 150 times the maximum recommended human dose) during the period of organogenesis in the rabbit caused an increased occurrence of various malformations. However, in another study in rabbits, no treatment-related malformations or embryofetotoxicity were observed at doses up to 8 mg/kg/day (approximately 300 times the maximum recommended human dose).

In rats, doses higher than 0.003 mg/kg/day (approximately 1/28 the maximum recommended human dose) from 6 days before parturition and throughout the lactation period inhibited growth and caused death of offspring due to decreased milk secretion.

There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.

Nursing Mothers

It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from cabergoline, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother. Use of DOSTINEX for the inhibition or suppression of physiologic lactation is not recommended (see PRECAUTIONS section).

The prolactin-lowering action of cabergoline suggests that it will interfere with lactation. Due to this interference with lactation, DOSTINEX should not be given to women postpartum who are breastfeeding or who are planning to breastfeed.

Pediatric Use

Safety and effectiveness of DOSTINEX in pediatric patients have not been established.

Geriatric Use

Clinical studies of DOSTINEX did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger patients. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

Last reviewed on RxList: 7/28/2011
This monograph has been modified to include the generic and brand name in many instances.

OVERDOSE

Overdosage might be expected to produce nasal congestion, syncope, or hallucinations. Measures to support blood pressure should be taken if necessary.

CONTRAINDICATIONS

DOSTINEX Tablets 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)

Last reviewed on RxList: 7/28/2011
This monograph has been modified to include the generic and brand name in many instances.

CLINICAL PHARMACOLOGY

Mechanism of Action

The secretion of prolactin by the anterior pituitary is mainly under hypothalamic inhibitory control, likely exerted through release of dopamine by tuberoinfundibular neurons. Cabergoline is a long-acting dopamine receptor agonist with a high affinity for D2 receptors. Results of in vitro studies demonstrate that cabergoline exerts a direct inhibitory effect on the secretion of prolactin by rat pituitary lactotrophs. Cabergoline decreased serum prolactin levels in reserpinized rats. Receptor-binding studies indicate that cabergoline has low affinity for dopamine D1, α1- and α2-adrenergic, and 5-HT1- and 5-HT2-serotonin receptors.

Clinical Studies

The prolactin-lowering efficacy of DOSTINEX was demonstrated in hyperprolactinemic women in two randomized, double-blind, comparative studies, one with placebo and the other with bromocriptine. In the placebo-controlled study (placebo n=20; cabergoline n=168), DOSTINEX produced a dose-related decrease in serum prolactin levels with prolactin normalized after 4 weeks of treatment in 29%, 76%, 74% and 95% of the patients receiving 0.125, 0.5, 0.75, and 1.0 mg twice weekly respectively.

In the 8-week, double-blind period of the comparative trial with bromocriptine (cabergoline n=223; bromocriptine n=236 in the intent-to-treat analysis), prolactin was normalized in 77% of the patients treated with DOSTINEX at 0.5 mg twice weekly compared with 59% of those treated with bromocriptine at 2.5 mg twice daily. Restoration of menses occurred in 77% of the women treated with DOSTINEX, compared with 70% of those treated with bromocriptine. Among patients with galactorrhea, this symptom disappeared in 73% of those treated with DOSTINEX compared with 56% of those treated with bromocriptine.

Pharmacokinetics

Absorption

Following single oral doses of 0.5 mg to 1.5 mg given to 12 healthy adult volunteers, mean peak plasma levels of 30 to 70 picograms (pg)/mL of cabergoline were observed within 2 to 3 hours. Over the 0.5-to-7 mg dose range, cabergoline plasma levels appeared to be dose-proportional in 12 healthy adult volunteers and nine adult parkinsonian patients. A repeat-dose study in 12 healthy volunteers suggests that steady-state levels following a once-weekly dosing schedule are expected to be twofold to threefold higher than after a single dose. The absolute bioavailability of cabergoline is unknown. A significant fraction of the administered dose undergoes a first-pass effect. The elimination half-life of cabergoline estimated from urinary data of 12 healthy subjects ranged between 63 to 69 hours. The prolonged prolactin-lowering effect of cabergoline may be related to its slow elimination and long half-life.

Distribution

In animals, based on total radioactivity, cabergoline (and/or its metabolites) has shown extensive tissue distribution. Radioactivity in the pituitary exceeded that in plasma by > 100-fold and was eliminated with a half-life of approximately 60 hours. This finding is consistent with the long-lasting prolactin-lowering effect of the drug. Whole body autoradiography studies in pregnant rats showed no fetal uptake but high levels in the uterine wall. Significant radioactivity (parent plus metabolites) detected in the milk of lactating rats suggests a potential for exposure to nursing infants. The drug is extensively distributed throughout the body. Cabergoline is moderately bound (40% to 42%) to human plasma proteins in a concentration-independent manner. Concomitant dosing of highly protein-bound drugs is unlikely to affect its disposition.

Metabolism

In both animals and humans, cabergoline is extensively metabolized, predominately via hydrolysis of the acylurea bond or the urea moiety. Cytochrome P-450 mediated metabolism appears to be minimal. Cabergoline does not cause enzyme induction and/or inhibition in the rat. Hydrolysis of the acylurea or urea moiety abolishes the prolactin-lowering effect of cabergoline, and major metabolites identified thus far do not contribute to the therapeutic effect.

Excretion

After oral dosing of radioactive cabergoline to five healthy volunteers, approximately 22% and 60% of the dose was excreted within 20 days in the urine and feces, respectively. Less than 4% of the dose was excreted unchanged in the urine. Nonrenal and renal clearances for cabergoline are about 3.2 L/min and 0.08 L/min, respectively. Urinary excretion in hyperprolactinemic patients was similar.

Special Populations

Renal Insufficiency: The pharmacokinetics of cabergoline were not altered in 12 patients with moderate-to-severe renal insufficiency as assessed by creatinine clearance.

Hepatic Insufficiency: In 12 patients with mild-to-moderate hepatic dysfunction (Child-Pugh score ≤ 10), no effect on mean cabergoline Cmax or area under the plasma concentration curve (AUC) was observed. However, patients with severe insufficiency (Child-Pugh score > 10) show a substantial increase in the mean cabergoline Cmax and AUC, and thus necessitate caution.

Elderly: Effect of age on the pharmacokinetics of cabergoline has not been studied.

Food-Drug Interaction

In 12 healthy adult volunteers, food did not alter cabergoline kinetics.

Pharmacodynamics

Dose response with inhibition of plasma prolactin, onset of maximal effect, and duration of effect has been documented following single cabergoline doses to healthy volunteers (0.05 to 1.5 mg) and hyperprolactinemic patients (0.3 to 1 mg). In volunteers, prolactin inhibition was evident at doses > 0.2 mg, while doses ≥ 0.5 mg caused maximal suppression in most subjects. Higher doses produce prolactin suppression in a greater proportion of subjects and with an earlier onset and longer duration of action. In 12 healthy volunteers, 0.5, 1, and 1.5 mg doses resulted in complete prolactin inhibition, with a maximum effect within 3 hours in 92% to 100% of subjects after the 1 and 1.5 mg doses compared with 50% of subjects after the 0.5 mg dose.

In hyperprolactinemic patients (N=51), the maximal prolactin decrease after a 0.6 mg single dose of cabergoline was comparable to 2.5 mg bromocriptine; however, the duration of effect was markedly longer (14 days vs. 24 hours). The time to maximal effect was shorter for bromocriptine than cabergoline (6 hours vs. 48 hours).

In 72 healthy volunteers, single or multiple doses (up to 2 mg) of cabergoline resulted in selective inhibition of prolactin with no apparent effect on other anterior pituitary hormones (GH, FSH, LH, ACTH, and TSH) or cortisol.

Last reviewed on RxList: 7/28/2011
This monograph has been modified to include the generic and brand name in many instances.

PATIENT INFORMATION

Patients should be instructed to notify their physician if they suspect they are pregnant, become pregnant, or intend to become pregnant during therapy. A pregnancy test should be done if there is any suspicion of pregnancy and continuation of treatment should be discussed with their physician.

Patients should notify their physician if they develop shortness of breath, persistent cough, difficulty with breathing when lying down, or swelling in their extremities.

Last reviewed on RxList: 7/28/2011
This monograph has been modified to include the generic and brand name in many instances.

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PATIENT INFORMATION

Patients should be instructed to notify their physician if they suspect they are pregnant, become pregnant, or intend to become pregnant during therapy. A pregnancy test should be done if there is any suspicion of pregnancy and continuation of treatment should be discussed with their physician.

Patients should notify their physician if they develop shortness of breath, persistent cough, difficulty with breathing when lying down, or swelling in their extremities.

Last reviewed on RxList: 7/28/2011
This monograph has been modified to include the generic and brand name in many instances.

Disclaimer

Dostinex Consumer

IMPORTANT: HOW TO USE THIS INFORMATION: This is a summary and does NOT have all possible information about this product. This information does not assure that this product is safe, effective, or appropriate for you. This information is not individual medical advice and does not substitute for the advice of your health care professional. Always ask your health care professional for complete information about this product and your specific health needs.

CABERGOLINE - ORAL

(ka-BER-goe-leen)

COMMON BRAND NAME(S): Dostinex

USES: This medication is used to treat high levels of prolactin hormone in your body. High levels of prolactin in women can cause symptoms such as unwanted breast milk and missed periods and can cause difficulty becoming pregnant. High levels of prolactin in men can cause symptoms such as enlarged breasts and decreased sexual ability/desire. Cabergoline is an ergot medication and works by blocking the release of prolactin from the pituitary gland.

HOW TO USE: Take this medication by mouth with or without food, usually twice a week or as directed by your doctor.

The dosage is based on your medical condition and response to treatment (prolactin levels). Your doctor will start you at a low dose and slowly increase your dose over several months to help decrease side effects. Follow your doctor's instructions carefully.

Take this medication regularly to get the most benefit from it. To help you remember, mark the days on the calendar when you need to take the medication.

Tell your doctor if your condition persists or worsens.

Disclaimer

Dostinex Consumer (continued)

SIDE EFFECTS: Nausea, vomiting, stomach upset, constipation, dizziness, lightheadedness, or tiredness may occur. If any of these effects persist or worsen, tell your doctor or pharmacist promptly.

Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

Tell your doctor immediately if any of these rare but serious side effects occur: shortness of breath, persistent cough, swelling ankles/feet, unusual tiredness, mental/mood changes (such as nervousness, compulsive behavior including urge to gamble), vision changes, painful menses, breast pain.

Get medical help right away if you have any serious side effects, including: chest pain, lower back/flank pain, change in the amount of urine.

A very serious allergic reaction to this drug is rare. However, seek immediate medical attention if you notice any symptoms of a serious allergic reaction, including: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

In the US -

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

In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.

Read the Dostinex (cabergoline) Side Effects Center for a complete guide to possible side effects »

PRECAUTIONS: Before taking cabergoline, tell your doctor or pharmacist if you are allergic to it; or to other ergot medications (such as ergotamine); or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: liver disease, high blood pressure (hypertension), heart valve disease, abnormal scarring/thickening of the lining in the lungs/heart/behind the abdomen (pulmonary/pericardial/retroperitoneal fibrosis).

This drug may make you dizzy. Do not drive, use machinery, or do any activity that requires alertness until you are sure you can perform such activities safely. Limit alcoholic beverages.

To reduce the risk of dizziness and lightheadedness, get up slowly when rising from a sitting or lying position.

Before having surgery, tell your doctor or dentist about all the products you use (including prescription drugs, nonprescription drugs, and herbal products).

During pregnancy, this medication should be used only when clearly needed. Discuss the risks and benefits with your doctor.

It is unknown if this medication passes into breast milk. However, this medication may affect breast milk production. Therefore, breast-feeding while using this drug is not recommended. Consult your doctor before breast-feeding.

Disclaimer

Dostinex Consumer (continued)

DRUG INTERACTIONS: The effects of some drugs can change if you take other drugs or herbal products at the same time. This can increase your risk for serious side effects or may cause your medications not to work correctly. These drug interactions are possible, but do not always occur. Your doctor or pharmacist can often prevent or manage interactions by changing how you use your medications or by close monitoring.

To help your doctor and pharmacist give you the best care, be sure to tell your doctor and pharmacist about all the products you use (including prescription drugs, nonprescription drugs, and herbal products) before starting treatment with this product. While using this product, do not start, stop, or change the dosage of any other medicines you are using without your doctor's approval.

Some products that may interact with this drug include: antipsychotic medications (such as chlorpromazine, haloperidol, thiothixene), metoclopramide.

This document does not contain all possible drug interactions. Keep a list of all the products you use. Share this list with your doctor and pharmacist to lessen your risk for serious medication problems.

OVERDOSE: If overdose is suspected, contact a poison control center or emergency room immediately. US residents can call the US National Poison Hotline at 1-800-222-1222. Canada residents can call a provincial poison control center. Symptoms of overdose may include severe dizziness, fainting, mental/mood changes (such as hallucinations).

NOTES: Do not share this medication with others.

Laboratory and/or medical tests (such as prolactin levels, EKG) should be performed before starting and while you are taking this medication to monitor your progress or check for side effects. Consult your doctor for more details.

MISSED DOSE: If you miss a dose, take it as soon as you remember. If it is near the time of the next dose, skip the missed dose and resume your usual dosing schedule. Do not double the dose to catch up.

STORAGE: Store at room temperature between 68-77 degrees F (20-25 degrees C) away from light and moisture. Do not store in the bathroom. Keep all medicines away from children and pets.

Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company for more details about how to safely discard your product.

Information last revised September 2011. Copyright(c) 2011 First Databank, Inc.

Dostinex Patient Information Including Side Effects

Brand Names: Dostinex

Generic Name: cabergoline (Pronunciation: ca BER goe leen)

What is cabergoline (Dostinex)?

Cabergoline is in a group of drugs called dopamine receptor antagonists. It works by reducing the amount of prolactin (a hormone) that is released from the pituitary gland.

Cabergoline is used to treat a hormone imbalance in which there is too much prolactin in the blood (also called hyperprolactinemia).

Cabergoline may also be used for other purposes not listed in this medication guide.

Cabergoline 0.5 mg-COB

oblong, white, imprinted with LOGO, C S

Cabergoline 0.5 mg-TEV

oval, white, imprinted with Logo 0.5, 5420

Dostinex 0.5 mg

oblong, white, imprinted with PU, 700

What are the possible side effects of cabergoline (Dostinex)?

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Stop using cabergoline and call your doctor at once if you have any of these serious side effects:

  • cough or trouble breathing; or
  • feeling light-headed, fainting.

Less serious side effects may include:

  • nausea, vomiting, stomach pain, constipation;
  • headache;
  • dizziness, drowsiness, nervousness;
  • numbness or tingly feeling; or
  • hot flashes.

This is not a complete list of side effects and others may occur. Tell your doctor about any unusual or bothersome side effect. You may report side effects to FDA at 1-800-FDA-1088.

Read the Dostinex (cabergoline) Side Effects Center for a complete guide to possible side effects »

What is the most important information I should know about cabergoline (Dostinex)?

Do not use this medication if you are allergic to cabergoline, or if you have uncontrolled high blood pressure, pregnancy-related high blood pressure, or if you are allergic to any type of ergot medicine such as ergotamine (Ergomar, Cafergot), dihydroergotamine (D.H.E. 45, Migranal Nasal Spray), ergonovine (Ergotrate), or methylergonovine (Methergine).

Before taking cabergoline, tell your doctor if you are allergic to any drugs, or 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.

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. Do not miss any scheduled visits.

Tell your doctor if you are also taking metoclopramide (Reglan), blood pressure medications, diuretics, or any medication to treat a psychiatric disorder.

Side Effects Centers

Dostinex Patient Information including How Should I Take

What should I discuss with my health care provider before taking cabergoline (Dostinex)?

Do not use this medication if you are allergic to cabergoline, or if you have:

  • uncontrolled high blood pressure (hypertension);
  • hypertension caused by pregnancy, including eclampsia and preeclampsia; or
  • if you are allergic to any type of ergot medicine such as ergotamine (Ergomar, Cafergot), dihydroergotamine (D.H.E. 45, Migranal Nasal Spray), ergonovine (Ergotrate), or methylergonovine (Methergine).

Before taking cabergoline, tell your doctor if you are allergic to any drugs, or if you have:

  • liver disease;
  • heart disease; or
  • a breathing disorder.

If you have any of these conditions, you may need a dose adjustment or special tests to safely take this medication.

FDA pregnancy category B. This medication is not expected to be harmful to an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant during treatment.

It is not known whether cabergoline passes into breast milk or if it could harm a nursing baby. Do not use this medication without telling your doctor if you are breast-feeding a baby.

How should I take cabergoline (Dostinex)?

Take this medication exactly as it was prescribed for you. Do not take the medication in larger amounts, or take it for longer than recommended by your doctor. Follow the directions on your prescription label.

Your doctor may occasionally change your dose to make sure you get the best results from this medication.

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.

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. Do not miss any scheduled appointments.

Store cabergoline at room temperature away from moisture and heat.

Side Effects Centers

Dostinex Patient Information including If I Miss a Dose

What happens if I miss a dose (Dostinex)?

Take the missed dose as soon as you remember. If it is almost time for your next dose, skip the missed dose and take the medicine at your next regularly scheduled time. Do not take extra medicine to make up the missed dose.

What happens if I overdose (Dostinex)?

Seek emergency medical attention if you think you have used too much of this medicine.

Overdose symptoms may include stuffy nose, confusion, hallucinations, feeling light-headed, or fainting.

What should I avoid while taking cabergoline (Dostinex)?

Follow your doctor's instructions about any restrictions on food, beverages, or activity while you are using cabergoline.

What other drugs will affect cabergoline (Dostinex)?

Before using cabergoline, tell your doctor if you are using any of the following drugs:

  • metoclopramide (Reglan);
  • an ACE inhibitor such as benazepril (Lotensin), captopril (Capoten), fosinopril (Monopril), enalapril (Vasotec), lisinopril (Prinivil, Zestril), moexipril (Univasc), perindopril (Aceon), quinapril (Accupril), ramipril (Altace), or trandolapril (Mavik);
  • a beta-blocker such as acebutolol (Sectral), atenolol (Tenormin), betaxolol (Kerlone), bisoprolol (Zebeta), carteolol (Cartrol), carvedilol (Coreg), esmolol (Brevibloc), labetalol (Normodyne, Trandate), metoprolol (Lopressor, Toprol), nadolol (Corgard), penbutolol (Levatol), pindolol (Visken), propranolol (Inderal, InnoPran), sotalol (Betapace), or timolol (Blocadren);
  • a calcium channel blocker such as amlodipine (Norvasc), diltiazem (Tiazac, Cartia, Cardizem), felodipine (Plendil), nicardipine (Cardene), nifedipine (Procardia, Adalat), nimodipine (Nimotop), nisoldipine (Sular), or verapamil (Calan, Covera, Isoptin, Verelan);
  • a diuretic (water pill) such as amiloride (Midamor, Moduretic), bumetanide (Bumex), chlorthalidone (Hygroton, Thalitone), ethacrynic acid (Edecrin), furosemide (Lasix), hydrochlorothiazide (HCTZ, HydroDiuril, Hyzaar, Lopressor, Vasoretic, Zestoretic), indapamide (Lozol), metolazone (Mykrox, Zarxolyn), spironolactone (Aldactazide, Aldactone), triamterene (Dyrenium, Maxzide, Dyazide), torsemide (Demadex), and others; or
  • other blood pressure medications such as irbesartan (Avapro), losartan (Cozaar), olmesartan (Benicar), telmisartan (Micardis), and valsartan (Diovan).

This list is not complete and there may be other drugs that can interact with cabergoline. Tell your doctor about all the prescription and over-the-counter medications you use. This includes vitamins, minerals, herbal products, and drugs prescribed by other doctors. Do not start using a new medication without telling your doctor.

Where can I get more information?

Your pharmacist can provide more information about cabergoline.


Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed.

Every effort has been made to ensure that the information provided by Cerner Multum, Inc. ('Multum') is accurate, up-to-date, and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. Multum information has been compiled for use by healthcare practitioners and consumers in the United States and therefore Multum does not warrant that uses outside of the United States are appropriate, unless specifically indicated otherwise. Multum's drug information does not endorse drugs, diagnose patients or recommend therapy. Multum's drug information is an informational resource designed to assist licensed healthcare practitioners in caring for their patients and/or to serve consumers viewing this service as a supplement to, and not a substitute for, the expertise, skill, knowledge and judgment of healthcare practitioners. The absence of a warning for a given drug or drug combination in no way should be construed to indicate that the drug or drug combination is safe, effective or appropriate for any given patient. Multum does not assume any responsibility for any aspect of healthcare administered with the aid of information Multum provides. The information contained herein is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. If you have questions about the drugs you are taking, check with your doctor, nurse or pharmacist.

Copyright 1996-2012 Cerner Multum, Inc. Version: 1.04. Revision date: 12/15/2010.

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Side Effects Centers

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