SYNONYM(S):

COMMON TRADE NAME(S): APO-BROMOCRIPTINE®, PMS-BROMOCRIPTINE®

CLASSIFICATION: hormonal agent

Special pediatric considerations are noted when applicable, otherwise adult provisions apply.

MECHANISM OF ACTION:

Bromocriptine is a dopaminergic ergot derivative.¹ Bromocriptine may decrease hormone production and the size of prolactin-dependent pituitary adenomas^2,3 by inhibiting the release and synthesis of prolactin from the anterior pituitary gland.¹

PHARMACOKINETICS:

Adapted from standard reference¹ unless specified otherwise.

USES:

*Health Canada approved indication

SPECIAL PRECAUTIONS:

Contraindications^1,7:

• history of hypersensitivity reaction to ergot derivatives
• uncontrolled hypertension

Caution:

• may cause hypotension¹; see paragraph following the Side Effects table
• severe renal or hepatic impairment ¹; see Dosage Guidelines
• history of, or current signs and/or clinical symptoms of, respiratory or cardiac disorders linked to fibrotic tissue⁴; see paragraph following the Side Effects table
• history of cardiovascular disease, Raynaud's syndrome, peptic ulcer, gastrointestinal bleeding
• history of serious, particularly psychotic, mental disease; particularly when taking concomitant psychoactive medication¹
• episodes of sudden sleep onset have occurred, more commonly in patients with Parkinson’s disease; the patient should use caution when driving or engaging in activities in which alertness is required⁷

Carcinogenicity: no information found

Mutagenicity: not mutagenic in Ames test and mammalian in vitro mutation test. Bromocriptine is not clastogenic in mammalian in vitro and in vivo chromosome tests.¹

Fertility: Since bromocriptine may restore fertility in hyperprolactinemic patients, women receiving bromocriptine who would like to prevent pregnancy should use contraceptive measures.²

Pregnancy: FDA Pregnancy Category B.⁴ Animal-reproduction studies have not shown a fetal risk but there are no controlled studies in pregnant women.¹

Breastfeeding is not recommended due to secretion into breast milk.⁴ Bromocriptine may interfere with lactation due to its prolactin-lowering action; bromocriptine should not be given to women who are breastfeeding or who are planning to breastfeed.¹

SIDE EFFECTS:

The table includes adverse events that presented during drug treatment but may not necessarily have a causal relationship with the drug. Because clinical trials are conducted under very specific conditions, the adverse event rates observed may not reflect the rates observed in clinical practice. Adverse events are generally included if they were reported in more than 1% of patients in the product monograph or pivotal trials, and/or determined to be clinically important.⁸ When placebo-controlled trials are available, adverse events are included if the incidence is >5% higher in the treatment group.⁹

Adapted from standard reference¹ unless specified otherwise.

The major side effects of dopamine agonists are nausea, lightheadedness after standing, and somnolence.³ These side effects are more likely to occur during treatment initiation or when the dose is increased.^2,3,11 Side effects are typically mild to moderate and may be minimized by starting with a low dose, increasing the dose slowly, using small doses more frequently, and taking the drug with food or at bedtime.^2,3,11 If side effects are severe or persist, a dose reduction to 1.25 mg daily with gradual dose escalation may be considered.¹ In women, intravaginal administration may also decrease or prevent nausea^2,3,12; see Dosage Guidelines.

The hypotensive effect of bromocriptine is due to its dopaminergic effect on vascular smooth muscle, peripheral sympathetic nerve terminals, and the CNS.¹ Monitor blood pressure periodically, especially during the first few days of therapy.¹ Use caution in patients taking concomitant medications known to affect blood pressure.¹ Hypotension occurs frequently but is symptomatic in only 1-5% of patients.⁶

Fibrosis(<1%)¹: As with other ergot derivatives, pleural and pericardial effusion, pleural and pulmonary fibrosis, and retroperitoneal fibrosis have been reported following long-term administration of bromocriptine.¹ These effects may be dose-related¹; use the lowest dose of bromocriptine necessary to reduce prolactin levels to normal.¹² Use with caution in patients with a history of, or current signs and/or symptoms of, respiratory or cardiac disorders linked to fibrotic tissue. Changes may be reversible if bromocriptine therapy is discontinued.¹

INTERACTIONS:

Bromocriptine is a major CYP3A4 substrate; therefore, drugs or herbs that are CYP3A4 inhibitors may increase the serum levels/effects of bromocriptine.⁴ Likewise, drugs or herbs that are CYP3A4 inducers may decrease the serum levels/effects of bromocriptine.⁴

SUPPLY AND STORAGE:

Oral: Apotex Canada Inc. supplies bromocriptine as a scored 2.5 mg tablet and 5 mg capsule. Selected non-medicinal ingredients: lactose. Store at room temperature and protect from light .⁴

Pharmascience Canada Inc. supplies bromocriptine as a scored 2.5 mg tablet and 5 mg capsule. Selected non-medicinal ingredients: lactose. Store at room temperature and protect from light.¹⁴

DOSAGE GUIDELINES:

Refer to protocol by which patient is being treated.

Adults:

Children:

References:

1. Apotex Inc. APO-BROMOCRIPTINE® Product Monograph. Weston, Ontario; 31 December 1996.

2. McEvoy GK, editor. AHFS 2007 Drug Information®. Bethesda, Maryland: American Society of Health-System Pharmacists, Inc. p. 3674-8.

3. Snyder PJ. Patient information: Lactotroph adenomas (prolactinomas). In: Rose BD, editor. UpToDate®. Waltham, Massachusetts: UpToDate 15.1; 26 October 2005.

4. Anonymous. Bromocriptine. In: Rose BD, editor. UpToDate. Waltham, Massachusetts: UpToDate 15.1; 2007.

5. DRUGDEX® Evaluations (database on the Internet). Bromocriptine. Thomson MICROMEDEX®, 2007. Available from http://www.micromedex.com/ Accessed 19 June 2007.

6. USPDI® Drug Information for the Health Care Professional (database on the Internet). Bromocriptine (Systemic). Thompson MICROMEDEX®, 2007. Available from http://www.micromedex.com/ Accessed 4 July 2007.

7. Novartis Pharmaceuticals Canada Inc. PARLODEL® product monograph. Dorval, Quebec; 26 October 2006.

8. Michelle Johnson, MD. Endocrinologist. Personal communication. Vancouver, British Columbia;27 September 2007.

9. Pfizer Canada Inc. DOSTINEX® product monograph. Kirkland, Quebec; 14 September 2006.

10. BC Cancer Agency. (SCNAUSEA) Guidelines for Prevention and Treatment of Chemotherapy-induced Nausea and Vomiting in Adults. Vancouver, British Columbia: BC Cancer Agency; 1 November 2005.

11. Abrahamson MJ, Snyder PJ. Treatment of hyperprolactinemia due to lactotroph adenoma and other causes. In: Rose BD, editor. UpToDate®. Waltham, Massachusetts: UpToDate 15.1; 10 January 2007.

12. BC Cancer Agency Neuro-Oncology. (CNB) BCCA Protocol Summary for Suppressive Therapy for Prolactinomas using Bromocriptine. Vancouver, British Columbia: BC Cancer Agency; 1 July 2001.

13. Juurlink D. Cytochrome P450 drug interactions. In: Welbanks L, editor. Compendium of Pharmaceutical Specialties. Ottawa, Ontario: Canadian Pharmacists Association; 2007. p. L60-83.

14. Repchinsky C, editor. PMS-Bromocriptine monograph, Compendium of Pharmaceuticals and Specialties. Ottawa, Ontario: Canadian Pharmacists Association; 2007. p. 1818.