Bromocriptine Mesylate

Pronunciation

Pronunciation: BROE-moe-KRIP-teen MES-i-late
Class: Antiparkinson agent

Trade Names

Cycloset
- Tablets 0.8 mg

Parlodel
- Capsules 5 mg

Parlodel SnapTabs
- Tablets 2.5 mg

Apo-Bromocriptine (Canada)
PMS-Bromocriptine (Canada)

Pharmacology

Stimulates dopamine receptors in the corpus striatum, relieving parkinsonian symptoms. Inhibits prolactin, which is responsible for lactation, and lowers elevated blood levels of growth hormone in acromegaly. The mechanism in glycemic control is unknown.

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Pharmacokinetics

Absorption

28% of oral dose absorbed (65% to 95% for Cycloset ). T max is 1 to 3 h. C max is 0.465 ng/mL (5 mg dose). Food increases AUC of Cycloset by approximately 55% to 65% and increases T max from 53 min to 90 to 120 min.

Distribution

90% to 96% bound to serum albumin. Vd is approximately 61 L.

Metabolism

Primarily metabolized in the GI tract and liver (CYP3A4). Undergoes extensive first-pass metabolism.

Elimination

Major elimination route is hepatic; 6% is renally eliminated. Terminal half-life of 15 h (6 h for Cycloset ).

Onset

1 to 2 h.

Peak

Peak plasma levels reached within 1 to 3 h.

Special Populations

Renal Function Impairment

Safety and efficacy not established. Use with caution in renal impairment.

Hepatic Function Impairment

Safety and efficacy not established. The speed of elimination may be retarded and plasma levels may increase. Dosage adjustments may be needed. Use with caution in hepatic impairment.

Gender

Plasma exposure is increased 18% to 30% in women compared with men.

Indications and Usage

Treatment of hyperprolactinemia-associated disorders (eg, amenorrhea with or without galactorrhea, infertility, hypogonadism) in patients with prolactin-secreting adenomas (excluding Cycloset ); treatment of acromegaly (excluding Cycloset ); therapy for Parkinson disease (idiopathic or postencephalitic) (excluding Cycloset ); therapy for type 2 diabetes ( Cycloset only).

Unlabeled Uses

Treatment of hyperprolactinemia associated with pituitary adenomas; therapy for NMS; treatment of cocaine addiction.

Contraindications

Hypersensitivity to bromocriptine, ergot alkaloids or ergot-related drugs, or any component of the product; breast-feeding.

Parlodel only

Uncontrolled hypertension; pregnancy (in treatment for acromegaly, prolactinoma, or Parkinson disease); postpartum period in women with a history of coronary artery disease or severe CV conditions.

Cycloset only

Syncopal migraine.

Dosage and Administration

Acromegaly
Adults

PO Initial dose: 1.25 to 2.5 mg at bedtime for 3 days; may be increased by 1.25 to 2.5 mg as tolerated every 3 to 7 days until optimum response occurs. Dose range, 20 to 30 mg/day; max, 100 mg/day.

Hyperprolactinemia
Adults and Children 11 yr of age and older

PO Initial dose: 1.25 to 2.5 mg/day; 2.5 mg may be added as tolerated every 2 to 7 days until optimum response. Dose range, 2.5 to 15 mg/day.

Parkinson Disease
Adults

PO Initial dose: 1.25 mg twice daily with meals; may be increased by 2.5 mg as tolerated every 14 to 28 days. Max, 100 mg/day.

Type 2 Diabetes Mellitus
Adults

PO Initial dose: 0.8 mg once daily; may be increased by 0.8 mg as tolerated every 7 days until optimum response occurs. Dose range, 1.6 to 4.8 mg/day; max, 4.8 mg/day.

General Advice

  • Evaluate patients frequently during dose escalation to determine the lowest dosage that produces a therapeutic response.
  • Give with milk or meals to reduce gastric distress.
  • Initial dose of Parlodel is usually given at bedtime because of adverse CNS reactions (eg, dizziness, fainting).
  • Administer Cycloset within 2 h after waking in the morning.

Storage/Stability

Store at or below 77°F in a tight, light-resistant container.

Drug Interactions

CYP3A4 strong inducers

Pharmacologic effects of bromocriptine may be decreased. Coadminister with caution.

CYP3A4 strong inhibitors (eg, azole antifungals, protease inhibitors)

Pharmacologic and toxic effects of bromocriptine may be increased. Coadminister with caution.

Dopamine antagonists (eg, butyrophenones, metoclopramide, phenothiazines)

Dopamine antagonists may reduce bromocriptine efficacy; bromocriptine may reduce effectiveness of dopamine antagonists. Concurrent use is not recommended.

Ergot drugs (eg, ergotamine)

Coadministration may increase occurrence of ergot-related side effects (eg, fatigue, nausea, vomiting) and may reduce effectiveness of ergot drugs when used to treat migraines. Concomitant use is not recommended.

Erythromycin, octreotide

May increase bromocriptine serum levels.

Ethanol

May potentiate adverse effects of bromocriptine.

Haloperidol, pimozide

May decrease efficacy of bromocriptine.

Highly protein—bound drugs (eg, chloramphenicol, probenecid, salicylates, sulfonamides)

Bromocriptine may increase the unbound fraction of other concomitantly used highly protein—bound drugs.

Methyldopa

Hypotensive effects may be increased.

Sympathomimetics (eg, isometheptene)

May exacerbate bromocriptine adverse effects. Concomitant use for more than 10 days is not recommended.

Triptans (eg, sumatriptan)

May have additive vasoconstrictive effects. Avoid concomitant use.

Laboratory Test Interactions

None well documented.

Adverse Reactions

Cardiovascular

Postural/orthostatic hypotension (6%); syncope (1%); cardiac valvulopathy, hypertension, MI, stroke (postmarketing).

CNS

Headache (19%); dizziness (17%); fatigue (14%); asthenia (13%); light-headedness (5%); somnolence (4%); drowsiness (3%); hypesthesia (1%); confusion, dyskinesia, hallucinations, NMS-like symptoms, psychomotor agitation, psychotic disorders, seizures (postmarketing).

EENT

Rhinitis (14%); sinusitis (10%); amblyopia (8%); dry mouth/nasal stuffiness (4%).

GI

Nausea (49%); constipation (14%); diarrhea (9%); dyspepsia (8%); vomiting (6%); anorexia (5%); abdominal cramps (4%); GI bleeding (less than 2%).

Metabolic

Hypoglycemia (4%).

Renal

Retroperitoneal fibrosis (postmarketing).

Respiratory

Constrictive pericarditis, pleural and pericardial effusion, pleural and pulmonary fibrosis, pleural thickening (postmarketing).

Miscellaneous

Flu syndrome (9%); common cold (8%); infection (6%); digital vasospasm (3%); exacerbation of Raynaud syndrome (less than 2%).

Precautions

Monitor

Assess for exacerbation of Raynaud syndrome (eg, muscle cramps in hands or feet, cold feet). Periodic evaluation of hepatic, hematopoietic, CV, and renal function is recommended. Monitor patients throughout pregnancy for signs and symptoms of a prolactin-secreting tumor. Monitor BP, particularly during the first weeks of therapy.


Pregnancy

Category B .

Lactation

Contraindicated in breast-feeding women.

Children

Safety and efficacy in children 8 yr of age and younger not established for hyperprolactinemia. Safety and efficacy in children not established for all other indications.

Elderly

No overall differences in safety or effectiveness were observed, but greater sensitivity of some older patients cannot be ruled out.

Renal Function

Use with caution.

Hepatic Function

Use with caution.

Hazardous Tasks

Exercise care when driving a vehicle or operating machinery because hypotensive reactions may occur, especially during the first days of treatment.

Acromegaly

Cold-sensitive digital vasospasms and severe GI bleeding from peptic ulcers have been reported in patients with acromegaly; institute appropriate treatment. Possible tumor expansion has occurred; monitor patient's condition and discontinue treatment if necessary.

CV effects

Symptomatic hypotension may occur. Hypertension, seizures, stroke, and MI have been reported in postpartum women on bromocriptine therapy. Use caution in patients with preeclampsia and in those who have received other drugs that may alter BP.

Cerebrospinal fluid rhinorrhea

May occur in patients with prolactin-secreting adenomas.

CNS effects

May be associated with confusion, mental disturbances, or hallucinations.

Galactose intolerance

Avoid use in patients with hereditary problems of galactose intolerance, severe lactase deficiency, or glucose-galactose malabsorption.

GI effects

Monitor for signs of GI bleeding.

MI

Exercise caution in patients with a history of MI who have a residual atrial, nodal, or ventricular arrhythmia.

Ophthalmic effects

Visual field impairment may occur. Monitor visual fields in patients with macroprolactinemia.

Parkinson disease

Safe use longer than 2 yr has not been established. Periodic evaluation of hepatic, hematopoietic, cardiac, and renal function is necessary.

Pituitary tumors

Evaluate pituitary before treatment to determine if tumor is present.

Psychotic disorders

May be exacerbated. Use in severe psychotic disorders is not recommended.

Pulmonary effects

Pleural and pericardial effusion, as well as pleural and pulmonary fibrosis and constrictive pericarditis, have been reported.

Retroperitoneal fibrosis

May occur. Monitor for signs of back pain, edema of lower limbs, or impaired kidney function.

Somnolence

May occur, particularly in patients with Parkinson disease.

Overdosage

Symptoms

Confusion, constipation, delusions, diaphoresis, dizziness, drowsiness, hallucinations, lethargy, malaise, nausea, pallor, severe hypotension, repetitive yawning, vomiting.

Patient Information

  • Advise patient not to skip doses or take double doses.
  • Caution patient not to discontinue drug suddenly to avoid rapid recurrence of original symptoms. Explain that dosage will be tapered slowly before stopping use of drug.
  • Advise women who are breast-feeding to avoid use.
  • Instruct patient to inform health care provider immediately if pregnancy is suspected.
  • When used for infertility, instruct patient to obtain daily basal body temperatures to determine when ovulation occurs.
  • Advise patients who are taking drug to suppress lactation that breast engorgement may occur as therapy is discontinued.
  • Inform patient that adverse reactions are common, especially during initial phase of therapy.
  • Instruct patient to notify health care provider if increasing dyspnea or nasal congestion occurs.
  • Advise patients who are taking bromocriptine for hyperprolactinemia associated with macroadenoma or those who have had previous transsphenoidal surgery to report any persistent watery nasal discharge.
  • Advise patient to seek medical advice during periods of stress such as fever, trauma, infection, or surgery. Dosage adjustment may be needed.
  • Caution patient to avoid sudden position changes to prevent orthostatic hypotension.
  • Advise patient to avoid intake of alcoholic beverages.
  • Advise patient that drug may cause dizziness, drowsiness, faintness, fainting, and syncope. Advise patient to use caution while driving or performing other tasks requiring mental alertness.

Copyright © 2009 Wolters Kluwer Health.

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