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Introduction

  1. Pharmacology. Bromocriptine mesylate is a semisynthetic derivative of the ergopeptide group of ergot alkaloids with dopaminergic agonist effects. It also has minor alpha-adrenergic antagonist properties. The dopaminergic effects account for its inhibition of prolactin secretion and its beneficial effects in the treatment of parkinsonism, acromegaly, neuroleptic malignant syndrome (NMS, and cocaine craving. A key limitation is the inability to administer bromocriptine by the parenteral route coupled with poor bioavailability (only about 6% of an oral dose is absorbed). The onset of therapeutic effects (eg, alleviation of muscle rigidity, hypertension, and hyperthermia) in the treatment of NMS may take several hours to days.
  2. Indications
    1. Treatment of NMS caused by neuroleptic drugs (eg, haloperidol and other antipsychotics) or levodopa withdrawal. Note: If the patient has significant hyperthermia (eg, rectal or core temperature ≥40°C [104°F]), bromocriptine should be considered secondary and adjunctive therapy to immediate life-saving measures such as neuromuscular paralysis and aggressive external cooling. Its efficacy to treat NMS is uncertain, and it can potentially worsen other types of hyperthermia (eg, malignant hyperthermia, heat stroke) owing to activation of dopamine and 5-HT2A receptors.
    2. Bromocriptine has been used experimentally to alleviate cocaine craving. However, a Cochrane database review (2015) concluded that current research does not support the use of dopamine agonists for the treatment of cocaine dependence. Caution: There is one case report of a severe adverse reaction (hypertension, seizures, and blindness) when bromocriptine was used in a cocaine abuser during the postpartum period.
    3. Note: Bromocriptine is not considered appropriate first-line therapy for acute drug-induced extrapyramidal or parkinsonian symptoms (Other Complications).
  3. Contraindications
    1. Uncontrolled hypertension or preeclampsia.
    2. Known hypersensitivity to the drug.
    3. A relative contraindication is a history of angina, myocardial infarction, stroke, vasospastic disorders (eg, Raynaud disease), or bipolar affective disorder. There is no published experience in children younger than 7 years. Children may achieve higher blood levels and require lower doses.
  4. Adverse effects
    1. The most common side effect is nausea. Epigastric pain, dyspepsia, and diarrhea also have been reported.
    2. Hypotension (usually transient) and syncope may occur at the initiation of treatment, and hypertension may occur later. Other cardiovascular effects include dysrhythmias (with high doses), exacerbation of angina and vasospastic disorders such as Raynaud disease, and intravascular thrombosis resulting in acute myocardial infarction (one case report).
    3. Nervous system side effects vary considerably and include headache, drowsiness, fatigue, hallucinations, mania, psychosis, agitation, seizures, and cerebrovascular accident. Multiple interrelated risk factors include dose, concurrent drug therapy, and preexisting medical and psychiatric disorders.
    4. Rare effects include pulmonary toxicity (infiltrates, pleural effusion, and thickening) and myopia with long-term, high-dose treatment (months). There has been one case of retroperitoneal fibrosis.
    5. Use in pregnancy. FDA Category B (Introduction). This drug has been used therapeutically during the last trimester of pregnancy for the treatment of a pituitary tumor. It has been shown to inhibit fetal prolactin secretion, and it may precipitate premature labor and inhibit lactation in the mother.
  5. Drug or laboratory interactions
    1. Bromocriptine may accentuate hypotension in patients receiving antihypertensive drugs.
    2. Theoretically, this drug may have additive effects with other ergot alkaloids, and its potential to cause peripheral vasospasm may be exacerbated by propranolol.
    3. Bromocriptine may reduce ethanol tolerance.
    4. There has been one case report of apparent serotonin syndrome in a patient with Parkinson's disease who received levodopa and carbidopa.
  6. Dosage and method of administration for NMS. In adults, administer 2.5-10 mg orally or by gastric tube 3-4 times daily (average adult dose, 5 mg every 8 hours). The pediatric dose is unknown (one case report of 0.08 mg/kg every 8 hours in a 7-year-old; the tablets were mixed in a 2.5-mg/10-mL slurry and given by feeding tube). Use small, frequent doses to minimize nausea.
    1. A therapeutic response is usually achieved with total daily doses of 5-30 mg (maximum daily dose for the treatment of NMS, 45 mg).
    2. Continue treatment for 7-10 days after control of rigidity and fever, then slowly taper the dose over 3 days (to prevent recurrence). Several days of therapy may be required for complete reversal of NMS.