bromocriptine

Bromocriptine is a medication used to treat hyperprolactinemia, a condition with high blood levels of the hormone prolactin, and associated disorders.

Hyperprolactinemia is often caused by large tumors in the pituitary gland that secrete prolactin (macroprolactinoma). Bromocriptine is also used in the treatment of Parkinson’s disease, excessive growth or gigantism (acromegaly), and type 2 diabetes mellitus.

Bromocriptine is a semisynthetic ergot alkaloid that works by enhancing the activity of dopamine, a chemical (neurotransmitter) released by nerve cells (neurons) in the brain to transmit signals. Dopamine is an important hormone/neurotransmitter that has multiple functions including regulation of movement, memory, motivation, and pleasure. Dopamine also regulates the release and activity of other hormones including prolactin and growth hormones.

Bromocriptine enhances dopamine activity by stimulating dopamine receptors, protein molecules on neurons that respond to dopamine and activate appropriate downstream actions. Enhancing dopamine activity reduces the secretion of prolactin and growth hormones. It is not clear how bromocriptine works in controlling blood glucose levels, but it appears effective in reducing blood glucose and triglycerides in patients with insulin-resistant diabetes.

Two brands of bromocriptine are approved by the FDA, Cycloset for diabetes and Parlodel for all the other indications. The FDA-approved uses of bromocriptine are:

Parlodel

• Treatment of hyperprolactinemia, a condition with high blood levels of prolactin, a hormone that regulates menstruation, sperm production and lactation
• Treatment of hyperprolactinemia-associated dysfunctions in adults, including:
  • Absence of menstruation (amenorrhea)
  • Breast milk secretion in men, or women in non-breastfeeding stage (galactorrhea)
  • Infertility and deficiency in the function of reproductive glands, ovaries, and testes (hypogonadism)
  • Macroprolactinoma
• Adjunctive treatment to dopamine in Parkinson’s disease, a progressive neurological disorder that affects movement
• Treatment of acromegaly, a condition that causes excessive growth of bones in face, hands, and feet due to high levels of growth hormones in adulthood
• Neuroleptic malignant syndrome (off-label), a rare life-threatening reaction to antipsychotic (neuroleptic) drugs

Cycloset

• Adjunct to diet and exercise to improve glycemic control in type 2 diabetes mellitus

• Do not prescribe bromocriptine to patients with known hypersensitivity to any ergot alkaloids, bromocriptine, or any of its components.
• Do not use bromocriptine (Parlodel) in the following conditions:
  • Uncontrolled hypertension
  • Pregnancy in patients treated for hyperprolactinemia
  • Postpartum women with a history of coronary artery disease and other severe cardiovascular conditions
• Do not use bromocriptine (Cycloset) in the following conditions:
  • Syncopal migraine
  • Severe psychotic disorders
  • Postpartum patients
  • Nursing mothers
• Hypertension, myocardial infarction, seizures, and stroke have been reported in postpartum women. If it is necessary to use bromocriptine in postpartum women, the patient should be monitored closely.
• Use bromocriptine with caution in patients with:
  • Cardiovascular disease
  • Dementia
  • Impaired liver function
  • Peptic ulcer disease
• Bromocriptine treatment should be withdrawn gradually whenever possible.
• Discontinuation of dopamine agonists including bromocriptine can cause withdrawal symptoms such as anxiety, depression, apathy, fatigue, insomnia, sweating, and pain. Patients should be informed and monitored, and if withdrawal symptoms are severe, re-administration in low doses may be considered.
• Bromocriptine can cause drowsiness, particularly in Parkinson’s patients, and hypotensive episodes. Caution patients appropriately.

Cautions specific to Parlodel:

• Avoid using for prevention of physiological lactation.
• Use with caution in patients with a history of psychosis.
• Avoid use in patients with galactose intolerance, severe lactase deficiency, or glucose-galactose malabsorption.
• In patients who have undergone surgery for removal of pituitary tumor or undergoing Parlodel treatment for hyperprolactinemia related to prolactinoma, persistent watery nasal discharge may be a sign of cerebrospinal fluid (CSF) leakage.
• Tumor size should be monitored in patients with prolactinoma and Parlodel should be discontinued if the tumor expands.
• Macroprolactinoma often causes visual field impairment. Patients on Parlodel therapy should be monitored for improvement in visual impairment.
• Patients with acromegaly receiving bromocriptine therapy may experience cold-related vasospasm in fingers and toes.
• Patients with a history of peptic ulcer disease or gastrointestinal bleeding should be monitored carefully during Parlodel therapy.
• High doses of Parlodel may cause confusion and mental disturbance, and mild dementia in patients with Parkinson’s disease. Use with caution.
• Parlodel may cause auditory and visual hallucinations. If hallucinations do not resolve with dose reduction of Parlodel, discontinue therapy.
• Patients treated with anti-Parkinson’s medications may experience intense sexual urges and urges to gamble or spend money uncontrollably. Caution the patients and their caregivers appropriately.
• Some patients on long-term therapy have developed inflammation and scarring in the abdominal cavity (retroperitoneal fibrosis).
• Studies show that patients with Parkinson’s disease have a higher risk of developing melanoma, a type of skin cancer. It is not clear whether it is due to the condition or the treatment, monitor Parkinson’s patients periodically for melanoma.

Cautions specific to Cycloset:

• Hypotension, including orthostatic hypotension, can occur with Cycloset therapy, particularly upon initiation. Advise patients appropriately and use with caution in patients on anti-hypertensive therapy.
• Chronic use of Cycloset may cause cardiac valve fibrosis.
• Cycloset may exacerbate the condition in patients with psychotic disorder or diminish the effectiveness of the drugs used to treat the disorder, avoid use.
• Do not administer Cycloset concurrently with dopamine receptor antagonists.
• Avoid concomitant use with other dopamine agonists.

Cycloset

Common side effects include:

• Nausea
• Headache
• Dizziness
• Nasal inflammation (rhinitis)
• Weakness (asthenia)
• Fatigue
• Constipation
• Diarrhea
• Indigestion (dyspepsia)
• Vomiting
• Loss of appetite (anorexia)
• Lazy eye (amblyopia)
• Infection
• Cold
• Sinus inflammation (sinusitis)
• Flu syndrome
• Drowsiness (somnolence)
• Drop in blood pressure when standing up from sitting or lying down (orthostatic hypotension)

Less common side effects include:

• Hallucinations
• Stroke
• High blood pressure (hypertension)
• Heart attack (myocardial infarction)
• Seizures
• Psychotic and psychiatric disorders
• Scar-tissue (fibrotic) complications including:
  • Retroperitoneal fibrosis
  • Pulmonary fibrosis
  • Pleural effusion
  • Pleural thickening
  • Pericarditis
  • Pericardial effusions
• Movement disorder symptoms like those caused by antipsychotic drugs (neuroleptic malignant syndrome-like symptoms)

Parlodel

Common side effects include:

• Nausea
• Headache
• Dizziness
• Constipation
• Diarrhea
• Vomiting
• Abdominal cramps and discomfort
• Loss of appetite (anorexia)
• Indigestion (dyspepsia)
• Gastrointestinal bleeding
• Dry mouth
• Fatigue
• Lightheadedness
• Drowsiness
• Low blood pressure (hypotension)
• Postural (orthostatic) hypotension
• Faint feeling
• Fainting (syncope)
• Nasal congestion
• Vasospasm in fingers and toes
• Exacerbation of Raynaud’s syndrome
• Abnormal involuntary movements (dyskinesia)
• “On-off” phenomenon with mobility
• Weakness (asthenia)
• Impairment of co-ordination, balance and speech (ataxia)
• Vertigo
• Visual disturbance
• Shortness of breath
• Confusion
• Hallucinations
• Insomnia

Less common side effects include:

• Blurred vision
• Eyelid twitches (blepharospasm)
• Ringing in the ears (tinnitus)
• Swelling of feet and ankles (peripheral edema)
• Skin redness and burning sensation in the extremities (erythromelalgia)
• Skin rash
• Mottling of skin
• Allergic skin reactions
• Hair loss
• Sweating
• Pain
• Lethargy
• Apathy
• Daytime drowsiness
• Sudden onset of sleep
• Nightmares
• Nervousness
• Anxiety
• Depression
• Psychomotor agitation
• Psychotic disorders
• Increased libido
• Hypersexuality
• Epileptiform seizure
• Abnormal skin sensations (paresthesia)
• Tingling of fingers
• Cold feet
• Numbness
• Muscle cramps in feet and legs
• Urinary frequency
• Urinary incontinence
• Urinary retention
• Inflammation of the membrane around the heart (pericarditis)
• Pericardial effusion
• Cardiac valve thickening (fibrosis)
• Rapid or slow heart rate (tachycardia/bradycardia)
• Irregular heart rhythm (arrhythmia)
• Fluid around the lungs (pleural effusion)
• Pleural fibrosis
• Pleural inflammation (pleurisy)
• Pulmonary fibrosis
• Difficulty swallowing (dysphagia)
• Gastrointestinal ulcer
• Retroperitoneal fibrosis
• Neuroleptic malignant syndrome-like symptoms on withdrawal of Parlodel

Call your doctor immediately if you experience any of the following symptoms or serious side effects while using this drug:

• Serious heart symptoms include fast or pounding heartbeats, fluttering in your chest, shortness of breath, and sudden dizziness;
• Severe headache, confusion, slurred speech, severe weakness, vomiting, loss of coordination, feeling unsteady;
• Severe nervous system reaction with very stiff muscles, high fever, sweating, confusion, fast or uneven heartbeats, tremors, and feeling like you might pass out; or
• Serious eye symptoms include blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights.

This is not a complete list of all side effects or adverse reactions that may occur from the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may also report side effects or health problems to the FDA at 1-800-FDA-1088.

Tablet (Parlodel)

• 2.5 mg

Capsule (Parlodel)

• 5 mg

Tablet (Cycloset)

• 0.8 mg

Adult:

Hyperprolactinemia-Associated Dysfunctions (Parlodel)

• Indicated for treatment of dysfunctions associated with hyperprolactinemia including amenorrhea with or without galactorrhea, infertility, or hypogonadism; also indicated in patients with prolactin-secreting adenomas
• 1.25-2.5 mg orally every day initially; may increase by 2.5 mg/day every 2-7 days until optimal therapeutic response achieved
• Usual therapeutic dosage ranges from 2.5-15 mg/day
• Up to 30 mg/day has been used in some patients with amenorrhea and/or galactorrhea

Parkinson’s Disease (Parlodel)

• Indicated as adjunctive treatment to levodopa for the signs and symptoms of idiopathic/postencephalitic Parkinson’s disease
• 1.25 mg orally every 12 hours initially; may increase the dose by 2.5 mg/day every 2-4 weeks until optimal therapeutic response achieved
• Safety of dosage above 100 mg/day not established

Acromegaly (Parlodel)

• Indicated for acromegaly
• 1.25-2.5 mg orally every night at bedtime for 3 days initially; may increase by 1.25-2.5 mg/day every 3-7 days until optimal therapeutic response achieved
• Not to exceed 100 mg/day

Type 2 Diabetes Mellitus (Cycloset)

• Quick release formulation (Cycloset) is the only bromocriptine product indicated for type 2 diabetes mellitus as an adjunct to diet and exercise to improve glycemic control; there is currently no therapeutically equivalent generic version of Cycloset available in the United States
• 0.8 mg orally every day initially; may increase by 0.8-mg increments every week as tolerated
• Usual dosage ranges between 1.5-4.8 mg orally every day; not to exceed 4.8 mg (6 tablets)/day
• Note: Cycloset is not indicated for hyperprolactinemia, Parkinson’s disease, or acromegaly
• See Dosage Modifications (Cycloset) and Administration (Cycloset)

Neuroleptic Malignant Syndrome (Off-label, Parlodel)

• 2.5-5 mg orally 2-3 times/day; not to exceed 45 mg/day

Dosage Modifications

• Hepatic impairment: Safety and efficacy has not been established; dosage adjustment may be necessary due to extensive hepatic metabolism; use with caution
• Renal impairment: Safety and efficacy has not been established

Cycloset

• Concomitant use with CYP3A4 inhibitor
  • Strong CYP3A4 inhibitor (e.g., azole antimycotics, HIV protease inhibitors): Avoid use; ensure adequate washout of the strong CYP3A4 inhibitor drug before initiating Cycloset treatment
  • Moderate CYP3A4 inhibitor (e.g., erythromycin): Dose should not exceed 1.6 mg orally every day

Dosing Considerations

• Dosage forms for Cycloset and Parlodel and not interchangeable

Cycloset

Limitations of use

• Not for the treatment of type 1 diabetes or diabetic ketoacidosis
• Limited efficacy data in combination with thiazolidinediones
• Efficacy has not been confirmed in combination with insulin

Parlodel

• Patients treated with pituitary irradiation should be withdrawn from Parlodel therapy on a yearly basis to assess both the clinical effects of radiation on the disease process and effects of Parlodel therapy; usual withdrawal period range, 4-8 weeks; recurrence of the signs/symptoms or increases in growth hormone indicate the disease is still active and further courses of Parlodel should be considered

Pediatric:

Hyperprolactinemia (Parlodel)

• Children 10 years and below: Safety and efficacy not established
• Children 11-15 years: 1.25-2.5 mg orally every day initially; therapeutic dosage ranges from 2.5-10 mg/day and above; may need to increase the dose for optimal therapeutic response
• Children 16 years: Safety and efficacy not established
• See Administration (Parlodel)

Administration

Parlodel

• Take with food

Cycloset

• Take with food; administer within 2 hours after waking in the morning
• If dose is missed, wait until the next morning to take the medication

• Bromocriptine overdose can cause nausea, vomiting, constipation, excessive sweating (diaphoresis), dizziness, pallor, severe low blood pressure (hypotension), malaise, confusion, lethargy, drowsiness, delusions, hallucinations, and repetitive yawning.
• Treatment includes induced vomiting, gastric lavage, and administration of activated charcoal and saline purgative to eliminate the undigested drug. Hypotension may be treated with intravenous fluids and medications, if necessary.

Inform your doctor of all medications you are currently taking, who can advise you on any possible drug interactions. Never begin taking, suddenly discontinue, or change the dosage of any medication without your doctor’s recommendation.

• Severe interactions of bromocriptine include:
  • almotriptan
  • chloramphenicol
  • eletriptan
  • frovatriptan
  • glyceryl trinitrate pr
  • lopinavir
  • naratriptan
  • nitroglycerin IV
  • nitroglycerin sublingual
  • nitroglycerin topical
  • nitroglycerin transdermal
  • nitroglycerin translingual
  • posaconazole
  • sumatriptan
  • sumatriptan intranasal
  • zolmitriptan
• Bromocriptine has serious interactions with at least 57 different drugs.
• Bromocriptine has moderate interactions with at least 91 different drugs.
• Mild interactions of bromocriptine include:
  • ruxolitinib
  • ruxolitinib topical

The drug interactions listed above are not all of the possible interactions or adverse effects. For more information on drug interactions, visit the RxList Drug Interaction Checker.

It is important to always tell your doctor, pharmacist, or health care provider of all prescription and over-the-counter medications you use, as well as the dosage for each, and keep a list of the information. Check with your doctor or health care provider if you have any questions about the medication.

• Available data do not show evidence of drug-related maternal or fetal adverse outcomes with the use of bromocriptine (Cycloset) to treat diabetes mellitus during pregnancy. Animal studies, however, do show the possibility of fetal harm. Poorly controlled diabetes in pregnancy can increase risks to both mother and fetus. Cycloset must be used in pregnancy only if clearly needed.
• Parlodel brand of bromocriptine is used to treat hyperprolactinemia, Parkinson’s, and acromegaly. The safety of Parlodel use in pregnancy is not established.
  • In patients treated for hyperprolactinemia, Parlodel should be discontinued if pregnancy takes place.
  • If Parlodel is reinstituted to control the growth of pituitary gland tumor (adenoma) and the patient experiences hypertensive disorder of pregnancy, treatment should be continued only if the benefits of therapy outweigh the risks from its use in a hypertensive state.
  • When Parlodel is used to treat acromegaly, prolactinoma, or Parkinson’s disease in patients who subsequently become pregnant, therapy may be withdrawn if not medically necessary.
• Bromocriptine should not be used in nursing mothers.

• Take bromocriptine exactly as prescribed by your physician.
• Cycloset and Parlodel brands of bromocriptine are used to treat different conditions and are not interchangeable.
• Bromocriptine may cause dizziness, drowsiness, and fainting. Avoid hazardous tasks such as driving and operating heavy machinery while on treatment.
• During the initial period of treatment with Cycloset, make slow postural changes to avoid a sudden drop in blood pressure (hypotension).
• If you are taking Parlodel for macroadenoma after a previous surgery to remove a macroadenoma, report to your physician if you experience persistent watery nasal discharge.
• You may experience intense and uncontrollable sexual and other urges such as gambling and profligate spending while on Parlodel therapy. Exercise caution.
• Store bromocriptine safely out of reach of children.
• In case of overdose, seek immediate medical help or contact Poison Control.