The P-I-E-N-O Parkinsn's List Drug Database
bromocriptine / ParlodelTM
ANTIPARKINSON:
Dopamine agonist
Description: Bromocriptine is a synthetic dopamine agonist that is chemically related to ergot alkaloids and lysergic acid. Bromocriptine was originally approved for use in the treatment of postpartum breast engorgement and parkinsonism. It now is used in a variety of hyperprolactinemia syndromes including acromegaly. It also has been beneficial in treating cocaine withdrawal. Related agents include pergolide and lisuride, which have 10 to 1000 times the potency of bromocriptine on a milligram basis. Bromocriptine was originally approved by the FDA in 1978 for the treatment of amenorrhea/galactorrhea secondary to hyperprolactinemia and was subsequently approved for infertility (1981), acromegaly (1984), prolactin-secreting pituitary adenomas (1985). On August 18, 1994, the manufacturer announced it was withdrawing the indication for bromocriptine for postpartum lactation suppression.
Mechanism of Action: Bromocriptine stimulates dopamine type-2 receptors and antagonizes type-1 receptors in the hypothalamus and the neostriatum of the CNS. Pergolide, another ergot derivative, stimulates both type-1 and type-2 receptors. Prolactin secretion from the anterior pituitary gland is suppressed. Following bromocriptine-induced reductions in serum prolactin levels, ovulation and ovarian function will resume in amenorrheic patients, and lactation will be suppressed in women with normal ovarian activity. Bromocriptine also induces menses in amenorrheic women with normal levels of serum prolactin (possibly via the release of luteinizing hormone), and may have a direct stimulatory effect on ovarian dopaminergic receptors. Resumption of menses usually occurs within 6-8 weeks following administration of the drug.
Bromocriptine can slow the growth rate of pituitary adenomas and can increase the secretion of growth hormone in normal patients. Patients with acromegaly who receive bromocriptine can experience a paradoxical decrease in the secretion of growth hormone; rates of secretion return to baseline within 2 weeks of therapy cessation. Patients with Parkinson's disease usually do not develop tolerance to the neurological effects of bromocriptine as they do to levodopa therapy. Bromocriptine also slightly increases sodium excretion and can reduce blood pressure. High doses of the drug can induce vasoconstriction.
Bromocriptine also has been beneficial in treating cocaine withdrawal. Chronic cocaine use decreases dopamine concentrations within the brain, leading to dopamine supersensitivity. This is believed to be the mechanism of craving during cocaine withdrawal. By stimulating dopamine receptors, bromocriptine has been shown to reduce the intensity of psychiatric symptoms associated with cocaine withdrawal.
Pharmacokinetics: Although 28% of an orally administered dose of bromocriptine is absorbed across the GI tract, only 6% reaches the circulation due to significant hepatic metabolism. Oral administration of a single 1.25-5.0 mg dose results in serum prolactin reductions within 2 hours. Bromocriptine therapy produces maximal reductions in the serum prolactin levels of hyperprolactinemic patients within 4 weeks and significantly reduces growth hormone levels in acromegaly patients within 1-2 hours. The drug binds extensively (90-96%) to serum albumin and does not appear to distribute into erythrocytes. More than 90% of an absorbed dose undergoes first-pass metabolism, with the remainder of the dose hydrolyzed in the liver to inactive metabolites. Bromocriptine has a half-life of 3 hours. Metabolites are eliminated in the bile, with only a small amount excreted by the kidneys.
CONTRAINDICATIONS/PRECAUTIONS: Bromocriptine is pregnancy risk category C. Although no adequate human studies have been performed on the effects of this drug on the fetus, animal reproduction studies have shown adverse fetal effects. Therefore, in making the decision to administer this drug during pregnancy, the potential risks to the fetus must be weighed against the potential benefits to the mother.
Bromocriptine should not be given to patients planning to breast-feed. Bromocriptine interferes with lactation and therefore should not be used during breast-feeding.
Bromocriptine can cause hypotension and should not be administered during the postpartum period unless vital signs are normal and at least 4 hours have passed.
Rarely, hypertension can occur, and the blood pressure of patients receiving bromocriptine should be closely monitored during initial therapy. The drug should be discontinued immediately if hypertension, severe headaches, or other adverse CNS signs appear. Bromocriptine is contraindicated in cases of uncontrolled hypertension.
Large doses of bromocriptine can cause confusion and CNS disturbances, so the drug should be used with extreme caution in parkinsonian patients who exhibit signs of dementia. Patients receiving bromocriptine alone or in combination with levodopa therapy can develop hallucinations. Dosage reduction usually eliminates these hallucinations, but discontinuance of the drug may be required. High-dose bromocriptine therapy can cause mental status changes including hallucinations that last for weeks after therapy has been discontinued. Bromocriptine can hamper the patient's ability to operate machinery or drive a motor vehicle, and patients should be advised of the drug's potential to impair mental alertness.
Bromocriptine should be used with caution in patients with hepatic disease. Dosage reduction may be required.
Bromocriptine should be used with caution in patients with cardiac arrhythmias of atrial, nodal, or ventricular origin. The drug should also be used with caution in patients with coronary artery disease or a history of acute myocardial infarction.
Although rare, CSF rhinorrhea can occur in patients receiving bromocriptine for the treatment of macroadenomas or in those receiving the drug post-surgery (following transsphenoid surgery). Such patients should be observed closely for signs of CSF rhinorrhea including nasal discharge.
Prolonged therapy with bromocriptine has resulted in the development of pulmonary infiltrates, thickening of the pleura, and pleural effusion. Patients receiving large doses of the drug should be observed for pulmonary abnormalities. These effects usually resolve with discontinuance of the drug. Retroperitoneal fibrosis also can occur in patients receiving high doses of the drug for more than 2 years.
A few of the preparations of bromocriptine contain sodium bisulfite, a compound that can precipitate anaphylaxis or severe asthmatic reactions in patients with sodium bisulfite hypersensitivity.
Bromocriptine is contraindicated in patients with eclampsia or toxemia of pregnancy.
Bromocriptine is contraindicated in patients with ergot alkaloid hypersensitivity.
DRUG INTERACTIONS: Drugs that increase the concentration of prolactin, such as butyrophenones including haloperidol; loxapine; molindone; monoamine oxidase inhibitors (MAOIs); imipramine; amitriptyline; methyldopa; phenothiazines; thioxanthines; and reserpine, can antagonize the effects of bromocriptine. Estrogens or progestins can produce amenorrhea or galactorrhea when administered, and use during bromocriptine administration is not recommended.
High doses of bromocriptine can decrease the tolerance to ethanol, so patients should be warned of this effect and advised to lessen ethanol consumption while receiving bromocriptine. A disulfiram-like reaction can occur during concomitant use of bromocriptine and ethanol, which is manifested as chest pain, tachycardia, throbbing headache, flushing of the face, severe weakness, sweating, nausea, vomiting, and blurred vision.
Bromocriptine and levodopa are both dopamine agonists. Concomitant use of these agents can cause additive neurologic effects. Although this drug combination may be necessary in some patients, dosages of levodopa may require reduction if bromocriptine is added.
Case reports have documented hypertension and seizures occurring as a result of concomitant use of bromocriptine and phenylpropanolamine. Until more data are available, this drug combination should be avoided whenever possible.
Bromocriptine is an ergot alkaloid derivative. Concomitant use of bromocriptine with other ergot alkaloids can lead to ergot toxicity.
Concomitant administration of bromocriptine and antihypertensive agents can result in additive hypotensive effects, and dosage reductions may be required.
Erythromycin has been shown to reduce the clearance of bromocriptine. Patients should be monitored for signs of bromocriptine toxicity if erythromycin is added.
ADVERSE REACTIONS: Adverse effects associated with bromocriptine administration occur often, are typically mild to moderate, and can be frequent during initiation of therapy or when dosages exceed 20 mg/day. Some of these adverse effects can be controlled with dosage reductions or by administering with food, but discontinuation of therapy may be necessary in a few patients. Patients with hyperprolactinemia and acromegaly are more sensitive, perhaps due to the higher doses used.
As with other ergot alkaloids, nausea/vomiting is a common adverse effect associated with bromocriptine therapy and occurs most frequently when the drug is administered for hyperprolactinemia (50%). Other adverse GI effects that occur during therapy include anorexia, epigastric discomfort or dyspepsia, abdominal pain, indigestion, diarrhea, and constipation. Dosage reductions can alleviate these effects. Peptic ulcer also has been reported in association with bromocriptine therapy and may be due to an increase in the secretion of gastric acid.
Large doses of bromocriptine can cause mental status changes including confusion, so the drug should be used with extreme caution in parkinsonian patients who exhibit signs of dementia. Hallucinations can develop in patients receiving bromocriptine alone or in combination with levodopa. Dosage reduction usually eliminates these hallucinations, but discontinuation of the drug may be required. High-dose bromocriptine therapy rarely can result in persistent hallucinations that last for weeks after therapy has been discontinued.
Bromocriptine can cause hypotension and should not be administered during the postpartum period unless vital signs are normal and at least 4 hours have passed. Orthostatic hypotension, syncope, and shock have also been reported. Some patients have experienced a worsening of angina with bromocriptine administration. Other cardiovascular reactions include sinus bradycardia, ventricular tachycardia, and pedal edema. Rarely, hypertension can occur; blood pressure of patients receiving bromocriptine should be closely monitored during initial therapy. Hypertension, seizures, myocardial infarction, and stroke have occurred during therapy, but it is not certain if there is a causal relationship to bromocriptine therapy. Patients who developed these effects experienced severe headaches beforehand, so the drug should be discontinued immediately if hypertension, severe headaches, or other adverse CNS signs appear. On August 18, 1994, the manufacturer announced it was withdrawing the indication for bromocriptine for postpartum lactation suppression stating the risk of stroke or myocardial infarction exceeded the benefit of the drug for this indication.
Prolonged therapy with bromocriptine has resulted in the development of pulmonary infiltrates, thickening of the pleura, and pleural effusion. Patients receiving large doses of the drug should be observed for pulmonary abnormalities. These effects usually resolve with discontinuation of the drug. Retroperitoneal fibrosis also can occur in patients receiving high doses of the drug for more than 2 years.
Although rare, CSF rhinorrhea can occur in patients receiving bromocriptine for the treatment of macroadenomas or in those receiving the drug post-surgically (following transsphenoid surgery). Such patients should be observed closely for signs of CSF rhinorrhea including nasal discharge.
Leg cramps, metallic taste, rash, urticaria, tinnitus, blurred vision, myopia, ocular irritation, nasal congestion, facial pallor, impotence, priapism (painful clitoral tumescence), nasal congestion, and xerostomia have been reported during therapy with bromocriptine. Ergotism (i.e., cold feet, tingling of fingers, muscle cramping, Raynaud's syndrome, urinary retention, urinary incontinence, and urinary frequency) has been reported rarely in parkinsonian patients receiving bromocriptine therapy.
PATIENT INFORMATION:
What do bromocriptine tablets or capsules do?
Bromocriptine (ParlodelTM ) comes from a group of medicines known as ergot alkaloids. It blocks the release of a hormone, called prolactin, that affects the menstrual cycle and breast milk production. Bromocriptine is useful in treating menstrual and fertility problems, and abnormal milk production. Bromocriptine can be used to treat Parkinson's disease. It is also helpful in treating acromegaly (excessive growth hormone). Generic bromocriptine tablets and capsules are not yet available.
What should my doctor, dentist, or pharmacist know before I take bromocriptine?
They need to know if you have any of these conditions:
How should I take this medicine? Take bromocriptine tablets or capsule by mouth. Follow the directions on the prescription label. Swallow the tablets or capsules with a drink of water. It is best to take bromocriptine with food. Take your doses at regular intervals. Do not take your medicine more often than directed. Do not stop taking except on your doctor's advice.
Special precautions for use in children:
This medicine is not for children under 15 years old.
What if I miss a dose?
If you miss a dose, take it as soon as you can. If it is more than 4 hours since your dose was due, wait until your next dose. Do not take double or extra doses.
What other medicines can interact with bromocriptine?
Tell your doctor or pharmacist: about all other medicines you are taking, including non-prescription medicines; if you are a frequent user of drinks with caffeine or alcohol; if you smoke; or if you use illegal drugs. These may affect the way your medicine works. Check before stopping or starting any of your medicines.
What side effects may I notice from taking bromocriptine?
Serious side effects with bromocriptine include:
Call your doctor as soon as you can if you get any of these side effects.
Minor side effects with bromocriptine include:
Let your doctor know about these side effects if they do not go away or if they annoy you.
What do I need to watch for while I take bromocriptine?
Visit your doctor for regular checks on your progress. Ask your doctor if you should check your blood pressure regularly, especially if you get severe headaches. Ask your doctor what your blood pressure should be and when you should contact him or her.
You may get dizzy or drowsy. Do not drive, use machinery, or do anything that needs mental alertness until you know how bromocriptine affects you. To reduce the risk of dizzy or fainting spells, do not stand or sit up quickly, especially if you are an older patient. Alcohol can make you more dizzy, and increase flushing and rapid heartbeats. Avoid alcoholic drinks. Dizziness is more common after the first dose. Take it before bedtime if possible and be careful getting out of bed.
Your mouth may get dry. Chewing sugarless gum or sucking hard candy, and drinking plenty of water will help.
If you are going to have surgery, tell your doctor or dentist that you are taking bromocriptine.
Where can I keep my medicine?
Keep out of the reach of children in a container that small children cannot open.
Store at room temperature below 25C (77F). Protect from light. Keep container tightly closed. Throw away any unused medicine after the expiration date.
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