Bromocriptine is a synthetic dopamine agonist that is chemically related to ergot alkaloids and lysergic acid. Bromocriptine is used in adult and pediatric patients 11 years and older with selected conditions. It was the first dopamine agonist marketed for the treatment of Parkinson's disease (PD) in adults as monotherapy or as an adjunct to levodopa-based treatment; however, newer dopamine agonists have largely replaced bromocriptine in the treatment of PD. Bromocriptine is a versatile drug and is indicated for a variety of endocrine conditions including pituitary-secreting adenomas and hyperprolactinemia-related conditions (e.g., amenorrhea with or without galactorrhea, hypogonadism, or infertility). Bromocriptine is also effective in patients with acromegaly, although newer agents directly targeting growth hormone have largely replaced bromocriptine in the treatment of patients with this condition. A bromocriptine micronized tablet (Cycloset) is indicated for the treatment of type 2 diabetes mellitus in adults. The American Diabetes Association (ADA) does not consider bromocriptine a common medication for use for type 2 diabetes; considerations include modest efficacy, potential for drug interactions, treatment cost, and frequent side effects, including nausea. Bromocriptine is also used as monotherapy, or in combination with dantrolene, for the treatment of Neuroleptic Malignant Syndrome. Bromocriptine interferes with proper lactation and should not be used during breast-feeding and should be avoided in the postpartum period in patients at potential cardiovascular risk. Although bromocriptine was previously used for postpartum breast engorgement and lactation suppression, the indication for postpartum lactation suppression was voluntarily withdrawn by the manufacturer in 1994, following a prior determination by the FDA Fertility and Maternal Health Drugs Advisory Committee that safer and more conservative supportive measures were available.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Route-Specific Administration
Oral Administration
-Administer bromocriptine orally with food; administration with food reduces gastrointestinal side effects such as nausea.
Oral Solid Formulations
Bromocriptine immediate release tablets (e.g., Parlodel):
-Timing of administration (with food) depends is individualized to the indication for use and recommended titration schedules.
-Higher daily doses can be given in divided doses (e.g., twice daily or every 6 hours), depending on the patient condition, to improve tolerance.
Micronized bromocriptine quick-release tablets ( e.g., Cycloset):
-Administer with food once daily in the morning within 2 hours after waking.
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 administration of the drug with food, but discontinuation of therapy may be necessary in some patients. Patients with hyperprolactinemia and acromegaly are more sensitive, perhaps due to the higher doses used. Approximately 69% of patients receiving bromocriptine for hyperprolactinemic indications experienced adverse effects from the drug during clinical trials, and approximately 5% of patients discontinued treatment due to adverse effects. In patients receiving bromocriptine for diabetes, 24% discontinued treatment due to an adverse effect compared to 9% of those receiving placebo.
Nausea is the most commonly reported adverse effect of bromocriptine administration, and is generally the most frequent cause of treatment discontinuation. During clinical trials for hyperprolactinemia, nausea resulted in nearly half of treatment discontinuations due to an adverse effect. Infrequent (< 1%) causes of treatment discontinuation included vomiting, abdominal cramps, constipation, and diarrhea. During clinical trials for acromegaly, about 18% of patients experienced nausea and 2% experienced vomiting. Other gastrointestinal effects reported by this patient population included constipation (14%), anorexia (4%), dyspepsia (4%), and xerostomia (4%). Among patients receiving bromocriptine (Cycloset 1.6-4.8 mg) for diabetic therapy either alone or with other antidiabetic medications, nausea and vomiting were among the mostly commonly reported adverse events, typically occurring during the initial titration phase, and lasting a median of 14 days. Nausea was reported in 25.4-32.5% of patients in the Cycloset groups compared to 4.8-7.6% of patients receiving placebo and vomiting was reported in 5.3-8.1% of patients in the Cycloset groups versus 1.3-3.2% of patients receiving placebo. Other GI events commonly reported in Cycloset versus placebo groups included: constipation (5.8-11.3% vs. 3.8-5.1%), diarrhea (8.1-8.8% vs. 5.1-8%), dyspepsia (7.5% vs. 2.5%), and anorexia (5% vs. 1.3%). Nausea/vomiting, abdominal discomfort, anorexia, xerostomia, dysphagia, and constipation were reported in those receiving the drug for Parkinson's disease. Less than 2% of acromegaly patients experienced GI bleeding during clinical trials. This rare but serious side effect is possibly the result of an increase in gastric acid secretion. Some cases of GI bleeding have been fatal, therefore signs and symptoms of peptic ulcer formation should be promptly evaluated. GI effects including nausea, constipation, vomiting, xerostomia, diarrhea, abdominal pain, peptic ulcer, and GI hemorrhage have been reported during post-market use. Dosage reductions or administration of the drug with food may help alleviate some GI symptoms such as nausea.
Bromocriptine may cause drowsiness. During clinical trials of bromocriptine (Cycloset) as an antidiabetic agent in combination with other antidiabetic agents, drowsiness was reported in 6.6% of patients in the Cycloset group and 2% of patients in the placebo group. Drowsiness/tiredness occurred in 3% of patients receiving bromocriptine for acromegaly during clinical trials. Drowsiness was also reported during clinical trials of bromocriptine for Parkinson's disease, although the frequency is unknown. Drowsiness was an infrequent (< 1%) cause of treatment discontinuation in those receiving the drug for hyperprolactinemia. There have been reports of patients receiving bromocriptine, particularly those with Parkinson's disease, who have fallen asleep while performing activities of daily living. It is possible for episodes of excessive drowsiness to occur well after the start of treatment. Sudden sleep onset with other dopamine agonists has, in some cases, resulted in auto accidents or other harmful events in the course of daily living. Symptoms of excessive drowsiness may not be preceded by warning signs. Patients should be cautioned against driving or operating machinery, working at heights, or performing other tasks that require alertness while receiving bromocriptine. Those who have experienced somnolence or a sudden episode of sleep while taking the drug should avoid these activities. Reassessment for oversedation is suggested throughout bromocriptine therapy. The use of concomitant CNS depressant medications or sleep disorders may increase the risk of falling asleep while taking this medication; patients should be assessed for these risk factors prior to initiation of the drug and be advised of the additive risks for somnolence. Bromocriptine should generally be discontinued in those experiencing episodes of falling asleep while engaged in activities of daily living. It is not known if a reduction in dosage will subsequently reduce or eliminate excessive somnolence or sudden sleep onset.
Bromocriptine exerts its therapeutic effects in the hypothalamus and the neostriatum of the CNS; therefore, centrally-derived adverse effects are relatively common. Dizziness and headache occurred in less than 2% of those with acromegaly receiving the drug in clinical trials. Rare CNS effects (less than 1%) in acromegalic patients included faintness, lightheadedness, decreased sleep requirement, visual hallucinations, lassitude, vertigo, sluggishness, delusional psychosis, paranoia, insomnia, and heavy headedness. Those with Parkinson's disease have reportedly experienced abnormal involuntary movements, hallucinations, confusion, asthenia, ataxia, depression, dizziness, insomnia, an on-off phenomenon, faintness or fainting, and vertigo from bromocriptine administration. Less commonly occurring CNS effects in Parkinson's patients include anxiety, fatigue, headache, lethargy, nervousness, epileptiform seizure, and nightmares. Confusion, psychomotor agitation, hallucinations, psychotic disorders (unspecified), insomnia, headache, dizziness, dyskinesia, and fatigue have been reported during postmarketing use. Among patients receiving bromocriptine for diabetic therapy (Cycloset), fatigue, dizziness, and headache were among the mostly commonly reported adverse events lasting a median of 14 days and typically occurring during the initial titration phase. Overall, CNS related adverse events commonly reported across phase 3 clinical trials in patients receiving Cycloset 1.6 mg to 4.8 mg, either alone or with other antidiabetic agents and at higher rates than with placebo include: fatigue (13.9%), dizziness (11.9% to 14.8%), headache (11.4% to 16.8%), asthenia (12.5% to 18.9%), and somnolence (6.6%). Of the 5% of hyperprolactinemic patients requiring discontinuation of therapy during clinical trials, the most frequent centrally-mediated cause was headache (19%), followed by dizziness (17%), fatigue (7%), lightheadedness (5%), and drowsiness (3%). Large doses of bromocriptine can cause mental status changes such as confusion. A dosage reduction may reduce or eliminate this symptom or other CNS effects. Mania has been reported in patients receiving bromocriptine without a diagnosis of Parkinson's disease. Although a combination of levodopa and bromocriptine is sometimes used in the treatment of Parkinson's disease, hallucinations can develop during concomitant treatment. In rare instances, hallucinations may persist for weeks after therapy has been discontinued. Dosages should be slowly titrated and patients should be closely monitored for mental status changes during combined use of these drugs. There have been no reported cases of hallucinations, delusions, or psychoses associated with bromocriptine use for diabetic therapy (Cycloset).
Bromocriptine has only minimal affinity for adrenergic receptors; however, hypotension can occur during bromocriptine administration and may lead to orthostatic hypotension and syncope. Bromocriptine should be used cautiously with other medications known to lower blood pressure such as antihypertensives. Monitoring of blood pressure should be considered, especially during the initial weeks of therapy or during dose increases. Orthostatic hypotension occurred in roughly 6% of acromegaly patients receiving the drug during clinical trials. Syncope was reported in less than 2% of patients. Rare cardiac effects (less than 1%) included arrhythmia, ventricular tachycardia, bradycardia, and vasovagal attack. In patients with Parkinson's disease, cardiovascular effects including hypotension and peripheral edema were reported during clinical trials, although the frequencies are unknown. Hypotension has been reported among patients receiving bromocriptine for diabetic therapy (Cycloset); in a 52-week safety trial, hypotension was reported in 2.2% of bromocriptine-treated patients compared to 0.8% of placebo-treated patients. In the majority of cases, patients reporting symptomatic hypotension were taking concomitant antihypertensive medications. Orthostatic hypotension was reported in 0.3% of bromocriptine-treated patients compared to 0.2% of placebo-treated patients; in every case, patients were on concomitant antihypertensive medications. In combined phase 2 and 3 clinical trials of patients receiving bromocriptine for diabetes (Cycloset), syncope was reported in 1.4% to 1.6% of bromocriptine-treated patients and 0.6% to 0.7% of the placebo-treated patients. Serious hypotension occurred more frequently (approximately 30%) in postpartum studies of bromocriptine, which in rare cases approached a decrease in supine pressure of almost 60 mmHg; the drug is contraindicated in all postpartum patients being treated for diabetes mellitus. For all other indications, bromocriptine is contraindicated in the postpartum period in women with a history of coronary artery disease and other severe cardiovascular conditions unless withdrawal is considered medically contraindicated. Cardiac effects reported during postmarket use include sinus tachycardia, bradycardia, arrhythmia (unspecified), peripheral edema, hypotension, and orthostatic hypotension.
The risk of serious cardiovascular and cerebrovascular events from bromocriptine may be increased in the post-partum use of the drug for suppression of lactation. The indication for postpartum lactation suppression was voluntarily withdrawn by the manufacturer in 1994, following a formal request by the FDA and a prior determination by the FDA Fertility and Maternal Health Drugs Advisory Committee that safer and more conservative supportive measures were available such as cold packs, compression aides, and pain relievers. Several cases of hypertension (89 cases) have been documented in postpartum patients receiving the drug for lactation suppression, with and without subsequent seizures (72 cases). Four cases of status epilepticus have been reported. Some of the patients who developed these effects experienced severe headaches or visual disturbances (e.g., changes in vision, blurriness, transient cortical blindness) prior to the event. Other rare but serious effects include myocardial infarction (9 cases) and stroke (30 cases). It is unknown if bromocriptine is the exact cause of these effects in postpartum women. In the rare postpartum women in whom bromocriptine therapy is absolutely required, periodic monitoring of blood pressure is advisable. The drug should be discontinued if signs of persistent headache, visual changes, or uncontrolled hypertension become evident. Serious cardiovascular events do not appear to be increased over placebo in patients receiving bromocriptine as adjunctive therapy for diabetes mellitus (Cycloset). The primary and secondary endpoints of a 52-week safety trial of Cycloset were occurrence of all serious adverse events, and occurrence of the composite of certain cardiovascular endpoints (e.g., myocardial infarction, stroke, coronary revascularization, hospitalization for angina, and hospitalization for congestive heart failure), respectively. Serious adverse events occurred in 8.5% of bromocriptine-treated patients and 9.6% of placebo-treated patients; hazard ratio for the time to first occurrence was 1.02 (upper bound of one-sided 96% confidence interval, 1.27), but none of the events were reported more often than 0.3% in bromocriptine-treated patients compared to placebo. The composite cardiovascular endpoint occurred in 1.5% of bromocriptine-treated patients and 3% of placebo-treated patients; hazard ratio for the time to first occurrence was 0.58 (two-sided 95% confidence interval, 0.35-0.96). There have been no reported cases of stroke associated with bromocriptine use for diabetic therapy (Cycloset).
A variety of symptoms affecting the extremities have been reported with bromocriptine administration including erythromelalgia, leg cramps, paresthesias, and exacerbation of Raynaud's Syndrome (less than 2% in acromegalic patients). Approximately 3% of acromegalic patients receiving bromocriptine developed digital vasospasm during clinical trials. Because this effect is caused by sensitivity to cold, it can be prevented by keeping the fingers warm. Dosage reduction is an effective treatment if digital vasospasm occurs. Reduced tolerance to cold, paresthesias, facial pallor, tingling of the ears, and muscle cramps have also been reported in acromegalic patients with incidences of less than 1%. Ergotism has been reported rarely in parkinsonian patients receiving bromocriptine. Symptoms of ergotism include angina, asthenia, chest pain (unspecified), coronary vasospasm, muscle cramps (claudication), myalgia, paresthesias, and palpitations or changes in heart rate (e.g., sinus bradycardia or sinus tachycardia). Pallor of the fingers and toes induced by cold (likely induced by peripheral vasoconstriction) particularly in patients with a history of Raynaud's disease, has been reported during post-market.
Fibrotic-related complications have been reported during bromocriptine administration. Prolonged therapy with high doses of bromocriptine (20-100 mg/day) 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, including pleural and pulmonary fibrosis. These effects usually resolve with discontinuation of the drug. Retroperitoneal fibrosis also can occur in patients receiving high doses of the drug (30-140 mg/day) for more than 2 years. Retroperitoneal fibrosis, pericardial effusion, constrictive pericarditis, cardiac valve fibrosis, pleural effusion, pleural fibrosis, pleurisy, and pulmonary fibrosis have been reported during post-market use of bromocriptine. Although many studies have investigated a possible correlation between bromocriptine use and cases of cardiac valvulopathy, no definitive association has been made. There have been no reported cases of retroperitoneal fibrosis, pulmonary infiltrates, pleural effusion, pleural thickening, pericarditis or pericardial effusions associated with bromocriptine use for diabetic therapy (Cycloset).
Respiratory effects including nasal congestion (4%) and dyspnea (< 1%) have been reported in acromegalic patients during clinical trials with bromocriptine. Nasal congestion and dyspnea have also been reported in Parkinson's disease patients receiving bromocriptine, although the frequencies are unknown. Certain respiratory related adverse events were reported in >= 5% of patients receiving bromocriptine for diabetic therapy (Cycloset) across phase 3 clinical trials. Respiratory adverse events occurring more often in patients receiving Cycloset 1.6 mg to 4.8 mg, either alone or with a sulfonylurea, versus placebo include: rhinitis (10.7-13.8% vs. 3.8-4.8%, respectively), sinusitis (7.4-10% vs. 2.5-6.4%, respectively), flu syndrome (influenza 9.4% vs. 7.6%, respectively), cold (8.2% vs. 8%, respectively), and infection (6.3% vs. 5.1%, respectively). Respiratory effects including nasal congestion and dyspnea have been reported during post-market use. Although rare, CSF rhinorrhea has occurred in patients receiving bromocriptine for the treatment of macroadenomas. Patients who developed this effect were typically receiving bromocriptine for tumor recurrence following previous transsphenoidal surgery and/or pituitary radiation. Such patients should be observed closely for signs of CSF rhinorrhea including nasal discharge. Patients should be instructed to notify their physician promptly if nasal discharge develops.
Patients should report any new and troublesome changes in vision during bromocriptine to their prescribers, for potential evaluation. During placebo-controlled clinical trials in patients receiving Cycloset 1.6 mg to 4.8 mg for diabetes, either alone or with a sulfonylurea, amblyopia was reported in 5.3-7.5% of patients in the active treatment groups versus 1.3-2.4% of patients receiving placebo. During clinical trials in Parkinson's disease patients, ophthalmic effects including blepharospasm and unspecified visual disturbance were reported, although the frequencies are unknown. Ophthalmic or otic effects reported during post-market use include visual disturbance (unspecified), blurred vision, and tinnitus. Visual field impairment is a known complication of macroprolactinoma. Effective treatment with bromocriptine leads to a reduction in hyperprolactinemia and often to a resolution of the visual impairment. In some patients, however, a secondary deterioration of visual fields may subsequently develop despite normalized prolactin levels and tumor shrinkage; the secondary deterioration may result from traction on the optic chiasm, which is pulled down in to the partially empty sella. In these cases, the visual field defect may improve on reduction of bromocriptine dosage while there is some elevation of prolactin and some tumor re-expansion. Monitoring of visual fields in patients with macroprolactinoma is recommended so that secondary field loss due to chiasmal herniation can be recognized early, and dosage adjustments can be made when necessary. The relative efficacy of bromocriptine versus surgery in preserving visual fields is unknown; patients with rapidly progressive visual field loss should be evaluated by a neurosurgeon to help decide on the most appropriate therapy.
Impulse control symptoms, such as pathological gambling, hypersexuality, or other intense urges, have been reported during the use of medications that increase dopaminergic tone. Libido increase and hypersexuality have been reported during postmarketing use of bromocriptine. Causality due to dopaminergic agents has not been established; however, in some cases, the urges stopped after the dose was reduced or the drug was discontinued. Practitioners should inquire periodically about new or worsening impulse control symptoms in patients receiving bromocriptine. Likewise, patients should be instructed to report such changes while receiving bromocriptine. Dose reduction or discontinuation should be considered in those who experience these effects. The use of bromocriptine, including for Parkinson's disease or diabetes, is not recommended in patients with impulse control symptoms or compulsive behaviors.
During clinical trials of bromocriptine in Parkinson's disease patients, the following genitourinary (GU) effects were reported although the frequencies are unknown: increased urinary frequency, urinary incontinence, and urinary retention.
When bromocriptine was used as monotherapy to treat patients with type 2 diabetes mellitus, hypoglycemia was reported in 3.7% of bromocriptine-treated patients and 1.3% of placebo-treated patients. In add-on to sulfonylurea trials, the incidence of hypoglycemia was 8.6% in the bromocriptine-treated patients and 5.2% in the placebo-treated patients. Results from a 52-week safety trial showed that the incidence of hypoglycemia was 6.9% in the bromocriptine-treated patients and 5.3% in the placebo-treated patients; severe hypoglycemia was reported in 0.5% of bromocriptine-treated patients and 1% of placebo-treated patients.
During clinical trials evaluation of bromocriptine in acromegalic patients, alopecia was reported in less than 1% of patients. Dermatologic effects reported in patients with Parkinson's disease included mottling of the skin and skin rash (unspecified) although the frequencies are unknown. Allergic skin reactions and alopecia have been reported during post-market use.
A withdrawal or discontinuation syndrome has been associated with the abrupt discontinuation of dopamine agonist medications, such as bromocriptine, in Parkinson's disease patients. Discontinuation symptoms of apathy, anxiety, depression, fatigue, insomnia, sweating, and pain have been reported in patients with Parkinson's disease during dosage tapering or treatment discontinuation; these symptoms generally do not respond to treatment with levodopa. Closely monitor these patients during and after treatment discontinuation; consider if a dosage taper is appropriate. Re-administration at the lowest effective bromocriptine dose may be considered if severe withdrawal symptoms develop. Rarely, neuroleptic malignant syndrome-like symptoms have been reported after dose reduction or discontinuation of bromocriptine in patients with advanced Parkinson's disease or patients with secondary parkinsonism. There have been no reported cases of discontinuation syndromes or neuroleptic malignant syndrome-like symptoms associated with bromocriptine use for the treatment of diabetes mellitus (Cycloset).
Bromocriptine is contraindicated in patients with a known bromocriptine hypersensitivity. The drug is also contraindicated in patients with any other ergot alkaloid hypersensitivity. The tablet formulations may contain lactose. Patients with rare hereditary problems of galactose intolerance, severe lactase deficiency or glucosegalactose malabsorption should not take the tablets.
Discontinuation of bromocriptine in patients with Parkinson's disease should be undertaken gradually whenever possible, even if the patient is to remain on levodopa. Avoid abrupt discontinuation. A symptom complex resembling the neuroleptic malignant syndrome (characterized by elevated temperature, muscular rigidity, altered consciousness, and autonomic instability), with no other obvious etiology, has been reported in association with rapid dose reduction, withdrawal of, or changes in antiparkinsonian therapy. Further, symptoms of apathy, anxiety, depression, fatigue, insomnia, sweating, and pain have been reported during dosage tapering or after discontinuation of dopamine agonists, such as bromocriptine. These symptoms generally do not respond to treatment with levodopa. Inform drug recipients about the potential for withdrawal symptoms prior to stopping bromocriptine, and closely monitor these patients during and after treatment discontinuation. Re-administration at the lowest effective dose may be considered if severe withdrawal symptoms develop.
Bromocriptine is contraindicated in patients with uncontrolled hypertension and should be used cautiously in patients with known cardiac disease or controlled hypertension. Monitor blood pressure, especially during the initial weeks of therapy. If hypertension, severe, progressive, or unremitting headache (with or without visual disturbance), or evidence of CNS toxicity develops during treatment, bromocriptine should be discontinued and the patient should be evaluated promptly. Particular attention should be paid to patients who have recently or are currently been treated with drugs that can alter blood pressure. When bromocriptine is used for the treatment of diabetes mellitus, it is contraindicated in all postpartum patients. For all other indications, bromocriptine is contraindicated in the postpartum period in women with a history of coronary artery disease and other severe cardiovascular conditions unless withdrawal is considered medically contraindicated. If the drug is used in the postpartum period, the patient should be monitored closely. Hypertension has been documented in postpartum patients receiving the drug, sometimes at the initiation of therapy, but often developing in the second week of therapy; seizures have also been reported both with and without the prior development of hypertension; stroke has been reported mostly in postpartum patients whose prenatal and obstetric courses had been uncomplicated. Many of these patients experiencing seizures (including cases of status epilepticus) and/or strokes reported developing a constant and often progressively severe headache hours to days prior to the acute event. Some cases of strokes and seizures were also preceded by visual disturbances (blurred vision, and transient cortical blindness). Cases of acute myocardial infarction (MI) have also been reported. A causal relationship between bromocriptine administration and hypertension, seizures, strokes, and myocardial infarction in postpartum women has not been established. When bromocriptine has been used for the treatment of Type 2 diabetes mellitus, no increase in the risk of cardiovascular events or stroke has been noted vs. placebo.
Symptomatic hypotension and/or orthostatic hypotension can occur in patients treated with bromocriptine for any indication. In postpartum studies, decreases in supine systolic and diastolic pressures of greater than 20 mmHg and 10 mmHg, respectively, have been observed in almost 30% of patients receiving bromocriptine. On occasion, the drop in supine systolic pressure was as much as 50 to 59 mmHg. Hypotensive reactions may occasionally occur and result in reduced alertness, especially in the first days of treatment and with dose titrations. Particular care should be exercised when driving a vehicle or operating machinery. The drug should be used cautiously with other medications known to lower blood pressure such as antihypertensives. Monitoring of blood pressure should be considered, especially during the initial weeks of combined therapy with medications known to affect blood pressure. Hypotension can lead to syncope, falls, and serious injury. Patients should be advised to make slow postural changes and to avoid situations that could predispose to serious injury if syncope was to occur.
Bromocriptine, when used for diabetic therapy, is contraindicated in patients with syncopal migraine (also known as basilar/hemiplegic migraine or basilar-type migraine); other forms of bromocriptine should likely also be avoided in these patients. Patients with syncopal migraine exhibit dramatic intolerance to bromocriptine; the drug increases the likelihood of syncope. The drug renders these patient unable to stand for a length of time (sometimes hours), due a fall in arterial blood pressure. Because bromocriptine is a dopamine receptor agonist, if a patient taking bromocriptine loses consciousness during a migraine, dopamine receptor hypersensitivity is possible.
In patients with severe psychotic disorders, treatment with a dopamine receptor agonist such as bromocriptine may exacerbate the psychosis or may diminish the effectiveness of neuroleptic drugs used to treat the disorder. Therefore, the use of bromocriptine in patients with severe psychotic disorders in not recommended. High doses of bromocriptine may be associated with confusion and mental disturbances. Since parkinsonian patients may manifest mild degrees of dementia, caution should be used when treating such patients. Bromocriptine, when administered alone or concomitantly with levodopa may cause hallucinations (visual or auditory). Hallucinations usually resolve with dosage reduction; occasionally, discontinuation of the drug is required. Rarely, after high doses, hallucinations have persisted for several weeks following discontinuation.
All patients receiving bromocriptine should be cautioned about driving or operating machinery until they know how the drug affects their cognition; somnolence is a reported side effect with bromocriptine use for any indication. Assessment for somnolence is necessary throughout bromocriptine therapy. There have been postmarketing reports of Parkinson's disease patients who have experienced sudden sleep onset during daily activities when taking dopaminergic agents and without pre-existing warning signs in some instances. Sleep disorders (e.g., narcolepsy, sleep apnea), ethanol ingestion, and coadministration with other CNS depressants or interacting medications may increase the risk of suddenly falling asleep while on this medication. Ethanol ingestion may also potentiate other side effects of bromocriptine. Patients may not acknowledge drowsiness or sleepiness until directly questioned about drowsiness or sleepiness during specific activities. If a patient develops significant daytime sleepiness or sudden episodes of falling asleep during activities that require active participation (e.g., conversations, eating, etc.), bromocriptine should ordinarily be discontinued. If a decision is made to continue the drug, patients should be advised to avoid driving or other potentially dangerous activities. There is insufficient information to establish if dose reduction will eliminate sudden episodes of falling asleep.
Some patients receiving medications for Parkinson's disease that increase dopaminergic tone, including bromocriptine, have reported intense and uncontrollable urges to gamble, increased sexual urges, hypersexuality, or other intense urges. Generally, these impulse control symptoms are reversible after the dose is reduced or the drug is discontinued. Practitioners should inquire periodically about new or worsening impulsivity in patients receiving bromocriptine. Likewise, patients should be instructed to report such changes while receiving bromocriptine. Dose reduction or discontinuation should be considered in those who experience these effects.
Bromocriptine is indicated as an adjunct to diet and exercise to improve glycemic control in adult patients with type 2 diabetes mellitus. However, bromocriptine should not be used to treat type 1 diabetes mellitus or diabetic ketoacidosis (DKA), which require insulin therapy.
Patients with diabetes mellitus treated with bromocriptine should be aware that in periods of stress on the body, such as fever or infection, trauma, or surgery, their antidiabetic medication needs may change and that they should notify their health care professional for advice.
Patients with a history of peptic ulcer disease or gastrointestinal (GI) bleeding should be observed carefully during treatment with bromocriptine. Less than 2% of acromegaly patients experience GI bleeding, which is possibly the result of an increase in gastric acid secretion. Cases of severe GI bleeding from peptic ulcers have been reported, some fatal. Although there is no evidence that bromocriptine increases the incidence of peptic ulcers in acromegalic patients, symptoms suggestive of peptic ulcer should be investigated thoroughly and treated appropriately.
Cold-sensitive digital vasospasm, similar to Raynaud's phenomenon, has been observed in some acromegalic patients treated with bromocriptine. The response, should it occur, it can be reversed by reducing the dose of bromocriptine and may be prevented by keeping the fingers warm. Use bromocriptine with caution in patients with peripheral vascular disease. All patients should be advised to report signs and symptoms associated with ergotism such as tingling of fingers, cold fingers or feet, numbness, or the exacerbation of Raynaud's syndrome to their health care providers.
Among patients on bromocriptine, particularly on long-term and high-dose treatment, pleural and pericardial effusions, as well as pleural and pulmonary fibrosis and constrictive pericarditis, have been reported. Patients with unexplained pleuropulmonary disorders should be examined thoroughly and discontinuation of bromocriptine should be considered. In those instances in which Parlodel treatment was terminated, the changes slowly reverted towards normal. In a few patients on bromocriptine, particularly on long-term and high-dose treatment, retroperitoneal fibrosis has been reported. To ensure recognition of retroperitoneal fibrosis at an early reversible stage it is recommended that its manifestations (e.g., back pain, edema of the lower limbs, impaired kidney function) should be watched in this category of patients. Bromocriptine should be withdrawn if fibrotic changes in the retroperitoneum are diagnosed or suspected. Although there have been no confirmed cases of retroperitoneal fibrosis, pulmonary infiltrates, pleural effusion, or pleural thickening among patients treated with bromocriptine for diabetes, these precautions still apply.
Epidemiological studies have shown that patients with Parkinson's disease have a higher risk (2- approximately 6-fold higher) of developing melanoma than the general population. Whether the increased risk observed was due to Parkinson's disease or other factors, such as drugs used to treat Parkinson's disease, is unclear. For the reasons stated above, patients and providers are advised to monitor for melanomas frequently and on a regular basis when using bromocriptine for any indication. Ideally, periodic skin examinations should be performed by appropriately qualified individuals (e.g., dermatologists).
Visual field impairment is a known complication of macroprolactinoma. Effective treatment with bromocriptine leads to a reduction in hyperprolactinemia and often to a resolution of the visual field impairment. In some patients, however, a secondary deterioration of visual fields may subsequently develop despite normalized prolactin levels and tumor shrinkage, which may result from traction on the optic chiasm which is pulled down into the now partially empty sella. In these cases, the visual field defect may improve on reduction of bromocriptine dosage while there is some elevation of prolactin and some tumor re-expansion. Monitoring of visual fields in patients with macroprolactinoma is therefore recommended for an early recognition of secondary field loss due to chiasmal herniation and adaptation of drug dosage. The relative efficacy of bromocriptine versus surgery in preserving visual fields is not known. Patients with rapidly progressive visual impairment or visual field loss should be evaluated by a neurosurgeon to help decide on the most appropriate therapy.
A few cases of cerebrospinal fluid rhinorrhea have been reported in patients receiving bromocriptine for treatment of large prolactin-secreting adenomas. This has occurred rarely, usually only in patients who have received previous transsphenoidal surgery, pituitary radiation therapy, or both, and who were receiving bromocriptine for tumor recurrence. It may also occur in previously untreated patients whose tumor extends into the sphenoid sinus. Such patients should be observed closely for signs of CSF rhinorrhea including nasal discharge. Patients should be instructed to notify their physician promptly for evaluation if persistent watery nasal discharge develops.
Use bromocriptine with caution in patients with hepatic disease. The safety and efficacy of bromocriptine in those with hepatic disease have not been evaluated. Given the extensive hepatic metabolism of the drug, it should be anticipated that elevated bromocriptine levels may occur in the presence of altered hepatic function.
The safety and efficacy of bromocriptine in those with renal disease have not been evaluated and caution is recommended in the absence of study data. Given the minimal excretion of drug metabolites by the kidney, renal impairment is not likely to significantly impact drug concentrations.
In patients being treated for hyperprolactinemia, bromocriptine should be withdrawn when pregnancy is diagnosed. In the event that bromocriptine is reinstituted to control a rapidly expanding macroadenoma and a patient experiences a hypertensive disorder of pregnancy, the benefit of continuing the drug must be weighed against the possible risk of its use during a hypertensive disorder of pregnancy. When bromocriptine is being used to treat acromegaly, prolactinoma, or Parkinson's disease in patients who subsequently become pregnant, a decision should be made whether the therapy continues to be medically necessary or can be withdrawn. If it is continued, the drug should be withdrawn in those who may experience hypertensive disorders of pregnancy (including eclampsia, preeclampsia, or pregnancy-induced hypertension) unless withdrawal of bromocriptine is considered to be medically contraindicated. If hypertension, severe, progressive, or unremitting headache (with or without visual disturbance), or evidence of CNS toxicity develops, drug therapy should be discontinued and the patient should be evaluated promptly. Studies in pregnant women and data from 4 different multicenter surveillance programs suggest that bromocriptine does not increase the risk of congenital abnormalities when administered during pregnancy. Data concerning 1,276 pregnancies in women taking bromocriptine for endocrine purposes has been collected. In the majority of cases, the drug was discontinued within 8 weeks into pregnancy (mean 28.7 days); however, 8 patients received the drug continuously throughout pregnancy. The mean daily dose for all patients was 5.8 mg (range 1 to 40 mg per day). The incidence of birth defects in the general population ranges from 2 to 4.5%. The incidence of birth defects in 1,109 live births from patients receiving bromocriptine was 3.3%. There is no suggestion that bromocriptine contributed to the type or incidence of birth defects observed. There are also precautions for the use of bromocriptine in the treatment of type 2 diabetes mellitus (T2DM) during pregnancy. However, prolonged experience with bromocriptine use during pregnancy for other indications over several decades, based on data from published clinical trials, case reports, and epidemiological studies, have not established a drug-associated risk for major birth defects, miscarriage, or adverse maternal or fetal outcomes. Furthermore, only a trace amount of bromocriptine was shown to be transported across the placenta in vitro in a published ex vivo human placental perfusion model. In animal reproduction studies in which bromocriptine mesylate was administered orally during the period of organogenesis, increased prenatal mortality occurred in rats and rabbits at maternally toxic dosages that were more than 24-times the human dose of 4.8 mg/day based on body surface area. No adverse developmental outcomes were observed in monkeys administered bromocriptine mesylate orally during various periods of gestation at doses up to 10-times a human dose of 4.8 mg daily.There are risks to the mother and fetus associated with poorly controlled diabetes in pregnancy. Bromocriptine is not a preferred medication for the treatment of T2DM during pregnancy. The American College of Obstetricians and Gynecologists (ACOG) and the American Diabetes Association (ADA) continue to recommend human insulin as the standard of care in pregnant women with diabetes mellitus and gestational diabetes mellitus (GDM) requiring medical therapy; insulin does not cross the placenta.
Since pregnancy is often the therapeutic objective in many hyperprolactinemic patients presenting with amenorrhea/galactorrhea and hypogonadism (infertility), a careful assessment of the pituitary is essential to detect the presence of a prolactin-secreting adenoma. Contraception requirements are advised for patients not seeking pregnancy, or those harboring large adenomas. These individuals should use contraceptive measures, other than oral contraceptives, during treatment with bromocriptine. Since pregnancy may occur prior to reinitiation of menses, pregnancy testing is recommended at least every 4 weeks during the amenorrheic period, and, once menses are reinitiated, every time a patient misses a menstrual period. Treatment with bromocriptine should be discontinued as soon as pregnancy has been established. Patients must be monitored closely throughout pregnancy for signs and symptoms that may signal the enlargement of a previously undetected or existing prolactin-secreting tumor. Discontinuation of Parlodel treatment in patients with known macroadenomas has been associated with rapid regrowth of tumor and increase in serum prolactin in most cases.
Due to the fact that it inhibits lactation, bromocriptine should not be used during breast-feeding, and bromocriptine use for hyperprolactinemia is contraindicated during the postpartum period in those individuals with a history of coronary artery disease and other severe cardiovascular conditions unless withdrawal is considered medically contraindicated; if use is continued, the postpartum individual must be closely monitored. The bromocriptine indication for lactation inhibition was withdrawn by the FDA in 1994. Bromocriptine use for the treatment of type 2 diabetes mellitus (T2DM) is contraindicated during breast-feeding and in all patients during the postpartum period. Serious and life-threatening adverse reactions including hypertension, myocardial infarction, seizures, stroke, and psychosis have been reported during the postpartum period in individuals who were administered bromocriptine for inhibition of lactation. These risks may be higher in postpartum patients with cardiovascular disease. If bromocriptine for treatment of T2DM is discontinued and blood glucose is not controlled on diet and exercise alone, insulin therapy or alternate oral hypoglycemics may be considered for the lactating individual. Possible alternative oral hypoglycemics for consideration include metformin monotherapy, glyburide, or acarbose. If any oral hypoglycemics are used during breast-feeding, the nursing infant should be monitored for signs of hypoglycemia, such as increased fussiness or somnolence.
The use of bromocriptine for the treatment of prolactin-secreting adenomas in pediatric patients 11 to under 16 years of age is supported by evidence from well-controlled trials in adults, with additional data in a limited number (n=14) of children and adolescents 11 to 15 years of age with prolactin-secreting pituitary macro- and microadenomas who have been treated with bromocriptine. Of the 14 reported patients, 9 had successful outcomes, 3 partial responses, and 2 failed to respond to bromocriptine treatment. Chronic hypopituitarism complicated macroadenoma treatment in 5 of the responders, both in patients receiving bromocriptine alone and in those who received bromocriptine in combination with surgical treatment and/or pituitary irradiation. No data are available for bromocriptine use in pediatric patients less than 8 years of age. A single 8-year-old patient treated with bromocriptine for a prolactin-secreting pituitary macroadenoma has been reported without therapeutic response. The safety and effectiveness of bromocriptine for other indications, including type 2 diabetes mellitus, have not been established in pediatric patients less than 18 years old.
For the treatment of idiopathic or postencephalitic Parkinson's disease:
Oral dosage:
Adults: 1.25 mg PO twice daily, initially. May increase the dose by 2.5 mg/day every 2 to 4 weeks based on clinical response and tolerability. Use the lowest effective dose. Usual dose: 10 to 30 mg/day. Max: 30 mg/day. Data are insufficient to evaluate potential benefit from treating newly diagnosed Parkinson's disease with bromocriptine. Persons unresponsive to levodopa are poor candidates for bromocriptine therapy.
For the treatment of acromegaly:
Oral dosage:
Adults: Initially, 1.25 mg to 2.5 mg PO once daily at bedtime (with food) for 3 days. May increase by 1.25 to 2.5 mg/day at 3 to 7 day intervals until the optimal therapeutic effect occurs. Typical maintenance dosage is 20 mg to 30 mg/day, in divided doses (with food); commonly divided every 6 hours. Max: 100 mg/day PO, in divided doses. In the literature, doses rarely exceed 60 mg/day total. Bromocriptine, alone or as adjunctive therapy with pituitary irradiation or surgery, reduces serum growth hormone by 50% or more in approximately half of patients treated, although not usually to normal levels. Patients treated with pituitary irradiation should be withdrawn from bromocriptine on a yearly basis to assess both the clinical effects of radiation and the effects of drug therapy. Usually a 4- to 8-week withdrawal period is adequate. Recurrence of the signs/symptoms or increases in growth hormone indicate an active disease process and further courses of bromocriptine should be considered.
Children* and Adolescents* 7 years and older: Safety and efficacy have not been established; not FDA-approved. Suggested off-label dosing is available. 1.25 mg PO once daily at bedtime (with food) is a usual starting dose. The starting dose should be titrated in response to Growth Hormone levels. The daily dose is given in divided doses (usually every 6 hours), with food. Max for pediatric patients 7 to 12 years is 10 mg/day PO. Max for adolescents 13 to 17 years: 20 mg/day PO.
For the treatment of hyperprolactinemia-associated dysfunctions, including amenorrhea with or without galactorrhea, hypogonadism, or infertility, and prolactin-secreting pituitary adenoma:
-for the treatment of hyperprolactinemia-associated dysfunctions, including amenorrhea with or without galactorrhea, hypogonadism, or infertility:
Oral dosage:
Adults: 1.25 to 2.5 mg PO once daily, initially. May increase dose by 2.5 mg/day every 2 to 7 days until an optimal therapeutic response is achieved. Dose range: 2.5 to 15 mg/day.
-for the treatment of prolactin-secreting pituitary adenoma:
Oral dosage:
Adults: 1.25 to 2.5 mg PO once daily, initially. May increase dose by 2.5 mg/day every 2 to 7 days until an optimal therapeutic response is achieved. Dose range: 2.5 to 15 mg/day.
Adolescents 16 to 17 years: 1.25 to 2.5 mg PO once daily, initially. May increase dose by 2.5 mg/day every 2 to 7 days until an optimal therapeutic response is achieved. Dose range: 2.5 to 15 mg/day.
Children and Adolescents 11 to 15 years: 1.25 to 2.5 mg PO once daily, initially. May increase dose by up to 2.5 mg/day every 2 to 7 days until an optimal therapeutic response is achieved. Dose range: 2.5 to 10 mg/day. Of the studied patients (n = 14), 9 had successful outcomes, 3 partial responses, and 2 patients did not respond.
For the treatment of type 2 diabetes mellitus as an adjunct to diet and exercise:
Oral dosage (Cycloset only):
Adults: 0.8 mg PO once daily in the morning within 2 hours of waking, initially. May increase dose by 0.8 mg/day every 7 days if needed. Usual dose: 1.6 to 4.8 mg/day. Max: 4.8 mg/day. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. There is limited efficacy data in combination with thiazolidinediones; efficacy has not been confirmed in combination with insulin. Guidelines do not consider bromocriptine a common medication for use for type 2 diabetes, except when patient specific factors are considered; considerations include modest efficacy, potential for drug interactions, treatment cost, and frequent side effects, including nausea.
For the treatment of mastalgia* associated with premenstrual syndrome (PMS)*:
Oral dosage:
Adult premenopausal females: Safety and efficacy not established; not a first-line treatment. 2.5 mg PO twice daily, given cyclically, has been used in 2 randomized controlled clinical trials with effectiveness better than placebo. Therapy is initiated 10 to 14 days prior to menses and discontinued when menses begins. The drug is rarely used for cyclic mastalgia, because frequent and intolerable adverse drug effects (ADRs), and potential severity of ADRs, outweigh the benefits for this indication in most women. The evidence, per one review, is considered of very low quality per applied GRADE criteria.
For the adjunct treatment of neuroleptic malignant syndrome* (NMS*):
Oral dosage:
Adults: 2.5 mg to 5 mg PO every 8 hours, in conjunction with dantrolene or other treatments, is the listed dosage in treatment algorithms for NMS.
Maximum Dosage Limits:
-Adults
4.8 mg/day PO for type 2 diabetes mellitus; usual maximum 30 mg/day PO for Parkinson's disease, hyperprolactinemic conditions, or prolactin-secreting adenomas. While maximum is 100 mg/day for acromegaly, patients rarely exceed 60 mg/day PO.
-Geriatric
4.8 mg/day PO for type 2 diabetes mellitus; usual maximum 30 mg/day PO for Parkinson's disease, hyperprolactinemic conditions, or prolactin-secreting adenomas. While maximum is 100 mg/day for acromegaly, patients rarely exceed 60 mg/day PO.
-Adolescents
16 years and older: 15 mg/day for hyperprolactinemic indications, some off-label data suggest 20 mg/day PO for selected conditions; safety and efficacy not established for diabetes.
13 to 15 years: 10 mg/day for prolactin-secreting pituitary adenoma, some off-label data suggest 20 mg/day PO; safety and efficacy not established for diabetes or other indications.
-Children
11 to 12 years: 10 mg/day PO for selected indications.
7 to 10 years: Safety and efficacy have not been established; some off-label data suggest 5 mg/day PO for selected indications.
-Infants
Safety and efficacy have not been established.
Patients with Hepatic Impairment Dosing
No dosage recommendations are available as no pharmacokinetic studies have been conducted. Because bromocriptine is predominantly metabolized by the liver, caution should be used in patients with hepatic impairment.
Patients with Renal Impairment Dosing
Caution is recommended due to lack of specific study in these patients. The kidney is a minor pathway (6%) for elimination of bromocriptine; the drug is almost completely excreted via metabolism and thus renal impairment may not have a significant impact on concentrations of bromocriptine and its metabolites.
*non-FDA-approved indication
Acetaminophen; Aspirin, ASA; Caffeine: (Minor) Bromocriptine is highly bound (more than 90%) to serum proteins. Therefore, it may increase the unbound fraction of other highly protein-bound medications (e.g., aspirin and other salicylates), which may alter their effectiveness and risk for side effects.
Acetaminophen; Aspirin: (Minor) Bromocriptine is highly bound (more than 90%) to serum proteins. Therefore, it may increase the unbound fraction of other highly protein-bound medications (e.g., aspirin and other salicylates), which may alter their effectiveness and risk for side effects.
Acetaminophen; Aspirin; Diphenhydramine: (Minor) Bromocriptine is highly bound (more than 90%) to serum proteins. Therefore, it may increase the unbound fraction of other highly protein-bound medications (e.g., aspirin and other salicylates), which may alter their effectiveness and risk for side effects.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) The combination of bromocriptine with phenylephrine may cause headache, tachycardia, other cardiovascular abnormalities, seizures, and other serious effects. Concurrent use of bromocriptine and phenylephrine should be approached with caution. One case report documented worsening headache, hypertension, premature ventricular complexes, and ventricular tachycardia in a post-partum patient receiving bromocriptine for lactation suppression who was subsequently prescribed acetaminophen; dichloralphenazone; isometheptene for a headache. A second case involved a post-partum patient receiving bromocriptine who was later prescribed phenylpropanolamine; guaifenesin and subsequently developed hypertension, tachycardia, seizures, and cerebral vasospasm.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) One case report documented worsening headache, hypertension, premature ventricular complexes, and ventricular tachycardia in a post-partum patient receiving bromocriptine for lactation suppression who was subsequently prescribed acetaminophen; dichloralphenazone; isometheptene for a headache. A second case involved a post-partum patient receiving bromocriptine who was later prescribed phenylpropanolamine; guaifenesin and subsequently developed hypertension, tachycardia, seizures, and cerebral vasospasm. Also, ergot alkaloids, which are chemically related to bromocriptine, should not be administered with other vasoconstrictors. Therefore, until more data become available, concurrent use of bromocriptine and some sympathomimetics such as vasopressors (e.g., norepinephrine, dopamine, phenylephrine), cocaine, epinephrine, phenylpropanolamine, ephedra, ma huang, ephedrine, pseudoephedrine, amphetamines, and phentermine should be approached with caution.
Acetaminophen; Chlorpheniramine; Phenylephrine : (Moderate) The combination of bromocriptine with phenylephrine may cause headache, tachycardia, other cardiovascular abnormalities, seizures, and other serious effects. Concurrent use of bromocriptine and phenylephrine should be approached with caution. One case report documented worsening headache, hypertension, premature ventricular complexes, and ventricular tachycardia in a post-partum patient receiving bromocriptine for lactation suppression who was subsequently prescribed acetaminophen; dichloralphenazone; isometheptene for a headache. A second case involved a post-partum patient receiving bromocriptine who was later prescribed phenylpropanolamine; guaifenesin and subsequently developed hypertension, tachycardia, seizures, and cerebral vasospasm.
Acetaminophen; Dextromethorphan; Guaifenesin; Phenylephrine: (Moderate) The combination of bromocriptine with phenylephrine may cause headache, tachycardia, other cardiovascular abnormalities, seizures, and other serious effects. Concurrent use of bromocriptine and phenylephrine should be approached with caution. One case report documented worsening headache, hypertension, premature ventricular complexes, and ventricular tachycardia in a post-partum patient receiving bromocriptine for lactation suppression who was subsequently prescribed acetaminophen; dichloralphenazone; isometheptene for a headache. A second case involved a post-partum patient receiving bromocriptine who was later prescribed phenylpropanolamine; guaifenesin and subsequently developed hypertension, tachycardia, seizures, and cerebral vasospasm.
Acetaminophen; Dextromethorphan; Guaifenesin; Pseudoephedrine: (Moderate) One case report documented worsening headache, hypertension, premature ventricular complexes, and ventricular tachycardia in a post-partum patient receiving bromocriptine for lactation suppression who was subsequently prescribed acetaminophen; dichloralphenazone; isometheptene for a headache. A second case involved a post-partum patient receiving bromocriptine who was later prescribed phenylpropanolamine; guaifenesin and subsequently developed hypertension, tachycardia, seizures, and cerebral vasospasm. Also, ergot alkaloids, which are chemically related to bromocriptine, should not be administered with other vasoconstrictors. Therefore, until more data become available, concurrent use of bromocriptine and some sympathomimetics such as vasopressors (e.g., norepinephrine, dopamine, phenylephrine), cocaine, epinephrine, phenylpropanolamine, ephedra, ma huang, ephedrine, pseudoephedrine, amphetamines, and phentermine should be approached with caution.
Acetaminophen; Dextromethorphan; Phenylephrine: (Moderate) The combination of bromocriptine with phenylephrine may cause headache, tachycardia, other cardiovascular abnormalities, seizures, and other serious effects. Concurrent use of bromocriptine and phenylephrine should be approached with caution. One case report documented worsening headache, hypertension, premature ventricular complexes, and ventricular tachycardia in a post-partum patient receiving bromocriptine for lactation suppression who was subsequently prescribed acetaminophen; dichloralphenazone; isometheptene for a headache. A second case involved a post-partum patient receiving bromocriptine who was later prescribed phenylpropanolamine; guaifenesin and subsequently developed hypertension, tachycardia, seizures, and cerebral vasospasm.
Acetaminophen; Dextromethorphan; Pseudoephedrine: (Moderate) One case report documented worsening headache, hypertension, premature ventricular complexes, and ventricular tachycardia in a post-partum patient receiving bromocriptine for lactation suppression who was subsequently prescribed acetaminophen; dichloralphenazone; isometheptene for a headache. A second case involved a post-partum patient receiving bromocriptine who was later prescribed phenylpropanolamine; guaifenesin and subsequently developed hypertension, tachycardia, seizures, and cerebral vasospasm. Also, ergot alkaloids, which are chemically related to bromocriptine, should not be administered with other vasoconstrictors. Therefore, until more data become available, concurrent use of bromocriptine and some sympathomimetics such as vasopressors (e.g., norepinephrine, dopamine, phenylephrine), cocaine, epinephrine, phenylpropanolamine, ephedra, ma huang, ephedrine, pseudoephedrine, amphetamines, and phentermine should be approached with caution.
Acetaminophen; Guaifenesin; Phenylephrine: (Moderate) The combination of bromocriptine with phenylephrine may cause headache, tachycardia, other cardiovascular abnormalities, seizures, and other serious effects. Concurrent use of bromocriptine and phenylephrine should be approached with caution. One case report documented worsening headache, hypertension, premature ventricular complexes, and ventricular tachycardia in a post-partum patient receiving bromocriptine for lactation suppression who was subsequently prescribed acetaminophen; dichloralphenazone; isometheptene for a headache. A second case involved a post-partum patient receiving bromocriptine who was later prescribed phenylpropanolamine; guaifenesin and subsequently developed hypertension, tachycardia, seizures, and cerebral vasospasm.
Acetaminophen; Phenylephrine: (Moderate) The combination of bromocriptine with phenylephrine may cause headache, tachycardia, other cardiovascular abnormalities, seizures, and other serious effects. Concurrent use of bromocriptine and phenylephrine should be approached with caution. One case report documented worsening headache, hypertension, premature ventricular complexes, and ventricular tachycardia in a post-partum patient receiving bromocriptine for lactation suppression who was subsequently prescribed acetaminophen; dichloralphenazone; isometheptene for a headache. A second case involved a post-partum patient receiving bromocriptine who was later prescribed phenylpropanolamine; guaifenesin and subsequently developed hypertension, tachycardia, seizures, and cerebral vasospasm.
Acetaminophen; Pseudoephedrine: (Moderate) One case report documented worsening headache, hypertension, premature ventricular complexes, and ventricular tachycardia in a post-partum patient receiving bromocriptine for lactation suppression who was subsequently prescribed acetaminophen; dichloralphenazone; isometheptene for a headache. A second case involved a post-partum patient receiving bromocriptine who was later prescribed phenylpropanolamine; guaifenesin and subsequently developed hypertension, tachycardia, seizures, and cerebral vasospasm. Also, ergot alkaloids, which are chemically related to bromocriptine, should not be administered with other vasoconstrictors. Therefore, until more data become available, concurrent use of bromocriptine and some sympathomimetics such as vasopressors (e.g., norepinephrine, dopamine, phenylephrine), cocaine, epinephrine, phenylpropanolamine, ephedra, ma huang, ephedrine, pseudoephedrine, amphetamines, and phentermine should be approached with caution.
Acrivastine; Pseudoephedrine: (Moderate) One case report documented worsening headache, hypertension, premature ventricular complexes, and ventricular tachycardia in a post-partum patient receiving bromocriptine for lactation suppression who was subsequently prescribed acetaminophen; dichloralphenazone; isometheptene for a headache. A second case involved a post-partum patient receiving bromocriptine who was later prescribed phenylpropanolamine; guaifenesin and subsequently developed hypertension, tachycardia, seizures, and cerebral vasospasm. Also, ergot alkaloids, which are chemically related to bromocriptine, should not be administered with other vasoconstrictors. Therefore, until more data become available, concurrent use of bromocriptine and some sympathomimetics such as vasopressors (e.g., norepinephrine, dopamine, phenylephrine), cocaine, epinephrine, phenylpropanolamine, ephedra, ma huang, ephedrine, pseudoephedrine, amphetamines, and phentermine should be approached with caution.
Adagrasib: (Major) When bromocriptine is used for diabetes, avoid coadministration with adagrasib ensuring adequate washout before initiating bromocriptine. Use this combination with caution in patients receiving bromocriptine for other indications. Concurrent use may significantly increase bromocriptine concentrations. Bromocriptine is extensively metabolized in the liver via CYP3A; adagrasib is a strong inhibitor of CYP3A.
Almotriptan: (Major) There are limited clinical trial data supporting the safety of giving a serotonin-receptor agonist ("triptan") with bromocriptine, an ergot derivative. The concomitant use of these agents with bromocriptine should be avoided. There is concern that prolonged vasospastic reactions, hypertension, tachycardia, or other side effects may occur.
Aminosalicylate sodium, Aminosalicylic acid: (Minor) Bromocriptine is highly bound (more than 90%) to serum proteins. Therefore, it may increase the unbound fraction of other highly protein-bound medications (e.g., aspirin and other salicylates), which may alter their effectiveness and risk for side effects.
Amoxicillin; Clarithromycin; Omeprazole: (Major) When bromocriptine is used for diabetes, avoid coadministration with clarithromycin ensuring adequate washout before initiating bromocriptine. Use this combination with caution in patients receiving bromocriptine for other indications. Concurrent use may significantly increase bromocriptine concentrations. Bromocriptine is extensively metabolized in the liver via CYP3A4; clarithromycin is a strong inhibitor of CYP3A4.
Amphetamine: (Moderate) Concurrent use of bromocriptine and some sympathomimetics such as amphetamines should be approached with caution. One case report documented worsening headache, hypertension, premature ventricular complexes, and ventricular tachycardia in a post-partum patient receiving bromocriptine for lactation suppression who was subsequently prescribed an isometheptene-containing medication for a headache. A second case involved a post-partum patient receiving bromocriptine who was later prescribed a phenylpropanolamine-expectorant combination and subsequently developed hypertension, tachycardia, seizures, and cerebral vasospasm.
Amphetamine; Dextroamphetamine Salts: (Moderate) Concurrent use of bromocriptine and some sympathomimetics such as amphetamines should be approached with caution. One case report documented worsening headache, hypertension, premature ventricular complexes, and ventricular tachycardia in a post-partum patient receiving bromocriptine for lactation suppression who was subsequently prescribed an isometheptene-containing medication for a headache. A second case involved a post-partum patient receiving bromocriptine who was later prescribed a phenylpropanolamine-expectorant combination and subsequently developed hypertension, tachycardia, seizures, and cerebral vasospasm.
Amphetamine; Dextroamphetamine: (Moderate) Concurrent use of bromocriptine and some sympathomimetics such as amphetamines should be approached with caution. One case report documented worsening headache, hypertension, premature ventricular complexes, and ventricular tachycardia in a post-partum patient receiving bromocriptine for lactation suppression who was subsequently prescribed an isometheptene-containing medication for a headache. A second case involved a post-partum patient receiving bromocriptine who was later prescribed a phenylpropanolamine-expectorant combination and subsequently developed hypertension, tachycardia, seizures, and cerebral vasospasm.
Apalutamide: (Moderate) Caution and close monitoring are advised if bromocriptine and apalutamide are used together. Concurrent use may decrease the plasma concentrations of bromocriptine resulting in loss of efficacy. Bromocriptine is extensively metabolized by the liver via CYP3A4; apalutamide is a strong inducer of CYP3A4.
Aprepitant, Fosaprepitant: (Major) When bromocriptine is used for diabetes, do not exceed a dose of 1.6 mg once daily during concomitant use of aprepitant, fosaprepitant. Use this combination with caution in patients receiving bromocriptine for other indications. Concurrent use may increase bromocriptine concentrations. Bromocriptine is extensively metabolized in the liver via CYP3A4; aprepitant, when administered as a 3-day oral regimen (125 mg/80 mg/80 mg), is a moderate CYP3A4 inhibitor. As a single 125 mg or 40 mg oral dose, the inhibitory effect of aprepitant on CYP3A4 is weak. After administration, fosaprepitant is rapidly converted to aprepitant and shares many of the same drug interactions. However, as a single 150 mg intravenous dose, fosaprepitant only weakly inhibits CYP3A4 for a duration of 2 days; there is no evidence of CYP3A4 induction. Administration of bromocriptine with a moderate inhibitor of CYP3A4 increased the bromocriptine mean AUC and Cmax by 3.7-fold and 4.6-fold, respectively.
Aripiprazole: (Moderate) The effectiveness of bromocriptine may be reduced by most of the atypical antipsychotics, via their action as dopamine antagonists. Monitor the patient for reduced response to bromocriptine. The atypical antipsychotics elevate prolactin to various degrees. Atypical antipsychotics may also aggravate diabetes mellitus and cause metabolic changes including hyperglycemia; use caution if bromocriptine is taken for diabetes. If bromocriptine is taken for diabetes, monitor for worsening glycemic control.
Articaine; Epinephrine: (Moderate) One case report documented worsening headache, hypertension, premature ventricular complexes, and ventricular tachycardia in a post-partum patient receiving bromocriptine for lactation suppression who was subsequently prescribed acetaminophen; dichloralphenazone; isometheptene for a headache. A second case involved a post-partum patient receiving bromocriptine who was later prescribed phenylpropanolamine; guaifenesin and subsequently developed hypertension, tachycardia, seizures, and cerebral vasospasm. Also, ergot alkaloids, which are chemically related to bromocriptine, should not be administered with other vasoconstrictors. Therefore, until more data become available, concurrent use of bromocriptine and some sympathomimetics such as vasopressors (e.g., norepinephrine, dopamine, phenylephrine), cocaine, epinephrine, phenylpropanolamine, ephedra, ma huang, ephedrine, pseudoephedrine, amphetamines, and phentermine should be approached with caution.
Asenapine: (Moderate) The effectiveness of bromocriptine may be reduced by most of the atypical antipsychotics, via their action as dopamine antagonists. Monitor the patient for reduced response to bromocriptine. The atypical antipsychotics elevate prolactin to various degrees. Atypical antipsychotics may also aggravate diabetes mellitus and cause metabolic changes including hyperglycemia; use caution if bromocriptine is taken for diabetes. If bromocriptine is taken for diabetes, monitor for worsening glycemic control.
Aspirin, ASA: (Minor) Bromocriptine is highly bound (more than 90%) to serum proteins. Therefore, it may increase the unbound fraction of other highly protein-bound medications (e.g., aspirin and other salicylates), which may alter their effectiveness and risk for side effects.
Aspirin, ASA; Butalbital; Caffeine: (Moderate) Caution and close monitoring are advised if bromocriptine and butalbital are used together. Concurrent use may decrease the plasma concentrations of bromocriptine resulting in loss of efficacy. Bromocriptine is extensively metabolized by the liver via CYP3A4; butalbital is a moderate inducer of CYP3A4. (Minor) Bromocriptine is highly bound (more than 90%) to serum proteins. Therefore, it may increase the unbound fraction of other highly protein-bound medications (e.g., aspirin and other salicylates), which may alter their effectiveness and risk for side effects.
Aspirin, ASA; Caffeine: (Minor) Bromocriptine is highly bound (more than 90%) to serum proteins. Therefore, it may increase the unbound fraction of other highly protein-bound medications (e.g., aspirin and other salicylates), which may alter their effectiveness and risk for side effects.
Aspirin, ASA; Caffeine; Orphenadrine: (Minor) Bromocriptine is highly bound (more than 90%) to serum proteins. Therefore, it may increase the unbound fraction of other highly protein-bound medications (e.g., aspirin and other salicylates), which may alter their effectiveness and risk for side effects.
Aspirin, ASA; Carisoprodol; Codeine: (Minor) Bromocriptine is highly bound (more than 90%) to serum proteins. Therefore, it may increase the unbound fraction of other highly protein-bound medications (e.g., aspirin and other salicylates), which may alter their effectiveness and risk for side effects.
Aspirin, ASA; Citric Acid; Sodium Bicarbonate: (Minor) Bromocriptine is highly bound (more than 90%) to serum proteins. Therefore, it may increase the unbound fraction of other highly protein-bound medications (e.g., aspirin and other salicylates), which may alter their effectiveness and risk for side effects.
Aspirin, ASA; Dipyridamole: (Minor) Bromocriptine is highly bound (more than 90%) to serum proteins. Therefore, it may increase the unbound fraction of other highly protein-bound medications (e.g., aspirin and other salicylates), which may alter their effectiveness and risk for side effects.
Aspirin, ASA; Omeprazole: (Minor) Bromocriptine is highly bound (more than 90%) to serum proteins. Therefore, it may increase the unbound fraction of other highly protein-bound medications (e.g., aspirin and other salicylates), which may alter their effectiveness and risk for side effects.
Aspirin, ASA; Oxycodone: (Minor) Bromocriptine is highly bound (more than 90%) to serum proteins. Therefore, it may increase the unbound fraction of other highly protein-bound medications (e.g., aspirin and other salicylates), which may alter their effectiveness and risk for side effects.
Atazanavir: (Major) When bromocriptine is used for diabetes, avoid coadministration with atazanavir ensuring adequate washout before initiating bromocriptine. Use this combination with caution in patients receiving bromocriptine for other indications. Concurrent use may significantly increase bromocriptine concentrations. Bromocriptine is extensively metabolized in the liver via CYP3A4; atazanavir is a strong inhibitor of CYP3A4.
Atazanavir; Cobicistat: (Major) When bromocriptine is used for diabetes, avoid coadministration with atazanavir ensuring adequate washout before initiating bromocriptine. Use this combination with caution in patients receiving bromocriptine for other indications. Concurrent use may significantly increase bromocriptine concentrations. Bromocriptine is extensively metabolized in the liver via CYP3A4; atazanavir is a strong inhibitor of CYP3A4. (Major) When bromocriptine is used for diabetes, avoid coadministration with cobicistat ensuring adequate washout before initiating bromocriptine. Use this combination with caution in patients receiving bromocriptine for other indications. Concurrent use may significantly increase bromocriptine concentrations. Bromocriptine is extensively metabolized in the liver via CYP3A4; cobicistat is a strong inhibitor of CYP3A4.
atypical antipsychotic: (Moderate) The effectiveness of bromocriptine may be reduced by most of the atypical antipsychotics, via their action as dopamine antagonists. Monitor the patient for reduced response to bromocriptine. The atypical antipsychotics elevate prolactin to various degrees. Atypical antipsychotics may also aggravate diabetes mellitus and cause metabolic changes including hyperglycemia; use caution if bromocriptine is taken for diabetes. If bromocriptine is taken for diabetes, monitor for worsening glycemic control.
Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Moderate) Theoretically, concurrent use of methylene blue and ergot alkaloid derivatives such as bromocriptine may increase the risk of serotonin syndrome. Methylene blue is a thiazine dye that is also a potent, reversible inhibitor of the enzyme responsible for the catabolism of serotonin in the brain (MAO-A) and ergot alkaloids increase central serotonin effects. Cases of serotonin syndrome have been reported, primarily following administration of standard infusions of methylene blue (1 to 8 mg/kg) as a visualizing agent in parathyroid surgery, in patients receiving selective serotonin reuptake inhibitors, serotonin/norepinephrine reuptake inhibitors, or clomipramine. It is not known if patients receiving other serotonergic psychiatric agents with intravenous methylene blue are at a comparable risk or if methylene blue administered by other routes (e.g., orally, local injection) or in doses less than 1 mg/kg IV can produce a similar outcome. Published interaction reports between intravenously administered methylene blue and serotonergic psychiatric agents have documented symptoms including lethargy, confusion, delirium, agitation, aggression, obtundation, myoclonus, expressive aphasia, hypertonia, pyrexia, elevated blood pressure, seizures, and/or coma. Serotonin syndrome is characterized by rapid development of various symptoms such as hyperthermia, hypertension, myoclonus, rigidity, hyperhidrosis, incoordination, diarrhea, mental status changes (e.g., confusion, delirium, or coma), and in rare cases, death. (Minor) Bromocriptine is highly bound (more than 90%) to serum proteins. Therefore, it may increase the unbound fraction of other highly protein-bound medications (e.g., aspirin and other salicylates), which may alter their effectiveness and risk for side effects.
Benzphetamine: (Moderate) Concurrent use of bromocriptine and some sympathomimetics such as amphetamines should be approached with caution. One case report documented worsening headache, hypertension, premature ventricular complexes, and ventricular tachycardia in a post-partum patient receiving bromocriptine for lactation suppression who was subsequently prescribed an isometheptene-containing medication for a headache. A second case involved a post-partum patient receiving bromocriptine who was later prescribed a phenylpropanolamine-expectorant combination and subsequently developed hypertension, tachycardia, seizures, and cerebral vasospasm.
Berotralstat: (Major) When bromocriptine is used for diabetes, do not exceed a dose of 1.6 mg once daily during concomitant use of berotralstat. Use this combination with caution in patients receiving bromocriptine for other indications. Concurrent use may increase bromocriptine concentrations. Bromocriptine is extensively metabolized in the liver via CYP3A4; berotralstat is a moderate inhibitor of CYP3A4. Coadministration with another moderate CYP3A4 inhibitor increased bromocriptine exposure by 2.8-fold.
Bexarotene: (Moderate) Caution and close monitoring are advised if bromocriptine and bexarotene are used together. Concurrent use may decrease the plasma concentrations of bromocriptine resulting in loss of efficacy. Bromocriptine is extensively metabolized by the liver via CYP3A4; bexarotene is a moderate inducer of CYP3A4.
Bismuth Subsalicylate: (Minor) Bromocriptine is highly bound (more than 90%) to serum proteins. Therefore, it may increase the unbound fraction of other highly protein-bound medications (e.g., aspirin and other salicylates), which may alter their effectiveness and risk for side effects.
Bismuth Subsalicylate; Metronidazole; Tetracycline: (Minor) Bromocriptine is highly bound (more than 90%) to serum proteins. Therefore, it may increase the unbound fraction of other highly protein-bound medications (e.g., aspirin and other salicylates), which may alter their effectiveness and risk for side effects.
Bosentan: (Moderate) Caution and close monitoring are advised if bromocriptine and bosentan are used together. Concurrent use may decrease the plasma concentrations of bromocriptine resulting in loss of efficacy. Bromocriptine is extensively metabolized by the liver via CYP3A4; bosentan is a moderate inducer of CYP3A4.
Brexpiprazole: (Moderate) The effectiveness of bromocriptine may be reduced by most of the atypical antipsychotics, via their action as dopamine antagonists. Monitor the patient for reduced response to bromocriptine. The atypical antipsychotics elevate prolactin to various degrees. Atypical antipsychotics may also aggravate diabetes mellitus and cause metabolic changes including hyperglycemia; use caution if bromocriptine is taken for diabetes. If bromocriptine is taken for diabetes, monitor for worsening glycemic control.
Brompheniramine; Dextromethorphan; Phenylephrine: (Moderate) The combination of bromocriptine with phenylephrine may cause headache, tachycardia, other cardiovascular abnormalities, seizures, and other serious effects. Concurrent use of bromocriptine and phenylephrine should be approached with caution. One case report documented worsening headache, hypertension, premature ventricular complexes, and ventricular tachycardia in a post-partum patient receiving bromocriptine for lactation suppression who was subsequently prescribed acetaminophen; dichloralphenazone; isometheptene for a headache. A second case involved a post-partum patient receiving bromocriptine who was later prescribed phenylpropanolamine; guaifenesin and subsequently developed hypertension, tachycardia, seizures, and cerebral vasospasm.
Brompheniramine; Phenylephrine: (Moderate) The combination of bromocriptine with phenylephrine may cause headache, tachycardia, other cardiovascular abnormalities, seizures, and other serious effects. Concurrent use of bromocriptine and phenylephrine should be approached with caution. One case report documented worsening headache, hypertension, premature ventricular complexes, and ventricular tachycardia in a post-partum patient receiving bromocriptine for lactation suppression who was subsequently prescribed acetaminophen; dichloralphenazone; isometheptene for a headache. A second case involved a post-partum patient receiving bromocriptine who was later prescribed phenylpropanolamine; guaifenesin and subsequently developed hypertension, tachycardia, seizures, and cerebral vasospasm.
Brompheniramine; Pseudoephedrine: (Moderate) One case report documented worsening headache, hypertension, premature ventricular complexes, and ventricular tachycardia in a post-partum patient receiving bromocriptine for lactation suppression who was subsequently prescribed acetaminophen; dichloralphenazone; isometheptene for a headache. A second case involved a post-partum patient receiving bromocriptine who was later prescribed phenylpropanolamine; guaifenesin and subsequently developed hypertension, tachycardia, seizures, and cerebral vasospasm. Also, ergot alkaloids, which are chemically related to bromocriptine, should not be administered with other vasoconstrictors. Therefore, until more data become available, concurrent use of bromocriptine and some sympathomimetics such as vasopressors (e.g., norepinephrine, dopamine, phenylephrine), cocaine, epinephrine, phenylpropanolamine, ephedra, ma huang, ephedrine, pseudoephedrine, amphetamines, and phentermine should be approached with caution.
Brompheniramine; Pseudoephedrine; Dextromethorphan: (Moderate) One case report documented worsening headache, hypertension, premature ventricular complexes, and ventricular tachycardia in a post-partum patient receiving bromocriptine for lactation suppression who was subsequently prescribed acetaminophen; dichloralphenazone; isometheptene for a headache. A second case involved a post-partum patient receiving bromocriptine who was later prescribed phenylpropanolamine; guaifenesin and subsequently developed hypertension, tachycardia, seizures, and cerebral vasospasm. Also, ergot alkaloids, which are chemically related to bromocriptine, should not be administered with other vasoconstrictors. Therefore, until more data become available, concurrent use of bromocriptine and some sympathomimetics such as vasopressors (e.g., norepinephrine, dopamine, phenylephrine), cocaine, epinephrine, phenylpropanolamine, ephedra, ma huang, ephedrine, pseudoephedrine, amphetamines, and phentermine should be approached with caution.
Bupivacaine; Epinephrine: (Moderate) One case report documented worsening headache, hypertension, premature ventricular complexes, and ventricular tachycardia in a post-partum patient receiving bromocriptine for lactation suppression who was subsequently prescribed acetaminophen; dichloralphenazone; isometheptene for a headache. A second case involved a post-partum patient receiving bromocriptine who was later prescribed phenylpropanolamine; guaifenesin and subsequently developed hypertension, tachycardia, seizures, and cerebral vasospasm. Also, ergot alkaloids, which are chemically related to bromocriptine, should not be administered with other vasoconstrictors. Therefore, until more data become available, concurrent use of bromocriptine and some sympathomimetics such as vasopressors (e.g., norepinephrine, dopamine, phenylephrine), cocaine, epinephrine, phenylpropanolamine, ephedra, ma huang, ephedrine, pseudoephedrine, amphetamines, and phentermine should be approached with caution.
Butalbital; Acetaminophen: (Moderate) Caution and close monitoring are advised if bromocriptine and butalbital are used together. Concurrent use may decrease the plasma concentrations of bromocriptine resulting in loss of efficacy. Bromocriptine is extensively metabolized by the liver via CYP3A4; butalbital is a moderate inducer of CYP3A4.
Butalbital; Acetaminophen; Caffeine: (Moderate) Caution and close monitoring are advised if bromocriptine and butalbital are used together. Concurrent use may decrease the plasma concentrations of bromocriptine resulting in loss of efficacy. Bromocriptine is extensively metabolized by the liver via CYP3A4; butalbital is a moderate inducer of CYP3A4.
Butalbital; Acetaminophen; Caffeine; Codeine: (Moderate) Caution and close monitoring are advised if bromocriptine and butalbital are used together. Concurrent use may decrease the plasma concentrations of bromocriptine resulting in loss of efficacy. Bromocriptine is extensively metabolized by the liver via CYP3A4; butalbital is a moderate inducer of CYP3A4.
Butalbital; Aspirin; Caffeine; Codeine: (Moderate) Caution and close monitoring are advised if bromocriptine and butalbital are used together. Concurrent use may decrease the plasma concentrations of bromocriptine resulting in loss of efficacy. Bromocriptine is extensively metabolized by the liver via CYP3A4; butalbital is a moderate inducer of CYP3A4. (Minor) Bromocriptine is highly bound (more than 90%) to serum proteins. Therefore, it may increase the unbound fraction of other highly protein-bound medications (e.g., aspirin and other salicylates), which may alter their effectiveness and risk for side effects.
Carbamazepine: (Moderate) Caution and close monitoring are advised if bromocriptine and carbamazepine are used together. Concurrent use may decrease the plasma concentrations of bromocriptine resulting in loss of efficacy. Bromocriptine is extensively metabolized by the liver via CYP3A4; carbamazepine is a strong inducer of CYP3A4.
Cariprazine: (Moderate) The effectiveness of bromocriptine may be reduced by most of the atypical antipsychotics, via their action as dopamine antagonists. Monitor the patient for reduced response to bromocriptine. The atypical antipsychotics elevate prolactin to various degrees. Atypical antipsychotics may also aggravate diabetes mellitus and cause metabolic changes including hyperglycemia; use caution if bromocriptine is taken for diabetes. If bromocriptine is taken for diabetes, monitor for worsening glycemic control.
Cenobamate: (Moderate) Caution and close monitoring are advised if bromocriptine and cenobamate are used together. Concurrent use may decrease the plasma concentrations of bromocriptine resulting in loss of efficacy. Bromocriptine is extensively metabolized by the liver via CYP3A4; cenobamate is a moderate inducer of CYP3A4.
Ceritinib: (Major) When bromocriptine is used for diabetes, avoid coadministration with ceritinib ensuring adequate washout before initiating bromocriptine. Use this combination with caution in patients receiving bromocriptine for other indications. Concurrent use may significantly increase bromocriptine concentrations. Bromocriptine is extensively metabolized in the liver via CYP3A4; ceritinib is a strong inhibitor of CYP3A4.
Cetirizine; Pseudoephedrine: (Moderate) One case report documented worsening headache, hypertension, premature ventricular complexes, and ventricular tachycardia in a post-partum patient receiving bromocriptine for lactation suppression who was subsequently prescribed acetaminophen; dichloralphenazone; isometheptene for a headache. A second case involved a post-partum patient receiving bromocriptine who was later prescribed phenylpropanolamine; guaifenesin and subsequently developed hypertension, tachycardia, seizures, and cerebral vasospasm. Also, ergot alkaloids, which are chemically related to bromocriptine, should not be administered with other vasoconstrictors. Therefore, until more data become available, concurrent use of bromocriptine and some sympathomimetics such as vasopressors (e.g., norepinephrine, dopamine, phenylephrine), cocaine, epinephrine, phenylpropanolamine, ephedra, ma huang, ephedrine, pseudoephedrine, amphetamines, and phentermine should be approached with caution.
Chlophedianol; Dexchlorpheniramine; Pseudoephedrine: (Moderate) One case report documented worsening headache, hypertension, premature ventricular complexes, and ventricular tachycardia in a post-partum patient receiving bromocriptine for lactation suppression who was subsequently prescribed acetaminophen; dichloralphenazone; isometheptene for a headache. A second case involved a post-partum patient receiving bromocriptine who was later prescribed phenylpropanolamine; guaifenesin and subsequently developed hypertension, tachycardia, seizures, and cerebral vasospasm. Also, ergot alkaloids, which are chemically related to bromocriptine, should not be administered with other vasoconstrictors. Therefore, until more data become available, concurrent use of bromocriptine and some sympathomimetics such as vasopressors (e.g., norepinephrine, dopamine, phenylephrine), cocaine, epinephrine, phenylpropanolamine, ephedra, ma huang, ephedrine, pseudoephedrine, amphetamines, and phentermine should be approached with caution.
Chloramphenicol: (Major) When bromocriptine is used for diabetes, avoid coadministration with chloramphenicol ensuring adequate washout before initiating bromocriptine. Use this combination with caution in patients receiving bromocriptine for other indications. Concurrent use may significantly increase bromocriptine concentrations. Bromocriptine is extensively metabolized in the liver via CYP3A4; chloramphenicol is a strong inhibitor of CYP3A4.
Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) The combination of bromocriptine with phenylephrine may cause headache, tachycardia, other cardiovascular abnormalities, seizures, and other serious effects. Concurrent use of bromocriptine and phenylephrine should be approached with caution. One case report documented worsening headache, hypertension, premature ventricular complexes, and ventricular tachycardia in a post-partum patient receiving bromocriptine for lactation suppression who was subsequently prescribed acetaminophen; dichloralphenazone; isometheptene for a headache. A second case involved a post-partum patient receiving bromocriptine who was later prescribed phenylpropanolamine; guaifenesin and subsequently developed hypertension, tachycardia, seizures, and cerebral vasospasm.
Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) One case report documented worsening headache, hypertension, premature ventricular complexes, and ventricular tachycardia in a post-partum patient receiving bromocriptine for lactation suppression who was subsequently prescribed acetaminophen; dichloralphenazone; isometheptene for a headache. A second case involved a post-partum patient receiving bromocriptine who was later prescribed phenylpropanolamine; guaifenesin and subsequently developed hypertension, tachycardia, seizures, and cerebral vasospasm. Also, ergot alkaloids, which are chemically related to bromocriptine, should not be administered with other vasoconstrictors. Therefore, until more data become available, concurrent use of bromocriptine and some sympathomimetics such as vasopressors (e.g., norepinephrine, dopamine, phenylephrine), cocaine, epinephrine, phenylpropanolamine, ephedra, ma huang, ephedrine, pseudoephedrine, amphetamines, and phentermine should be approached with caution.
Chlorpheniramine; Ibuprofen; Pseudoephedrine: (Moderate) One case report documented worsening headache, hypertension, premature ventricular complexes, and ventricular tachycardia in a post-partum patient receiving bromocriptine for lactation suppression who was subsequently prescribed acetaminophen; dichloralphenazone; isometheptene for a headache. A second case involved a post-partum patient receiving bromocriptine who was later prescribed phenylpropanolamine; guaifenesin and subsequently developed hypertension, tachycardia, seizures, and cerebral vasospasm. Also, ergot alkaloids, which are chemically related to bromocriptine, should not be administered with other vasoconstrictors. Therefore, until more data become available, concurrent use of bromocriptine and some sympathomimetics such as vasopressors (e.g., norepinephrine, dopamine, phenylephrine), cocaine, epinephrine, phenylpropanolamine, ephedra, ma huang, ephedrine, pseudoephedrine, amphetamines, and phentermine should be approached with caution.
Chlorpheniramine; Phenylephrine: (Moderate) The combination of bromocriptine with phenylephrine may cause headache, tachycardia, other cardiovascular abnormalities, seizures, and other serious effects. Concurrent use of bromocriptine and phenylephrine should be approached with caution. One case report documented worsening headache, hypertension, premature ventricular complexes, and ventricular tachycardia in a post-partum patient receiving bromocriptine for lactation suppression who was subsequently prescribed acetaminophen; dichloralphenazone; isometheptene for a headache. A second case involved a post-partum patient receiving bromocriptine who was later prescribed phenylpropanolamine; guaifenesin and subsequently developed hypertension, tachycardia, seizures, and cerebral vasospasm.
Chlorpheniramine; Pseudoephedrine: (Moderate) One case report documented worsening headache, hypertension, premature ventricular complexes, and ventricular tachycardia in a post-partum patient receiving bromocriptine for lactation suppression who was subsequently prescribed acetaminophen; dichloralphenazone; isometheptene for a headache. A second case involved a post-partum patient receiving bromocriptine who was later prescribed phenylpropanolamine; guaifenesin and subsequently developed hypertension, tachycardia, seizures, and cerebral vasospasm. Also, ergot alkaloids, which are chemically related to bromocriptine, should not be administered with other vasoconstrictors. Therefore, until more data become available, concurrent use of bromocriptine and some sympathomimetics such as vasopressors (e.g., norepinephrine, dopamine, phenylephrine), cocaine, epinephrine, phenylpropanolamine, ephedra, ma huang, ephedrine, pseudoephedrine, amphetamines, and phentermine should be approached with caution.
Chlorpromazine: (Major) Avoid concurrent use of phenothiazines and bromocriptine when possible. Bromocriptine may interact with dopamine antagonists such as the phenothiazines. The phenothiazines are noted to result in a decreased efficacy of bromocriptine. The prolactin-lowering effect of bromocriptine is antagonized; the elevation in prolactin levels produced by phenothiazines persists with chronic administration. In addition, bromocriptine, a dopamine agonist, may theoretically diminish the effectiveness of central dopamine antagonists such as the phenothiazines; however, such interactions are not certain.
Choline Salicylate; Magnesium Salicylate: (Minor) Bromocriptine is highly bound (more than 90%) to serum proteins. Therefore, it may increase the unbound fraction of other highly protein-bound medications (e.g., aspirin and other salicylates), which may alter their effectiveness and risk for side effects.
Ciprofloxacin: (Major) When bromocriptine is used for diabetes, do not exceed a dose of 1.6 mg once daily during concomitant use of ciprofloxacin. Use this combination with caution in patients receiving bromocriptine for other indications. Concurrent use may increase bromocriptine concentrations. Bromocriptine is extensively metabolized in the liver via CYP3A4; ciprofloxacin is a moderate inhibitor of CYP3A4. Administration of bromocriptine with a moderate inhibitor of CYP3A4 increased the bromocriptine mean AUC and Cmax by 3.7-fold and 4.6-fold, respectively.
Clarithromycin: (Major) When bromocriptine is used for diabetes, avoid coadministration with clarithromycin ensuring adequate washout before initiating bromocriptine. Use this combination with caution in patients receiving bromocriptine for other indications. Concurrent use may significantly increase bromocriptine concentrations. Bromocriptine is extensively metabolized in the liver via CYP3A4; clarithromycin is a strong inhibitor of CYP3A4.
Clozapine: (Moderate) The effectiveness of bromocriptine may be reduced by most of the atypical antipsychotics, via their action as dopamine antagonists. Monitor the patient for reduced response to bromocriptine. The atypical antipsychotics elevate prolactin to various degrees. Atypical antipsychotics may also aggravate diabetes mellitus and cause metabolic changes including hyperglycemia; use caution if bromocriptine is taken for diabetes. If bromocriptine is taken for diabetes, monitor for worsening glycemic control.
Cobicistat: (Major) When bromocriptine is used for diabetes, avoid coadministration with cobicistat ensuring adequate washout before initiating bromocriptine. Use this combination with caution in patients receiving bromocriptine for other indications. Concurrent use may significantly increase bromocriptine concentrations. Bromocriptine is extensively metabolized in the liver via CYP3A4; cobicistat is a strong inhibitor of CYP3A4.
Cocaine: (Moderate) One case report documented worsening headache, hypertension, premature ventricular complexes, and ventricular tachycardia in a post-partum patient receiving bromocriptine for lactation suppression who was subsequently prescribed acetaminophen; dichloralphenazone; isometheptene for a headache. A second case involved a post-partum patient receiving bromocriptine who was later prescribed phenylpropanolamine; guaifenesin and subsequently developed hypertension, tachycardia, seizures, sudden loss of vision, and cerebral vasospasm. Also, ergot alkaloids, which are chemically related to bromocriptine, should not be administered with other vasoconstrictors. Therefore, until more data become available, concurrent use of bromocriptine and some sympathomimetics such as vasopressors (e.g., norepinephrine, dopamine), cocaine, epinephrine, phenylpropanolamine, ephedra, ma huang, pseudoephedrine, amphetamines, and phentermine should be approached with caution.
Codeine; Guaifenesin; Pseudoephedrine: (Moderate) One case report documented worsening headache, hypertension, premature ventricular complexes, and ventricular tachycardia in a post-partum patient receiving bromocriptine for lactation suppression who was subsequently prescribed acetaminophen; dichloralphenazone; isometheptene for a headache. A second case involved a post-partum patient receiving bromocriptine who was later prescribed phenylpropanolamine; guaifenesin and subsequently developed hypertension, tachycardia, seizures, and cerebral vasospasm. Also, ergot alkaloids, which are chemically related to bromocriptine, should not be administered with other vasoconstrictors. Therefore, until more data become available, concurrent use of bromocriptine and some sympathomimetics such as vasopressors (e.g., norepinephrine, dopamine, phenylephrine), cocaine, epinephrine, phenylpropanolamine, ephedra, ma huang, ephedrine, pseudoephedrine, amphetamines, and phentermine should be approached with caution.
Codeine; Phenylephrine; Promethazine: (Major) Avoid concurrent use of phenothiazines and bromocriptine when possible. Bromocriptine may interact with dopamine antagonists such as the phenothiazines. The phenothiazines are noted to result in a decreased efficacy of bromocriptine. The prolactin-lowering effect of bromocriptine is antagonized; the elevation in prolactin levels produced by phenothiazines persists with chronic administration. In addition, bromocriptine, a dopamine agonist, may theoretically diminish the effectiveness of central dopamine antagonists such as the phenothiazines; however, such interactions are not certain. (Moderate) The combination of bromocriptine with phenylephrine may cause headache, tachycardia, other cardiovascular abnormalities, seizures, and other serious effects. Concurrent use of bromocriptine and phenylephrine should be approached with caution. One case report documented worsening headache, hypertension, premature ventricular complexes, and ventricular tachycardia in a post-partum patient receiving bromocriptine for lactation suppression who was subsequently prescribed acetaminophen; dichloralphenazone; isometheptene for a headache. A second case involved a post-partum patient receiving bromocriptine who was later prescribed phenylpropanolamine; guaifenesin and subsequently developed hypertension, tachycardia, seizures, and cerebral vasospasm.
Codeine; Promethazine: (Major) Avoid concurrent use of phenothiazines and bromocriptine when possible. Bromocriptine may interact with dopamine antagonists such as the phenothiazines. The phenothiazines are noted to result in a decreased efficacy of bromocriptine. The prolactin-lowering effect of bromocriptine is antagonized; the elevation in prolactin levels produced by phenothiazines persists with chronic administration. In addition, bromocriptine, a dopamine agonist, may theoretically diminish the effectiveness of central dopamine antagonists such as the phenothiazines; however, such interactions are not certain.
Conivaptan: (Major) When bromocriptine is used for diabetes, do not exceed a dose of 1.6 mg once daily during concomitant use of conivaptan. Use this combination with caution in patients receiving bromocriptine for other indications. Concurrent use may increase bromocriptine concentrations. Bromocriptine is extensively metabolized in the liver via CYP3A; conivaptan is a moderate inhibitor of CYP3A. Coadministration with another moderate CYP3A inhibitor increased bromocriptine exposure by 2.8-fold.
Conjugated Estrogens: (Minor) Bromocriptine is used to restore ovulation and ovarian function in amenorrheic women. Estrogens and progestins can cause amenorrhea and, therefore, counteract the desired effects of bromocriptine. Concurrent use is not recommended; an alternate form of contraception is recommended during bromocriptine therapy.
Conjugated Estrogens; Bazedoxifene: (Minor) Bromocriptine is used to restore ovulation and ovarian function in amenorrheic women. Estrogens and progestins can cause amenorrhea and, therefore, counteract the desired effects of bromocriptine. Concurrent use is not recommended; an alternate form of contraception is recommended during bromocriptine therapy.
Conjugated Estrogens; Medroxyprogesterone: (Minor) Bromocriptine is used to restore ovulation and ovarian function in amenorrheic women. Estrogens and progestins can cause amenorrhea and, therefore, counteract the desired effects of bromocriptine. Concurrent use is not recommended; an alternate form of contraception is recommended during bromocriptine therapy. (Minor) Bromocriptine is used to restore ovulation and ovarian function in amenorrheic women. Progestins can cause amenorrhea and, therefore, counteract the desired effects of bromocriptine. Concurrent use is not recommended; an alternate form of contraception is recommended during bromocriptine therapy.
Crizotinib: (Major) When bromocriptine is used for diabetes, do not exceed a dose of 1.6 mg once daily during concomitant use of crizotinib. Use this combination with caution in patients receiving bromocriptine for other indications. Concurrent use may increase bromocriptine concentrations. Bromocriptine is extensively metabolized in the liver via CYP3A4; crizotinib is a moderate inhibitor of CYP3A4. Coadministration with another moderate CYP3A4 inhibitor increased bromocriptine exposure by 2.8-fold.
Cyclosporine: (Major) When bromocriptine is used for diabetes, do not exceed a dose of 1.6 mg once daily during concomitant use of cyclosporine. Use this combination with caution in patients receiving bromocriptine for other indications. Concurrent use may increase bromocriptine concentrations. Bromocriptine is extensively metabolized in the liver via CYP3A4; cyclosporine is a moderate inhibitor of CYP3A4. Administration of bromocriptine with a moderate inhibitor of CYP3A4 increased the bromocriptine mean AUC and Cmax by 3.7-fold and 4.6-fold, respectively.
Dabrafenib: (Moderate) Caution and close monitoring are advised if bromocriptine and dabrafenib are used together. Concurrent use may decrease the plasma concentrations of bromocriptine resulting in loss of efficacy. Bromocriptine is extensively metabolized by the liver via CYP3A4; dabrafenib is a moderate inducer of CYP3A4.
Danazol: (Major) When bromocriptine is used for diabetes, do not exceed a dose of 1.6 mg once daily during concomitant use of danazol. Use this combination with caution in patients receiving bromocriptine for other indications. Concurrent use may increase bromocriptine concentrations. Bromocriptine is extensively metabolized in the liver via CYP3A4; danazol is a moderate inhibitor of CYP3A4. Administration of bromocriptine with a moderate inhibitor of CYP3A4 increased the bromocriptine mean AUC and Cmax by 3.7-fold and 4.6-fold, respectively.
Darunavir: (Major) When bromocriptine is used for diabetes, avoid coadministration with darunavir ensuring adequate washout before initiating bromocriptine. Use this combination with caution in patients receiving bromocriptine for other indications. Concurrent use may significantly increase bromocriptine concentrations. Bromocriptine is extensively metabolized in the liver via CYP3A4; boosted darunavir is a strong inhibitor of CYP3A4.
Darunavir; Cobicistat: (Major) When bromocriptine is used for diabetes, avoid coadministration with cobicistat ensuring adequate washout before initiating bromocriptine. Use this combination with caution in patients receiving bromocriptine for other indications. Concurrent use may significantly increase bromocriptine concentrations. Bromocriptine is extensively metabolized in the liver via CYP3A4; cobicistat is a strong inhibitor of CYP3A4. (Major) When bromocriptine is used for diabetes, avoid coadministration with darunavir ensuring adequate washout before initiating bromocriptine. Use this combination with caution in patients receiving bromocriptine for other indications. Concurrent use may significantly increase bromocriptine concentrations. Bromocriptine is extensively metabolized in the liver via CYP3A4; boosted darunavir is a strong inhibitor of CYP3A4.
Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Major) When bromocriptine is used for diabetes, avoid coadministration with cobicistat ensuring adequate washout before initiating bromocriptine. Use this combination with caution in patients receiving bromocriptine for other indications. Concurrent use may significantly increase bromocriptine concentrations. Bromocriptine is extensively metabolized in the liver via CYP3A4; cobicistat is a strong inhibitor of CYP3A4. (Major) When bromocriptine is used for diabetes, avoid coadministration with darunavir ensuring adequate washout before initiating bromocriptine. Use this combination with caution in patients receiving bromocriptine for other indications. Concurrent use may significantly increase bromocriptine concentrations. Bromocriptine is extensively metabolized in the liver via CYP3A4; boosted darunavir is a strong inhibitor of CYP3A4.
Deferasirox: (Moderate) Caution and close monitoring are advised if bromocriptine and deferasirox are used together. Concurrent use may decrease the plasma concentrations of bromocriptine resulting in loss of efficacy. Bromocriptine is extensively metabolized by the liver via CYP3A4; deferasirox is a moderate inducer of CYP3A4.
Delavirdine: (Major) When bromocriptine is used for diabetes, avoid coadministration with delavirdine ensuring adequate washout before initiating bromocriptine. Use this combination with caution in patients receiving bromocriptine for other indications. Concurrent use may significantly increase bromocriptine concentrations. Bromocriptine is extensively metabolized in the liver via CYP3A4; delavirdine is a strong inhibitor of CYP3A4.
Desloratadine; Pseudoephedrine: (Moderate) One case report documented worsening headache, hypertension, premature ventricular complexes, and ventricular tachycardia in a post-partum patient receiving bromocriptine for lactation suppression who was subsequently prescribed acetaminophen; dichloralphenazone; isometheptene for a headache. A second case involved a post-partum patient receiving bromocriptine who was later prescribed phenylpropanolamine; guaifenesin and subsequently developed hypertension, tachycardia, seizures, and cerebral vasospasm. Also, ergot alkaloids, which are chemically related to bromocriptine, should not be administered with other vasoconstrictors. Therefore, until more data become available, concurrent use of bromocriptine and some sympathomimetics such as vasopressors (e.g., norepinephrine, dopamine, phenylephrine), cocaine, epinephrine, phenylpropanolamine, ephedra, ma huang, ephedrine, pseudoephedrine, amphetamines, and phentermine should be approached with caution.
Desogestrel; Ethinyl Estradiol: (Minor) Bromocriptine is used to restore ovulation and ovarian function in amenorrheic women. Estrogens and progestins can cause amenorrhea and, therefore, counteract the desired effects of bromocriptine. Concurrent use is not recommended; an alternate form of contraception is recommended during bromocriptine therapy. (Minor) Bromocriptine is used to restore ovulation and ovarian function in amenorrheic women. Progestins can cause amenorrhea and, therefore, counteract the desired effects of bromocriptine. Concurrent use is not recommended; an alternate form of contraception is recommended during bromocriptine therapy.
Dexbrompheniramine; Pseudoephedrine: (Moderate) One case report documented worsening headache, hypertension, premature ventricular complexes, and ventricular tachycardia in a post-partum patient receiving bromocriptine for lactation suppression who was subsequently prescribed acetaminophen; dichloralphenazone; isometheptene for a headache. A second case involved a post-partum patient receiving bromocriptine who was later prescribed phenylpropanolamine; guaifenesin and subsequently developed hypertension, tachycardia, seizures, and cerebral vasospasm. Also, ergot alkaloids, which are chemically related to bromocriptine, should not be administered with other vasoconstrictors. Therefore, until more data become available, concurrent use of bromocriptine and some sympathomimetics such as vasopressors (e.g., norepinephrine, dopamine, phenylephrine), cocaine, epinephrine, phenylpropanolamine, ephedra, ma huang, ephedrine, pseudoephedrine, amphetamines, and phentermine should be approached with caution.
Dexchlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) One case report documented worsening headache, hypertension, premature ventricular complexes, and ventricular tachycardia in a post-partum patient receiving bromocriptine for lactation suppression who was subsequently prescribed acetaminophen; dichloralphenazone; isometheptene for a headache. A second case involved a post-partum patient receiving bromocriptine who was later prescribed phenylpropanolamine; guaifenesin and subsequently developed hypertension, tachycardia, seizures, and cerebral vasospasm. Also, ergot alkaloids, which are chemically related to bromocriptine, should not be administered with other vasoconstrictors. Therefore, until more data become available, concurrent use of bromocriptine and some sympathomimetics such as vasopressors (e.g., norepinephrine, dopamine, phenylephrine), cocaine, epinephrine, phenylpropanolamine, ephedra, ma huang, ephedrine, pseudoephedrine, amphetamines, and phentermine should be approached with caution.
Dexmethylphenidate: (Moderate) Increased dopaminergic effects may occur during coadministration of methylphenidate derivatives, inhibitors of dopamine reuptake, and dopamine agonists such as bromocriptine. Dopaminergic side effects, such as nausea, loss of appetite, weight loss, insomnia, tremor, nervousness, or changes in mood or behavior, are possible.
Dextroamphetamine: (Moderate) Concurrent use of bromocriptine and some sympathomimetics such as amphetamines should be approached with caution. One case report documented worsening headache, hypertension, premature ventricular complexes, and ventricular tachycardia in a post-partum patient receiving bromocriptine for lactation suppression who was subsequently prescribed an isometheptene-containing medication for a headache. A second case involved a post-partum patient receiving bromocriptine who was later prescribed a phenylpropanolamine-expectorant combination and subsequently developed hypertension, tachycardia, seizures, and cerebral vasospasm.
Dextromethorphan; Diphenhydramine; Phenylephrine: (Moderate) The combination of bromocriptine with phenylephrine may cause headache, tachycardia, other cardiovascular abnormalities, seizures, and other serious effects. Concurrent use of bromocriptine and phenylephrine should be approached with caution. One case report documented worsening headache, hypertension, premature ventricular complexes, and ventricular tachycardia in a post-partum patient receiving bromocriptine for lactation suppression who was subsequently prescribed acetaminophen; dichloralphenazone; isometheptene for a headache. A second case involved a post-partum patient receiving bromocriptine who was later prescribed phenylpropanolamine; guaifenesin and subsequently developed hypertension, tachycardia, seizures, and cerebral vasospasm.
Dextromethorphan; Guaifenesin; Phenylephrine: (Moderate) The combination of bromocriptine with phenylephrine may cause headache, tachycardia, other cardiovascular abnormalities, seizures, and other serious effects. Concurrent use of bromocriptine and phenylephrine should be approached with caution. One case report documented worsening headache, hypertension, premature ventricular complexes, and ventricular tachycardia in a post-partum patient receiving bromocriptine for lactation suppression who was subsequently prescribed acetaminophen; dichloralphenazone; isometheptene for a headache. A second case involved a post-partum patient receiving bromocriptine who was later prescribed phenylpropanolamine; guaifenesin and subsequently developed hypertension, tachycardia, seizures, and cerebral vasospasm.
Dextromethorphan; Guaifenesin; Pseudoephedrine: (Moderate) One case report documented worsening headache, hypertension, premature ventricular complexes, and ventricular tachycardia in a post-partum patient receiving bromocriptine for lactation suppression who was subsequently prescribed acetaminophen; dichloralphenazone; isometheptene for a headache. A second case involved a post-partum patient receiving bromocriptine who was later prescribed phenylpropanolamine; guaifenesin and subsequently developed hypertension, tachycardia, seizures, and cerebral vasospasm. Also, ergot alkaloids, which are chemically related to bromocriptine, should not be administered with other vasoconstrictors. Therefore, until more data become available, concurrent use of bromocriptine and some sympathomimetics such as vasopressors (e.g., norepinephrine, dopamine, phenylephrine), cocaine, epinephrine, phenylpropanolamine, ephedra, ma huang, ephedrine, pseudoephedrine, amphetamines, and phentermine should be approached with caution.
Dienogest; Estradiol valerate: (Minor) Bromocriptine is used to restore ovulation and ovarian function in amenorrheic women. Estrogens and progestins can cause amenorrhea and, therefore, counteract the desired effects of bromocriptine. Concurrent use is not recommended; an alternate form of contraception is recommended during bromocriptine therapy. (Minor) Bromocriptine is used to restore ovulation and ovarian function in amenorrheic women. Progestins can cause amenorrhea and, therefore, counteract the desired effects of bromocriptine. Concurrent use is not recommended; an alternate form of contraception is recommended during bromocriptine therapy.
Diethylpropion: (Major) There is a risk of hypertension and seizures in patients receiving bromocriptine and sympathomimetics concomitantly. Until more data are available, the combination of a sympathomimetic and bromocriptine should be approached with caution and avoided whenever possible.
Dihydroergotamine: (Contraindicated) The concomitant use of bromocriptine, an ergot derivative, with ergot alkaloids may potentially lead to ergot toxicity; therefore the combination should be avoided. Symptoms of ergotism include angina, asthenia, chest pain (unspecified), coronary vasospasm, muscle cramps (claudication), myalgia, paresthesias, and palpitations or changes in heart rate (e.g., sinus bradycardia or sinus tachycardia). Peripheral vasoconstriction of the arteries may result in hypothermia or tissue necrosis, which may lead to gangrene. Other serious complications include hypertension (portal), mesenteric artery thrombosis, myocardial infarction, and renal tubular necrosis. Symptoms such as confusion, depression, drowsiness, and seizures rarely occur.
Diltiazem: (Major) When bromocriptine is used for diabetes, do not exceed a dose of 1.6 mg once daily during concomitant use of diltiazem. Use this combination with caution in patients receiving bromocriptine for other indications. Concurrent use may increase bromocriptine concentrations. Bromocriptine is extensively metabolized in the liver via CYP3A4; diltiazem is a moderate inhibitor of CYP3A4. Administration of bromocriptine with a moderate inhibitor of CYP3A4 increased the bromocriptine mean AUC and Cmax by 3.7-fold and 4.6-fold, respectively.
Diphenhydramine; Phenylephrine: (Moderate) The combination of bromocriptine with phenylephrine may cause headache, tachycardia, other cardiovascular abnormalities, seizures, and other serious effects. Concurrent use of bromocriptine and phenylephrine should be approached with caution. One case report documented worsening headache, hypertension, premature ventricular complexes, and ventricular tachycardia in a post-partum patient receiving bromocriptine for lactation suppression who was subsequently prescribed acetaminophen; dichloralphenazone; isometheptene for a headache. A second case involved a post-partum patient receiving bromocriptine who was later prescribed phenylpropanolamine; guaifenesin and subsequently developed hypertension, tachycardia, seizures, and cerebral vasospasm.
Donepezil; Memantine: (Moderate) The pharmacologic effects of dopaminergic agents, including the ergot derivative bromocriptine, may be enhanced with use of memantine; dosage adjustments of dopaminergic agents may be required when memantine is coadministered.
Dopamine: (Moderate) The combination of bromocriptine with dopamine may cause headache, tachycardia, other cardiovascular abnormalities, seizures, and other serious effects. Concurrent use of bromocriptine and dopamine should be approached with caution. One case report documented worsening headache, hypertension, premature ventricular complexes, and ventricular tachycardia in a post-partum patient receiving bromocriptine for lactation suppression who was subsequently prescribed acetaminophen; dichloralphenazone; isometheptene for a headache. A second case involved a post-partum patient receiving bromocriptine who was later prescribed phenylpropanolamine; guaifenesin and subsequently developed hypertension, tachycardia, seizures, and cerebral vasospasm.
Dronedarone: (Major) When bromocriptine is used for diabetes, do not exceed a dose of 1.6 mg once daily during concomitant use of dronedarone. Use this combination with caution in patients receiving bromocriptine for other indications. Concurrent use may increase bromocriptine concentrations. Bromocriptine is extensively metabolized in the liver via CYP3A4; dronedarone is a moderate inhibitor of CYP3A4. Administration of bromocriptine with a moderate inhibitor of CYP3A4 increased the bromocriptine mean AUC and Cmax by 3.7-fold and 4.6-fold, respectively.
Droperidol: (Moderate) Droperidol, a butyrophenone derivative, is a dopamine D2 receptor antagonist and thus, may reduce the therapeutic effects of bromocriptine, an agonist at dopamine D2 receptors with chronic use. However, droperidol is usually only indicated for short-term use in peri-surgical settings.
Drospirenone: (Minor) Bromocriptine is used to restore ovulation and ovarian function in amenorrheic women. Progestins can cause amenorrhea and, therefore, counteract the desired effects of bromocriptine. Concurrent use is not recommended; an alternate form of contraception is recommended during bromocriptine therapy.
Drospirenone; Estetrol: (Minor) Bromocriptine is used to restore ovulation and ovarian function in amenorrheic women. Estrogens and progestins can cause amenorrhea and, therefore, counteract the desired effects of bromocriptine. Concurrent use is not recommended; an alternate form of contraception is recommended during bromocriptine therapy. (Minor) Bromocriptine is used to restore ovulation and ovarian function in amenorrheic women. Progestins can cause amenorrhea and, therefore, counteract the desired effects of bromocriptine. Concurrent use is not recommended; an alternate form of contraception is recommended during bromocriptine therapy.
Drospirenone; Estradiol: (Minor) Bromocriptine is used to restore ovulation and ovarian function in amenorrheic women. Estrogens and progestins can cause amenorrhea and, therefore, counteract the desired effects of bromocriptine. Concurrent use is not recommended; an alternate form of contraception is recommended during bromocriptine therapy. (Minor) Bromocriptine is used to restore ovulation and ovarian function in amenorrheic women. Progestins can cause amenorrhea and, therefore, counteract the desired effects of bromocriptine. Concurrent use is not recommended; an alternate form of contraception is recommended during bromocriptine therapy.
Drospirenone; Ethinyl Estradiol: (Minor) Bromocriptine is used to restore ovulation and ovarian function in amenorrheic women. Estrogens and progestins can cause amenorrhea and, therefore, counteract the desired effects of bromocriptine. Concurrent use is not recommended; an alternate form of contraception is recommended during bromocriptine therapy. (Minor) Bromocriptine is used to restore ovulation and ovarian function in amenorrheic women. Progestins can cause amenorrhea and, therefore, counteract the desired effects of bromocriptine. Concurrent use is not recommended; an alternate form of contraception is recommended during bromocriptine therapy.
Drospirenone; Ethinyl Estradiol; Levomefolate: (Minor) Bromocriptine is used to restore ovulation and ovarian function in amenorrheic women. Estrogens and progestins can cause amenorrhea and, therefore, counteract the desired effects of bromocriptine. Concurrent use is not recommended; an alternate form of contraception is recommended during bromocriptine therapy. (Minor) Bromocriptine is used to restore ovulation and ovarian function in amenorrheic women. Progestins can cause amenorrhea and, therefore, counteract the desired effects of bromocriptine. Concurrent use is not recommended; an alternate form of contraception is recommended during bromocriptine therapy.
Duvelisib: (Major) When bromocriptine is used for diabetes, do not exceed a dose of 1.6 mg once daily during concomitant use of duvelisib. Use this combination with caution in patients receiving bromocriptine for other indications. Concurrent use may increase bromocriptine concentrations. Bromocriptine is extensively metabolized in the liver via CYP3A4; duvelisib is a moderate inhibitor of CYP3A4.
Efavirenz: (Moderate) Caution and close monitoring are advised if bromocriptine and efavirenz are used together. Concurrent use may decrease the plasma concentrations of bromocriptine resulting in loss of efficacy. Bromocriptine is extensively metabolized by the liver via CYP3A4; efavirenz is a moderate inducer of CYP3A4.
Efavirenz; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Caution and close monitoring are advised if bromocriptine and efavirenz are used together. Concurrent use may decrease the plasma concentrations of bromocriptine resulting in loss of efficacy. Bromocriptine is extensively metabolized by the liver via CYP3A4; efavirenz is a moderate inducer of CYP3A4.
Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Moderate) Caution and close monitoring are advised if bromocriptine and efavirenz are used together. Concurrent use may decrease the plasma concentrations of bromocriptine resulting in loss of efficacy. Bromocriptine is extensively metabolized by the liver via CYP3A4; efavirenz is a moderate inducer of CYP3A4.
Elagolix: (Moderate) Caution and close monitoring are advised if bromocriptine and elagolix are used together. Concurrent use may decrease the plasma concentrations of bromocriptine resulting in loss of efficacy. Bromocriptine is extensively metabolized by the liver via CYP3A4; elagolix is a weak to moderate inducer of CYP3A4.
Elagolix; Estradiol; Norethindrone acetate: (Moderate) Caution and close monitoring are advised if bromocriptine and elagolix are used together. Concurrent use may decrease the plasma concentrations of bromocriptine resulting in loss of efficacy. Bromocriptine is extensively metabolized by the liver via CYP3A4; elagolix is a weak to moderate inducer of CYP3A4. (Minor) Bromocriptine is used to restore ovulation and ovarian function in amenorrheic women. Estrogens and progestins can cause amenorrhea and, therefore, counteract the desired effects of bromocriptine. Concurrent use is not recommended; an alternate form of contraception is recommended during bromocriptine therapy. (Minor) Bromocriptine is used to restore ovulation and ovarian function in amenorrheic women. Progestins can cause amenorrhea and, therefore, counteract the desired effects of bromocriptine. Concurrent use is not recommended; an alternate form of contraception is recommended during bromocriptine therapy.
Eletriptan: (Major) There are limited clinical trial data supporting the safety of giving a serotonin-receptor agonist ("triptan") with bromocriptine, an ergot derivative. The concomitant use of these agents with bromocriptine should be avoided. There is concern that prolonged vasospastic reactions, hypertension, tachycardia, or other side effects may occur.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Major) When bromocriptine is used for diabetes, avoid coadministration with cobicistat ensuring adequate washout before initiating bromocriptine. Use this combination with caution in patients receiving bromocriptine for other indications. Concurrent use may significantly increase bromocriptine concentrations. Bromocriptine is extensively metabolized in the liver via CYP3A4; cobicistat is a strong inhibitor of CYP3A4.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Major) When bromocriptine is used for diabetes, avoid coadministration with cobicistat ensuring adequate washout before initiating bromocriptine. Use this combination with caution in patients receiving bromocriptine for other indications. Concurrent use may significantly increase bromocriptine concentrations. Bromocriptine is extensively metabolized in the liver via CYP3A4; cobicistat is a strong inhibitor of CYP3A4.
Encorafenib: (Moderate) Caution and close monitoring are advised if bromocriptine and encorafenib are used together. Concurrent use may decrease the plasma concentrations of bromocriptine resulting in loss of efficacy. Bromocriptine is extensively metabolized by the liver via CYP3A; encorafenib is a strong inducer of CYP3A.
Enzalutamide: (Moderate) Caution and close monitoring are advised if bromocriptine and enzalutamide are used together. Concurrent use may decrease the plasma concentrations of bromocriptine resulting in loss of efficacy. Bromocriptine is extensively metabolized by the liver via CYP3A4; enzalutamide is a strong inducer of CYP3A4.
Ephedrine: (Moderate) One case report documented worsening headache, hypertension, premature ventricular complexes, and ventricular tachycardia in a post-partum patient receiving bromocriptine for lactation suppression who was subsequently prescribed acetaminophen; dichloralphenazone; isometheptene for a headache. A second case involved a post-partum patient receiving bromocriptine who was later prescribed phenylpropanolamine; guaifenesin and subsequently developed hypertension, tachycardia, seizures, sudden loss of vision, and cerebral vasospasm. Also, ergot alkaloids, which are chemically related to bromocriptine, should not be administered with other vasoconstrictors. Therefore, until more data become available, concurrent use of bromocriptine and some sympathomimetics such as vasopressors (e.g., norepinephrine, dopamine), cocaine, epinephrine, phenylpropanolamine, ephedra, ma huang, pseudoephedrine, amphetamines, and phentermine should be approached with caution.
Ephedrine; Guaifenesin: (Moderate) One case report documented worsening headache, hypertension, premature ventricular complexes, and ventricular tachycardia in a post-partum patient receiving bromocriptine for lactation suppression who was subsequently prescribed acetaminophen; dichloralphenazone; isometheptene for a headache. A second case involved a post-partum patient receiving bromocriptine who was later prescribed phenylpropanolamine; guaifenesin and subsequently developed hypertension, tachycardia, seizures, sudden loss of vision, and cerebral vasospasm. Also, ergot alkaloids, which are chemically related to bromocriptine, should not be administered with other vasoconstrictors. Therefore, until more data become available, concurrent use of bromocriptine and some sympathomimetics such as vasopressors (e.g., norepinephrine, dopamine), cocaine, epinephrine, phenylpropanolamine, ephedra, ma huang, pseudoephedrine, amphetamines, and phentermine should be approached with caution.
Epinephrine: (Moderate) One case report documented worsening headache, hypertension, premature ventricular complexes, and ventricular tachycardia in a post-partum patient receiving bromocriptine for lactation suppression who was subsequently prescribed acetaminophen; dichloralphenazone; isometheptene for a headache. A second case involved a post-partum patient receiving bromocriptine who was later prescribed phenylpropanolamine; guaifenesin and subsequently developed hypertension, tachycardia, seizures, and cerebral vasospasm. Also, ergot alkaloids, which are chemically related to bromocriptine, should not be administered with other vasoconstrictors. Therefore, until more data become available, concurrent use of bromocriptine and some sympathomimetics such as vasopressors (e.g., norepinephrine, dopamine, phenylephrine), cocaine, epinephrine, phenylpropanolamine, ephedra, ma huang, ephedrine, pseudoephedrine, amphetamines, and phentermine should be approached with caution.
Ergoloid Mesylates: (Contraindicated) The concomitant use of bromocriptine, an ergot derivative, with ergot alkaloids may potentially lead to ergot toxicity; therefore the combination should be avoided. Symptoms of ergotism include angina, asthenia, chest pain (unspecified), coronary vasospasm, muscle cramps (claudication), myalgia, paresthesias, and palpitations or changes in heart rate (e.g., sinus bradycardia or sinus tachycardia). Peripheral vasoconstriction of the arteries may result in hypothermia or tissue necrosis, which may lead to gangrene. Other serious complications include hypertension (portal), mesenteric artery thrombosis, myocardial infarction, and renal tubular necrosis. Symptoms such as confusion, depression, drowsiness, and seizures rarely occur.
Ergot alkaloids: (Contraindicated) The concomitant use of bromocriptine, an ergot derivative, with ergot alkaloids may potentially lead to ergot toxicity; therefore the combination should be avoided. Symptoms of ergotism include angina, asthenia, chest pain (unspecified), coronary vasospasm, muscle cramps (claudication), myalgia, paresthesias, and palpitations or changes in heart rate (e.g., sinus bradycardia or sinus tachycardia). Peripheral vasoconstriction of the arteries may result in hypothermia or tissue necrosis, which may lead to gangrene. Other serious complications include hypertension (portal), mesenteric artery thrombosis, myocardial infarction, and renal tubular necrosis. Symptoms such as confusion, depression, drowsiness, and seizures rarely occur.
Ergotamine: (Contraindicated) The concomitant use of bromocriptine, an ergot derivative, with ergot alkaloids may potentially lead to ergot toxicity; therefore the combination should be avoided. Symptoms of ergotism include angina, asthenia, chest pain (unspecified), coronary vasospasm, muscle cramps (claudication), myalgia, paresthesias, and palpitations or changes in heart rate (e.g., sinus bradycardia or sinus tachycardia). Peripheral vasoconstriction of the arteries may result in hypothermia or tissue necrosis, which may lead to gangrene. Other serious complications include hypertension (portal), mesenteric artery thrombosis, myocardial infarction, and renal tubular necrosis. Symptoms such as confusion, depression, drowsiness, and seizures rarely occur.
Ergotamine; Caffeine: (Contraindicated) The concomitant use of bromocriptine, an ergot derivative, with ergot alkaloids may potentially lead to ergot toxicity; therefore the combination should be avoided. Symptoms of ergotism include angina, asthenia, chest pain (unspecified), coronary vasospasm, muscle cramps (claudication), myalgia, paresthesias, and palpitations or changes in heart rate (e.g., sinus bradycardia or sinus tachycardia). Peripheral vasoconstriction of the arteries may result in hypothermia or tissue necrosis, which may lead to gangrene. Other serious complications include hypertension (portal), mesenteric artery thrombosis, myocardial infarction, and renal tubular necrosis. Symptoms such as confusion, depression, drowsiness, and seizures rarely occur.
Erythromycin: (Major) When bromocriptine is used for diabetes, do not exceed a dose of 1.6 mg once daily during concomitant use of erythromycin. Use this combination with caution in patients receiving bromocriptine for other indications. Concurrent use may increase bromocriptine concentrations. Bromocriptine is extensively metabolized in the liver via CYP3A4; erythromycin is a moderate inhibitor of CYP3A4. Administration of bromocriptine with a moderate inhibitor of CYP3A4 increased the bromocriptine mean AUC and Cmax by 3.7-fold and 4.6-fold, respectively.
Eslicarbazepine: (Moderate) Caution and close monitoring are advised if bromocriptine and eslicarbazepine are used together. Concurrent use may decrease the plasma concentrations of bromocriptine resulting in loss of efficacy. Bromocriptine is extensively metabolized by the liver via CYP3A4; eslicarbazepine is a moderate inducer of CYP3A4.
Esterified Estrogens: (Minor) Bromocriptine is used to restore ovulation and ovarian function in amenorrheic women. Estrogens and progestins can cause amenorrhea and, therefore, counteract the desired effects of bromocriptine. Concurrent use is not recommended; an alternate form of contraception is recommended during bromocriptine therapy.
Esterified Estrogens; Methyltestosterone: (Minor) Bromocriptine is used to restore ovulation and ovarian function in amenorrheic women. Estrogens and progestins can cause amenorrhea and, therefore, counteract the desired effects of bromocriptine. Concurrent use is not recommended; an alternate form of contraception is recommended during bromocriptine therapy.
Estradiol: (Minor) Bromocriptine is used to restore ovulation and ovarian function in amenorrheic women. Estrogens and progestins can cause amenorrhea and, therefore, counteract the desired effects of bromocriptine. Concurrent use is not recommended; an alternate form of contraception is recommended during bromocriptine therapy.
Estradiol; Levonorgestrel: (Minor) Bromocriptine is used to restore ovulation and ovarian function in amenorrheic women. Estrogens and progestins can cause amenorrhea and, therefore, counteract the desired effects of bromocriptine. Concurrent use is not recommended; an alternate form of contraception is recommended during bromocriptine therapy. (Minor) Bromocriptine is used to restore ovulation and ovarian function in amenorrheic women. Progestins can cause amenorrhea and, therefore, counteract the desired effects of bromocriptine. Concurrent use is not recommended; an alternate form of contraception is recommended during bromocriptine therapy.
Estradiol; Norethindrone: (Minor) Bromocriptine is used to restore ovulation and ovarian function in amenorrheic women. Estrogens and progestins can cause amenorrhea and, therefore, counteract the desired effects of bromocriptine. Concurrent use is not recommended; an alternate form of contraception is recommended during bromocriptine therapy. (Minor) Bromocriptine is used to restore ovulation and ovarian function in amenorrheic women. Progestins can cause amenorrhea and, therefore, counteract the desired effects of bromocriptine. Concurrent use is not recommended; an alternate form of contraception is recommended during bromocriptine therapy.
Estradiol; Norgestimate: (Minor) Bromocriptine is used to restore ovulation and ovarian function in amenorrheic women. Estrogens and progestins can cause amenorrhea and, therefore, counteract the desired effects of bromocriptine. Concurrent use is not recommended; an alternate form of contraception is recommended during bromocriptine therapy. (Minor) Bromocriptine is used to restore ovulation and ovarian function in amenorrheic women. Progestins can cause amenorrhea and, therefore, counteract the desired effects of bromocriptine. Concurrent use is not recommended; an alternate form of contraception is recommended during bromocriptine therapy.
Estradiol; Progesterone: (Minor) Bromocriptine is used to restore ovulation and ovarian function in amenorrheic women. Estrogens and progestins can cause amenorrhea and, therefore, counteract the desired effects of bromocriptine. Concurrent use is not recommended; an alternate form of contraception is recommended during bromocriptine therapy. (Minor) Bromocriptine is used to restore ovulation and ovarian function in amenorrheic women. Progestins can cause amenorrhea and, therefore, counteract the desired effects of bromocriptine. Concurrent use is not recommended; an alternate form of contraception is recommended during bromocriptine therapy.
Estrogens: (Minor) Bromocriptine is used to restore ovulation and ovarian function in amenorrheic women. Estrogens and progestins can cause amenorrhea and, therefore, counteract the desired effects of bromocriptine. Concurrent use is not recommended; an alternate form of contraception is recommended during bromocriptine therapy.
Estropipate: (Minor) Bromocriptine is used to restore ovulation and ovarian function in amenorrheic women. Estrogens and progestins can cause amenorrhea and, therefore, counteract the desired effects of bromocriptine. Concurrent use is not recommended; an alternate form of contraception is recommended during bromocriptine therapy.
Ethanol: (Major) Alcohol may potentiate some of the side effects of bromocriptine, including hypotension and somnolence. Patients should be advised to avoid alcohol and not to drive or engage in activities where impaired alertness may put themselves or others at risk of serious injury (e.g., operating machines) until the effects of bromocriptine are known.
Ethinyl Estradiol; Norelgestromin: (Minor) Bromocriptine is used to restore ovulation and ovarian function in amenorrheic women. Estrogens and progestins can cause amenorrhea and, therefore, counteract the desired effects of bromocriptine. Concurrent use is not recommended; an alternate form of contraception is recommended during bromocriptine therapy. (Minor) Bromocriptine is used to restore ovulation and ovarian function in amenorrheic women. Progestins can cause amenorrhea and, therefore, counteract the desired effects of bromocriptine. Concurrent use is not recommended; an alternate form of contraception is recommended during bromocriptine therapy.
Ethinyl Estradiol; Norethindrone Acetate: (Minor) Bromocriptine is used to restore ovulation and ovarian function in amenorrheic women. Estrogens and progestins can cause amenorrhea and, therefore, counteract the desired effects of bromocriptine. Concurrent use is not recommended; an alternate form of contraception is recommended during bromocriptine therapy. (Minor) Bromocriptine is used to restore ovulation and ovarian function in amenorrheic women. Progestins can cause amenorrhea and, therefore, counteract the desired effects of bromocriptine. Concurrent use is not recommended; an alternate form of contraception is recommended during bromocriptine therapy.
Ethinyl Estradiol; Norgestrel: (Minor) Bromocriptine is used to restore ovulation and ovarian function in amenorrheic women. Estrogens and progestins can cause amenorrhea and, therefore, counteract the desired effects of bromocriptine. Concurrent use is not recommended; an alternate form of contraception is recommended during bromocriptine therapy. (Minor) Bromocriptine is used to restore ovulation and ovarian function in amenorrheic women. Progestins can cause amenorrhea and, therefore, counteract the desired effects of bromocriptine. Concurrent use is not recommended; an alternate form of contraception is recommended during bromocriptine therapy.
Ethynodiol Diacetate; Ethinyl Estradiol: (Minor) Bromocriptine is used to restore ovulation and ovarian function in amenorrheic women. Estrogens and progestins can cause amenorrhea and, therefore, counteract the desired effects of bromocriptine. Concurrent use is not recommended; an alternate form of contraception is recommended during bromocriptine therapy. (Minor) Bromocriptine is used to restore ovulation and ovarian function in amenorrheic women. Progestins can cause amenorrhea and, therefore, counteract the desired effects of bromocriptine. Concurrent use is not recommended; an alternate form of contraception is recommended during bromocriptine therapy.
Etonogestrel: (Minor) Bromocriptine is used to restore ovulation and ovarian function in amenorrheic women. Progestins can cause amenorrhea and, therefore, counteract the desired effects of bromocriptine. Concurrent use is not recommended; an alternate form of contraception is recommended during bromocriptine therapy.
Etonogestrel; Ethinyl Estradiol: (Minor) Bromocriptine is used to restore ovulation and ovarian function in amenorrheic women. Estrogens and progestins can cause amenorrhea and, therefore, counteract the desired effects of bromocriptine. Concurrent use is not recommended; an alternate form of contraception is recommended during bromocriptine therapy. (Minor) Bromocriptine is used to restore ovulation and ovarian function in amenorrheic women. Progestins can cause amenorrhea and, therefore, counteract the desired effects of bromocriptine. Concurrent use is not recommended; an alternate form of contraception is recommended during bromocriptine therapy.
Etravirine: (Moderate) Caution and close monitoring are advised if bromocriptine and etravirine are used together. Concurrent use may decrease the plasma concentrations of bromocriptine resulting in loss of efficacy. Bromocriptine is extensively metabolized by the liver via CYP3A4; etravirine is a moderate inducer of CYP3A4.
Fedratinib: (Major) When bromocriptine is used for diabetes, do not exceed a dose of 1.6 mg once daily during concomitant use of fedratinib. Use this combination with caution in patients receiving bromocriptine for other indications. Concurrent use may increase bromocriptine concentrations. Bromocriptine is extensively metabolized in the liver via CYP3A4; fedratinib is a moderate inhibitor of CYP3A4. Coadministration with another moderate CYP3A4 inhibitor increased bromocriptine exposure by 2.8-fold.
Fexofenadine; Pseudoephedrine: (Moderate) One case report documented worsening headache, hypertension, premature ventricular complexes, and ventricular tachycardia in a post-partum patient receiving bromocriptine for lactation suppression who was subsequently prescribed acetaminophen; dichloralphenazone; isometheptene for a headache. A second case involved a post-partum patient receiving bromocriptine who was later prescribed phenylpropanolamine; guaifenesin and subsequently developed hypertension, tachycardia, seizures, and cerebral vasospasm. Also, ergot alkaloids, which are chemically related to bromocriptine, should not be administered with other vasoconstrictors. Therefore, until more data become available, concurrent use of bromocriptine and some sympathomimetics such as vasopressors (e.g., norepinephrine, dopamine, phenylephrine), cocaine, epinephrine, phenylpropanolamine, ephedra, ma huang, ephedrine, pseudoephedrine, amphetamines, and phentermine should be approached with caution.
Fluconazole: (Major) When bromocriptine is used for diabetes, do not exceed a dose of 1.6 mg once daily during concomitant use of fluconazole. Use this combination with caution in patients receiving bromocriptine for other indications. Concurrent use may increase bromocriptine concentrations. Bromocriptine is extensively metabolized in the liver via CYP3A4; fluconazole is a moderate inhibitor of CYP3A4. Administration of bromocriptine with a moderate inhibitor of CYP3A4 increased the bromocriptine mean AUC and Cmax by 3.7-fold and 4.6-fold, respectively.
Fluphenazine: (Major) Avoid concurrent use of phenothiazines and bromocriptine when possible. Bromocriptine may interact with dopamine antagonists such as the phenothiazines. The phenothiazines are noted to result in a decreased efficacy of bromocriptine. The prolactin-lowering effect of bromocriptine is antagonized; the elevation in prolactin levels produced by phenothiazines persists with chronic administration. In addition, bromocriptine, a dopamine agonist, may theoretically diminish the effectiveness of central dopamine antagonists such as the phenothiazines; however, such interactions are not certain.
Flutamide: (Moderate) Caution and close monitoring are advised if bromocriptine and flutamide are used together. Concurrent use may decrease the plasma concentrations of bromocriptine resulting in loss of efficacy. Bromocriptine is extensively metabolized by the liver via CYP3A4; in vitro data show that flutamide is a moderate inducer of CYP3A4.
Fluvoxamine: (Major) When bromocriptine is used for diabetes, limit the dose of bromocriptine (Cycloset) to 1.6 mg/day during coadministration of moderate CYP3A4 inhibitors such as fluvoxamine. Use this combination with caution in patients receiving bromocriptine for other indications. Concurrent use may significantly increase bromocriptine concentrations.
Fosamprenavir: (Major) When bromocriptine is used for diabetes, do not exceed a dose of 1.6 mg once daily during concomitant use of fosamprenavir. Use this combination with caution in patients receiving bromocriptine for other indications. Concurrent use may increase bromocriptine concentrations. Bromocriptine is extensively metabolized in the liver via CYP3A; fosamprenavir is a moderate inhibitor of CYP3A. Coadministration with another moderate CYP3A inhibitor increased bromocriptine exposure by 2.8-fold.
Fosphenytoin: (Moderate) Caution and close monitoring are advised if bromocriptine and fosphenytoin are used together. Concurrent use may decrease the plasma concentrations of bromocriptine resulting in loss of efficacy. Bromocriptine is extensively metabolized by the liver via CYP3A4; fosphenytoin is a strong inducer of CYP3A4.
Frovatriptan: (Major) There are limited clinical trial data supporting the safety of giving a serotonin-receptor agonist ("triptan") with bromocriptine, an ergot derivative. The concomitant use of these agents with bromocriptine should be avoided. There is concern that prolonged vasospastic reactions, hypertension, tachycardia, or other side effects may occur.
Grapefruit juice: (Major) Patients should avoid the use of grapefruit juice when bromocriptine is used for treatment of diabetes, ensuring adequate washout before initiating bromocriptine. Use this combination with caution in patients receiving bromocriptine for other indications. Concurrent use may significantly increase bromocriptine concentrations. Bromocriptine is extensively metabolized in the liver via CYP3A4; grapefruit juice is a strong inhibitor of CYP3A4.
Guaifenesin; Phenylephrine: (Moderate) The combination of bromocriptine with phenylephrine may cause headache, tachycardia, other cardiovascular abnormalities, seizures, and other serious effects. Concurrent use of bromocriptine and phenylephrine should be approached with caution. One case report documented worsening headache, hypertension, premature ventricular complexes, and ventricular tachycardia in a post-partum patient receiving bromocriptine for lactation suppression who was subsequently prescribed acetaminophen; dichloralphenazone; isometheptene for a headache. A second case involved a post-partum patient receiving bromocriptine who was later prescribed phenylpropanolamine; guaifenesin and subsequently developed hypertension, tachycardia, seizures, and cerebral vasospasm.
Guaifenesin; Pseudoephedrine: (Moderate) One case report documented worsening headache, hypertension, premature ventricular complexes, and ventricular tachycardia in a post-partum patient receiving bromocriptine for lactation suppression who was subsequently prescribed acetaminophen; dichloralphenazone; isometheptene for a headache. A second case involved a post-partum patient receiving bromocriptine who was later prescribed phenylpropanolamine; guaifenesin and subsequently developed hypertension, tachycardia, seizures, and cerebral vasospasm. Also, ergot alkaloids, which are chemically related to bromocriptine, should not be administered with other vasoconstrictors. Therefore, until more data become available, concurrent use of bromocriptine and some sympathomimetics such as vasopressors (e.g., norepinephrine, dopamine, phenylephrine), cocaine, epinephrine, phenylpropanolamine, ephedra, ma huang, ephedrine, pseudoephedrine, amphetamines, and phentermine should be approached with caution.
Haloperidol: (Major) Avoid concurrent use of haloperidol and bromocriptine when possible. Haloperidol results in a decreased efficacy of bromocriptine. The prolactin-lowering effect of bromocriptine is antagonized; the elevation in prolactin levels produced by haloperidol persists with chronic administration. Until more data are available, it is advisable to closely monitor for adverse events when these medications must be co-administered.
Hydroxyprogesterone: (Minor) Bromocriptine is used to restore ovulation and ovarian function in amenorrheic women. Hydroxyprogesterone can cause amenorrhea and, therefore, counteract the desired effects of bromocriptine. Concurrent use is not recommended.
Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate; Sodium Biphosphate: (Moderate) Theoretically, concurrent use of methylene blue and ergot alkaloid derivatives such as bromocriptine may increase the risk of serotonin syndrome. Methylene blue is a thiazine dye that is also a potent, reversible inhibitor of the enzyme responsible for the catabolism of serotonin in the brain (MAO-A) and ergot alkaloids increase central serotonin effects. Cases of serotonin syndrome have been reported, primarily following administration of standard infusions of methylene blue (1 to 8 mg/kg) as a visualizing agent in parathyroid surgery, in patients receiving selective serotonin reuptake inhibitors, serotonin/norepinephrine reuptake inhibitors, or clomipramine. It is not known if patients receiving other serotonergic psychiatric agents with intravenous methylene blue are at a comparable risk or if methylene blue administered by other routes (e.g., orally, local injection) or in doses less than 1 mg/kg IV can produce a similar outcome. Published interaction reports between intravenously administered methylene blue and serotonergic psychiatric agents have documented symptoms including lethargy, confusion, delirium, agitation, aggression, obtundation, myoclonus, expressive aphasia, hypertonia, pyrexia, elevated blood pressure, seizures, and/or coma. Serotonin syndrome is characterized by rapid development of various symptoms such as hyperthermia, hypertension, myoclonus, rigidity, hyperhidrosis, incoordination, diarrhea, mental status changes (e.g., confusion, delirium, or coma), and in rare cases, death. (Minor) Bromocriptine is highly bound (more than 90%) to serum proteins. Therefore, it may increase the unbound fraction of other highly protein-bound medications (e.g., aspirin and other salicylates), which may alter their effectiveness and risk for side effects.
Ibuprofen; Pseudoephedrine: (Moderate) One case report documented worsening headache, hypertension, premature ventricular complexes, and ventricular tachycardia in a post-partum patient receiving bromocriptine for lactation suppression who was subsequently prescribed acetaminophen; dichloralphenazone; isometheptene for a headache. A second case involved a post-partum patient receiving bromocriptine who was later prescribed phenylpropanolamine; guaifenesin and subsequently developed hypertension, tachycardia, seizures, and cerebral vasospasm. Also, ergot alkaloids, which are chemically related to bromocriptine, should not be administered with other vasoconstrictors. Therefore, until more data become available, concurrent use of bromocriptine and some sympathomimetics such as vasopressors (e.g., norepinephrine, dopamine, phenylephrine), cocaine, epinephrine, phenylpropanolamine, ephedra, ma huang, ephedrine, pseudoephedrine, amphetamines, and phentermine should be approached with caution.
Idelalisib: (Major) When bromocriptine is used for diabetes, avoid coadministration with idelalisib ensuring adequate washout before initiating bromocriptine. Use this combination with caution in patients receiving bromocriptine for other indications. Concurrent use may significantly increase bromocriptine concentrations. Bromocriptine is extensively metabolized in the liver via CYP3A4; idelalisib is a strong inhibitor of CYP3A4.
Iloperidone: (Moderate) The effectiveness of bromocriptine may be reduced by most of the atypical antipsychotics, via their action as dopamine antagonists. Monitor the patient for reduced response to bromocriptine. The atypical antipsychotics elevate prolactin to various degrees. Atypical antipsychotics may also aggravate diabetes mellitus and cause metabolic changes including hyperglycemia; use caution if bromocriptine is taken for diabetes. If bromocriptine is taken for diabetes, monitor for worsening glycemic control.
Imatinib: (Major) When bromocriptine is used for diabetes, do not exceed a dose of 1.6 mg once daily during concomitant use of imatinib. Use this combination with caution in patients receiving bromocriptine for other indications. Concurrent use may increase bromocriptine concentrations. Bromocriptine is extensively metabolized in the liver via CYP3A4; imatinib is a moderate inhibitor of CYP3A4. Administration of bromocriptine with a moderate inhibitor of CYP3A4 increased the bromocriptine mean AUC and Cmax by 3.7-fold and 4.6-fold, respectively.
Indinavir: (Major) When bromocriptine is used for diabetes, avoid coadministration with indinavir ensuring adequate washout before initiating bromocriptine. Use this combination with caution in patients receiving bromocriptine for other indications. Concurrent use may significantly increase bromocriptine concentrations. Bromocriptine is extensively metabolized in the liver via CYP3A4; indinavir is a strong inhibitor of CYP3A4.
Isavuconazonium: (Major) When bromocriptine is used for diabetes, do not exceed a dose of 1.6 mg once daily during concomitant use of isavuconazonium. Use this combination with caution in patients receiving bromocriptine for other indications. Concurrent use may increase bromocriptine concentrations. Bromocriptine is extensively metabolized in the liver via CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of CYP3A4. Administration of bromocriptine with a moderate inhibitor of CYP3A4 increased the bromocriptine mean AUC and Cmax by 3.7-fold and 4.6-fold, respectively.
Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Moderate) Caution and close monitoring are advised if bromocriptine and rifampin are used together. Concurrent use may decrease the plasma concentrations of bromocriptine resulting in loss of efficacy. Bromocriptine is extensively metabolized by the liver via CYP3A4; rifampin is a strong inducer of CYP3A4.
Isoniazid, INH; Rifampin: (Moderate) Caution and close monitoring are advised if bromocriptine and rifampin are used together. Concurrent use may decrease the plasma concentrations of bromocriptine resulting in loss of efficacy. Bromocriptine is extensively metabolized by the liver via CYP3A4; rifampin is a strong inducer of CYP3A4.
Itraconazole: (Major) When bromocriptine is used for diabetes, avoid coadministration with itraconazole ensuring adequate washout before initiating bromocriptine. Use this combination with caution in patients receiving bromocriptine for other indications. Concurrent use may significantly increase bromocriptine concentrations. Bromocriptine is extensively metabolized in the liver via CYP3A4; itraconazole is a strong inhibitor of CYP3A4.
Ketoconazole: (Major) When bromocriptine is used for diabetes, avoid coadministration with ketoconazole ensuring adequate washout before initiating bromocriptine. Use this combination with caution in patients receiving bromocriptine for other indications. Concurrent use may significantly increase bromocriptine concentrations. Bromocriptine is extensively metabolized in the liver via CYP3A4; ketoconazole is a strong inhibitor of CYP3A4.
Lanreotide: (Moderate) Monitor for an increase in bromocriptine-related adverse reactions if coadministration with lanreotide is necessary. Limited published data indicate that concomitant administration of a somatostatin analog and bromocriptine may increase the absorption of bromocriptine.
Lansoprazole; Amoxicillin; Clarithromycin: (Major) When bromocriptine is used for diabetes, avoid coadministration with clarithromycin ensuring adequate washout before initiating bromocriptine. Use this combination with caution in patients receiving bromocriptine for other indications. Concurrent use may significantly increase bromocriptine concentrations. Bromocriptine is extensively metabolized in the liver via CYP3A4; clarithromycin is a strong inhibitor of CYP3A4.
Lefamulin: (Major) When bromocriptine is used for diabetes, do not exceed a dose of 1.6 mg once daily during concomitant use of oral lefamulin. Use this combination with caution in patients receiving bromocriptine for other indications. Concurrent use may increase bromocriptine concentrations. Bromocriptine is extensively metabolized in the liver via CYP3A4; oral lefamulin is a moderate CYP3A4 inhibitor; an interaction is not expected with intravenous lefamulin. Coadministration with another moderate CYP3A4 inhibitor increased bromocriptine exposure by 2.8-fold.
Lenacapavir: (Major) When bromocriptine is used for diabetes, do not exceed a dose of 1.6 mg once daily during concomitant use of lenacapavir. Use this combination with caution in patients receiving bromocriptine for other indications. Concurrent use may increase bromocriptine concentrations. Bromocriptine is extensively metabolized in the liver via CYP3A; lenacapavir is a moderate inhibitor of CYP3A. Coadministration with another moderate CYP3A inhibitor increased bromocriptine exposure by 2.8-fold.
Letermovir: (Major) When bromocriptine is used for diabetes, do not exceed a dose of 1.6 mg once daily during concomitant use of letermovir. If the patient is also receiving cyclosporine, avoid coadministration ensuring adequate washout before initiating bromocriptine; the addition of cyclosporine may increase the magnitude of the interaction. When bromocriptine is used for other indications, use caution during coadministration of letermovir with or without cyclosporine. Concurrent use may increase bromocriptine concentrations. Bromocriptine is a substrate of CYP3A4. Letermovir is a moderate CYP3A4 inhibitor. The combined effect of letermovir and cyclosporine on CYP3A4 substrates may be similar to a strong CYP3A4 inhibitor. The AUC of bromocriptine was increased by 3.7-fold in the presence of a moderate CYP3A4 inhibitor.
Leuprolide; Norethindrone: (Minor) Bromocriptine is used to restore ovulation and ovarian function in amenorrheic women. Progestins can cause amenorrhea and, therefore, counteract the desired effects of bromocriptine. Concurrent use is not recommended; an alternate form of contraception is recommended during bromocriptine therapy.
Levoketoconazole: (Major) When bromocriptine is used for diabetes, avoid coadministration with ketoconazole ensuring adequate washout before initiating bromocriptine. Use this combination with caution in patients receiving bromocriptine for other indications. Concurrent use may significantly increase bromocriptine concentrations. Bromocriptine is extensively metabolized in the liver via CYP3A4; ketoconazole is a strong inhibitor of CYP3A4.
Levonorgestrel: (Minor) Bromocriptine is used to restore ovulation and ovarian function in amenorrheic women. Progestins can cause amenorrhea and, therefore, counteract the desired effects of bromocriptine. Concurrent use is not recommended; an alternate form of contraception is recommended during bromocriptine therapy.
Levonorgestrel; Ethinyl Estradiol: (Minor) Bromocriptine is used to restore ovulation and ovarian function in amenorrheic women. Estrogens and progestins can cause amenorrhea and, therefore, counteract the desired effects of bromocriptine. Concurrent use is not recommended; an alternate form of contraception is recommended during bromocriptine therapy. (Minor) Bromocriptine is used to restore ovulation and ovarian function in amenorrheic women. Progestins can cause amenorrhea and, therefore, counteract the desired effects of bromocriptine. Concurrent use is not recommended; an alternate form of contraception is recommended during bromocriptine therapy.
Levonorgestrel; Ethinyl Estradiol; Ferrous Bisglycinate: (Minor) Bromocriptine is used to restore ovulation and ovarian function in amenorrheic women. Estrogens and progestins can cause amenorrhea and, therefore, counteract the desired effects of bromocriptine. Concurrent use is not recommended; an alternate form of contraception is recommended during bromocriptine therapy. (Minor) Bromocriptine is used to restore ovulation and ovarian function in amenorrheic women. Progestins can cause amenorrhea and, therefore, counteract the desired effects of bromocriptine. Concurrent use is not recommended; an alternate form of contraception is recommended during bromocriptine therapy.
Levonorgestrel; Ethinyl Estradiol; Ferrous Fumarate: (Minor) Bromocriptine is used to restore ovulation and ovarian function in amenorrheic women. Estrogens and progestins can cause amenorrhea and, therefore, counteract the desired effects of bromocriptine. Concurrent use is not recommended; an alternate form of contraception is recommended during bromocriptine therapy. (Minor) Bromocriptine is used to restore ovulation and ovarian function in amenorrheic women. Progestins can cause amenorrhea and, therefore, counteract the desired effects of bromocriptine. Concurrent use is not recommended; an alternate form of contraception is recommended during bromocriptine therapy.
Lidocaine; Epinephrine: (Moderate) One case report documented worsening headache, hypertension, premature ventricular complexes, and ventricular tachycardia in a post-partum patient receiving bromocriptine for lactation suppression who was subsequently prescribed acetaminophen; dichloralphenazone; isometheptene for a headache. A second case involved a post-partum patient receiving bromocriptine who was later prescribed phenylpropanolamine; guaifenesin and subsequently developed hypertension, tachycardia, seizures, and cerebral vasospasm. Also, ergot alkaloids, which are chemically related to bromocriptine, should not be administered with other vasoconstrictors. Therefore, until more data become available, concurrent use of bromocriptine and some sympathomimetics such as vasopressors (e.g., norepinephrine, dopamine, phenylephrine), cocaine, epinephrine, phenylpropanolamine, ephedra, ma huang, ephedrine, pseudoephedrine, amphetamines, and phentermine should be approached with caution.
Linezolid: (Moderate) Serious CNS reactions, such as serotonin syndrome, have been reported during the concurrent use of linezolid and psychiatric medications that enhance central serotonergic activity; therefore, caution is warranted with concomitant use of other agents with serotonergic activity, including ergot alkaloids.
Lisdexamfetamine: (Moderate) Concurrent use of bromocriptine and some sympathomimetics such as amphetamines should be approached with caution. One case report documented worsening headache, hypertension, premature ventricular complexes, and ventricular tachycardia in a post-partum patient receiving bromocriptine for lactation suppression who was subsequently prescribed an isometheptene-containing medication for a headache. A second case involved a post-partum patient receiving bromocriptine who was later prescribed a phenylpropanolamine-expectorant combination and subsequently developed hypertension, tachycardia, seizures, and cerebral vasospasm.
Lonafarnib: (Major) When bromocriptine is used for diabetes, avoid coadministration with lonafarnib ensuring adequate washout before initiating bromocriptine. Use this combination with caution in patients receiving bromocriptine for other indications. Concurrent use may significantly increase bromocriptine concentrations. Bromocriptine is extensively metabolized in the liver via CYP3A4; lonafarnib is a strong inhibitor of CYP3A4.
Lopinavir; Ritonavir: (Major) When bromocriptine is used for diabetes, avoid coadministration with ritonavir ensuring adequate washout before initiating bromocriptine. Use this combination with caution in patients receiving bromocriptine for other indications. Concurrent use may significantly increase bromocriptine concentrations. Bromocriptine is extensively metabolized in the liver via CYP3A4; ritonavir is a strong inhibitor of CYP3A4.
Loratadine; Pseudoephedrine: (Moderate) One case report documented worsening headache, hypertension, premature ventricular complexes, and ventricular tachycardia in a post-partum patient receiving bromocriptine for lactation suppression who was subsequently prescribed acetaminophen; dichloralphenazone; isometheptene for a headache. A second case involved a post-partum patient receiving bromocriptine who was later prescribed phenylpropanolamine; guaifenesin and subsequently developed hypertension, tachycardia, seizures, and cerebral vasospasm. Also, ergot alkaloids, which are chemically related to bromocriptine, should not be administered with other vasoconstrictors. Therefore, until more data become available, concurrent use of bromocriptine and some sympathomimetics such as vasopressors (e.g., norepinephrine, dopamine, phenylephrine), cocaine, epinephrine, phenylpropanolamine, ephedra, ma huang, ephedrine, pseudoephedrine, amphetamines, and phentermine should be approached with caution.
Lorlatinib: (Moderate) Caution and close monitoring are advised if bromocriptine and lorlatinib are used together. Concurrent use may decrease the plasma concentrations of bromocriptine resulting in loss of efficacy. Bromocriptine is extensively metabolized by the liver via CYP3A4; lorlatinib is a moderate inducer of CYP3A4.
Loxapine: (Major) Avoid concurrent use of loxapine and bromocriptine when possible. Loxapine, like other older antipsychotics, results in a decreased efficacy of bromocriptine. The prolactin-lowering effect of bromocriptine is antagonized; the elevation in prolactin levels produced by loxapine persists with chronic administration.
Lumacaftor; Ivacaftor: (Moderate) Caution and close monitoring are advised if bromocriptine and lumacaftor; ivacaftor are used together. Concurrent use may decrease the plasma concentrations of bromocriptine resulting in loss of efficacy. Bromocriptine is extensively metabolized by the liver via CYP3A; lumacaftor is a strong inducer of CYP3A.
Lumacaftor; Ivacaftor: (Moderate) Caution and close monitoring are advised if bromocriptine and lumacaftor; ivacaftor are used together. Concurrent use may decrease the plasma concentrations of bromocriptine resulting in loss of efficacy. Bromocriptine is extensively metabolized by the liver via CYP3A; lumacaftor is a strong inducer of CYP3A.
Lumateperone: (Moderate) The effectiveness of bromocriptine may be reduced by most of the atypical antipsychotics, via their action as dopamine antagonists. Monitor the patient for reduced response to bromocriptine. The atypical antipsychotics elevate prolactin to various degrees. Atypical antipsychotics may also aggravate diabetes mellitus and cause metabolic changes including hyperglycemia; use caution if bromocriptine is taken for diabetes. If bromocriptine is taken for diabetes, monitor for worsening glycemic control.
Lurasidone: (Moderate) The effectiveness of bromocriptine may be reduced by most of the atypical antipsychotics, via their action as dopamine antagonists. Monitor the patient for reduced response to bromocriptine. The atypical antipsychotics elevate prolactin to various degrees. Atypical antipsychotics may also aggravate diabetes mellitus and cause metabolic changes including hyperglycemia; use caution if bromocriptine is taken for diabetes. If bromocriptine is taken for diabetes, monitor for worsening glycemic control.
Mafenide: (Moderate) Sulfonamides may enhance the hypoglycemic action of antidiabetic agents; patients with diabetes mellitus should be closely monitored during sulfonamide treatment. Sulfonamides may induce hypoglycemia in some patients by increasing the secretion of insulin from the pancreas. Patients at risk include those with compromised renal function, those fasting for prolonged periods, those that are malnourished, and those receiving high or excessive doses of sulfonamides. Bromocriptine is highly bound to serum proteins. Therefore, it may increase the unbound fraction of other highly protein-bound medications (e.g., sulfonamides), which may alter their effectiveness and risk for side effects.
Magnesium Salicylate: (Minor) Bromocriptine is highly bound (more than 90%) to serum proteins. Therefore, it may increase the unbound fraction of other highly protein-bound medications (e.g., aspirin and other salicylates), which may alter their effectiveness and risk for side effects.
Mavacamten: (Moderate) Caution and close monitoring are advised if bromocriptine and mavacamten are used together. Concurrent use may decrease the plasma concentrations of bromocriptine resulting in loss of efficacy. Bromocriptine is extensively metabolized by the liver via CYP3A; mavacamten is a moderate inducer of CYP3A.
Mecamylamine: (Minor) Bromocriptine has only minimal affinity for adrenergic receptors; however, hypotension can occur during bromocriptine administration. Orthostatic hypotension occurs in 6% of acromegaly patients receiving the drug. Hypotension occurred frequently (approximately 30%) in postpartum studies, which in rare cases approached a decline in supine pressure of almost 60 mmHg. It is unknown if bromocriptine is the exact cause of this effect. However, the drug should be used cautiously with other medications known to lower blood pressure such as antihypertensive agents. Monitoring of blood pressure should be considered, especially during the initial weeks of concomitant therapy.
Medroxyprogesterone: (Minor) Bromocriptine is used to restore ovulation and ovarian function in amenorrheic women. Progestins can cause amenorrhea and, therefore, counteract the desired effects of bromocriptine. Concurrent use is not recommended; an alternate form of contraception is recommended during bromocriptine therapy.
Memantine: (Moderate) The pharmacologic effects of dopaminergic agents, including the ergot derivative bromocriptine, may be enhanced with use of memantine; dosage adjustments of dopaminergic agents may be required when memantine is coadministered.
Methamphetamine: (Moderate) Concurrent use of bromocriptine and some sympathomimetics such as amphetamines should be approached with caution. One case report documented worsening headache, hypertension, premature ventricular complexes, and ventricular tachycardia in a post-partum patient receiving bromocriptine for lactation suppression who was subsequently prescribed an isometheptene-containing medication for a headache. A second case involved a post-partum patient receiving bromocriptine who was later prescribed a phenylpropanolamine-expectorant combination and subsequently developed hypertension, tachycardia, seizures, and cerebral vasospasm.
Methenamine; Sodium Acid Phosphate; Methylene Blue; Hyoscyamine: (Moderate) Theoretically, concurrent use of methylene blue and ergot alkaloid derivatives such as bromocriptine may increase the risk of serotonin syndrome. Methylene blue is a thiazine dye that is also a potent, reversible inhibitor of the enzyme responsible for the catabolism of serotonin in the brain (MAO-A) and ergot alkaloids increase central serotonin effects. Cases of serotonin syndrome have been reported, primarily following administration of standard infusions of methylene blue (1 to 8 mg/kg) as a visualizing agent in parathyroid surgery, in patients receiving selective serotonin reuptake inhibitors, serotonin/norepinephrine reuptake inhibitors, or clomipramine. It is not known if patients receiving other serotonergic psychiatric agents with intravenous methylene blue are at a comparable risk or if methylene blue administered by other routes (e.g., orally, local injection) or in doses less than 1 mg/kg IV can produce a similar outcome. Published interaction reports between intravenously administered methylene blue and serotonergic psychiatric agents have documented symptoms including lethargy, confusion, delirium, agitation, aggression, obtundation, myoclonus, expressive aphasia, hypertonia, pyrexia, elevated blood pressure, seizures, and/or coma. Serotonin syndrome is characterized by rapid development of various symptoms such as hyperthermia, hypertension, myoclonus, rigidity, hyperhidrosis, incoordination, diarrhea, mental status changes (e.g., confusion, delirium, or coma), and in rare cases, death.
Methenamine; Sodium Salicylate: (Minor) Bromocriptine is highly bound (more than 90%) to serum proteins. Therefore, it may increase the unbound fraction of other highly protein-bound medications (e.g., aspirin and other salicylates), which may alter their effectiveness and risk for side effects.
Methylene Blue: (Moderate) Theoretically, concurrent use of methylene blue and ergot alkaloid derivatives such as bromocriptine may increase the risk of serotonin syndrome. Methylene blue is a thiazine dye that is also a potent, reversible inhibitor of the enzyme responsible for the catabolism of serotonin in the brain (MAO-A) and ergot alkaloids increase central serotonin effects. Cases of serotonin syndrome have been reported, primarily following administration of standard infusions of methylene blue (1 to 8 mg/kg) as a visualizing agent in parathyroid surgery, in patients receiving selective serotonin reuptake inhibitors, serotonin/norepinephrine reuptake inhibitors, or clomipramine. It is not known if patients receiving other serotonergic psychiatric agents with intravenous methylene blue are at a comparable risk or if methylene blue administered by other routes (e.g., orally, local injection) or in doses less than 1 mg/kg IV can produce a similar outcome. Published interaction reports between intravenously administered methylene blue and serotonergic psychiatric agents have documented symptoms including lethargy, confusion, delirium, agitation, aggression, obtundation, myoclonus, expressive aphasia, hypertonia, pyrexia, elevated blood pressure, seizures, and/or coma. Serotonin syndrome is characterized by rapid development of various symptoms such as hyperthermia, hypertension, myoclonus, rigidity, hyperhidrosis, incoordination, diarrhea, mental status changes (e.g., confusion, delirium, or coma), and in rare cases, death.
Methylergonovine: (Contraindicated) The concomitant use of bromocriptine, an ergot derivative, with ergot alkaloids may potentially lead to ergot toxicity; therefore the combination should be avoided. Symptoms of ergotism include angina, asthenia, chest pain (unspecified), coronary vasospasm, muscle cramps (claudication), myalgia, paresthesias, and palpitations or changes in heart rate (e.g., sinus bradycardia or sinus tachycardia). Peripheral vasoconstriction of the arteries may result in hypothermia or tissue necrosis, which may lead to gangrene. Other serious complications include hypertension (portal), mesenteric artery thrombosis, myocardial infarction, and renal tubular necrosis. Symptoms such as confusion, depression, drowsiness, and seizures rarely occur.
Methylphenidate Derivatives: (Moderate) Increased dopaminergic effects may occur during coadministration of methylphenidate derivatives, inhibitors of dopamine reuptake, and dopamine agonists such as bromocriptine. Dopaminergic side effects, such as nausea, loss of appetite, weight loss, insomnia, tremor, nervousness, or changes in mood or behavior, are possible.
Methylphenidate: (Moderate) Increased dopaminergic effects may occur during coadministration of methylphenidate derivatives, inhibitors of dopamine reuptake, and dopamine agonists such as bromocriptine. Dopaminergic side effects, such as nausea, loss of appetite, weight loss, insomnia, tremor, nervousness, or changes in mood or behavior, are possible.
Metoclopramide: (Major) Metoclopramide is a central dopamine antagonist. Metoclopramide can antagonize the actions of dopamine agonists such as bromocriptine; therefore, the combined use of these agents is not recommended.
Metyrapone: (Moderate) In patients taking insulin or other antidiabetic agents such as bromocriptine, the signs and symptoms of acute metyrapone toxicity (e.g., symptoms of acute adrenal insufficiency) may be aggravated or modified.
Midodrine: (Moderate) The combination of bromocriptine with mdodrine may cause headache, tachycardia, other cardiovascular abnormalities, seizures, and other serious effects. Concurrent use of bromocriptine and midodrine should be approached with caution. One case report documented worsening headache, hypertension, premature ventricular complexes, and ventricular tachycardia in a post-partum patient receiving bromocriptine for lactation suppression who was subsequently prescribed acetaminophen; dichloralphenazone; isometheptene for a headache. A second case involved a post-partum patient receiving bromocriptine who was later prescribed phenylpropanolamine; guaifenesin and subsequently developed hypertension, tachycardia, seizures, and cerebral vasospasm.
Mifepristone: (Major) Concomitant use of strong CYP3A4 inhibitors like mifepristone should be avoided when bromocriptine is used for diabetes, and likely when used for other indications. Consider alternative treatments. Concurrent use may increase bromocriptine concentrations substantially, and increase the risk for side effects. Side effects associated with increased blood levels of bromocriptine include nausea, vomiting, constipation, diaphoresis, dizziness, pallor, severe hypotension, confusion, lethargy, drowsiness, and delusions or hallucinations. Bromocriptine is extensively metabolized in the liver via CYP3A4; mifepristone is a strong inhibitor of CYP3A4. Administration of bromocriptine with a moderate inhibitor of CYP3A4 increased the bromocriptine mean AUC and Cmax by 3.7-fold and 4.6-fold, respectively. The prolonged action and long half-life of mifepristone may result in prolonged inhibition of CYP3A4.
Mitotane: (Moderate) Caution and close monitoring are advised if bromocriptine and mitotane are used together. Concurrent use may decrease the plasma concentrations of bromocriptine resulting in loss of efficacy. Bromocriptine is extensively metabolized by the liver via CYP3A4; mitotane is a strong inducer of CYP3A4.
Modafinil: (Moderate) Caution and close monitoring are advised if bromocriptine and modafinil are used together. Concurrent use may decrease the plasma concentrations of bromocriptine resulting in loss of efficacy. Bromocriptine is extensively metabolized by the liver via CYP3A4; modafinil is a moderate inducer of CYP3A4.
Molindone: (Major) Avoid concurrent use of molindone and bromocriptine when possible. Molindone results in a decreased efficacy of bromocriptine. The prolactin-lowering effect of bromocriptine is antagonized; the elevation in prolactin levels produced by molindone persists with chronic administration.
Nafcillin: (Moderate) Caution and close monitoring are advised if bromocriptine and griseofulvin are used together. Concurrent use may decrease the plasma concentrations of bromocriptine resulting in loss of efficacy. Bromocriptine is extensively metabolized by the liver via CYP3A4; In vitro data suggest that nafcillin may induce the CYP3A4 isoenzyme.
Naproxen; Pseudoephedrine: (Moderate) One case report documented worsening headache, hypertension, premature ventricular complexes, and ventricular tachycardia in a post-partum patient receiving bromocriptine for lactation suppression who was subsequently prescribed acetaminophen; dichloralphenazone; isometheptene for a headache. A second case involved a post-partum patient receiving bromocriptine who was later prescribed phenylpropanolamine; guaifenesin and subsequently developed hypertension, tachycardia, seizures, and cerebral vasospasm. Also, ergot alkaloids, which are chemically related to bromocriptine, should not be administered with other vasoconstrictors. Therefore, until more data become available, concurrent use of bromocriptine and some sympathomimetics such as vasopressors (e.g., norepinephrine, dopamine, phenylephrine), cocaine, epinephrine, phenylpropanolamine, ephedra, ma huang, ephedrine, pseudoephedrine, amphetamines, and phentermine should be approached with caution.
Naratriptan: (Major) There are limited clinical trial data supporting the safety of giving a serotonin-receptor agonist ("triptan") with bromocriptine, an ergot derivative. The concomitant use of these agents with bromocriptine should be avoided. There is concern that prolonged vasospastic reactions, hypertension, tachycardia, or other side effects may occur.
Nefazodone: (Major) When bromocriptine is used for diabetes, avoid coadministration with nefazodone ensuring adequate washout before initiating bromocriptine. Use this combination with caution in patients receiving bromocriptine for other indications. Concurrent use may significantly increase bromocriptine concentrations. Bromocriptine is extensively metabolized in the liver via CYP3A4; nefazodone is a strong inhibitor of CYP3A4.
Nelfinavir: (Major) When bromocriptine is used for diabetes, avoid coadministration with nelfinavir ensuring adequate washout before initiating bromocriptine. Use this combination with caution in patients receiving bromocriptine for other indications. Concurrent use may significantly increase bromocriptine concentrations. Bromocriptine is extensively metabolized in the liver via CYP3A4; nelfinavir is a strong inhibitor of CYP3A4.
Netupitant, Fosnetupitant; Palonosetron: (Major) When bromocriptine is used for diabetes, do not exceed a dose of 1.6 mg once daily during concomitant use of netupitant; palonosetron. Use this combination with caution in patients receiving bromocriptine for other indications. Concurrent use may increase bromocriptine concentrations. Bromocriptine is extensively metabolized in the liver via CYP3A4; netupitant is a moderate inhibitor of CYP3A4. Administration of bromocriptine with a moderate inhibitor of CYP3A4 increased the bromocriptine mean AUC and Cmax by 3.7-fold and 4.6-fold, respectively.
Nicotine: (Minor) Use caution during use of tobacco or other nicotine-containing products while taking bromocriptine. Concurrent use of vasoconstrictors, such as nicotine, may result in enhanced vasoconstriction from ergot-based medications. Published reports of interactions between bromocriptine, an ergot derivative, and tobacco smoking or nicotine are not available. Safety and efficacy of bromocriptine for helping patients with smoking cessation is under investigation, but safety of use with nicotine products concurrently or if the patient continues to smoke is not established.
Nilotinib: (Major) When bromocriptine is used for diabetes, do not exceed a dose of 1.6 mg once daily during concomitant use of nilotinib. Use this combination with caution in patients receiving bromocriptine for other indications. Concurrent use may increase bromocriptine concentrations. Bromocriptine is extensively metabolized in the liver via CYP3A4; nilotinib is a moderate inhibitor of CYP3A4. Administration of bromocriptine with a moderate inhibitor of CYP3A4 increased the bromocriptine mean AUC and Cmax by 3.7-fold and 4.6-fold, respectively.
Nirmatrelvir; Ritonavir: (Major) When bromocriptine is used for diabetes, avoid coadministration with ritonavir ensuring adequate washout before initiating bromocriptine. Use this combination with caution in patients receiving bromocriptine for other indications. Concurrent use may significantly increase bromocriptine concentrations. Bromocriptine is extensively metabolized in the liver via CYP3A4; ritonavir is a strong inhibitor of CYP3A4.
Nirogacestat: (Major) When bromocriptine is used for diabetes, do not exceed a dose of 1.6 mg once daily during concomitant use of nirogacestat. Use this combination with caution in patients receiving bromocriptine for other indications. Concurrent use may increase bromocriptine concentrations. Bromocriptine is extensively metabolized in the liver via CYP3A; nirogacestat is a moderate inhibitor of CYP3A. Coadministration with another moderate CYP3A inhibitor increased bromocriptine exposure by 2.8-fold.
Norepinephrine: (Moderate) The combination of bromocriptine with norepinephrine may cause headache, tachycardia, other cardiovascular abnormalities, seizures, and other serious effects. Concurrent use of bromocriptine and norepinephrine should be approached with caution. One case report documented worsening headache, hypertension, premature ventricular complexes, and ventricular tachycardia in a post-partum patient receiving bromocriptine for lactation suppression who was subsequently prescribed acetaminophen; dichloralphenazone; isometheptene for a headache. A second case involved a post-partum patient receiving bromocriptine who was later prescribed phenylpropanolamine; guaifenesin and subsequently developed hypertension, tachycardia, seizures, and cerebral vasospasm.
Norethindrone Acetate; Ethinyl Estradiol; Ferrous fumarate: (Minor) Bromocriptine is used to restore ovulation and ovarian function in amenorrheic women. Estrogens and progestins can cause amenorrhea and, therefore, counteract the desired effects of bromocriptine. Concurrent use is not recommended; an alternate form of contraception is recommended during bromocriptine therapy. (Minor) Bromocriptine is used to restore ovulation and ovarian function in amenorrheic women. Progestins can cause amenorrhea and, therefore, counteract the desired effects of bromocriptine. Concurrent use is not recommended; an alternate form of contraception is recommended during bromocriptine therapy.
Norethindrone: (Minor) Bromocriptine is used to restore ovulation and ovarian function in amenorrheic women. Progestins can cause amenorrhea and, therefore, counteract the desired effects of bromocriptine. Concurrent use is not recommended; an alternate form of contraception is recommended during bromocriptine therapy.
Norethindrone; Ethinyl Estradiol: (Minor) Bromocriptine is used to restore ovulation and ovarian function in amenorrheic women. Estrogens and progestins can cause amenorrhea and, therefore, counteract the desired effects of bromocriptine. Concurrent use is not recommended; an alternate form of contraception is recommended during bromocriptine therapy. (Minor) Bromocriptine is used to restore ovulation and ovarian function in amenorrheic women. Progestins can cause amenorrhea and, therefore, counteract the desired effects of bromocriptine. Concurrent use is not recommended; an alternate form of contraception is recommended during bromocriptine therapy.
Norethindrone; Ethinyl Estradiol; Ferrous fumarate: (Minor) Bromocriptine is used to restore ovulation and ovarian function in amenorrheic women. Estrogens and progestins can cause amenorrhea and, therefore, counteract the desired effects of bromocriptine. Concurrent use is not recommended; an alternate form of contraception is recommended during bromocriptine therapy. (Minor) Bromocriptine is used to restore ovulation and ovarian function in amenorrheic women. Progestins can cause amenorrhea and, therefore, counteract the desired effects of bromocriptine. Concurrent use is not recommended; an alternate form of contraception is recommended during bromocriptine therapy.
Norgestimate; Ethinyl Estradiol: (Minor) Bromocriptine is used to restore ovulation and ovarian function in amenorrheic women. Estrogens and progestins can cause amenorrhea and, therefore, counteract the desired effects of bromocriptine. Concurrent use is not recommended; an alternate form of contraception is recommended during bromocriptine therapy. (Minor) Bromocriptine is used to restore ovulation and ovarian function in amenorrheic women. Progestins can cause amenorrhea and, therefore, counteract the desired effects of bromocriptine. Concurrent use is not recommended; an alternate form of contraception is recommended during bromocriptine therapy.
Norgestrel: (Minor) Bromocriptine is used to restore ovulation and ovarian function in amenorrheic women. Progestins can cause amenorrhea and, therefore, counteract the desired effects of bromocriptine. Concurrent use is not recommended; an alternate form of contraception is recommended during bromocriptine therapy.
Octreotide: (Major) When bromocriptine is used for diabetes, do not exceed a dose of 1.6 mg once daily during concomitant use of octreotide. Use this combination with caution in patients receiving bromocriptine for other indications. Concurrent use may increase bromocriptine concentrations. Bromocriptine is extensively metabolized in the liver via CYP3A4; octreotide is a moderate inhibitor of CYP3A4. The concomitant treatment of acromegalic patients with bromocriptine and octreotide increased the bromocriptine AUC by 38%.
Olanzapine: (Moderate) The effectiveness of bromocriptine may be reduced by most of the atypical antipsychotics, via their action as dopamine antagonists. Monitor the patient for reduced response to bromocriptine. The atypical antipsychotics elevate prolactin to various degrees. Atypical antipsychotics may also aggravate diabetes mellitus and cause metabolic changes including hyperglycemia; use caution if bromocriptine is taken for diabetes. If bromocriptine is taken for diabetes, monitor for worsening glycemic control.
Olanzapine; Fluoxetine: (Moderate) The effectiveness of bromocriptine may be reduced by most of the atypical antipsychotics, via their action as dopamine antagonists. Monitor the patient for reduced response to bromocriptine. The atypical antipsychotics elevate prolactin to various degrees. Atypical antipsychotics may also aggravate diabetes mellitus and cause metabolic changes including hyperglycemia; use caution if bromocriptine is taken for diabetes. If bromocriptine is taken for diabetes, monitor for worsening glycemic control.
Olanzapine; Samidorphan: (Moderate) The effectiveness of bromocriptine may be reduced by most of the atypical antipsychotics, via their action as dopamine antagonists. Monitor the patient for reduced response to bromocriptine. The atypical antipsychotics elevate prolactin to various degrees. Atypical antipsychotics may also aggravate diabetes mellitus and cause metabolic changes including hyperglycemia; use caution if bromocriptine is taken for diabetes. If bromocriptine is taken for diabetes, monitor for worsening glycemic control.
Omeprazole; Amoxicillin; Rifabutin: (Moderate) Caution and close monitoring are advised if bromocriptine and rifabutin are used together. Concurrent use may decrease the plasma concentrations of bromocriptine resulting in loss of efficacy. Bromocriptine is extensively metabolized by the liver via CYP3A4; rifabutin is a moderate inducer of CYP3A4.
Paliperidone: (Moderate) The effectiveness of bromocriptine may be reduced by most of the atypical antipsychotics, via their action as dopamine antagonists. Monitor the patient for reduced response to bromocriptine. The atypical antipsychotics elevate prolactin to various degrees. Atypical antipsychotics may also aggravate diabetes mellitus and cause metabolic changes including hyperglycemia; use caution if bromocriptine is taken for diabetes. If bromocriptine is taken for diabetes, monitor for worsening glycemic control.
Pasireotide: (Moderate) Monitor blood glucose levels regularly in patients taking bromocriptine for diabetes, especially when pasireotide treatment is initiated or when the dose is altered. Adjust treatment with antidiabetic agents as clinically indicated. Pasireotide inhibits the secretion of insulin and glucagon. Patients treated with pasireotide may experience either hypoglycemia or hyperglycemia.
Pazopanib: (Moderate) Pazopanib is a weak inhibitor of CYP3A4. Coadministration of pazopanib and bromocriptine, a CYP3A4 substrate, may cause an increase in systemic concentrations of bromocriptine. Use caution when administering these drugs concomitantly.
Pegvisomant: (Moderate) Monitor blood glucose levels regularly in patients with diabetes, especially when pegvisomant treatment is initiated or when the dose is altered. Adjust treatment with antidiabetic agents as clinically indicated. Pegvisomant increases sensitivity to insulin by lowering the activity of growth hormone, and in some patients glucose tolerance improves with treatment. Patients with diabetes treated with pegvisomant and antidiabetic agents may be more likely to experience hypoglycemia.
Perphenazine: (Major) Avoid concurrent use of phenothiazines and bromocriptine when possible. Bromocriptine may interact with dopamine antagonists such as the phenothiazines. The phenothiazines are noted to result in a decreased efficacy of bromocriptine. The prolactin-lowering effect of bromocriptine is antagonized; the elevation in prolactin levels produced by phenothiazines persists with chronic administration. In addition, bromocriptine, a dopamine agonist, may theoretically diminish the effectiveness of central dopamine antagonists such as the phenothiazines; however, such interactions are not certain.
Perphenazine; Amitriptyline: (Major) Avoid concurrent use of phenothiazines and bromocriptine when possible. Bromocriptine may interact with dopamine antagonists such as the phenothiazines. The phenothiazines are noted to result in a decreased efficacy of bromocriptine. The prolactin-lowering effect of bromocriptine is antagonized; the elevation in prolactin levels produced by phenothiazines persists with chronic administration. In addition, bromocriptine, a dopamine agonist, may theoretically diminish the effectiveness of central dopamine antagonists such as the phenothiazines; however, such interactions are not certain.
Pexidartinib: (Moderate) Caution and close monitoring are advised if bromocriptine and pexidartinib are used together. Concurrent use may decrease the plasma concentrations of bromocriptine resulting in loss of efficacy. Bromocriptine is extensively metabolized by the liver via CYP3A4; pexidartinib is a moderate inducer of CYP3A4.
Phendimetrazine: (Major) Phendimetrazine use should be avoided in patients receiving ergot alkaloids, such as bromocriptine. Although no data are available, it is possible that concomitant use of phendimetrazine with bromocriptine could cause additive and possibly severe peripheral vasoconstriction. Hypertension, headache, myocardial ectopy, and seizures have occurred when bromocriptine was combined with various sympathomimetic drugs.
Phenobarbital: (Moderate) Caution and close monitoring are advised if bromocriptine and phenobarbital are used together. Concurrent use may decrease the plasma concentrations of bromocriptine resulting in loss of efficacy. Bromocriptine is extensively metabolized by the liver via CYP3A4; phenobarbital is a strong inducer of CYP3A4.
Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Moderate) Caution and close monitoring are advised if bromocriptine and phenobarbital are used together. Concurrent use may decrease the plasma concentrations of bromocriptine resulting in loss of efficacy. Bromocriptine is extensively metabolized by the liver via CYP3A4; phenobarbital is a strong inducer of CYP3A4.
Phenothiazines: (Major) Avoid concurrent use of phenothiazines and bromocriptine when possible. Bromocriptine may interact with dopamine antagonists such as the phenothiazines. The phenothiazines are noted to result in a decreased efficacy of bromocriptine. The prolactin-lowering effect of bromocriptine is antagonized; the elevation in prolactin levels produced by phenothiazines persists with chronic administration. In addition, bromocriptine, a dopamine agonist, may theoretically diminish the effectiveness of central dopamine antagonists such as the phenothiazines; however, such interactions are not certain.
Phenoxybenzamine: (Minor) Bromocriptine has only minimal affinity for adrenergic receptors; however, hypotension can occur during bromocriptine administration. Orthostatic hypotension occurs in 6% of acromegaly patients receiving the drug. Hypotension occurred frequently (approximately 30%) in postpartum studies, which in rare cases approached a decline in supine pressure of almost 60 mmHg. It is unknown if bromocriptine is the exact cause of this effect. However, the drug should be used cautiously with other medications known to lower blood pressure such as antihypertensive agents. Monitoring of blood pressure should be considered, especially during the initial weeks of concomitant therapy.
Phentermine: (Moderate) The combination of bromocriptine with phentermine may cause headache, tachycardia, other cardiovascular abnormalities, seizures, and other serious effects. Concurrent use of bromocriptine and phentermine should be approached with caution.
Phentermine; Topiramate: (Moderate) The combination of bromocriptine with phentermine may cause headache, tachycardia, other cardiovascular abnormalities, seizures, and other serious effects. Concurrent use of bromocriptine and phentermine should be approached with caution.
Phentolamine: (Minor) Bromocriptine has only minimal affinity for adrenergic receptors; however, hypotension can occur during bromocriptine administration. Orthostatic hypotension occurs in 6% of acromegaly patients receiving the drug. Hypotension occurred frequently (approximately 30%) in postpartum studies, which in rare cases approached a decline in supine pressure of almost 60 mmHg. It is unknown if bromocriptine is the exact cause of this effect. However, the drug should be used cautiously with other medications known to lower blood pressure such as antihypertensive agents. Monitoring of blood pressure should be considered, especially during the initial weeks of concomitant therapy.
Phenylephrine: (Moderate) The combination of bromocriptine with phenylephrine may cause headache, tachycardia, other cardiovascular abnormalities, seizures, and other serious effects. Concurrent use of bromocriptine and phenylephrine should be approached with caution. One case report documented worsening headache, hypertension, premature ventricular complexes, and ventricular tachycardia in a post-partum patient receiving bromocriptine for lactation suppression who was subsequently prescribed acetaminophen; dichloralphenazone; isometheptene for a headache. A second case involved a post-partum patient receiving bromocriptine who was later prescribed phenylpropanolamine; guaifenesin and subsequently developed hypertension, tachycardia, seizures, and cerebral vasospasm.
Phenytoin: (Moderate) Caution and close monitoring are advised if bromocriptine and phenytoin are used together. Concurrent use may decrease the plasma concentrations of bromocriptine resulting in loss of efficacy. Bromocriptine is extensively metabolized by the liver via CYP3A4; phenytoin is a strong inducer of CYP3A4.
Pimozide: (Major) The prolactin-lowering effect of bromocriptine at the anterior pituitary may be antagonized by medications that increase prolactin levels, such as the pimozide. In addition, bromocriptine, a dopamine agonist, may diminish the effectiveness of central dopamine antagonists such as the antipsychotics.
Posaconazole: (Contraindicated) Coadministration of ergot alkaloids with inhibitors of CYP3A4, such as posaconazole, is contraindicated due to the risk of acute ergot toxicity (e.g., vasospasm leading to cerebral ischemia, peripheral ischemia, and/or other serious effects).
Prilocaine; Epinephrine: (Moderate) One case report documented worsening headache, hypertension, premature ventricular complexes, and ventricular tachycardia in a post-partum patient receiving bromocriptine for lactation suppression who was subsequently prescribed acetaminophen; dichloralphenazone; isometheptene for a headache. A second case involved a post-partum patient receiving bromocriptine who was later prescribed phenylpropanolamine; guaifenesin and subsequently developed hypertension, tachycardia, seizures, and cerebral vasospasm. Also, ergot alkaloids, which are chemically related to bromocriptine, should not be administered with other vasoconstrictors. Therefore, until more data become available, concurrent use of bromocriptine and some sympathomimetics such as vasopressors (e.g., norepinephrine, dopamine, phenylephrine), cocaine, epinephrine, phenylpropanolamine, ephedra, ma huang, ephedrine, pseudoephedrine, amphetamines, and phentermine should be approached with caution.
Primidone: (Moderate) Caution and close monitoring are advised if bromocriptine and primidone are used together. Concurrent use may decrease the plasma concentrations of bromocriptine resulting in loss of efficacy. Bromocriptine is extensively metabolized by the liver via CYP3A4; phenobarbital, the active metabolite of primidone, is a strong inducer of CYP3A4.
Probenecid: (Moderate) Bromocriptine is highly bound to serum proteins. Therefore, it may increase the unbound fraction of other highly protein-bound medications (e.g., probenecid), which may alter their effectiveness and risk for side effects.
Probenecid; Colchicine: (Moderate) Bromocriptine is highly bound to serum proteins. Therefore, it may increase the unbound fraction of other highly protein-bound medications (e.g., probenecid), which may alter their effectiveness and risk for side effects.
Prochlorperazine: (Major) Avoid concurrent use of phenothiazines and bromocriptine when possible. Bromocriptine may interact with dopamine antagonists such as the phenothiazines. The phenothiazines are noted to result in a decreased efficacy of bromocriptine. The prolactin-lowering effect of bromocriptine is antagonized; the elevation in prolactin levels produced by phenothiazines persists with chronic administration. In addition, bromocriptine, a dopamine agonist, may theoretically diminish the effectiveness of central dopamine antagonists such as the phenothiazines; however, such interactions are not certain.
Progesterone: (Minor) Bromocriptine is used to restore ovulation and ovarian function in amenorrheic women. Progestins can cause amenorrhea and, therefore, counteract the desired effects of bromocriptine. Concurrent use is not recommended; an alternate form of contraception is recommended during bromocriptine therapy.
Progestins: (Minor) Bromocriptine is used to restore ovulation and ovarian function in amenorrheic women. Progestins can cause amenorrhea and, therefore, counteract the desired effects of bromocriptine. Concurrent use is not recommended; an alternate form of contraception is recommended during bromocriptine therapy.
Promethazine: (Major) Avoid concurrent use of phenothiazines and bromocriptine when possible. Bromocriptine may interact with dopamine antagonists such as the phenothiazines. The phenothiazines are noted to result in a decreased efficacy of bromocriptine. The prolactin-lowering effect of bromocriptine is antagonized; the elevation in prolactin levels produced by phenothiazines persists with chronic administration. In addition, bromocriptine, a dopamine agonist, may theoretically diminish the effectiveness of central dopamine antagonists such as the phenothiazines; however, such interactions are not certain.
Promethazine; Dextromethorphan: (Major) Avoid concurrent use of phenothiazines and bromocriptine when possible. Bromocriptine may interact with dopamine antagonists such as the phenothiazines. The phenothiazines are noted to result in a decreased efficacy of bromocriptine. The prolactin-lowering effect of bromocriptine is antagonized; the elevation in prolactin levels produced by phenothiazines persists with chronic administration. In addition, bromocriptine, a dopamine agonist, may theoretically diminish the effectiveness of central dopamine antagonists such as the phenothiazines; however, such interactions are not certain.
Promethazine; Phenylephrine: (Major) Avoid concurrent use of phenothiazines and bromocriptine when possible. Bromocriptine may interact with dopamine antagonists such as the phenothiazines. The phenothiazines are noted to result in a decreased efficacy of bromocriptine. The prolactin-lowering effect of bromocriptine is antagonized; the elevation in prolactin levels produced by phenothiazines persists with chronic administration. In addition, bromocriptine, a dopamine agonist, may theoretically diminish the effectiveness of central dopamine antagonists such as the phenothiazines; however, such interactions are not certain. (Moderate) The combination of bromocriptine with phenylephrine may cause headache, tachycardia, other cardiovascular abnormalities, seizures, and other serious effects. Concurrent use of bromocriptine and phenylephrine should be approached with caution. One case report documented worsening headache, hypertension, premature ventricular complexes, and ventricular tachycardia in a post-partum patient receiving bromocriptine for lactation suppression who was subsequently prescribed acetaminophen; dichloralphenazone; isometheptene for a headache. A second case involved a post-partum patient receiving bromocriptine who was later prescribed phenylpropanolamine; guaifenesin and subsequently developed hypertension, tachycardia, seizures, and cerebral vasospasm.
Pseudoephedrine: (Moderate) One case report documented worsening headache, hypertension, premature ventricular complexes, and ventricular tachycardia in a post-partum patient receiving bromocriptine for lactation suppression who was subsequently prescribed acetaminophen; dichloralphenazone; isometheptene for a headache. A second case involved a post-partum patient receiving bromocriptine who was later prescribed phenylpropanolamine; guaifenesin and subsequently developed hypertension, tachycardia, seizures, and cerebral vasospasm. Also, ergot alkaloids, which are chemically related to bromocriptine, should not be administered with other vasoconstrictors. Therefore, until more data become available, concurrent use of bromocriptine and some sympathomimetics such as vasopressors (e.g., norepinephrine, dopamine, phenylephrine), cocaine, epinephrine, phenylpropanolamine, ephedra, ma huang, ephedrine, pseudoephedrine, amphetamines, and phentermine should be approached with caution.
Pseudoephedrine; Triprolidine: (Moderate) One case report documented worsening headache, hypertension, premature ventricular complexes, and ventricular tachycardia in a post-partum patient receiving bromocriptine for lactation suppression who was subsequently prescribed acetaminophen; dichloralphenazone; isometheptene for a headache. A second case involved a post-partum patient receiving bromocriptine who was later prescribed phenylpropanolamine; guaifenesin and subsequently developed hypertension, tachycardia, seizures, and cerebral vasospasm. Also, ergot alkaloids, which are chemically related to bromocriptine, should not be administered with other vasoconstrictors. Therefore, until more data become available, concurrent use of bromocriptine and some sympathomimetics such as vasopressors (e.g., norepinephrine, dopamine, phenylephrine), cocaine, epinephrine, phenylpropanolamine, ephedra, ma huang, ephedrine, pseudoephedrine, amphetamines, and phentermine should be approached with caution.
Quetiapine: (Moderate) The effectiveness of bromocriptine may be reduced by most of the atypical antipsychotics, via their action as dopamine antagonists. Monitor the patient for reduced response to bromocriptine. The atypical antipsychotics elevate prolactin to various degrees. Atypical antipsychotics may also aggravate diabetes mellitus and cause metabolic changes including hyperglycemia; use caution if bromocriptine is taken for diabetes. If bromocriptine is taken for diabetes, monitor for worsening glycemic control.
Quinine: (Major) When bromocriptine is used for diabetes, do not exceed a dose of 1.6 mg once daily during concomitant use of quinine. Use this combination with caution in patients receiving bromocriptine for other indications. Concurrent use may alter bromocriptine concentrations. Bromocriptine is extensively metabolized in the liver via CYP3A4; quinine is both a moderate inhibitor and inducer of CYP3A4. The net effect on CYP3A4 substrates is unclear. Administration of bromocriptine with a moderate inhibitor of CYP3A4 increased the bromocriptine mean AUC and Cmax by 3.7-fold and 4.6-fold, respectively.
Relugolix; Estradiol; Norethindrone acetate: (Minor) Bromocriptine is used to restore ovulation and ovarian function in amenorrheic women. Estrogens and progestins can cause amenorrhea and, therefore, counteract the desired effects of bromocriptine. Concurrent use is not recommended; an alternate form of contraception is recommended during bromocriptine therapy. (Minor) Bromocriptine is used to restore ovulation and ovarian function in amenorrheic women. Progestins can cause amenorrhea and, therefore, counteract the desired effects of bromocriptine. Concurrent use is not recommended; an alternate form of contraception is recommended during bromocriptine therapy.
Repotrectinib: (Moderate) Caution and close monitoring are advised if bromocriptine and repotrectinib are used together. Concurrent use may decrease the plasma concentrations of bromocriptine resulting in loss of efficacy. Bromocriptine is extensively metabolized by the liver via CYP3A; repotrectinib is a moderate inducer of CYP3A.
Ribociclib: (Major) When bromocriptine is used for diabetes, avoid coadministration with ribociclib ensuring adequate washout before initiating bromocriptine. Use this combination with caution in patients receiving bromocriptine for other indications. Concurrent use may significantly increase bromocriptine concentrations. Bromocriptine is extensively metabolized in the liver via CYP3A4; ribociclib is a strong inhibitor of CYP3A4.
Ribociclib; Letrozole: (Major) When bromocriptine is used for diabetes, avoid coadministration with ribociclib ensuring adequate washout before initiating bromocriptine. Use this combination with caution in patients receiving bromocriptine for other indications. Concurrent use may significantly increase bromocriptine concentrations. Bromocriptine is extensively metabolized in the liver via CYP3A4; ribociclib is a strong inhibitor of CYP3A4.
Rifabutin: (Moderate) Caution and close monitoring are advised if bromocriptine and rifabutin are used together. Concurrent use may decrease the plasma concentrations of bromocriptine resulting in loss of efficacy. Bromocriptine is extensively metabolized by the liver via CYP3A4; rifabutin is a moderate inducer of CYP3A4.
Rifampin: (Moderate) Caution and close monitoring are advised if bromocriptine and rifampin are used together. Concurrent use may decrease the plasma concentrations of bromocriptine resulting in loss of efficacy. Bromocriptine is extensively metabolized by the liver via CYP3A4; rifampin is a strong inducer of CYP3A4.
Rifapentine: (Moderate) Caution and close monitoring are advised if bromocriptine and rifapentine are used together. Concurrent use may decrease the plasma concentrations of bromocriptine resulting in loss of efficacy. Bromocriptine is extensively metabolized by the liver via CYP3A4; rifapentine is a strong inducer of CYP3A4.
Risperidone: (Moderate) The effectiveness of bromocriptine may be reduced by most of the atypical antipsychotics, via their action as dopamine antagonists. Monitor the patient for reduced response to bromocriptine. The atypical antipsychotics elevate prolactin to various degrees. Atypical antipsychotics may also aggravate diabetes mellitus and cause metabolic changes including hyperglycemia; use caution if bromocriptine is taken for diabetes. If bromocriptine is taken for diabetes, monitor for worsening glycemic control.
Ritonavir: (Major) When bromocriptine is used for diabetes, avoid coadministration with ritonavir ensuring adequate washout before initiating bromocriptine. Use this combination with caution in patients receiving bromocriptine for other indications. Concurrent use may significantly increase bromocriptine concentrations. Bromocriptine is extensively metabolized in the liver via CYP3A4; ritonavir is a strong inhibitor of CYP3A4.
Rizatriptan: (Major) There are limited clinical trial data supporting the safety of giving a serotonin-receptor agonist ("triptan") with bromocriptine, an ergot derivative. The concomitant use of these agents with bromocriptine should be avoided. There is concern that prolonged vasospastic reactions, hypertension, tachycardia, or other side effects may occur.
Salicylates: (Minor) Bromocriptine is highly bound (more than 90%) to serum proteins. Therefore, it may increase the unbound fraction of other highly protein-bound medications (e.g., aspirin and other salicylates), which may alter their effectiveness and risk for side effects.
Salsalate: (Minor) Bromocriptine is highly bound (more than 90%) to serum proteins. Therefore, it may increase the unbound fraction of other highly protein-bound medications (e.g., aspirin and other salicylates), which may alter their effectiveness and risk for side effects.
Saquinavir: (Major) When bromocriptine is used for diabetes, avoid coadministration with saquinavir ensuring adequate washout before initiating bromocriptine. Use this combination with caution in patients receiving bromocriptine for other indications. Concurrent use may significantly increase bromocriptine concentrations. Bromocriptine is extensively metabolized in the liver via CYP3A4; saquinavir boosted with ritonavir is a strong inhibitor of CYP3A4.
Secobarbital: (Moderate) Caution and close monitoring are advised if bromocriptine and secobarbital are used together. Concurrent use may decrease the plasma concentrations of bromocriptine resulting in loss of efficacy. Bromocriptine is extensively metabolized by the liver via CYP3A4; secobarbital is a moderate inducer of CYP3A4.
Segesterone Acetate; Ethinyl Estradiol: (Minor) Bromocriptine is used to restore ovulation and ovarian function in amenorrheic women. Estrogens and progestins can cause amenorrhea and, therefore, counteract the desired effects of bromocriptine. Concurrent use is not recommended; an alternate form of contraception is recommended during bromocriptine therapy. (Minor) Bromocriptine is used to restore ovulation and ovarian function in amenorrheic women. Progestins can cause amenorrhea and, therefore, counteract the desired effects of bromocriptine. Concurrent use is not recommended; an alternate form of contraception is recommended during bromocriptine therapy.
Serdexmethylphenidate; Dexmethylphenidate: (Moderate) Increased dopaminergic effects may occur during coadministration of methylphenidate derivatives, inhibitors of dopamine reuptake, and dopamine agonists such as bromocriptine. Dopaminergic side effects, such as nausea, loss of appetite, weight loss, insomnia, tremor, nervousness, or changes in mood or behavior, are possible.
Serotonin-Receptor Agonists: (Major) There are limited clinical trial data supporting the safety of giving a serotonin-receptor agonist ("triptan") with bromocriptine, an ergot derivative. The concomitant use of these agents with bromocriptine should be avoided. There is concern that prolonged vasospastic reactions, hypertension, tachycardia, or other side effects may occur.
Sirolimus: (Moderate) Monitor sirolimus concentrations and adjust sirolimus dosage as appropriate during concomitant use of bromocriptine. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects.
Solriamfetol: (Moderate) Monitor for dopamine-mediated effects including nausea, vomiting, dizziness, tremor, and changes in moods or behaviors if solriamfetol, a central dopamine and norepinephrine reuptake inhibitor, is administered with other dopaminergic drugs, such as bromocriptine. Caution is recommended since this combination has not been evaluated.
Sotorasib: (Moderate) Caution and close monitoring are advised if bromocriptine and sotorasib are used together. Concurrent use may decrease the plasma concentrations of bromocriptine resulting in loss of efficacy. Bromocriptine is extensively metabolized by the liver via CYP3A4; sotorasib is a moderate inducer of CYP3A4.
St. John's Wort, Hypericum perforatum: (Moderate) Caution and close monitoring are advised if bromocriptine and St. John's Wort are used together. Concurrent use may decrease the plasma concentrations of bromocriptine resulting in loss of efficacy. Bromocriptine is extensively metabolized by the liver via CYP3A4; St. John's Wort is a strong inducer of CYP3A4.
Sulfadiazine: (Moderate) Sulfonamides may enhance the hypoglycemic action of antidiabetic agents; patients with diabetes mellitus should be closely monitored during sulfonamide treatment. Sulfonamides may induce hypoglycemia in some patients by increasing the secretion of insulin from the pancreas. Patients at risk include those with compromised renal function, those fasting for prolonged periods, those that are malnourished, and those receiving high or excessive doses of sulfonamides. Bromocriptine is highly bound to serum proteins. Therefore, it may increase the unbound fraction of other highly protein-bound medications (e.g., sulfonamides), which may alter their effectiveness and risk for side effects.
Sulfamethoxazole; Trimethoprim, SMX-TMP, Cotrimoxazole: (Moderate) Sulfonamides may enhance the hypoglycemic action of antidiabetic agents; patients with diabetes mellitus should be closely monitored during sulfonamide treatment. Sulfonamides may induce hypoglycemia in some patients by increasing the secretion of insulin from the pancreas. Patients at risk include those with compromised renal function, those fasting for prolonged periods, those that are malnourished, and those receiving high or excessive doses of sulfonamides. Bromocriptine is highly bound to serum proteins. Therefore, it may increase the unbound fraction of other highly protein-bound medications (e.g., sulfonamides), which may alter their effectiveness and risk for side effects.
Sulfasalazine: (Moderate) Sulfonamides may enhance the hypoglycemic action of antidiabetic agents; patients with diabetes mellitus should be closely monitored during sulfonamide treatment. Sulfonamides may induce hypoglycemia in some patients by increasing the secretion of insulin from the pancreas. Patients at risk include those with compromised renal function, those fasting for prolonged periods, those that are malnourished, and those receiving high or excessive doses of sulfonamides. Bromocriptine is highly bound to serum proteins. Therefore, it may increase the unbound fraction of other highly protein-bound medications (e.g., sulfonamides), which may alter their effectiveness and risk for side effects.
Sulfonamides: (Moderate) Sulfonamides may enhance the hypoglycemic action of antidiabetic agents; patients with diabetes mellitus should be closely monitored during sulfonamide treatment. Sulfonamides may induce hypoglycemia in some patients by increasing the secretion of insulin from the pancreas. Patients at risk include those with compromised renal function, those fasting for prolonged periods, those that are malnourished, and those receiving high or excessive doses of sulfonamides. Bromocriptine is highly bound to serum proteins. Therefore, it may increase the unbound fraction of other highly protein-bound medications (e.g., sulfonamides), which may alter their effectiveness and risk for side effects.
Sumatriptan: (Major) There are limited clinical trial data supporting the safety of giving a serotonin-receptor agonist ("triptan") with bromocriptine, an ergot derivative. The concomitant use of these agents with bromocriptine should be avoided. There is concern that prolonged vasospastic reactions, hypertension, tachycardia, or other side effects may occur.
Sumatriptan; Naproxen: (Major) There are limited clinical trial data supporting the safety of giving a serotonin-receptor agonist ("triptan") with bromocriptine, an ergot derivative. The concomitant use of these agents with bromocriptine should be avoided. There is concern that prolonged vasospastic reactions, hypertension, tachycardia, or other side effects may occur.
Tacrolimus: (Minor) Bromocriptine may decrease the clearance of tacrolimus with the potential to either reduce immunosuppressant dosage requirements or cause drug-related toxicity. Close monitoring of tacrolimus concentrations is recommended if bromocriptine is coadministered.
Thioridazine: (Major) Avoid concurrent use of phenothiazines and bromocriptine when possible. Bromocriptine may interact with dopamine antagonists such as the phenothiazines. The phenothiazines are noted to result in a decreased efficacy of bromocriptine. The prolactin-lowering effect of bromocriptine is antagonized; the elevation in prolactin levels produced by phenothiazines persists with chronic administration. In addition, bromocriptine, a dopamine agonist, may theoretically diminish the effectiveness of central dopamine antagonists such as the phenothiazines; however, such interactions are not certain.
Thiothixene: (Major) Avoid concurrent use of thiothixene and bromocriptine when possible. Thiothixene is noted to result in a decreased efficacy of bromocriptine. The prolactin-lowering effect of bromocriptine is antagonized; the elevation in prolactin levels produced by thiothixene persists with chronic administration. However, bromocriptine does not appear to interfere with the antipsychotic effects of thiothixene if it is added to a stable neuroleptic regimen.
Tipranavir: (Major) When bromocriptine is used for diabetes, avoid coadministration with tipranavir ensuring adequate washout before initiating bromocriptine. Use this combination with caution in patients receiving bromocriptine for other indications. Concurrent use may significantly increase bromocriptine concentrations. Bromocriptine is extensively metabolized in the liver via CYP3A4; tipranavir is a strong inhibitor of CYP3A4.
Trandolapril; Verapamil: (Major) When bromocriptine is used for diabetes, do not exceed a dose of 1.6 mg once daily during concomitant use of verapamil. Use this combination with caution in patients receiving bromocriptine for other indications. Concurrent use may increase bromocriptine concentrations. Bromocriptine is extensively metabolized in the liver via CYP3A4; verapamil is a moderate inhibitor of CYP3A4. Administration of bromocriptine with a moderate inhibitor of CYP3A4 increased the bromocriptine mean AUC and Cmax by 3.7-fold and 4.6-fold, respectively.
Trifluoperazine: (Major) Avoid concurrent use of phenothiazines and bromocriptine when possible. Bromocriptine may interact with dopamine antagonists such as the phenothiazines. The phenothiazines are noted to result in a decreased efficacy of bromocriptine. The prolactin-lowering effect of bromocriptine is antagonized; the elevation in prolactin levels produced by phenothiazines persists with chronic administration. In addition, bromocriptine, a dopamine agonist, may theoretically diminish the effectiveness of central dopamine antagonists such as the phenothiazines; however, such interactions are not certain.
Tucatinib: (Major) When bromocriptine is used for diabetes, avoid coadministration with tucatinib ensuring adequate washout before initiating bromocriptine. Use this combination with caution in patients receiving bromocriptine for other indications. Concurrent use may significantly increase bromocriptine concentrations. Bromocriptine is extensively metabolized in the liver via CYP3A4; tucatinib is a strong inhibitor of CYP3A4.
Verapamil: (Major) When bromocriptine is used for diabetes, do not exceed a dose of 1.6 mg once daily during concomitant use of verapamil. Use this combination with caution in patients receiving bromocriptine for other indications. Concurrent use may increase bromocriptine concentrations. Bromocriptine is extensively metabolized in the liver via CYP3A4; verapamil is a moderate inhibitor of CYP3A4. Administration of bromocriptine with a moderate inhibitor of CYP3A4 increased the bromocriptine mean AUC and Cmax by 3.7-fold and 4.6-fold, respectively.
Vonoprazan; Amoxicillin; Clarithromycin: (Major) When bromocriptine is used for diabetes, avoid coadministration with clarithromycin ensuring adequate washout before initiating bromocriptine. Use this combination with caution in patients receiving bromocriptine for other indications. Concurrent use may significantly increase bromocriptine concentrations. Bromocriptine is extensively metabolized in the liver via CYP3A4; clarithromycin is a strong inhibitor of CYP3A4.
Voriconazole: (Major) When bromocriptine is used for diabetes, avoid coadministration with voriconazole ensuring adequate washout before initiating bromocriptine. Use this combination with caution in patients receiving bromocriptine for other indications. Concurrent use may significantly increase bromocriptine concentrations. Bromocriptine is extensively metabolized in the liver via CYP3A4; voriconazole is a strong inhibitor of CYP3A4.
Voxelotor: (Major) When bromocriptine is used for diabetes, do not exceed a dose of 1.6 mg once daily during concomitant use of voxelotor. Use this combination with caution in patients receiving bromocriptine for other indications. Concurrent use may increase bromocriptine concentrations. Bromocriptine is extensively metabolized in the liver via CYP3A; voxelotor is a moderate inhibitor of CYP3A. Coadministration with another moderate CYP3A inhibitor increased bromocriptine exposure by 2.8-fold.
Zafirlukast: (Minor) Bromocriptine is a cytochrome P450 3A4 substrate. In theory, inhibitors of this isoenzyme like zafirlukast may decrease the metabolism of bromocriptine.
Ziprasidone: (Moderate) The effectiveness of bromocriptine may be reduced by most of the atypical antipsychotics, via their action as dopamine antagonists. Monitor the patient for reduced response to bromocriptine. The atypical antipsychotics elevate prolactin to various degrees. Atypical antipsychotics may also aggravate diabetes mellitus and cause metabolic changes including hyperglycemia; use caution if bromocriptine is taken for diabetes. If bromocriptine is taken for diabetes, monitor for worsening glycemic control.
Zolmitriptan: (Major) There are limited clinical trial data supporting the safety of giving a serotonin-receptor agonist ("triptan") with bromocriptine, an ergot derivative. The concomitant use of these agents with bromocriptine should be avoided. There is concern that prolonged vasospastic reactions, hypertension, tachycardia, or other side effects may occur.
Bromocriptine stimulates dopamine type-2 receptors and antagonizes dopamine type-1 receptors in the hypothalamus and the neostriatum of the CNS. Patients with Parkinson's disease usually do not develop tolerance to the neurological effects of bromocriptine as they do to levodopa therapy.
Prolactin secretion from the anterior pituitary gland is suppressed by bromocriptine. Following bromocriptine-induced reductions in serum prolactin levels, ovulation and ovarian function will resume in amenorrheic female 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 to 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.
Bromocriptine has minimal affinity for adrenergic receptors. It slightly increases sodium excretion and can reduce blood pressure. However, high doses of the drug can induce vasoconstriction.
Bromocriptine improves glycemic control in patients with type 2 diabetes mellitus. The mechanism of action is unknown; however, postprandial glucose concentrations were improved without increasing plasma insulin concentrations in a clinical study.
Bromocriptine is administered orally. The drug binds extensively (90% to 96%) to serum albumin and does not appear to distribute into erythrocytes. The volume of distribution is approximately 61 L. Bromocriptine (93% of the dose) undergoes extensive first-pass biotransformation after oral administration, reflected by complex metabolite profiles and by almost complete absence of parent drug in urine and feces. Bromocriptine mesylate is extensively metabolized in the gastrointestinal tract and liver. Metabolism by CYP3A4 is the major metabolic pathway. Hydroxylations at the proline ring of the cyclopeptide moiety constituted a main metabolic pathway. The metabolites are primarily eliminated in the bile and feces, with only a small amount (e.g., 2 to 6%) of the administered bromocriptine dose excreted by the kidneys as metabolites. The elimination half-life is approximately 4.85 to 6 hours.
Affected Cytochrome P450 (CYP450) isoenzymes and drug transporters: CYP3A4
Although bromocriptine is a competitive inhibitor of CYP3A4, in vivo drug interaction potential is low because the inhibitory potency for CYP3A4 is thousands-fold higher than the maximum plasma levels reached in vivo with clinical oral doses of bromocriptine for the various indications. The use of potent inhibitors of CYP3A4 has been shown to increase the AUC and maximum concentrations (Cmax) of bromocriptine in vivo. Caution should therefore be used when co-administering drugs which are inhibitors of CYP3A4 with bromocriptine for hormonal uses and Parkinson's disease; avoidance of potent CYP3A4 inhibitors is recommended when treating type 2 diabetes mellitus (T2DM) with bromocriptine. Dosage adjustments are necessary for those treated with bromocriptine for T2DM who are receiving moderate CYP3A4 inhibitors. Also use caution in patients receiving potent inducers of CYP3A4, as use of these drugs concomitantly with bromocriptine would be expected to decrease bromocriptine plasma levels. There was no significant in vitro inhibition of other major CYP450 enzymes (1A2, 2C9, 2C19, 2D6) by bromocriptine.
-Route-Specific Pharmacokinetics
Oral Route
-Bromocriptine immediate-release tablets: Although 28% of an orally administered dose of bromocriptine is absorbed across the GI tract, only 6% reaches the circulation due to significant first-pass hepatic metabolism. Oral administration of a single 1.25 to 5 mg dose results in rapid and sustained serum prolactin reductions. Following 5 mg PO twice daily for 14 days, the bromocriptine Cmax and AUC at steady-state were 628 +/- 375 pg/mL and 2377 +/- 1186 pg x hour/mL, respectively. Food does not appreciably alter oral absorption. It is recommended that the drug be taken with food because of the high percentage of subjects who vomit upon receiving bromocriptine under fasting conditions.
-Micronized bromocriptine quick-release tablets: When administered orally, approximately 65% to 95% of the dose of bromocriptine mesylate is absorbed. Due to extensive first-pass metabolism, approximately 7% of the dose reaches the systemic circulation. Under fasting conditions the time to maximum plasma concentration (Tmax) is 53 minutes. In contrast, following a standard high-fat meal, the Tmax is increased to approximately 90 to 120 minutes. Also, the relative bioavailability is increased under fed as compared to fasting conditions by approximately 55% to 65% (increase in AUC). The tablets should be taken with food to potentially reduce gastrointestinal side effects such as nausea.
-Special Populations
Hepatic Impairment
Bromocriptine is extensively metabolized in the liver. There are no specific pharmacokinetic studies in patients with hepatic impairment. Liver impairment may increase the plasma levels of bromocriptine, therefore, caution may be necessary.
Renal Impairment
Pharmacokinetics in renal impairment have not been studied. The kidney is a minor pathway for elimination of bromocriptine; the drug is almost completely excreted via metabolism, and only 6% eliminated via the kidney, renal impairment may not have a significant impact on concentrations of bromocriptine and its metabolites.
Pediatrics
The effect of age on the pharmacokinetics of bromocriptine and its metabolites has not been evaluated. There are limited clinical data in children 11 to 15 years of age.
Geriatric
No pharmacokinetic studies have been conducted in geriatric subjects.
Gender Differences
The plasma exposure of bromocriptine from the quick-release tablets is increased 18% to 30% in females compared to males.
Ethnic Differences
Studies characterizing the pharmacokinetics of bromocriptine among different ethnic groups have not been performed.