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  • CLASSES

    Anti-Parkinson drugs, Dopamine Agonists
    Other Antidiabetic Drugs
    Prolactin Inhibitors

    DEA CLASS

    Rx

    DESCRIPTION

    Synthetic dopamine agonist; chemically related to ergot alkaloids; used in a variety of hyperprolactinemia syndromes, infertility, cocaine addiction, mastalgia, Neuroleptic Malignant Syndrome (NMS), acromegaly, pituitary adenomas, Parkinson's disease, and diabetes mellitus; no longer recommended for postpartum breast engorgement or lactation prevention due to risk:benefit concerns.

    COMMON BRAND NAMES

    Cycloset, Parlodel

    HOW SUPPLIED

    Bromocriptine/Bromocriptine Mesylate/Cycloset/Parlodel Oral Tab: 0.8mg, 2.5mg
    Bromocriptine/Bromocriptine Mesylate/Parlodel Oral Cap: 5mg

    DOSAGE & INDICATIONS

    For the treatment of Parkinson's disease.
    Oral dosage
    Adults

    1.25 mg PO twice daily, increasing the total daily dose by 2.5 mg every 14—28 days until the desired therapeutic response occurs. Levodopa therapy should be continued while bromocriptine is being instituted.

    For the treatment of acromegaly.
    Oral dosage
    Adults

    Initially, 1.25—2.5 mg PO once daily at bedtime for 3 days. May increase by 1.25—2.5 mg/day at 3—7 day periods until the optimal therapeutic effect occurs. Typical maintenance dosage is 20—30 mg/day; do not exceed 100 mg/day. Dosages may also be given in divided doses if desired.

    For the treatment of prolactin-secreting pituitary adenoma or disorders associated with hyperprolactinemia including amenorrhea with or without galactorrhea, male hypogonadism, or female infertility.
    Oral dosage
    Adults and Adolescents >= 16 years

    Initially, 1.25—2.5 mg PO daily, with titration of 2.5 mg/day PO at 2—7 day intervals as needed until the desired therapeutic response occurs. Typical dosage ranges from 2.5—15 mg/day PO, but up to 30 mg/day may be necessary in amenorrheic or galactorrheic patients. A reduction in tumor size has been demonstrated in patients with pituitary adenoma receiving bromocriptine.

    Children and Adolescents 11—15 years

    Based on limited data, the dose for prolactin-secreting pituitary adenomas is initially 1.25—2.5 mg PO once daily, and dosing may need to be increased as tolerated until a therapeutic response is achieved. Limited data in 14 patients indicated that the therapeutic dosage ranges from 2.5—10 mg/day PO in these children. Of the 14-reported patients, 9 had successful outcomes, 3 partial responses, and 2 patients did not respond.

    For use as an adjunct to diet and exercise in the treatment of type 2 diabetes mellitus.
    Oral dosage (Cycloset only)
    Adults

    Initially 0.8 mg PO once daily in the morning within 2 hours of waking; titrate the dose by 0.8 mg/day no more frequently than weekly until a maximum dose of 1.6—4.8 mg/day PO is achieved.

    For the treatment of mastalgia† associated with premenstrual syndrome (PMS)†.
    Oral dosage
    Adults

    2.5—7.5 mg PO twice daily, starting therapy 10—14 days prior to menses; discontinue when menses begins. Dose titration should strike a balance between adverse reactions and therapeutic benefits. Bromocriptine may be a good choice in patients also demonstrating galactorrhea or hyperprolactinemia.

    For the maintenance treatment of alcohol dependence†.
    Oral dosage
    Adults

    7.5 mg/day PO has been used. A 6-week study of 52 alcoholics revealed that bromocriptine produced statistically-significant reductions in alcohol craving and anxiety but not depression. Pharmacotherapy should be used as a part of a comprehensive management program that includes psychosocial support and treatment.

    For the treatment of symptoms associated with cocaine withdrawal†.
    Oral dosage
    Adults

    0.625 mg PO 4 times daily has been used for 42 days; bromocriptine was superior to placebo in reducing symptoms of withdrawal in a group of 24 male cocaine addicts.

    For the treatment of symptoms associated with neuroleptic malignant syndrome†.
    Oral dosage
    Adults

    Initiate with 2.5 mg PO 3 times daily; usual dosage range is 5—10 mg PO 3 times daily. Complete or substantial response is expected within 2—3 days of initiating therapy.

    †Indicates off-label use

    MAXIMUM DOSAGE

    Adults

    4.8 mg/day PO for type 2 diabetes mellitus; up to 100 mg/day PO has been used for other indications.

    Geriatric

    4.8 mg/day PO for type 2 diabetes mellitus; up to 100 mg/day PO has been used for other indications.

    Adolescents

    Safety and efficacy have not been demonstrated for diabetes mellitus; for other indications, maximum dosage information is not available; do not exceed adult maximum dosage.

    Children

    >= 11 years: Safety and efficacy have not been demonstrated for diabetes mellitus; for other indications, maximum dosage information is not available; do not exceed adult maximum dosage.
    < 11 years: Safety and efficacy have not been established.

    Infants

    Safety and efficacy have not been established.

    Neonates

    Safety and efficacy have not been established.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    The safety and efficacy of bromocriptine in those with hepatic disease have not been evaluated and specific dosage guidelines are not available. Given the extensive hepatic metabolism of the drug, it should be anticipated that elevated bromocriptine levels, with the potential for ergot toxicity, may occur in the presence of hepatic impairment.

    Renal Impairment

    The safety and efficacy of bromocriptine in those with renal disease have not been evaluated and specific dosage guidelines are not available. Bromocriptine for diabetic therapy should be used with caution in patients with renal impairment; specific dosage guidelines are not available.

    ADMINISTRATION

    Oral Administration

    Administer with food.

    Oral Solid Formulations

    Cycloset tablets: Administer with food in the morning within 2 hours after waking.

    STORAGE

    Cycloset:
    - Store at or below 77 degrees F
    Parlodel:
    - Protect from moisture
    - Store below 77 degrees F

    CONTRAINDICATIONS / PRECAUTIONS

    General Information

    Visual fields should be monitored in patients with macroprolactinoma. Visual field impairment is a known complication of macroprolactinoma. Effective treatment with bromocriptine often resolves visual impairment. However, a secondary deterioration of visual fields may 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.

    Ergot alkaloid hypersensitivity

    Bromocriptine is contraindicated in patients with a known bromocriptine hypersensitivity. The drug is also contraindicated in patients with any other ergot alkaloid hypersensitivity.

    Abrupt discontinuation

    When used for the treatment of Parkinson's disease, abrupt discontinuation of bromocriptine should be avoided, if possible. Cases of a symptom complex resembling neuroleptic malignant syndrome have been associated with dose reductions and withdrawal of any anti-Parkinson's drug, including bromocriptine. Patients should be observed closely for manifestations of this symptom complex including tachycardia, muscular rigidity, elevation of body temperature, mental status changes, diaphoresis, tachypnea, and increases in serum creatinine concentrations. Although no cases of neuroleptic-like malignant syndrome were reported during clinical evaluation and follow-up of bromocriptine for type 2 diabetes mellitus, the same precautions still apply.

    Acute myocardial infarction, angina, cardiac arrhythmias, cardiac disease, coronary artery disease, hypertension, peripheral vascular disease

    Several cardiac precautions should be observed in those receiving bromocriptine. Bromocriptine (Parlodel) is contraindicated in uncontrolled hypertension. Hypertension has been documented in postpartum patients receiving the drug. Seizures and rare cases of status epilepticus have also been reported, some of which were unrelated to a prior hypertensive episode. Some of the patients who developed these effects experienced severe headaches or visual disturbances (i.e. blurred vision, transient cortical blindness) prior to the event. Other rare but serious adverse reactions include acute myocardial infarction and stroke. It is unknown if bromocriptine is the exact cause of these effects. Monitor blood pressure, especially during the initial weeks of therapy. Bromocriptine should be discontinued if signs of persistent headache, visual impairment, or uncontrolled hypertension become evident. Syncope, worsening of angina, and shock can also occur during bromocriptine administration. Other cardiovascular reactions include sinus bradycardia, ventricular tachycardia, and peripheral edema. Bromocriptine should be used cautiously in those with peripheral vascular disease, or cardiac disease including cardiac arrhythmias, coronary artery disease, or a history of acute myocardial infarction. The drug is contraindicated in the post-partum 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 post-partum period, the patient should be monitored closely.

    Hypotension, orthostatic hypotension

    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 decrease in supine pressure of almost 60 mmHg. 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, including orthostatic hypotension can occur in patients receiving bromocriptine for diabetic therapy (Cycloset), particularly upon initiation and dose titration. Hypotension can lead to syncope (see Adverse Reactions) and serious injury. Clinicians should use caution when adding bromocriptine to a patient on an anti-hypertensive medication and orthostatic vital signs should be monitored prior to initiation of bromocriptine and periodically thereafter. Further, patients should advised of the risk of hypotension and syncope.

    Bipolar disorder, dementia, depression, driving or operating machinery, schizophrenia

    In those with a history of psychiatric disorders including depression, bipolar disorder, or schizophrenia, bromocriptine should be used cautiously. In addition, the use of bromocriptine for diabetic therapy (Cycloset) is not recommended in patients with severe psychotic disorders. In rare instances, patients receiving bromocriptine have developed various psychiatric adverse effects including delusional psychosis, mania, and paranoia.  Those with Parkinson's disease have experienced CNS effects including confusion, depression, dizziness, drowsiness, and hallucinations from bromocriptine. 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. A dosage reduction usually alleviates this symptom, but discontinuance of the drug may be required. Dosages should be slowly titrated and patients should be closely monitored for mental status changes during combined use of drugs affecting dopaminergic functioning. Bromocriptine should be used with extreme caution in Parkinson's patients who exhibit signs of dementia. During post-marketing use of bromocriptine in patients with Parkinson's disease, bromocriptine (Parlodel) has been associated with episodes of sudden sleep onset, sometimes during daily activities and, in some cases, without awareness of warning signs (see Adverse Reactions).In addition, somnolence was reported during clinical evaluation of bromocriptine for diabetic therapy (Cycloset). Reassessment for drowsiness or oversedation is necessary throughout bromocriptine therapy. Sleep disorders, use of concomitant CNS depressant medications, or interacting medications may increase the risk of falling asleep while on this medication. 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. All patients receiving the drug should be cautioned about driving or operating machinery until they know how the drug affects their cognition.

    Hepatic disease

    The safety and efficacy of bromocriptine in those with hepatic disease have not been evaluated and specific dosage guidelines are not available. Given the extensive hepatic metabolism of the drug, it should be anticipated that elevated bromocriptine levels, with the potential for ergot toxicity, may occur in the presence of altered hepatic functioning.

    Surgery

    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.

    Pulmonary fibrosis, retroperitoneal fibrosis

    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 pulmonary fibrosis. These effects usually resolve with discontinuance 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. Although there have been no confirmed cases of retroperitoneal fibrosis, pulmonary infiltrates, pleural effusion, or pleural thickening among patients treated with bromocriptine for diabetes, precautions still apply.
     

    GI bleeding, peptic ulcer disease

    When used for acromegaly, bromocriptine should be used cautiously in patients with active or previously diagnosed peptic ulcer disease. Less than 2% of acromegaly patients experience gastrointestinal bleeding, which 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.

    Geriatric

    In general, bromocriptine dosing should be more cautious in the geriatric patient, starting at the lower end of the dose range to account for differences in renal, hepatic, or cardiac systems as well as concomitant disease states and medications. Reported clinical experiences, including postmarketing reports of adverse events, have not identified differences in response or tolerability between elderly and younger adult patients. In clinical studies of bromocriptine as monotherapy and in combination with sulfonylurea therapy for diabetes, no overall differences in safety or effectiveness were observed between geriatric and younger patients. Even though no variation in efficacy or adverse reaction profile has been observed, greater sensitivity of some geriatric individuals to bromocriptine cannot be ruled out. The federal Omnibus Budget Reconciliation Act (OBRA) regulates medication use in residents of long-term care facilities (LTCFs). According to OBRA, antiparkinson medications (e.g., Parlodel) may cause significant confusion, restlessness, delirium, dyskinesia, nausea, dizziness, hallucinations, and agitation. In addition, there is an increased risk of postural hypotension and falls, particularly during concurrent use of antihypertensive medications. The use of antidiabetic medications (e.g., Cycloset) should include monitoring (e.g., periodic blood glucose) for effectiveness based on desired goals for that individual and to identify complications of treatment such as hypoglycemia or impaired renal function.

    Basilar/hemiplegic migraine

    Bromocriptine for diabetic therapy (Cycloset) is contraindicated in patients with syncopal migraine (also known as basilar/hemiplegic migraine or basilar-type migraine); other forms of bromocriptine should 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.

    Renal disease, renal impairment

    The safety and efficacy of bromocriptine in those with renal disease have not been evaluated and specific dosage guidelines are not available. In addition, bromocriptine for diabetic therapy should be used with caution in patients with renal impairment.

    Diabetic ketoacidosis, type 1 diabetes mellitus

    Bromocriptine (Cycloset) 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. In clinical evaluation, bromocriptine was studied as monotherapy and as an add-on to sulfonylurea therapy. Only limited data are available regarding the efficacy of bromocriptine in combination with thiazolidinediones, and efficacy has not been established in combination with insulin.

    Eclampsia, preeclampsia, pregnancy

    Bromocriptine should be withdrawn when pregnancy is diagnosed whenever possible, unless a rapidly expanding macroadenoma necessitates continued use. In patients being treated for acromegaly, prolactinoma, diabetes mellitus, or Parkinson's disease, consider the medical necessity of bromocriptine or if the therapy can be withdrawn. If a patient continuing bromocriptine during pregnancy experiences a hypertensive disorder of pregnancy (including preeclampsia, eclampsia, or pregnancy-induced hypertension), the benefit of continuing the drug must be weighed against cardiovascular risks. In making the decision to administer bromocriptine during pregnancy, the potential risks to the fetus must be weighed against the potential maternal benefits, which are dependent on the initial indication for use. From a teratogenic perspective, bromocriptine is classified as FDA pregnancy risk category B. Although no adequate human studies have been performed on the effects of this drug on the fetus, data concerning 1276 pregnancies in women taking bromocriptine are available. In the majority of cases, bromocriptine 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—40 mg). After delivery, the drug is also contraindicated in the post-partum period in women with a history of coronary artery disease and other severe cardiovascular conditions unless withdrawal is considered medically contraindicated. If bromocriptine (Parlodel) is used in the post-partum period, the patient should be observed with caution.

    Breast-feeding

    Bromocriptine (Parlodel) interferes with lactation and therefore should not be used during breast-feeding. The manufacturer of Cycloset contraindicates bromocriptine use in diabetic women who are breast-feeding due to the inhibition of lactation. In addition, there are post-marketing reports of stroke in post-partum females, although causality has not been proven. Bromocriptine was previously approved as a lactation suppressant, however, this indication 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 such as cold packs, compression aides, and pain relievers. This decision followed several reports in postpartum women of significant adverse reactions including hypotension, hypertension, myocardial infarction, stroke, seizures, and rare cases of status epilepticus. The exact relationship between bromocriptine and the development of these effects remains unclear. If bromocriptine for diabetic therapy (Cycloset) is discontinued and blood glucose is not controlled on diet and exercise alone, insulin therapy should be considered. Other oral hypoglycemics may be considered as possible alternatives during breast-feeding. Because acarbose has limited systemic absorption, which results in minimal maternal plasma concentrations, clinically significant exposure via breast milk is not expected. Also, while the manufacturers of metformin recommend against breast-feeding while taking the drug, data have shown that metformin is excreted into breast milk in small amounts and adverse effects on infant plasma glucose have not been reported in human studies. The American Academy of Pediatrics (AAP) regards tolbutamide as usually compatible with breast-feeding. Although other sulfonylureas have not been evaluated by the AAP, glyburide may be a suitable alternative since it was not detected in the breast milk of lactating women who received single and multiple doses of glyburide. 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.

    Children, infants, neonates

    Bromocriptine is used and approved for the treatment of prolactin-secreting adenomas in patients aged 16 years and up. There are limited data on the use of bromocriptine in children aged 11—15 years of age for prolactin-secreting pituitary adenomas. The safety and effectiveness of bromocriptine in neonates, infants and children under age 11 years have not been established. The safety and effectiveness of bromocriptine for type 2 diabetes mellitus have not been established in pediatric patients < 18 years.

    ADVERSE REACTIONS

    Severe

    GI bleeding / Delayed / 0-2.0
    ventricular tachycardia / Early / 0-1.0
    bradycardia / Rapid / 0-1.0
    myocardial infarction / Delayed / 0-1.0
    seizures / Delayed / 0-1.0
    stroke / Early / 0-1.0
    peptic ulcer / Delayed / Incidence not known
    cardiac valvulopathy / Delayed / Incidence not known
    pulmonary fibrosis / Delayed / Incidence not known
    pleural effusion / Delayed / Incidence not known
    pericardial effusion / Delayed / Incidence not known
    retroperitoneal fibrosis / Delayed / Incidence not known
    pericarditis / Delayed / Incidence not known
    visual impairment / Early / Incidence not known
    neuroleptic malignant syndrome-like symptoms / Delayed / Incidence not known

    Moderate

    constipation / Delayed / 5.8-14.0
    hypoglycemia / Early / 3.7-8.6
    amblyopia / Delayed / 5.3-7.5
    orthostatic hypotension / Delayed / 0.3-6.0
    hypotension / Rapid / 2.0-3.0
    hallucinations / Early / 0-1.0
    psychosis / Early / 0-1.0
    hypertension / Early / 0-1.0
    peripheral vasoconstriction / Rapid / 0-1.0
    dyspnea / Early / 0-1.0
    dysphagia / Delayed / Incidence not known
    sudden sleep onset / Delayed / Incidence not known
    ataxia / Delayed / Incidence not known
    mania / Early / Incidence not known
    confusion / Early / Incidence not known
    depression / Delayed / Incidence not known
    dyskinesia / Delayed / Incidence not known
    involuntary movements / Delayed / Incidence not known
    sinus tachycardia / Rapid / Incidence not known
    peripheral edema / Delayed / Incidence not known
    blurred vision / Early / Incidence not known
    blepharospasm / Early / Incidence not known
    urinary retention / Early / Incidence not known
    urinary incontinence / Early / Incidence not known
    impulse control symptoms / Delayed / Incidence not known

    Mild

    nausea / Early / 18.0-32.5
    asthenia / Delayed / 12.5-18.9
    headache / Early / 0-16.8
    fatigue / Early / 13.9-13.9
    rhinitis / Early / 10.7-13.8
    sinusitis / Delayed / 7.4-10.0
    influenza / Delayed / 9.4-9.4
    diarrhea / Early / 8.1-8.8
    vomiting / Early / 2.0-8.1
    dyspepsia / Early / 4.0-7.5
    drowsiness / Early / 3.0-6.6
    infection / Delayed / 6.3-6.3
    anorexia / Delayed / 4.0-5.0
    xerostomia / Early / 4.0-4.0
    nasal congestion / Early / 4.0-4.0
    dizziness / Early / 0-2.0
    syncope / Early / 0-2.0
    insomnia / Early / 0-1.0
    paranoia / Early / 0-1.0
    vertigo / Early / 0-1.0
    muscle cramps / Delayed / 0-1.0
    paresthesias / Delayed / 0-1.0
    pallor / Early / 0-1.0
    rhinorrhea / Early / 0-1.0
    alopecia / Delayed / 0-1.0
    abdominal pain / Early / Incidence not known
    lethargy / Early / Incidence not known
    nightmares / Early / Incidence not known
    anxiety / Delayed / Incidence not known
    tinnitus / Delayed / Incidence not known
    increased urinary frequency / Early / Incidence not known
    libido increase / Delayed / Incidence not known
    rash (unspecified) / Early / Incidence not known

    DRUG INTERACTIONS

    Acetaminophen; Aspirin, ASA; Caffeine: (Moderate) Bromocriptine is highly bound to serum proteins. Therefore, it may increase the unbound fraction of other highly protein-bound medications (e.g., salicylates), which may alter their effectiveness and risk for side effects.
    Acetaminophen; Butalbital: (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.
    Acetaminophen; 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.
    Acetaminophen; Butalbital; 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.
    Acetaminophen; Caffeine; Magnesium Salicylate; Phenyltoloxamine: (Moderate) Bromocriptine is highly bound to serum proteins. Therefore, it may increase the unbound fraction of other highly protein-bound medications (e.g., salicylates), which may alter their effectiveness and risk for side effects.
    Acetaminophen; Caffeine; Phenyltoloxamine; Salicylamide: (Moderate) Bromocriptine is highly bound to serum proteins. Therefore, it may increase the unbound fraction of other highly protein-bound medications (e.g., 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; Phenyltoloxamine: (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; 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; Dichloralphenazone; Isometheptene: (Major) A case report documented worsening headache with hypertension and myocardial ectopy in a patient receiving bromocriptine who was prescribed acetaminophen; dichloralphenazone; isometheptene for her headache. Since isometheptene is a sympathomimetic, it is possible that this reaction was the result of an interaction between bromocriptine and sympathomimetics. Other case reports have documented hypertension and seizures occurring as a result of concomitant use of bromocriptine and phenylpropanolamine. Until more data are available, the combination of a sympathomimetic and bromocriptine should be avoided whenever possible.
    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; 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.
    Aliskiren: (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.
    Aliskiren; Amlodipine: (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.
    Aliskiren; Amlodipine; Hydrochlorothiazide, HCTZ: (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.
    Aliskiren; Hydrochlorothiazide, HCTZ: (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.
    Aliskiren; Valsartan: (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.
    Almotriptan: (Major) Bromocriptine is an ergot alkaloid derivative. Serotonin-receptor agonists (e.g., "triptans" such as almotriptan, eletriptan, frovatriptan, naratriptan, rizatriptan, sumatriptan, zolmitriptan) are contraindicated for use within 24 hours of treatment with traditional ergot alkaloids (e.g., dihydroergotamine, methysergide) or ergot-type medications. Ergot alkaloids have been reported to cause prolonged vasospastic reactions which may be additive with the effects of serotonin-receptor agonists. While interactions have not been specifically reported between bromocriptine and triptans, combined use of these agents should be avoided if possible.
    Ambrisentan: (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.
    Amiloride: (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.
    Amiloride; Hydrochlorothiazide, HCTZ: (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.
    Aminosalicylate sodium, Aminosalicylic acid: (Moderate) Bromocriptine is highly bound to serum proteins. Therefore, it may increase the unbound fraction of other highly protein-bound medications (e.g., salicylates), which may alter their effectiveness and risk for side effects.
    Amiodarone: (Major) When bromocriptine is used for diabetes, do not exceed a dose of 1.6 mg once daily during concomitant use of amiodarone. 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; amiodarone 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.
    Amlodipine; Benazepril: (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.
    Amlodipine; Hydrochlorothiazide, HCTZ; Olmesartan: (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.
    Amlodipine; Hydrochlorothiazide, HCTZ; Valsartan: (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.
    Amlodipine; Olmesartan: (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.
    Amlodipine; Telmisartan: (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.
    Amlodipine; Valsartan: (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.
    Amoxicillin; Clarithromycin; Lansoprazole: (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.
    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.
    Angiotensin II receptor antagonists: (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.
    Angiotensin-converting enzyme inhibitors: (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.
    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 prolactin-lowering effect of bromocriptine at the anterior pituitary may be antagonized by medications that increase prolactin levels, such as the atypical antipsychotics. The atypical antipsychotics elevate prolactin to various degrees. Like other drugs that antagonize dopamine D2 receptors, the elevation in prolactin from atypical antipsychotics can persist during chronic administration. Monitor the patient for reduced response to bromocriptine.
    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 prolactin-lowering effect of bromocriptine at the anterior pituitary may be antagonized by medications that increase prolactin levels, such as the atypical antipsychotics. The atypical antipsychotics elevate prolactin to various degrees. Like other drugs that antagonize dopamine D2 receptors, the elevation in prolactin from atypical antipsychotics can persist during chronic administration. Monitor the patient for reduced response to bromocriptine.
    Aspirin, ASA: (Moderate) Bromocriptine is highly bound to serum proteins. Therefore, it may increase the unbound fraction of other highly protein-bound medications (e.g., salicylates), which may alter their effectiveness and risk for side effects.
    Aspirin, ASA; Butalbital; Caffeine: (Moderate) Bromocriptine is highly bound to serum proteins. Therefore, it may increase the unbound fraction of other highly protein-bound medications (e.g., salicylates), which may alter their effectiveness and risk for side effects. (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.
    Aspirin, ASA; Butalbital; Caffeine; Codeine: (Moderate) Bromocriptine is highly bound to serum proteins. Therefore, it may increase the unbound fraction of other highly protein-bound medications (e.g., salicylates), which may alter their effectiveness and risk for side effects. (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.
    Aspirin, ASA; Caffeine; Dihydrocodeine: (Moderate) Bromocriptine is highly bound to serum proteins. Therefore, it may increase the unbound fraction of other highly protein-bound medications (e.g., salicylates), which may alter their effectiveness and risk for side effects.
    Aspirin, ASA; Carisoprodol: (Moderate) Bromocriptine is highly bound to serum proteins. Therefore, it may increase the unbound fraction of other highly protein-bound medications (e.g., salicylates), which may alter their effectiveness and risk for side effects.
    Aspirin, ASA; Carisoprodol; Codeine: (Moderate) Bromocriptine is highly bound to serum proteins. Therefore, it may increase the unbound fraction of other highly protein-bound medications (e.g., salicylates), which may alter their effectiveness and risk for side effects.
    Aspirin, ASA; Dipyridamole: (Moderate) Bromocriptine is highly bound to serum proteins. Therefore, it may increase the unbound fraction of other highly protein-bound medications (e.g., salicylates), which may alter their effectiveness and risk for side effects.
    Aspirin, ASA; Omeprazole: (Moderate) Bromocriptine is highly bound to serum proteins. Therefore, it may increase the unbound fraction of other highly protein-bound medications (e.g., salicylates), which may alter their effectiveness and risk for side effects.
    Aspirin, ASA; Oxycodone: (Moderate) Bromocriptine is highly bound to serum proteins. Therefore, it may increase the unbound fraction of other highly protein-bound medications (e.g., salicylates), which may alter their effectiveness and risk for side effects.
    Aspirin, ASA; Pravastatin: (Moderate) Bromocriptine is highly bound to serum proteins. Therefore, it may increase the unbound fraction of other highly protein-bound medications (e.g., 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, do not exceed a dose of 1.6 mg once daily during concomitant use of cobicistat. 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; cobicistat 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.
    Atenolol; Chlorthalidone: (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.
    Atropine; Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Moderate) Bromocriptine is highly bound to serum proteins. Therefore, it may increase the unbound fraction of other highly protein-bound medications (e.g., salicylates), which may alter their effectiveness and risk for side effects. (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.
    Atropine; Hyoscyamine; Phenobarbital; 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.
    atypical antipsychotic: (Moderate) The prolactin-lowering effect of bromocriptine at the anterior pituitary may be antagonized by medications that increase prolactin levels, such as the atypical antipsychotics. The atypical antipsychotics elevate prolactin to various degrees. Like other drugs that antagonize dopamine D2 receptors, the elevation in prolactin from atypical antipsychotics can persist during chronic administration. Monitor the patient for reduced response to bromocriptine.
    Azilsartan: (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.
    Azilsartan; Chlorthalidone: (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.
    Belladonna Alkaloids; Ergotamine; Phenobarbital: (Severe) 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. (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.
    Benazepril: (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.
    Benazepril; Hydrochlorothiazide, HCTZ: (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.
    Bendroflumethiazide; Nadolol: (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.
    Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Moderate) Bromocriptine is highly bound to serum proteins. Therefore, it may increase the unbound fraction of other highly protein-bound medications (e.g., salicylates), which may alter their effectiveness and risk for side effects. (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.
    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.
    Beta-blockers: (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.
    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: (Moderate) Bromocriptine is highly bound to serum proteins. Therefore, it may increase the unbound fraction of other highly protein-bound medications (e.g., salicylates), which may alter their effectiveness and risk for side effects.
    Bismuth Subsalicylate; Metronidazole; Tetracycline: (Moderate) Bromocriptine is highly bound to serum proteins. Therefore, it may increase the unbound fraction of other highly protein-bound medications (e.g., salicylates), which may alter their effectiveness and risk for side effects.
    Bisoprolol; Hydrochlorothiazide, HCTZ: (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.
    Boceprevir: (Major) When bromocriptine is used for diabetes, avoid coadministration with boceprevir 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; boceprevir is a strong inhibitor of CYP3A4.
    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 prolactin-lowering effect of bromocriptine at the anterior pituitary may be antagonized by medications that increase prolactin levels, such as the atypical antipsychotics. The atypical antipsychotics elevate prolactin to various degrees. Like other drugs that antagonize dopamine D2 receptors, the elevation in prolactin from atypical antipsychotics can persist during chronic administration. Monitor the patient for reduced response to bromocriptine.
    Brigatinib: (Moderate) Monitor for decreased efficacy of bromocriptine if coadministration with brigatinib is necessary. Bromocriptine is a CYP3A substrate and brigatinib induces CYP3A in vitro; plasma concentrations of bromocriptine may decrease.
    Brompheniramine; Carbetapentane; 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; Hydrocodone; 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: (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.
    Bumetanide: (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.
    Butabarbital: (Moderate) Caution and close monitoring are advised if bromocriptine and butabarbital 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; butabarbital is a moderate inducer of CYP3A4.
    Cabozantinib: (Moderate) Monitor for an increase in cabozantinib-related adverse events if concomitant use with bromocriptine is necessary. Cabozantinib is primarily metabolized by CYP3A4 and bromocriptine is a CYP3A4 inhibitor in vitro. Coadministration with a strong CYP3A4 inhibitor, ketoconazole (400 mg daily for 27 days), increased cabozantinib (single dose) exposure by 38%. The manufacturer of cabozantinib recommends a dose reduction when used with strong CYP3A4 inhibitors; however, recommendations are not available for concomitant use with a moderate inhibitor of CYP3A4.
    Caffeine; Ergotamine: (Severe) 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.
    Candesartan: (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.
    Candesartan; Hydrochlorothiazide, HCTZ: (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.
    Captopril: (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.
    Captopril; Hydrochlorothiazide, HCTZ: (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.
    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.
    Carbetapentane; 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.
    Carbetapentane; 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.
    Carbetapentane; 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.
    Carbetapentane; 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.
    Carbetapentane; Phenylephrine; Pyrilamine: (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.
    Carbetapentane; 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.
    Carbinoxamine; 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.
    Carbinoxamine; Hydrocodone; 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.
    Carbinoxamine; Hydrocodone; 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.
    Carbinoxamine; 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.
    Carbinoxamine; 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.
    Cariprazine: (Moderate) The prolactin-lowering effect of bromocriptine at the anterior pituitary may be antagonized by medications that increase prolactin levels, such as the atypical antipsychotics. The atypical antipsychotics elevate prolactin to various degrees. Like other drugs that antagonize dopamine D2 receptors, the elevation in prolactin from atypical antipsychotics can persist during chronic administration. Monitor the patient for reduced response to bromocriptine.
    Central-acting adrenergic agents: (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. Bromocriptine suppresses prolactin secretion from the anterior pituitary gland; therefore, the reduction in prolactin levels resulting from bromocriptine administration may be antagonized by prolactin-enhancing antihypertensive medications such as methyldopa and reserpine.
    Ceritinib: (Major) Avoid coadministration of ceritinib with bromocriptine due to increased bromocriptine exposure. If coadministration is unavoidable, monitor for bromocriptine-related adverse reactions; when bromocriptine is used for diabetes, do not exceed a dose of 1.6 mg once daily when administered with ceritinib. Ceritinib is a CYP3A4 inhibitor and bromocriptine is primarily metabolized by CYP3A4. Administration of bromocriptine with a moderate CYP3A4 inhibitor increased the mean AUC and Cmax of bromocriptine by 3.7-fold and 4.6-fold, respectively.
    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.
    Chlophedianol; 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.
    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.
    Chlorothiazide: (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.
    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; Dihydrocodeine; 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; Dihydrocodeine; 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; Guaifenesin; Hydrocodone; 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; Hydrocodone; 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; Hydrocodone; 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.
    Chlorthalidone: (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.
    Chlorthalidone; Clonidine: (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. (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. Bromocriptine suppresses prolactin secretion from the anterior pituitary gland; therefore, the reduction in prolactin levels resulting from bromocriptine administration may be antagonized by prolactin-enhancing antihypertensive medications such as methyldopa and reserpine.
    Choline Salicylate; Magnesium Salicylate: (Moderate) Bromocriptine is highly bound to serum proteins. Therefore, it may increase the unbound fraction of other highly protein-bound medications (e.g., 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.
    Clonidine: (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. Bromocriptine suppresses prolactin secretion from the anterior pituitary gland; therefore, the reduction in prolactin levels resulting from bromocriptine administration may be antagonized by prolactin-enhancing antihypertensive medications such as methyldopa and reserpine.
    Clozapine: (Moderate) The prolactin-lowering effect of bromocriptine at the anterior pituitary may be antagonized by medications that increase prolactin levels, such as the atypical antipsychotics. The atypical antipsychotics elevate prolactin to various degrees. Like other drugs that antagonize dopamine D2 receptors, the elevation in prolactin from atypical antipsychotics can persist during chronic administration. Monitor the patient for reduced response to bromocriptine.
    Cobicistat: (Major) When bromocriptine is used for diabetes, do not exceed a dose of 1.6 mg once daily during concomitant use of cobicistat. 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; cobicistat 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.
    Cobicistat; Elvitegravir; Emtricitabine; Tenofovir Alafenamide: (Major) When bromocriptine is used for diabetes, do not exceed a dose of 1.6 mg once daily during concomitant use of cobicistat. 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; cobicistat 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.
    Cobicistat; Elvitegravir; Emtricitabine; Tenofovir Disoproxil Fumarate: (Major) When bromocriptine is used for diabetes, do not exceed a dose of 1.6 mg once daily during concomitant use of cobicistat. 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; cobicistat 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.
    Codeine; Phenylephrine; Promethazine: (Moderate) Phenothiazines, such as promethazine, may reduce the therapeutic effects of bromocriptine, though an interaction has not been formally evaluated. Patients taking promethazine with bromocriptine for longer periods of time should be carefully observed for loss of therapeutic response. (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: (Moderate) Phenothiazines, such as promethazine, may reduce the therapeutic effects of bromocriptine, though an interaction has not been formally evaluated. Patients taking promethazine with bromocriptine for longer periods of time should be carefully observed for loss of therapeutic response.
    Conivaptan: (Major) Avoid concomitant use of bromocriptine and conivaptan. Concurrent use may significantly increase bromocriptine concentrations. Bromocriptine is extensively metabolized in the liver via CYP3A4; conivaptan is a strong inhibitor of CYP3A4. Subsequent treatment with CYP3A substrates, such as bromocriptine, may be initiated no sooner than 1 week after completion of conivaptan therapy.
    Conjugated Estrogens; 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.
    Crizotinib: (Major) Do not exceed a maximum dose of bromocriptine (Cycloset) 1.6 mg once daily for the treatment of Type 2 diabetes if coadministration with crizotinib is necessary. The manufacturer of bromocriptine (Parlodel) recommends monitoring for bromocriptine-related adverse reactions if concomitant use with crizotinib is necessary. Bromocriptine is a CYP3A4 substrate and crizotinib is a moderate CYP3A4 inhibitor. 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.
    Dalfopristin; Quinupristin: (Major) When bromocriptine is used for diabetes, avoid coadministration with dalfopristin; quinupristin 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; dalfopristin; quinupristin is a strong inhibitor 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 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. (Major) When bromocriptine is used for diabetes, do not exceed a dose of 1.6 mg once daily during concomitant use of cobicistat. 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; cobicistat 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.
    Dasabuvir; Ombitasvir; Paritaprevir; 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.
    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.
    Desvenlafaxine: (Major) Because of the potential risk and severity of serotonin syndrome or neuroleptic malignant syndrome-like reactions, caution should be observed when administering serotonin norepinephrine reuptake inhibitors (SNRIs) with other drugs that have serotonergic properties such as bromocriptine. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome. Patients receiving these combinations should be monitored for the emergence of serotonin syndrome or neuroleptic malignant syndrome-like reactions.
    Dexamethasone: (Moderate) Caution and close monitoring are advised if bromocriptine and dexamethasone 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; dexamethasone is a moderate inducer of CYP3A4.
    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 dexmethylphenidate, an inhibitor 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.
    Dextromethorphan; Promethazine: (Moderate) Phenothiazines, such as promethazine, may reduce the therapeutic effects of bromocriptine, though an interaction has not been formally evaluated. Patients taking promethazine with bromocriptine for longer periods of time should be carefully observed for loss of therapeutic response.
    Diazoxide: (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.
    Dienogest; Estradiol valerate: (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.
    Dihydrocodeine; 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.
    Dihydroergotamine: (Severe) 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. Additionally, bromocriptine should be used cautiously with other medications known to lower blood pressure such as diltiazem. Monitoring of blood pressure should be considered, especially during the initial weeks of therapy or during dose increases. 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; Hydrocodone; 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.
    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.
    Doxazosin: (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.
    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; Estradiol: (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. 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. 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.
    Duloxetine: (Major) Because of the potential risk and severity of serotonin syndrome or neuroleptic malignant syndrome-like reactions, caution should be observed when administering serotonin norepinephrine reuptake inhibitors (SNRIs) with other drugs that have serotonergic properties such as bromocriptine. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome. Patients receiving these combinations should be monitored for the emergence of serotonin syndrome or neuroleptic malignant syndrome-like reactions.
    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: (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.
    Eletriptan: (Major) Bromocriptine is an ergot alkaloid derivative. Serotonin-receptor agonists (e.g., "triptans" such as almotriptan, eletriptan, frovatriptan, naratriptan, rizatriptan, sumatriptan, zolmitriptan) are contraindicated for use within 24 hours of treatment with traditional ergot alkaloids (e.g., dihydroergotamine, methysergide) or ergot-type medications. Ergot alkaloids have been reported to cause prolonged vasospastic reactions which may be additive with the effects of serotonin-receptor agonists. While interactions have not been specifically reported between bromocriptine and triptans, combined use of these agents should be avoided if possible.
    Enalapril, Enalaprilat: (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.
    Enalapril; Felodipine: (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.
    Enalapril; Hydrochlorothiazide, HCTZ: (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.
    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.
    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.
    Epoprostenol: (Minor) Bromocriptine has only minimal affinity for adrenergic receptors; however, hypotension can occur during bromocriptine administration. 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.
    Eprosartan: (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.
    Eprosartan; Hydrochlorothiazide, HCTZ: (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.
    Ergoloid Mesylates: (Severe) 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.
    Ergonovine: (Severe) 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: (Severe) 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: (Severe) 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.
    Erythromycin; Sulfisoxazole: (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. (Moderate) 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.
    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.
    Estradiol Cypionate; 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.
    Estradiol; 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.
    Estradiol; 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.
    Estradiol; Norgestimate: (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.
    Ethacrynic Acid: (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.
    Ethanol: (Moderate) Caution and close monitoring are advised if bromocriptine and alcohol 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; alcohol is a moderate inducer of CYP3A4.
    Ethinyl Estradiol; Desogestrel: (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; Ethynodiol Diacetate: (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; 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.
    Ethinyl Estradiol; 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.
    Ethinyl Estradiol; Levonorgestrel; Folic Acid; Levomefolate: (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; Norelgestromin: (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. 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; Ferrous fumarate: (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: (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; Ferrous fumarate: (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; Norgestimate: (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. 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.
    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.
    Felodipine: (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.
    Fenoldopam: (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.
    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.
    Fluoxetine; Olanzapine: (Moderate) The prolactin-lowering effect of bromocriptine at the anterior pituitary may be antagonized by medications that increase prolactin levels, such as the atypical antipsychotics. The atypical antipsychotics elevate prolactin to various degrees. Like other drugs that antagonize dopamine D2 receptors, the elevation in prolactin from atypical antipsychotics can persist during chronic administration. Monitor the patient for reduced response to bromocriptine.
    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, avoid coadministration with fosamprenavir ensuring adequate washout before initiating bromocriptine. Use this combination with caution in patients receiving bromocriptine for other indications. Concurrent use may significantly alter bromocriptine concentrations. Bromocriptine is extensively metabolized in the liver via CYP3A4; fosamprenavir is both a strong inhibitor and moderate inducer of CYP3A4. The net effect on CYP3A4 substrates is unclear.
    Fosinopril: (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.
    Fosinopril; Hydrochlorothiazide, HCTZ: (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.
    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) Bromocriptine is an ergot alkaloid derivative. Serotonin-receptor agonists (e.g., "triptans" such as almotriptan, eletriptan, frovatriptan, naratriptan, rizatriptan, sumatriptan, zolmitriptan) are contraindicated for use within 24 hours of treatment with traditional ergot alkaloids (e.g., dihydroergotamine, methysergide) or ergot-type medications. Ergot alkaloids have been reported to cause prolonged vasospastic reactions which may be additive with the effects of serotonin-receptor agonists. While interactions have not been specifically reported between bromocriptine and triptans, combined use of these agents should be avoided if possible.
    Furosemide: (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.
    Grapefruit juice: (Major) When bromocriptine is used for diabetes, avoid coadministration with grapefruit juice 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.
    Griseofulvin: (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 griseofulvin may induce the CYP3A4 isoenzyme.
    Guaifenesin; Hydrocodone; 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.
    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.
    Guanabenz: (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. Bromocriptine suppresses prolactin secretion from the anterior pituitary gland; therefore, the reduction in prolactin levels resulting from bromocriptine administration may be antagonized by prolactin-enhancing antihypertensive medications such as methyldopa and reserpine.
    Guanfacine: (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. Bromocriptine suppresses prolactin secretion from the anterior pituitary gland; therefore, the reduction in prolactin levels resulting from bromocriptine administration may be antagonized by prolactin-enhancing antihypertensive medications such as methyldopa and reserpine.
    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.
    Hydralazine: (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.
    Hydralazine; Hydrochlorothiazide, HCTZ: (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.
    Hydralazine; Isosorbide Dinitrate, ISDN: (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.
    Hydrochlorothiazide, HCTZ: (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.
    Hydrochlorothiazide, HCTZ; Irbesartan: (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.
    Hydrochlorothiazide, HCTZ; Lisinopril: (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.
    Hydrochlorothiazide, HCTZ; Losartan: (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.
    Hydrochlorothiazide, HCTZ; Methyldopa: (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. (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. Bromocriptine suppresses prolactin secretion from the anterior pituitary gland; therefore, the reduction in prolactin levels resulting from bromocriptine administration may be antagonized by prolactin-enhancing antihypertensive medications such as methyldopa and reserpine.
    Hydrochlorothiazide, HCTZ; Metoprolol: (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.
    Hydrochlorothiazide, HCTZ; Moexipril: (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.
    Hydrochlorothiazide, HCTZ; Olmesartan: (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.
    Hydrochlorothiazide, HCTZ; Propranolol: (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.
    Hydrochlorothiazide, HCTZ; Quinapril: (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.
    Hydrochlorothiazide, HCTZ; Spironolactone: (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.
    Hydrochlorothiazide, HCTZ; Telmisartan: (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.
    Hydrochlorothiazide, HCTZ; Triamterene: (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.
    Hydrochlorothiazide, HCTZ; Valsartan: (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.
    Hydrocodone; 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.
    Hydrocodone; Potassium Guaiacolsulfonate; 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.
    Hydrocodone; 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.
    Hydroxyprogesterone: (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.
    Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate; Sodium Biphosphate: (Moderate) Bromocriptine is highly bound to serum proteins. Therefore, it may increase the unbound fraction of other highly protein-bound medications (e.g., salicylates), which may alter their effectiveness and risk for side effects. (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.
    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 prolactin-lowering effect of bromocriptine at the anterior pituitary may be antagonized by medications that increase prolactin levels, such as the atypical antipsychotics. The atypical antipsychotics elevate prolactin to various degrees. Like other drugs that antagonize dopamine D2 receptors, the elevation in prolactin from atypical antipsychotics can persist during chronic administration. Monitor the patient for reduced response to bromocriptine.
    Iloprost: (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.
    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.
    Indapamide: (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.
    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.
    Irbesartan: (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.
    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: (Major) When bromocriptine is used for diabetes, do not exceed a dose of 1.6 mg once daily during concomitant use of isoniazid. 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; isoniazid 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: (Major) When bromocriptine is used for diabetes, do not exceed a dose of 1.6 mg once daily during concomitant use of isoniazid. 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; isoniazid 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. (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: (Major) When bromocriptine is used for diabetes, do not exceed a dose of 1.6 mg once daily during concomitant use of isoniazid. 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; isoniazid 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. (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.
    Isradipine: (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.
    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.
    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.
    Levomilnacipran: (Major) Because of the potential risk and severity of serotonin syndrome or neuroleptic malignant syndrome-like reactions, caution should be observed when administering serotonin norepinephrine reuptake inhibitors (SNRIs) with other drugs that have serotonergic properties such as bromocriptine. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome. Patients receiving these combinations should be monitored for the emergence of serotonin syndrome or neuroleptic malignant syndrome-like reactions.
    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.
    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.
    Lisinopril: (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.
    Loop diuretics: (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.
    Lopinavir; Ritonavir: (Major) When bromocriptine is used for diabetes, avoid coadministration with lopinavir; 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; lopinavir; ritonavir is a strong inhibitor of CYP3A4. (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.
    Losartan: (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.
    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 CYP3A4; lumacaftor is a strong inducer of CYP3A4
    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 CYP3A4; lumacaftor is a strong inducer of CYP3A4
    Lurasidone: (Moderate) The prolactin-lowering effect of bromocriptine at the anterior pituitary may be antagonized by medications that increase prolactin levels, such as the atypical antipsychotics. The atypical antipsychotics elevate prolactin to various degrees. Like other drugs that antagonize dopamine D2 receptors, the elevation in prolactin from atypical antipsychotics can persist during chronic administration. Monitor the patient for reduced response to bromocriptine.
    Magnesium Salicylate: (Moderate) Bromocriptine is highly bound to serum proteins. Therefore, it may increase the unbound fraction of other highly protein-bound medications (e.g., salicylates), which may alter their effectiveness and risk for side effects.
    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.
    Megestrol: (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.
    Meperidine; Promethazine: (Moderate) Phenothiazines, such as promethazine, may reduce the therapeutic effects of bromocriptine, though an interaction has not been formally evaluated. Patients taking promethazine with bromocriptine for longer periods of time should be carefully observed for loss of therapeutic response.
    Mepivacaine: (Moderate) Avoid the combination of epinephrine and mepivacaine if possible in patients receiving the ergot derivatives, such as bromocriptine, due to severe reactions (severe, persistent hypertension or CVA) that can occur between some sympathomimetics such as epinephrine with ergot alkaloids.
    Mepivacaine; Levonordefrin: (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. (Moderate) Avoid the combination of epinephrine and mepivacaine if possible in patients receiving the ergot derivatives, such as bromocriptine, due to severe reactions (severe, persistent hypertension or CVA) that can occur between some sympathomimetics such as epinephrine with ergot alkaloids.
    Mesoridazine: (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.
    Mestranol; 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.
    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.
    Methyclothiazide: (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.
    Methyldopa: (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. Bromocriptine suppresses prolactin secretion from the anterior pituitary gland; therefore, the reduction in prolactin levels resulting from bromocriptine administration may be antagonized by prolactin-enhancing antihypertensive medications such as methyldopa and reserpine.
    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: (Severe) 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: (Moderate) Increased dopaminergic effects may occur during coadministration of methylphenidate, an inhibitor 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.
    Methysergide: (Severe) 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.
    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.
    Metolazone: (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.
    Metyrapone: (Moderate) Caution and close monitoring are advised if bromocriptine and metyrapone 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; metyrapone is a moderate inducer of CYP3A4.
    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, RU-486: (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.
    Milnacipran: (Major) Because of the potential risk and severity of serotonin syndrome or neuroleptic malignant syndrome-like reactions, caution should be observed when administering serotonin norepinephrine reuptake inhibitors (SNRIs) with other drugs that have serotonergic properties such as bromocriptine. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome. Patients receiving these combinations should be monitored for the emergence of serotonin syndrome or neuroleptic malignant syndrome-like reactions.
    Minoxidil: (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.
    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.
    Moexipril: (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.
    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.
    Naproxen; Sumatriptan: (Major) Bromocriptine is an ergot alkaloid derivative. Serotonin-receptor agonists (e.g., "triptans" such as almotriptan, eletriptan, frovatriptan, naratriptan, rizatriptan, sumatriptan, zolmitriptan) are contraindicated for use within 24 hours of treatment with traditional ergot alkaloids (e.g., dihydroergotamine, methysergide) or ergot-type medications. Ergot alkaloids have been reported to cause prolonged vasospastic reactions which may be additive with the effects of serotonin-receptor agonists. While interactions have not been specifically reported between bromocriptine and triptans, combined use of these agents should be avoided if possible.
    Naratriptan: (Major) Bromocriptine is an ergot alkaloid derivative. Serotonin-receptor agonists (e.g., "triptans" such as almotriptan, eletriptan, frovatriptan, naratriptan, rizatriptan, sumatriptan, zolmitriptan) are contraindicated for use within 24 hours of treatment with traditional ergot alkaloids (e.g., dihydroergotamine, methysergide) or ergot-type medications. Ergot alkaloids have been reported to cause prolonged vasospastic reactions which may be additive with the effects of serotonin-receptor agonists. While interactions have not been specifically reported between bromocriptine and triptans, combined use of these agents should be avoided if possible.
    Nebivolol; Valsartan: (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.
    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; 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.
    Nevirapine: (Moderate) Caution and close monitoring are advised if bromocriptine and nevirapine 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; nevirapine is a moderate inducer of CYP3A4.
    Nicardipine: (Major) When bromocriptine is used for diabetes, do not exceed a dose of 1.6 mg once daily during concomitant use of nicardipine. Use this combination with caution in patients receiving bromocriptine for other indications. Concurrent use may increase bromocriptine concentrations. Additionally, bromocriptine should be used cautiously with other medications known to lower blood pressure such as nicardipine. Monitoring of blood pressure should be considered, especially during the initial weeks of therapy or during dose increases. Bromocriptine is extensively metabolized in the liver via CYP3A4; nicardipine 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: (Moderate) Concurrent use of vasoconstrictors, such as nicotine, with bromocriptine, may result in enhanced vasoconstriction. Nicotine acts indirectly as a sympathomimetic agent by releasing catecholamines, potentially resulting in effects such as hypertension, which may be additive with ergot derivatives such as bromocriptine. Use of bromocriptine with some sympathomimetics has resulted in adverse effects such as worsening headache, hypertension, ventricular tachycardia, seizures, sudden loss of vision, and cerebral vasospasm. Caution is advisable during use of tobacco or other nicotine-containing products while taking bromocriptine.
    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.
    Nisoldipine: (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.
    Nitroglycerin: (Moderate) Nitroglycerin can cause hypotension, and bromocriptine can cause hypotension or hypertension. Bromocriptine also is contraindicated in patients with uncontrolled hypertension and should not be used in patients with a history of coronary artery disease or other severe cardiovascular conditions, which are the primary patient populations for which nitroglycerin is utilized. If concomitant use is necessary, blood pressure should be monitored closely.
    Nitroprusside: (Moderate) Nitroprusside can cause hypotension, and bromocriptine can cause hypotension or hypertension. In addition, bromocriptine is contraindicated in patients with uncontrolled hypertension and should not be used in patients with a history of coronary artery disease or other severe cardiovascular conditions, which are the primary patient populations for which nitroprusside is utilized. If concomitant use is necessary, blood pressure should be monitored closely.
    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: (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 prolactin-lowering effect of bromocriptine at the anterior pituitary may be antagonized by medications that increase prolactin levels, such as the atypical antipsychotics. The atypical antipsychotics elevate prolactin to various degrees. Like other drugs that antagonize dopamine D2 receptors, the elevation in prolactin from atypical antipsychotics can persist during chronic administration. Monitor the patient for reduced response to bromocriptine.
    Olmesartan: (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.
    Ombitasvir; Paritaprevir; 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.
    Oxcarbazepine: (Moderate) Caution and close monitoring are advised if bromocriptine and oxcarbazepine 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; oxcarbazepine is a moderate inducer of CYP3A4.
    Paliperidone: (Moderate) The prolactin-lowering effect of bromocriptine at the anterior pituitary may be antagonized by medications that increase prolactin levels, such as the atypical antipsychotics. The atypical antipsychotics elevate prolactin to various degrees. Like other drugs that antagonize dopamine D2 receptors, the elevation in prolactin from atypical antipsychotics can persist during chronic administration. Monitor the patient for reduced response to bromocriptine.
    Pasireotide: (Moderate) Pasireotide and bromocriptine coadministration may increase bromocriptine blood concentrations. Bromocriptine dose reduction may be needed.
    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.
    Pergolide: (Severe) 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.
    Perindopril: (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.
    Perindopril; Amlodipine: (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.
    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.
    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.
    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.
    Phenylephrine; Promethazine: (Moderate) Phenothiazines, such as promethazine, may reduce the therapeutic effects of bromocriptine, though an interaction has not been formally evaluated. Patients taking promethazine with bromocriptine for longer periods of time should be carefully observed for loss of therapeutic response. (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: (Severe) 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).
    Potassium-sparing diuretics: (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.
    Prazosin: (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.
    Prilocaine: (Moderate) Avoid the combination of epinephrine and prilocaine if possible in patients receiving the ergot derivatives, such as bromocriptine, due to severe reactions (severe, persistent hypertension or CVA) that can occur between some sympathomimetics such as epinephrine with ergot alkaloids.
    Prilocaine; Epinephrine: (Moderate) Avoid the combination of epinephrine and prilocaine if possible in patients receiving the ergot derivatives, such as bromocriptine, due to severe reactions (severe, persistent hypertension or CVA) that can occur between some sympathomimetics such as epinephrine with ergot alkaloids. (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.
    Procaine: (Moderate) Avoid the combination of epinephrine and procaine if possible in patients receiving the ergot derivatives, such as bromocriptine, due to severe reactions (severe, persistent hypertension or CVA) that can occur between some sympathomimetics such as epinephrine with ergot alkaloids.
    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: (Moderate) Phenothiazines, such as promethazine, may reduce the therapeutic effects of bromocriptine, though an interaction has not been formally evaluated. Patients taking promethazine with bromocriptine for longer periods of time should be carefully observed for loss of therapeutic response.
    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.
    Pyrimethamine; Sulfadoxine: (Moderate) 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.
    Quetiapine: (Moderate) The prolactin-lowering effect of bromocriptine at the anterior pituitary may be antagonized by medications that increase prolactin levels, such as the atypical antipsychotics. The atypical antipsychotics elevate prolactin to various degrees. Like other drugs that antagonize dopamine D2 receptors, the elevation in prolactin from atypical antipsychotics can persist during chronic administration. Monitor the patient for reduced response to bromocriptine.
    Quinapril: (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.
    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.
    Ramipril: (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.
    Reserpine: (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. Bromocriptine suppresses prolactin secretion from the anterior pituitary gland; therefore, the reduction in prolactin levels resulting from bromocriptine administration may be antagonized by prolactin-enhancing antihypertensive medications such as reserpine.
    Ribociclib: (Major) When bromocriptine is used for diabetes, do not exceed a dose of 1.6 mg once daily during concomitant use of ribociclib. 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; ribociclib is a moderate inhibitor of CYP3A4.
    Ribociclib; Letrozole: (Major) When bromocriptine is used for diabetes, do not exceed a dose of 1.6 mg once daily during concomitant use of ribociclib. 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; ribociclib is a moderate 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 moderate inducer of CYP3A4.
    Rifaximin: (Moderate) Caution and close monitoring are advised if bromocriptine and rifaximin 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. Rifaximin is a CYP3A4 inducer in vitro; however, in patients with normal liver function, rifaximin at the recommended dosing regimen is not expected to induce CYP3A4. It is unknown whether rifaximin can have a significant effect on the pharmacokinetics of concomitant CYP3A4 substrates in patients with reduced liver function who have elevated rifaximin concentrations.
    Risperidone: (Moderate) The prolactin-lowering effect of bromocriptine at the anterior pituitary may be antagonized by medications that increase prolactin levels, such as the atypical antipsychotics. The atypical antipsychotics elevate prolactin to various degrees. Like other drugs that antagonize dopamine D2 receptors, the elevation in prolactin from atypical antipsychotics can persist during chronic administration. Monitor the patient for reduced response to bromocriptine.
    Ritodrine: (Major) Ritodrine use should be avoided in patients receiving ergot alkaloids, such as bromocriptine. Although no data are available, it is possible that concomitant use of ritodrine 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.
    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) Bromocriptine is an ergot alkaloid derivative. Serotonin-receptor agonists (e.g., "triptans" such as almotriptan, eletriptan, frovatriptan, naratriptan, rizatriptan, sumatriptan, zolmitriptan) are contraindicated for use within 24 hours of treatment with traditional ergot alkaloids (e.g., dihydroergotamine, methysergide) or ergot-type medications. Ergot alkaloids have been reported to cause prolonged vasospastic reactions which may be additive with the effects of serotonin-receptor agonists. While interactions have not been specifically reported between bromocriptine and triptans, combined use of these agents should be avoided if possible.
    Sacubitril; Valsartan: (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.
    Salicylates: (Moderate) Bromocriptine is highly bound to serum proteins. Therefore, it may increase the unbound fraction of other highly protein-bound medications (e.g., salicylates), which may alter their effectiveness and risk for side effects.
    Salsalate: (Moderate) Bromocriptine is highly bound to serum proteins. Therefore, it may increase the unbound fraction of other highly protein-bound medications (e.g., 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.
    Serotonin norepinephrine reuptake inhibitors: (Major) Because of the potential risk and severity of serotonin syndrome or neuroleptic malignant syndrome-like reactions, caution should be observed when administering serotonin norepinephrine reuptake inhibitors (SNRIs) with other drugs that have serotonergic properties such as bromocriptine. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome. Patients receiving these combinations should be monitored for the emergence of serotonin syndrome or neuroleptic malignant syndrome-like reactions.
    Serotonin-Receptor Agonists: (Major) Bromocriptine is an ergot alkaloid derivative. Serotonin-receptor agonists (e.g., "triptans" such as almotriptan, eletriptan, frovatriptan, naratriptan, rizatriptan, sumatriptan, zolmitriptan) are contraindicated for use within 24 hours of treatment with traditional ergot alkaloids (e.g., dihydroergotamine, methysergide) or ergot-type medications. Ergot alkaloids have been reported to cause prolonged vasospastic reactions which may be additive with the effects of serotonin-receptor agonists. While interactions have not been specifically reported between bromocriptine and triptans, combined use of these agents should be avoided if possible.
    Spironolactone: (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.
    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.
    Streptogramins: (Major) When bromocriptine is used for diabetes, avoid coadministration with dalfopristin; quinupristin 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; dalfopristin; quinupristin is a strong inhibitor of CYP3A4.
    Sulfadiazine: (Moderate) 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) 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) 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.
    Sulfisoxazole: (Moderate) 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) 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) Bromocriptine is an ergot alkaloid derivative. Serotonin-receptor agonists (e.g., "triptans" such as almotriptan, eletriptan, frovatriptan, naratriptan, rizatriptan, sumatriptan, zolmitriptan) are contraindicated for use within 24 hours of treatment with traditional ergot alkaloids (e.g., dihydroergotamine, methysergide) or ergot-type medications. Ergot alkaloids have been reported to cause prolonged vasospastic reactions which may be additive with the effects of serotonin-receptor agonists. While interactions have not been specifically reported between bromocriptine and triptans, combined use of these agents should be avoided if possible.
    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.
    Telithromycin: (Major) When bromocriptine is used for diabetes, avoid coadministration with telithromycin 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; telithromycin is a strong inhibitor of CYP3A4.
    Telmisartan: (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.
    Telotristat Ethyl: (Moderate) Use caution if coadministration of telotristat ethyl and bromocriptine is necessary, as the systemic exposure of bromocriptine may be decreased resulting in reduced efficacy. If these drugs are used together, monitor patients for suboptimal efficacy of bromocriptine; consider increasing the dose of bromocriptine if necessary. Bromocriptine is extensively metabolized by CYP3A4. The mean Cmax and AUC of another sensitive CYP3A4 substrate was decreased by 25% and 48%, respectively, when coadministered with telotristat ethyl; the mechanism of this interaction appears to be that telotristat ethyl increases the glucuronidation of the CYP3A4 substrate.
    Terazosin: (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.
    Tetracaine: (Moderate) Avoid the combination of epinephrine and tetracaine if possible in patients receiving the ergot derivatives, such as bromocriptine, due to severe reactions (severe, persistent hypertension or CVA) that can occur between some sympathomimetics such as epinephrine with ergot alkaloids.
    Thiazide diuretics: (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.
    Thiethylperazine: (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.
    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.
    Tobacco: (Moderate) Concurrent use of vasoconstrictors, such as nicotine, with bromocriptine, may result in enhanced vasoconstriction. Nicotine acts indirectly as a sympathomimetic agent by releasing catecholamines, potentially resulting in effects such as hypertension, which may be additive with ergot derivatives such as bromocriptine. Use of bromocriptine with some sympathomimetics has resulted in adverse effects such as worsening headache, hypertension, ventricular tachycardia, seizures, sudden loss of vision, and cerebral vasospasm. Caution is advisable during use of tobacco or other nicotine-containing products while taking bromocriptine.
    Torsemide: (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.
    Trandolapril: (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.
    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. Additionally, bromocriptine should be used cautiously with other medications known to lower blood pressure such as verapamil. Monitoring of blood pressure should be considered, especially during the initial weeks of therapy or during dose increases. 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. (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.
    Treprostinil: (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.
    Triamterene: (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.
    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.
    Valsartan: (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.
    Venlafaxine: (Major) Because of the potential risk and severity of serotonin syndrome or neuroleptic malignant syndrome-like reactions, caution should be observed when administering serotonin norepinephrine reuptake inhibitors (SNRIs) with other drugs that have serotonergic properties such as bromocriptine. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome. Patients receiving these combinations should be monitored for the emergence of serotonin syndrome or neuroleptic malignant syndrome-like reactions.
    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. Additionally, bromocriptine should be used cautiously with other medications known to lower blood pressure such as verapamil. Monitoring of blood pressure should be considered, especially during the initial weeks of therapy or during dose increases. 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.
    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.
    Zafirlukast: (Minor) Bromocriptine is a cytochrome P450 3A4 substrate. In theory, inhibitors of this isoenzyme like zafirlukast may decrease the metabolism of bromocriptine.
    Zileuton: (Major) Bromocriptine is a cytochrome P450 3A4 substrate. In theory, inhibitors of this isoenzyme, such as zileuton, may decrease the metabolism of bromocriptine.
    Ziprasidone: (Moderate) The prolactin-lowering effect of bromocriptine at the anterior pituitary may be antagonized by medications that increase prolactin levels, such as the atypical antipsychotics. The atypical antipsychotics elevate prolactin to various degrees. Like other drugs that antagonize dopamine D2 receptors, the elevation in prolactin from atypical antipsychotics can persist during chronic administration. Monitor the patient for reduced response to bromocriptine.
    Zolmitriptan: (Major) Bromocriptine is an ergot alkaloid derivative. Serotonin-receptor agonists (e.g., "triptans" such as almotriptan, eletriptan, frovatriptan, naratriptan, rizatriptan, sumatriptan, zolmitriptan) are contraindicated for use within 24 hours of treatment with traditional ergot alkaloids (e.g., dihydroergotamine, methysergide) or ergot-type medications. Ergot alkaloids have been reported to cause prolonged vasospastic reactions which may be additive with the effects of serotonin-receptor agonists. While interactions have not been specifically reported between bromocriptine and triptans, combined use of these agents should be avoided if possible.

    PREGNANCY AND LACTATION

    Pregnancy

    Bromocriptine should be withdrawn when pregnancy is diagnosed whenever possible, unless a rapidly expanding macroadenoma necessitates continued use. In patients being treated for acromegaly, prolactinoma, diabetes mellitus, or Parkinson's disease, consider the medical necessity of bromocriptine or if the therapy can be withdrawn. If a patient continuing bromocriptine during pregnancy experiences a hypertensive disorder of pregnancy (including preeclampsia, eclampsia, or pregnancy-induced hypertension), the benefit of continuing the drug must be weighed against cardiovascular risks. In making the decision to administer bromocriptine during pregnancy, the potential risks to the fetus must be weighed against the potential maternal benefits, which are dependent on the initial indication for use. From a teratogenic perspective, bromocriptine is classified as FDA pregnancy risk category B. Although no adequate human studies have been performed on the effects of this drug on the fetus, data concerning 1276 pregnancies in women taking bromocriptine are available. In the majority of cases, bromocriptine 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—40 mg). After delivery, the drug is also contraindicated in the post-partum period in women with a history of coronary artery disease and other severe cardiovascular conditions unless withdrawal is considered medically contraindicated. If bromocriptine (Parlodel) is used in the post-partum period, the patient should be observed with caution.

    MECHANISM OF ACTION

    Bromocriptine stimulates dopamine type-2 receptors and antagonizes type-1 receptors in the hypothalamus and the neostriatum of the CNS. Pergolide, another ergot derivative, stimulates both type-1 and type-2 receptors. Prolactin secretion from the anterior pituitary gland is suppressed. Following bromocriptine-induced reductions in serum prolactin levels, ovulation and ovarian function will resume in amenorrheic patients, and lactation will be suppressed in women with normal ovarian activity. Bromocriptine also induces menses in amenorrheic women with normal levels of serum prolactin (possibly via the release of luteinizing hormone), and may have a direct stimulatory effect on ovarian dopaminergic receptors. Resumption of menses usually occurs within 6—8 weeks following administration of the drug.
     
    Bromocriptine can slow the growth rate of pituitary adenomas and can increase the secretion of growth hormone in normal patients. Patients with acromegaly who receive bromocriptine can experience a paradoxical decrease in the secretion of growth hormone; rates of secretion return to baseline within 2 weeks of therapy cessation. Patients with Parkinson's disease usually do not develop tolerance to the neurological effects of bromocriptine as they do to levodopa therapy.
     
    Bromocriptine has been beneficial in treating cocaine addiction. Chronic cocaine use decreases dopamine concentrations within the brain, leading to dopamine supersensitivity. This is believed to be the mechanism of craving during cocaine withdrawal. By stimulating dopamine receptors, bromocriptine has been shown to reduce the intensity of psychiatric symptoms associated with cocaine withdrawal.
     
    Bromocriptine has minimal affinity for adrenergic receptors. It slightly increases sodium excretion and can reduce blood pressure. 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 one clinical study.

    PHARMACOKINETICS

    Bromocriptine is administered orally. Bromocriptine therapy produces maximal reductions in the serum prolactin levels of hyperprolactinemic patients within 4 weeks and significantly reduces growth hormone levels in acromegaly patients within 1—2 hours. The drug binds extensively (90—96%) to serum albumin and does not appear to distribute into erythrocytes. In general, bromocriptine has a half-life of 3 hours; however, the rapid-release dosage form (Cycloset) has a longer half-life of approximately 6 hours. Metabolites are eliminated in the bile, with only a small amount (2.5—5.5 %) excreted by the kidneys.

    Oral Route

    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—5 mg dose results in serum prolactin reductions within 2 hours. More than 90% of an absorbed dose of bromocriptine undergoes first-pass metabolism, with the remainder of the dose hydrolyzed in the liver to inactive metabolites.