Bromocriptine Mesylate

Drug overview for BROMOCRIPTINE MESYLATE (bromocriptine mesylate):

Generic name: BROMOCRIPTINE MESYLATE (BROE-moe-KRIP-teen)
Drug class: Antiparkinsonian Dopamine Agonists
Therapeutic class: Central Nervous System Agents

Bromocriptine mesylate, an ergot-derivative dopamine receptor agonist and a prolactin inhibitor, is an antiparkinsonian agent and also causes sustained suppression of somatropin (growth hormone) secretion in acromegaly.

No enhanced Uses information available for this drug.

DRUG IMAGES

BROMOCRIPTINE 2.5 MG TABLET

The following indications for BROMOCRIPTINE MESYLATE (bromocriptine mesylate) have been approved by the FDA:

Indications:
Acromegaly
Hyperprolactinemia
Idiopathic parkinsonism
Postencephalitic parkinsonism

Professional Synonyms:
Acromegalia
Marie's disease
Marie's syndrome
Paralysis agitans
Parkinsonian syndrome
Primary Parkinson's disease

The following dosing information is available for BROMOCRIPTINE MESYLATE (bromocriptine mesylate):

Dosing
Administration
Dosing Information
BROMOCRIPTINE MESYLATE

Dosage of bromocriptine mesylate is expressed in terms of bromocriptine. Dosage of bromocriptine should be individualized and carefully adjusted, using frequent evaluation during dosage adjustment and employing the lowest possible effective dosage. A temporary reduction in dosage or discontinuance of the drug may occasionally be necessary in patients who develop intolerable adverse effects.

When bromocriptine therapy is discontinued (e.g., during pregnancy) in patients receiving the drug for hyperprolactinemic disorders, the patient should be carefully monitored for signs and symptoms of tumor development or progression. (See Cautions: Carcinogenicity.) Patients receiving bromocriptine for the treatment of macroadenomas should be warned to not discontinue the drug unless otherwise directed by their physician, since such discontinuance could result in rapid regrowth of the tumor and recurrence of symptoms.

The manufacturer recommends an initial adult bromocriptine dosage of 1.25 to 2.5 mg daily for the treatment of dysfunctions associated with hyperprolactinemia such as amenorrhea, galactorrhea, hypogonadism, infertility, and prolactin-secreting adenomas.

Dosage may be increased in increments of 2.5 mg daily at 2- to 7-day intervals as tolerated until the desired therapeutic response is achieved. The usual therapeutic dosage in these patients is 5-7.5

mg daily but ranges from 2.5-15 mg daily. Up to 30 mg daily has been required in some patients with amenorrhea and/or galactorrhea.

For the treatment of hypogonadism in hyperprolactinemic males, dosages up to 40 mg daily have occasionally been used.

During initial therapy for female infertility, the manufacturer recommends that a mechanical contraceptive be used in conjunction with bromocriptine therapy until normal ovulatory menstrual cycles have been restored. Contraception can then be discontinued in patients desiring pregnancy. If menstruation does not occur within 3 days of the expected date, bromocriptine should be discontinued and a pregnancy test performed.

Women not desiring pregnancy and women with large adenomas should use a mechanical contraceptive throughout bromocriptine therapy. (See Cautions: Carcinogenicity.)

Based on limited data, a bromocriptine dosage of 1.25-2.5 mg daily is recommended for the treatment of hyperprolactinemia in children 11 years of age or older.

Dosage may be increased as tolerated until therapeutic response is achieved. The usual dosage range in children with prolactin-secreting pituitary adenomas is 2.5-10 mg daily.

Bromocriptine is administered orally with food.

No dosing information available.

Generic dosing information for BROMOCRIPTINE MESYLATE
DRUG LABEL	DOSING TYPE	DOSING INSTRUCTIONS
BROMOCRIPTINE 2.5 MG TABLET	Maintenance	Adults take 1 tablet (2.5 mg) by oral route 2 times per day with food

The following drug interaction information is available for BROMOCRIPTINE MESYLATE (bromocriptine mesylate):

Contraindicated
Severe
Moderate

There are 0 contraindications.

There are 5 severe interactions. These drug interactions can produce serious consequences in most patients. Actions required for severe interactions include, but are not limited to, discontinuing one or both agents, adjusting dosage, altering administration scheduling, and providing additional patient monitoring. Review the full interaction monograph for more information.

Drug Interaction	Drug Names
Selected Dopamine Agonists/Selected Antipsychotics SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Selected dopamine agonists are used to treat neurologic conditions such as Parkinson Disease (PD)or restless legs syndrome, and endocrine disorders such as hyperprolactinemia by directly or indirectly increasing dopamine concentrations at D2 receptors in the central nervous system (CNS). Antipsychotic agents counteract this effect by blocking dopamine activity at CNS D2 receptors.(1-5) CLINICAL EFFECTS: The efficacy of either agent may be decreased, leading to exacerbation of the disease being treated. In patients with Parkinson disease motor symptoms may worsen, increasing the risk for falls, dysphagia or aspiration.(4,7) Compared with Parkinson patients not receiving antipsychotic therapy, Parkinson patients receiving antipsychotics appear to have an increased mortality risk.(6) Patients with other conditions such as restless legs syndrome or a psychotic disorder may also experience symptom exacerbation due to this combination. PREDISPOSING FACTORS: Patients with Parkinson or Diffuse Lewy Body (DLB) disease are particularly susceptible to adverse effects of dopamine blockade by antipsychotics. PATIENT MANAGEMENT: Reassess the need for antipsychotic therapy. If psychosis or hallucinations are due to an antiparkinson agent, when possible consider reducing the dose or changing the antiparkinson agent before initiating antipsychotic therapy. In patients with PD and dementia, addition of a cholinesterase inhibitor (e.g. rivastigmine) may improve psychosis. If an antipsychotic is required, then an atypical antipsychotic should be used.(6,7) In patients with major psychotic disorders, consider reducing the dose, changing or stopping the dopamine agonist. The US manufacturer of ropinirole recommends treatment with dopamine agonists only if potential benefits outweigh risks.(1) The US manufacturer of entacapone states it should not ordinarily be used in patients with major psychotic disorders as entacapone may lead to an exacerbation of psychosis.(4) DISCUSSION: An epidemiologic study evaluated 21,043 elderly patients with Parkinson disease to determine if recent initiation of a typical or atypical antipsychotic was associated with increased mortality. They found an adjusted odds ratio of 2.0 for death associated with atypical antipsychotics versus no antipsychotic They found an adjusted odds ratio of 2.4 for death associated with typical versus atypical antipsychotics. The authors noted the increased mortality found with typical antipsychotics supports current treatment recommendations to use atypical antipsychotic agents in patients with Parkinson disease.(6,7)	ADASUVE, FLUPHENAZINE DECANOATE, FLUPHENAZINE HCL, LOXAPINE, LYBALVI, MOLINDONE HCL, OLANZAPINE, OLANZAPINE ODT, OLANZAPINE-FLUOXETINE HCL, PERPHENAZINE, PERPHENAZINE-AMITRIPTYLINE, THIOTHIXENE, TRIFLUOPERAZINE HCL, ZYPREXA
Selected Dopamine Agonists/Selected Antiemetics SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Selected dopamine agonists are used to treat neurologic conditions such as Parkinson Disease (PD)or restless legs syndrome (RLS), and endocrine disorders such as hyperprolactinemia by directly or indirectly increasing dopamine concentrations at dopamine-2 (D2) receptors in the central nervous system (CNS). Antiemetic agents which block CNS D2 receptors may counteract this effect.(1-5) CLINICAL EFFECTS: The efficacy of the dopamine agonist may be decreased, leading to exacerbation of the disease being treated. In patients with Parkinson disease motor symptoms may worsen, increasing the risk for falls, dysphagia or aspiration.(5) Patients with other conditions such as restless legs syndrome may also experience symptom exacerbation due to this combination. PREDISPOSING FACTORS: Patients with Parkinson or Diffuse Lewy Body (DLB) disease are particularly susceptible to adverse effects of dopamine blockade. PATIENT MANAGEMENT: Reassess antiemetic therapy and use an antiemetic without dopamine (D2) blocking effects if possible. If clinically appropriate and available, consider the use of a 5HT3 blocker (e.g. ondansetron) or domperidone (not available in the US).(4) If concomitant treatment is needed, monitor for loss of efficacy for the disease being treated by the dopamine agonist (e.g. Parkinson disease, restless legs syndrome) and adjust medication(s) or dosage if needed.(1-4) Counsel patients to report symptoms of disease exacerbation. DISCUSSION: Patients with Parkinson or DLB disease are particularly susceptible to adverse effects of dopamine blockade. The European Academy of Neurology guideline for late Parkinson disease states that metoclopramide, cinnarizine and prochlorperazine must be avoided. Ondansetron or domperidone(not available in the US) may be used for nausea and vomiting.(5) Prescribing information for dopamine agonists warn of the risk for disease exacerbation when dopamine blocking agents are co-prescribed.(1-4)	COMPAZINE, COMPRO, GIMOTI, METOCLOPRAMIDE HCL, PROCHLORPERAZINE, PROCHLORPERAZINE EDISYLATE, PROCHLORPERAZINE MALEATE, REGLAN
Selected CYP3A4 Substrates/Lonafarnib SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Lonafarnib is a strong inhibitor of CYP3A4 and may decrease the metabolism of drugs metabolized by the CYP3A4 enzyme. Lonafarnib is also an inhibitor of P-glycoprotein (P-gp) and may increase the absorption of sirolimus. CLINICAL EFFECTS: Concurrent use of lonafarnib may lead to increased serum levels and adverse effects of drugs sensitive to inhibition of the CYP3A4 pathway or P-gp.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The manufacturer of lonafarnib states that coadministration of CYP3A4 substrates should be avoided. If concomitant use is unavoidable, monitor for adverse effects and consider dose reduction of the CYP3A4 substrate according to its prescribing information.(1) The manufacturer of lonafarnib states that the dose of P-gp substrates may need to be reduced with coadministration with lonafarnib.(1) DISCUSSION: In a study of healthy volunteers, lonafarnib (100 mg twice daily for 5 days) increased the area-under-the-curve (AUC) and maximum concentration (Cmax) of a single dose of midazolam (3 mg) by 639% and 180%, respectively.(1) In a study of healthy volunteers, lonafarnib (100 mg twice daily for 5 days) increased the AUC and Cmax of single-dose fexofenadine (180 mg) by 24% and 21%, respectively.(1) CYP3A4 substrates with a narrow therapeutic index linked to this monograph include: bromocriptine, cabergoline, cannabidiol-tetrahydrocannabinol, clonazepam, darolutamide, felodipine, mefloquine, nisoldipine, oliceridine, pomalidomide, regorafenib, sirolimus, and zanubrutinib.(1-3)	ZOKINVY
Selected Dopamine Agonists/Slt Antipsychotics SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Selected dopamine agonists are used to treat neurologic conditions such as Parkinson Disease (PD) or restless legs syndrome, and endocrine disorders such as hyperprolactinemia by directly or indirectly increasing dopamine concentrations at D2 receptors in the central nervous system (CNS). Antipsychotic agents counteract this effect by blocking dopamine activity at CNS D2 receptors.(1-5) CLINICAL EFFECTS: The efficacy of either agent may be decreased, leading to exacerbation of the disease being treated. In patients with Parkinson disease motor symptoms may worsen, increasing the risk for falls, dysphagia or aspiration.(4,7) Compared with Parkinson patients not receiving antipsychotic therapy, Parkinson patients receiving antipsychotics appear to have an increased mortality risk.(6) Patients with other conditions such as restless legs syndrome or a psychotic disorder may also experience symptom exacerbation due to this combination. PREDISPOSING FACTORS: Patients with Parkinson or Diffuse Lewy Body (DLB) disease are particularly susceptible to adverse effects of dopamine blockade by antipsychotics. PATIENT MANAGEMENT: Reassess the need for antipsychotic therapy. If psychosis or hallucinations are due to an antiparkinson agent, when possible consider reducing the dose or changing the antiparkinson agent before initiating antipsychotic therapy. In patients with PD and dementia, addition of a cholinesterase inhibitor (e.g. rivastigmine) may improve psychosis. If an antipsychotic is required, then an atypical antipsychotic should be used.(6,7) In patients with major psychotic disorders, consider reducing the dose, changing or stopping the dopamine agonist. The US manufacturer of ropinirole recommends treatment with dopamine agonists only if potential benefits outweigh risks.(1) The US manufacturer of entacapone states it should not ordinarily be used in patients with major psychotic disorders as entacapone may lead to an exacerbation of psychosis.(4) DISCUSSION: An epidemiologic study evaluated 21,043 elderly patients with Parkinson disease to determine if recent initiation of a typical or atypical antipsychotic was associated with increased mortality. They found an adjusted odds ratio of 2.0 for death associated with atypical antipsychotics versus no antipsychotic They found an adjusted odds ratio of 2.4 for death associated with typical versus atypical antipsychotics. The authors noted the increased mortality found with typical antipsychotics supports current treatment recommendations to use atypical antipsychotic agents in patients with Parkinson disease.(6,7)	BARHEMSYS, CHLORPROMAZINE HCL, DROPERIDOL, HALDOL DECANOATE 100, HALDOL DECANOATE 50, HALOPERIDOL, HALOPERIDOL DECANOATE, HALOPERIDOL DECANOATE 100, HALOPERIDOL LACTATE, PIMOZIDE, THIORIDAZINE HCL, THIORIDAZINE HYDROCHLORIDE
Bromocriptine; Cabergoline/Selected Macrolide Antibiotics SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Selected macrolide antibiotics that are strong CYP3A4 inhibitors may inhibit the metabolism of bromocriptine and cabergoline.(1-3) CLINICAL EFFECTS: Concurrent use of selected macrolide antibiotics may result in increased levels of bromocriptine and cabergoline, which may result in increased side effects of these agents.(1-3) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Use caution with concurrent therapy with bromocriptine and cabergoline with selected macrolide antibiotics.(1-3) The US manufacturer of bromocriptine states use caution when co-administering drugs that are inhibitors of CYP3A4. Concomitant use of strong CYP3A4 inhibitors should be avoided. Ensure adequate washout of strong CYP3A4 inhibitor drug before initiating bromocriptine.(2) DISCUSSION: Concurrent administration of selected macrolide antibiotics with bromocriptine or cabergoline may increase the side effects of these agents. Clarithromycin, josamycin, telithromycin and troleandomycin are strong CYP3A4 inhibitors.(4) Itraconazole has been shown to increase cabergoline concentrations with concurrent use. A case report including 2 patients with concurrent therapy of cabergoline and itraconazole noted plasma levels of cabergoline to be increased by 300% in one of the patients. This increase in cabergoline concentrations was noted to increase clinical improvement.(6) A study compared ten healthy male volunteers taking cabergoline (1 mg/day) alone for 6 days or a single oral dose of cabergoline plus clarithromycin (400 mg/day) for 6 days. Mean plasma cabergoline concentrations increased 2.6-fold with clarithromycin coadministration. The study also compared seven patients with Parkinson's disease receiving stable doses of cabergoline alone and with the addition of clarithromycin (400 mg/day for 6 days). Cabergoline plasma concentrations increased 1.7-fold during clarithromycin coadministration.(7) A study in five healthy subjects found that concurrent administration of erythromycin, a moderate CYP3A4 inhibitor, and bromocriptine resulted in a 268% increase in area-under-curve (AUC) for bromocriptine and a 4.6-fold increase in bromocriptine maximum concentration (Cmax).(8)	CLARITHROMYCIN, CLARITHROMYCIN ER, LANSOPRAZOL-AMOXICIL-CLARITHRO, OMECLAMOX-PAK, VOQUEZNA TRIPLE PAK

There are 4 moderate interactions. The clinician should assess the patient’s characteristics and take action as needed. Actions required for moderate interactions include, but are not limited to, discontinuing one or both agents, adjusting dosage, altering administration.

Drug Interaction	Drug Names
Selected Dopamine Agonists/Select Atypical Antipsychotics SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Selected dopamine agonists are used to treat neurologic conditions such as Parkinson Disease (PD) or restless legs syndrome, and endocrine disorders such as hyperprolactinemia by directly or indirectly increasing dopamine concentrations at D2 receptors in the central nervous system (CNS). Antipsychotic agents counteract this effect by blocking dopamine activity at CNS D2 receptors.(1-5) CLINICAL EFFECTS: The efficacy of either agent may be decreased, leading to exacerbation of the disease being treated, e.g. Parkinson disease or a psychotic disorder. Dopamine agonists linked to this monograph are: bromocriptine, entacapone, levodopa, pergolide, pramipexole, ropinirole and rotigotine. Atypical antipsychotics linked to this monograph are: aripiprazole, asenapine, iloperidone, lumateperone, lurasidone, paliperidone, quetiapine, risperidone, ziprasidone and zotepine. PREDISPOSING FACTORS: Patients with Parkinson or Diffuse Lewy Body (DLB) disease are particularly susceptible to adverse effects of dopamine blockade by antipsychotics. PATIENT MANAGEMENT: Reassess the need for antipsychotic therapy. If psychosis or hallucinations are due to an antiparkinson agent, when possible consider reducing the dose or changing the antiparkinson agent before initiating antipsychotic therapy. In patients with PD and dementia, addition of a cholinesterase inhibitor (e.g. rivastigmine) may improve psychosis. If an antipsychotic is required, then an atypical antipsychotic should be used.(6,7) In patients with major psychotic disorders, consider reducing the dose, changing, or stopping the dopamine agonist. The US manufacturer of ropinirole recommends treatment with dopamine agonists only if potential benefits outweigh risks.(1) The US manufacturer of entacapone states it should not ordinarily be used in patients with major psychotic disorders as entacapone may lead to an exacerbation of psychosis.(4) DISCUSSION: An epidemiologic study evaluated 21,043 elderly patients with Parkinson disease to determine if recent initiation of a typical or atypical antipsychotic was associated with increased mortality. They found an adjusted odds ratio of 2.0 for death associated with atypical antipsychotics versus no antipsychotic. They found an adjusted odds ratio of 2.4 for death associated with typical versus atypical antipsychotics. The authors noted the increased mortality found with typical antipsychotics supports current treatment recommendations to use atypical antipsychotic agents in patients with Parkinson disease.(6,7) Two clozapine trials showed significant improvement in psychosis without worsening of motor symptoms. In contrast, two olanzapine trials were associated with unacceptable worsening of motor symptoms. Risperidone has also been associated with motor worsening in case reports. Quetiapine evaluations have been conflicting with several small studies showing improvement in psychotic symptoms while a more rigorous trial showed no improvement.(6)	ABILIFY, ABILIFY ASIMTUFII, ABILIFY MAINTENA, ARIPIPRAZOLE, ARIPIPRAZOLE ODT, ARISTADA, ARISTADA INITIO, ASENAPINE MALEATE, CAPLYTA, ERZOFRI, FANAPT, GEODON, INVEGA, INVEGA HAFYERA, INVEGA SUSTENNA, INVEGA TRINZA, LATUDA, LURASIDONE HCL, OPIPZA, PALIPERIDONE ER, PERSERIS, QUETIAPINE FUMARATE, QUETIAPINE FUMARATE ER, REXULTI, RISPERDAL, RISPERDAL CONSTA, RISPERIDONE, RISPERIDONE ER, RISPERIDONE ODT, RYKINDO, SAPHRIS, SECUADO, SEROQUEL, SEROQUEL XR, UZEDY, VRAYLAR, ZIPRASIDONE HCL, ZIPRASIDONE MESYLATE
Bromocriptine; Cabergoline/Selected CYP3A4 Inhibitors SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Certain azole antifungals (itraconazole(1,6), ketoconazole(2), posaconazole(3,4), and voriconazole(5)), protease inhibitors (amprenavir(7), atazanavir(8), boceprevir(9), darunavir(10), fosamprenavir(11), indinavir(12), lopinavir(13), nelfinavir(14), nirmatrelvir/ritonavir,(15) ritonavir(16), saquinavir(17), telaprevir(18), and tipranavir(19)), and other strong CYP3A4 inhibitors (cobicistat, idelalisib, levoketoconazole, mibefradil, nefazodone, and ribociclib(20)) may inhibit the metabolism of bromocriptine and cabergoline by CYP3A4. CLINICAL EFFECTS: Concurrent use of bromocriptine or cabergoline with azole antifungals, protease inhibitors, or other strong CYP3A4 inhibitors may result in increased levels of bromocriptine and cabergoline, which may result in increased side effects of these agents. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Use caution with concurrent therapy with bromocriptine and cabergoline with azole antifungals, protease inhibitors, or other strong CYP3A4 inhibitors. DISCUSSION: Itraconazole has been shown to increase cabergoline concentrations with concurrent use. A case report including 2 patients with concurrent therapy of cabergoline and itraconazole noted plasma levels of cabergoline to be increased by 300% in one of the patients. This increase in cabergoline concentrations was noted to increase clinical improvement.(6) Posaconazole has been shown to inhibit the CYP3A4 mediated metabolism of midazolam by 83%.(3) Voriconazole (400 mg every 12 hours for one day, then 200 mg every 12 hours for 8 days) increased the maximum concentration (Cmax) and area-under-curve (AUC) of a single dose of sirolimus (2 mg) by 7-fold and 11-fold, respectively. Ergot alkaloids are metabolized by the same isoenzyme system.(5)	APTIVUS, ATAZANAVIR SULFATE, DARUNAVIR, FOSAMPRENAVIR CALCIUM, GENVOYA, ITRACONAZOLE, ITRACONAZOLE MICRONIZED, KALETRA, KETOCONAZOLE, KISQALI, LOPINAVIR-RITONAVIR, NEFAZODONE HCL, NORVIR, NOXAFIL, PAXLOVID, POSACONAZOLE, PREZISTA, RECORLEV, REYATAZ, RITONAVIR, SPORANOX, STRIBILD, TOLSURA, TYBOST, VFEND, VFEND IV, VIRACEPT, VORICONAZOLE, ZYDELIG
Bromocriptine; Cabergoline/Selected Macrolide Antibiotics SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Selected macrolide antibiotics may inhibit the metabolism of bromocriptine and cabergoline by inhibition of CYP3A4.(1-3) Erythromycin has shown to inhibit the hepatic uptake of bromocriptine through inhibition of organic anion transporting polypeptide C (OATP-C) mediated uptake, as well as inhibit CYP3A4 metabolism of bromocriptine.(4) CLINICAL EFFECTS: Concurrent use of selected macrolide antibiotics may result in increased levels of bromocriptine and cabergoline, which may result in increased side effects of these agents.(1-3) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Use caution with concurrent therapy with bromocriptine and cabergoline with selected macrolide antibiotics. The US manufacturer of bromocriptine states use caution when co-administering drugs that are inhibitors of CYP3A4. Bromocriptine dose should not exceed 1.6 mg per day when used with a moderate CYP3A4 inhibitor. Concomitant use of strong CYP3A4 inhibitors should be avoided. Ensure adequate washout of strong CYP3A4 inhibitor drug before initiating bromocriptine.(2) DISCUSSION: Concurrent administration of selected macrolide antibiotics with bromocriptine or cabergoline may increase the side effects of these agents. Erythromycin is a moderate inhibitor of CYP3A4.(5) A study in five healthy subjects found that concurrent administration of erythromycin and bromocriptine resulted in a 268% increase in area-under-curve (AUC) for bromocriptine and a 4.6-fold increase in bromocriptine maximum concentration (Cmax).(6)	E.E.S. 200, E.E.S. 400, ERY-TAB, ERYPED 200, ERYPED 400, ERYTHROCIN LACTOBIONATE, ERYTHROCIN STEARATE, ERYTHROMYCIN, ERYTHROMYCIN ESTOLATE, ERYTHROMYCIN ETHYLSUCCINATE, ERYTHROMYCIN LACTOBIONATE
Bromocriptine/Moderate CYP3A4 Inhibitors SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Moderate CYP3A4 inhibitors may inhibit the metabolism of bromocriptine. CLINICAL EFFECTS: Concurrent use of a moderate CYP3A4 inhibitor may result in increased levels of bromocriptine, which may result in increased side effects of these agents. PREDISPOSING FACTORS: Patients receiving the maximum recommended (or higher than recommended) dosages of ergotamine derivatives may be at a higher risk of adverse effects from this combination. PATIENT MANAGEMENT: Use caution with concurrent therapy with bromocriptine with azole antifungals. The US manufacturer of bromocriptine states use caution when co-administering drugs that are inhibitors of CYP3A4. Bromocriptine dose should not exceed 1.6 mg per day when used with a moderate CYP3A4 inhibitor. Concomitant use of strong CYP3A4 inhibitors should be avoided. Ensure adequate washout of strong CYP3A4 inhibitor drug before initiating bromocriptine.(1) DISCUSSION: A study in five healthy subjects found that concurrent administration of erythromycin and bromocriptine resulted in a 268% increase in area-under-curve (AUC) for bromocriptine and a 4.6-fold increase in bromocriptine maximum concentration (Cmax).(2) Inhibition of ergotamine derivative metabolism by moderate inhibitors would also be expected, but to a lesser degree. Moderate CYP3A4 inhibitors linked to this monograph are aprepitant, avacopan, berotralstat, clofazimine, conivaptan, crizotinib, diltiazem, dronedarone, duvelisib, fedratinib, fluconazole, fluvoxamine, fosnetupitant, imatinib, isavuconazonium, ledipasvir, lenacapavir, letermovir, netupitant, nilotinib, schisandra, stiripentol, tofisopam, treosulfan and verapamil.(3,4)	AKYNZEO, APONVIE, APREPITANT, CARDIZEM, CARDIZEM CD, CARDIZEM LA, CARTIA XT, CINVANTI, CLOFAZIMINE, CONIVAPTAN-D5W, COPIKTRA, CRESEMBA, DANZITEN, DIACOMIT, DIFLUCAN, DILT-XR, DILTIAZEM 12HR ER, DILTIAZEM 24HR ER, DILTIAZEM 24HR ER (CD), DILTIAZEM 24HR ER (LA), DILTIAZEM 24HR ER (XR), DILTIAZEM HCL, DILTIAZEM HCL-0.7% NACL, DILTIAZEM HCL-0.9% NACL, DILTIAZEM HCL-NACL, DILTIAZEM-D5W, EMEND, FLUCONAZOLE, FLUCONAZOLE-NACL, FLUVOXAMINE MALEATE, FLUVOXAMINE MALEATE ER, GLEEVEC, GRAFAPEX, IMATINIB MESYLATE, IMKELDI, INREBIC, MATZIM LA, MULTAQ, NILOTINIB HCL, ORLADEYO, PREVYMIS, SUNLENCA, TASIGNA, TAVNEOS, TIADYLT ER, TIAZAC, TRANDOLAPRIL-VERAPAMIL ER, VAPRISOL-5% DEXTROSE, VERAPAMIL ER, VERAPAMIL ER PM, VERAPAMIL HCL, VERAPAMIL SR, XALKORI

The following contraindication information is available for BROMOCRIPTINE MESYLATE (bromocriptine mesylate):

Overview
Contraindicated
Severe
Moderate

Drug contraindication overview.

No enhanced Contraindications information available for this drug.

There are 2 contraindications. Absolute contraindication.

Contraindication List
Lactation
Severe uncontrolled hypertension

There are 3 severe contraindications. Adequate patient monitoring is recommended for safer drug use.

Severe List
Cerebrovascular accident
Coronary artery disease
Psychotic disorder

There are 3 moderate contraindications. Clinically significant contraindication, where the condition can be managed or treated before the drug may be given safely.

Moderate List
Disease of liver
Hypertension
Hypotension

The following adverse reaction information is available for BROMOCRIPTINE MESYLATE (bromocriptine mesylate):

Overview
Severe
Less Severe

Adverse reaction overview.

No enhanced Common Adverse Effects information available for this drug.

There are 24 severe adverse reactions.

More Frequent	Less Frequent
Hypotension	Acute cognitive impairment Dyskinesia Dyspnea Hallucinations Peripheral edema Skin rash Syncope Visual changes

Rare/Very Rare
Acute myocardial infarction Cardiac arrhythmia Cerebrovascular accident Drug-induced psychosis Fibrotic drug-induced cardiac valvulopathy Gastrointestinal hemorrhage Hypertension Peptic ulcer Pericardial effusion Pericarditis Pleural effusions Pleural fibrosis Pulmonary fibrosis Retroperitoneal fibrosis Seizure disorder

There are 41 less severe adverse reactions.

More Frequent	Less Frequent
Dizziness Dyspepsia Fatigue General weakness Headache disorder Infection Nausea Rhinitis Sinusitis Toxic amblyopia Vomiting	Abdominal pain with cramps Anorexia Constipation Cramps in legs Depression Diarrhea Drowsy Dysphagia Increased urinary frequency Insomnia Nasal congestion Nervousness Nightmares Paresthesia Raynaud's phenomenon Symptoms of anxiety Urinary incontinence Urinary retention Vertigo Xerostomia

Rare/Very Rare
Agitation Alopecia Anticholinergic toxicity Blurred vision Impulse control disorder Increased libido Orthostatic hypotension Pallor Sudden onset of sleep Tinnitus

The following precautions are available for BROMOCRIPTINE MESYLATE (bromocriptine mesylate):

Pediatric
Pregnant
Lactation
Geriatric

No enhanced Pediatric Use information available for this drug.

Contraindicated

None

Severe Precaution

None

Management or Monitoring Precaution

None

Cumulative data in women who have taken bromocriptine during pregnancy indicate that the incidence of spontaneous abortions and congenital malformations appears to be similar to that reported in the general population. Most of these women received the drug during the first 2-3 weeks of pregnancy, although some received the drug throughout pregnancy. Use of bromocriptine to reduce serum prolactin concentrations and prevent possible pituitary tumor expansion has been reported in some women during the last week of pregnancy.

However, dopamine agonists generally should not be used during pregnancy and should be discontinued immediately if pregnancy occurs. In pregnant women with underlying prolactin-secreting pituitary tumors, sudden enlargement of the tumors as a result of an increase in pituitary size which normally occurs during pregnancy may cause optic nerve compression, visual impairment, and even blindness, which usually disappear after delivery. In pregnant women receiving bromocriptine, fetal prolactin (but not growth hormone) concentrations are suppressed; concentrations of prolactin in amniotic fluid are not affected. Prolactin concentrations return to normal in these infants after birth.

Since bromocriptine interferes with lactation, the drug should not be used in nursing women (some manufacturers state that the drug is contraindicated in this population).

No enhanced Geriatric Use information available for this drug.

The following icd codes are available for BROMOCRIPTINE MESYLATE (bromocriptine mesylate)'s list of indications:

Acromegaly
E22.0	Acromegaly and pituitary gigantism
Hyperprolactinemia
E22.1	Hyperprolactinemia
Idiopathic parkinsonism
G20	Parkinson's disease
G20.A	Parkinson's disease without dyskinesia
G20.A1	Parkinson's disease without dyskinesia, without mention of fluctuations
G20.A2	Parkinson's disease without dyskinesia, with fluctuations
G20.B	Parkinson's disease with dyskinesia
G20.B1	Parkinson's disease with dyskinesia, without mention of fluctuations
G20.B2	Parkinson's disease with dyskinesia, with fluctuations
G20.C	Parkinsonism, unspecified
Postencephalitic parkinsonism
G21.3	Postencephalitic parkinsonism