Bromocriptine is an ergot derivative that activates post-synaptic dopamine receptors in the brain. It is used in the treatment of the following conditions:
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Treatment of acromegaly.
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For glycemic control in adults with Diabetes Mellitus Type 2 as an adjunct to diet and exercise.
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For the treatment of prolactin-secreting pituitary adenoma
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Treatment of amenorrhea, galactorrhea, hypogonadism, or infertility associated with hyperprolactinemia.
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For the symptomatic treatment of idiopathic or post-encephalitic Parkinson disease as an adjunct to levodopa or levodopa/carbidopa.
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For the treatment of Neuroleptic malignant syndrome as an Off label Use.
Bromocriptine Dose in Adults
Use in the treatment of Acromegaly:
- 1.25 - 2.5 mg orally once a day.
- The dose may be increased by 1.25 - 2.5 mg daily every 3 - 7 days to the usual dose of 20 - 30 mg daily and a maximum dose of 100 mg/day.
Use in the treatment of Type 2 Diabetes mellitus (Cycloset only):
Note: It is not a recommended treatment choice
- 0.8 mg orally once a day in the morning
- The dose may be increased at weekly intervals in 0.8 mg increments to the usual dose of 1.6 - 4.8 mg once a day and a maximum dose of 4.8 mg/day.
- Cycloset dose adjustment in patients on concomitant moderate CYP3A4 inhibitor therapy like erythromycin:
- The maximum dose should not exceed 1.6 mg/day.
- Patients on Strong CYP3A4 inhibitors like azole antimycotics and HIV protease inhibitors:
- Avoid treatment and ensure an adequate washout of the strong CYP3A4 inhibitor before initiating treatment with bromocriptine.
Use in the treatment of Hyperprolactinemia:
- 1.25 - 2.5 mg orally once a day initially.
- The dose may be increased by 2.5 mg daily as tolerated every 2 - 7 days until optimal response (The usual dose ranges between 2.5 - 15 mg/day).
Use in the treatment of Parkinsonism:
- 25 mg two times a day orally
- The dose may be increased by 2.5 mg per day in 2 to 4-week intervals to a maximum dose of 100 mg/day if needed.
Off label use in the treatment of Neuroleptic malignant syndrome:
- 5 mg orally or via nasogastric tube twice or thrice daily to a maximum dose of 45 mg per day.
- Treatment should be slowly tapered off when the disease is controlled.
Bromocriptine Dose in Childrens
Use in the treatment of Hyperprolactinemia secondary to pituitary adenoma:
- Children and Adolescents less than16 years:
- 1.25 - 2.5 mg orally once a day initially
- The dose may be increased to the usual effective dose of 5 - 7.5 mg and to a maximum dose of 10 mg per day in divided doses to achieve a therapeutic response.
- Adolescents older than 16 years:
- 1.25 - 2.5 mg orally once a day initially.
- The dose may be increased by 2.5 mg per day as tolerated every 2 - 7 days until optimal response to the maximum daily dose of 15 mg/day in divided doses (The usual effective dose ranges from 5 - 7.5 mg/day)
Pregnancy Risk Factor B
- Bromocriptine passes the placental barrier.
- Bromocriptine-treated patients may be advised to use mechanical contraception, which can be stopped if they desire pregnancy.
- It should not be used during pregnancy, except for patients with rapidly expanding macroadenomas.
- Treatment may be stopped if it is used to treat Parkinson's disease or acromegaly.
- Patients should be closely monitored after discontinuation for any signs of an enlarging cancer.
- After 4 weeks of treatment with bromocriptine, patients should undergo a pregnancy test. A pregnancy test can be performed in patients who have normal periods.
- Patients who do not desire to become pregnant should be advised of the benefits of effective contraception.
Bromocriptine use during breastfeeding:
- Nursing women should not use this medication. It can also inhibit lactation.
- Although it was once used to prevent postpartum lactation, the risks of stroke, myocardial injury, seizures and hypertension mean that it is not recommended anymore.
Bromocriptine Dose in Renal Disease:
- Dose adjustment is not required in patients with renal disease.
Bromocriptine Dose in Liver Disease:
- It should be used with caution in patients with severe hepatic impairment.
- Dose adjustment may be necessary as it undergoes an extensive first-pass hepatic metabolism.
Note: Frequency of adverse effects may vary by dose and/or indication.
Common Side Effects of Bromocriptine Include:
- Central Nervous System:
- Dizziness
- Fatigue
- Headache
- Gastrointestinal:
- Constipation
- Nausea
- Neuromuscular & Skeletal:
- Weakness
- Respiratory:
- Rhinitis
Less Common Side Effects of Bromocriptine Include:
- Cardiovascular:
- Hypotension
- Raynaud's Phenomenon
- Syncope
- Vasospasm
- Central Nervous System:
- Drowsiness
- Lightheadedness
- Endocrine & Metabolic:
- Hypoglycemia
- Gastrointestinal:
- Abdominal Cramps
- Anorexia
- Diarrhea
- Dyspepsia
- Gastrointestinal Hemorrhage
- Vomiting
- Xerostomia
- Infection:
- Increased Susceptibility To Infection
- Ophthalmic:
- Amblyopia
- Respiratory:
- Flu-Like Symptoms
- Nasal Congestion
- Sinusitis
Contraindication to Bromocriptine include:
- Bromocriptine, ergot and any other component of the formulation can cause allergic reactions
Contraindications to Cycloset
- Syncopal migraine
- Breastfeeding
Contraindications to Parlodel
- Hypertension uncontrolled
- Pregnancy
- Women who have had CAD (coronary artery diseases) or other serious cardiovascular conditions postpartum may be at higher risk.
Warnings and Precautions
- Cardiac valvular fibrosis:
- Fibrotic valve thickening has been linked to long-term and chronic use of ergotalkaloids and their derivatives.
- Cardiovascular effects
- After therapy is initiated and escalated, patients may experience hypotension, particularly orthostatic hypotension, and syncope.
- It has been linked to hypertension, stroke, myocardial infarction, and seizures.
- If severe headaches, neurotoxicity, or uncontrolled hypertension occur, it is best to stop treatment.
- In its scientific statement, the AHA has stated that it causes direct myocardial toxicities.
- CNS depression:
- It can cause impairment of physical and mental capabilities, as well as episodes of sudden sleep onset in Parkinson's patients.
- Patients who engage in activities that require mental alertness, such as driving heavy machinery or operating heavy machinery, should be warned.
- Hallucinations
- Patients can experience visual and auditory hallucinations, which may last for several weeks.
- Impulse control disorders:
- Compulsive behavior and/or loss in impulse control can manifest as increased or new gambling urges, increased spending, excessive money, or other intense urges. These urges may or may not be improved by a decrease in dosage.
- Melanoma
- For melanoma development, monitor the patient regularly.
- Retroperitoneal and pleural fibrosis
- High doses and prolonged therapy have been linked to pericardial and pleural effusions as well as retroperitoneal, pleural, and/or pulmonary fibrosis, and constrictive pericarditis.
- You must stop all treatment immediately.
- Acromegaly:
- If tumor growth is observed in patients being treated for acromegaly should be stopped immediately.
- Treatment must be stopped for between 4 and 8 weeks before pituitary radiation.
- Digital vasospasm may occur in patients with acromegaly. This may necessitate a reduction of the dosage.
- Cardiovascular disease
- Patients who have had a history of myocardial injury, residual atrial, nodal or ventricular arrhythmias, should be cautious about taking the drug.
- Dementia
- High doses of bromocriptine can cause confusion in patients with dementia.
- Galactose intolerance (Parlodel),
- Galactose intolerance, severe galactose malnutrition or glucose-galactose malabsorption patients should not take parlodel.
- Hepatic impairment
- Patients suffering from liver disease might need to adjust the dosage. Patients with hepatic impairment should be cautious.
- Macroadenomas:
- Patients with macroadenomas might experience rapid tumor growth and an increase in prolactin.
- Peptic ulcer disease:
- Patients with a history or peptic ulcer disease may experience GI bleeding.
- Adenomas that secrete prolactin:
- Patients may develop CSF rhinorrhea.
- Psychosis:
- Patients with severe psychosis should be avoided as it can worsen the condition and reduce the effectiveness of therapy.
Bromocriptine: Drug Interaction
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Alcohol (Ethyl) |
May enhance the adverse/toxic effect of Bromocriptine. Bromocriptine may enhance the adverse/toxic effect of Alcohol (Ethyl). |
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Alfuzosin |
May enhance the hypotensive effect of Blood Pressure Lowering Agents. |
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Alpha-Lipoic Acid |
May enhance the hypoglycemic effect of Antidiabetic Agents. |
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Androgens |
May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Exceptions: Danazol. |
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Antiemetics (5HT3 Antagonists) |
May enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. |
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Barbiturates |
May enhance the hypotensive effect of Blood Pressure Lowering Agents. |
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Blood Pressure Lowering Agents |
May enhance the hypotensive effect of HypotensionAssociated Agents. |
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Brimonidine (Topical) |
May enhance the hypotensive effect of Blood Pressure Lowering Agents. |
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Bromopride |
May diminish the therapeutic effect of Anti-Parkinson Agents (Dopamine Agonist). |
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BuPROPion |
Anti-Parkinson Agents (Dopamine Agonist) may enhance the adverse/toxic effect of BuPROPion. |
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Chloroprocaine |
May enhance the hypertensive effect of Ergot Derivatives. |
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Clofazimine |
May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). |
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Diazoxide |
May enhance the hypotensive effect of Blood Pressure Lowering Agents. |
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Diethylstilbestrol |
May enhance the adverse/toxic effect of Bromocriptine. Specifically, the risk for amenorrhea may be increased with the combination. |
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Direct Acting Antiviral Agents (HCV) |
May enhance the hypoglycemic effect of Antidiabetic Agents. |
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DULoxetine |
Blood Pressure Lowering Agents may enhance the hypotensive effect of DULoxetine. |
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Fosaprepitant |
May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). |
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Guanethidine |
May enhance the hypoglycemic effect of Antidiabetic Agents. |
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Herbs (Hypotensive Properties) |
May enhance the hypotensive effect of Blood Pressure Lowering Agents. |
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Hyperglycemia-Associated Agents |
May diminish the therapeutic effect of Antidiabetic Agents. |
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Hypoglycemia-Associated Agents |
Antidiabetic Agents may enhance the hypoglycemic effect of Hypoglycemia-Associated Agents. |
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Hypotension-Associated Agents |
Blood Pressure Lowering Agents may enhance the hypotensive effect of Hypotension-Associated Agents. |
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Larotrectinib |
May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). |
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Levodopa-Containing Products |
Blood Pressure Lowering Agents may enhance the hypotensive effect of Levodopa-Containing Products. |
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Lormetazepam |
May enhance the hypotensive effect of Blood Pressure Lowering Agents. |
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Maitake |
May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. |
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Metaxalone |
May enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. |
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Methylphenidate |
May enhance the adverse/toxic effect of Anti-Parkinson Agents (Dopamine Agonist). |
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Methylphenidate |
May enhance the adverse/toxic effect of Serotonin Modulators. Specifically, the risk of serotonin syndrome or serotonin toxicity may be increased. |
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Metoclopramide |
May diminish the therapeutic effect of Anti-Parkinson Agents (Dopamine Agonist). |
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Metoclopramide |
Serotonin Modulators may enhance the adverse/toxic effect of Metoclopramide. This may be manifest as symptoms consistent with serotonin syndrome or neuroleptic malignant syndrome. |
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Molsidomine |
May enhance the hypotensive effect of Blood Pressure Lowering Agents. |
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Monoamine Oxidase Inhibitors |
May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. |
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Naftopidil |
May enhance the hypotensive effect of Blood Pressure Lowering Agents. |
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Nicergoline |
May enhance the hypotensive effect of Blood Pressure Lowering Agents. |
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Nicorandil |
May enhance the hypotensive effect of Blood Pressure Lowering Agents. |
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Nitroprusside |
Blood Pressure Lowering Agents may enhance the hypotensive effect of Nitroprusside. |
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Opioid Agonists |
May enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. |
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Palbociclib |
May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). |
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Pegvisomant |
May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. |
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Pentoxifylline |
May enhance the hypotensive effect of Blood Pressure Lowering Agents. |
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Pholcodine |
Blood Pressure Lowering Agents may enhance the hypotensive effect of Pholcodine. |
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Phosphodiesterase 5 Inhibitors |
May enhance the hypotensive effect of Blood Pressure Lowering Agents. |
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Prostacyclin Analogues |
May enhance the hypotensive effect of Blood Pressure Lowering Agents. |
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Prothionamide |
May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. |
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Quinagolide |
May enhance the hypotensive effect of Blood Pressure Lowering Agents. |
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Quinolones |
May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Quinolones may diminish the therapeutic effect of Blood Glucose Lowering Agents. Specifically, if an agent is being used to treat diabetes, loss of blood sugar control may occur with quinolone use. |
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Reboxetine |
May enhance the hypertensive effect of Ergot Derivatives. |
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Ritodrine |
May diminish the therapeutic effect of Antidiabetic Agents. |
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Salicylates |
May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. |
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Selective Serotonin Reuptake Inhibitors |
May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. |
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Serotonin Modulators |
May enhance the adverse/toxic effect of other Serotonin Modulators. The development of serotonin syndrome may occur. Exceptions: Nicergoline; Tedizolid. |
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Simeprevir |
May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). |
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Solriamfetol |
Anti-Parkinson Agents (Dopamine Agonist) may enhance the hypertensive effect of Solriamfetol. |
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Somatostatin Analogs |
May increase the serum concentration of Bromocriptine. Somatostatin Analogs may also delay bromocriptine absorption and time to maximum plasma concentrations. |
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Tedizolid |
May enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. |
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Thiazide and Thiazide-Like Diuretics |
May diminish the therapeutic effect of Antidiabetic Agents. |
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TraMADol |
Serotonin Modulators may enhance the adverse/toxic effect of TraMADol. The risk of seizures may be increased. TraMADol may enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. |
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Risk Factor D (Consider therapy modification) |
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Amifostine |
Blood Pressure Lowering Agents may enhance the hypotensive effect of Amifostine. Management: When amifostine is used at chemotherapy doses, blood pressure lowering medications should be withheld for 24 hours prior to amifostine administration. If blood pressure lowering therapy cannot be withheld, amifostine should not be administered. |
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Anti-Parkinson Agents (Monoamine Oxidase Inhibitor) |
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Antipsychotic Agents (First Generation [Typical]) |
May diminish the therapeutic effect of AntiParkinson Agents (Dopamine Agonist). Anti-Parkinson Agents (Dopamine Agonist) may diminish the therapeutic effect of Antipsychotic Agents (First Generation [Typical]). Management: Avoid concomitant therapy if possible and monitor for decreased effects of both agents when these combinations cannot be avoided. Atypical antipsychotics such as clozapine and quetiapine may be less likely to reduce the effects of anti-Parkinson agents. |
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Antipsychotic Agents (Second Generation [Atypical]) |
May diminish the therapeutic effect of AntiParkinson Agents (Dopamine Agonist). Management: Consider using an alternative antipsychotic agent when possible in patients with Parkinson disease. If an atypical antipsychotic is necessary, consider using clozapine or quetiapine, which may convey the lowest interaction risk. |
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Beta-Blockers |
May enhance the vasoconstricting effect of Ergot Derivatives. |
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CYP3A4 Inhibitors (Moderate) |
May increase the serum concentration of Bromocriptine. Management: The bromocriptine dose should not exceed 1.6 mg daily with use of a moderate CYP3A4 inhibitor. The Cycloset brand specifically recommends this dose limitation, but other bromocriptine products do not make such specific recommendations. |
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Linezolid |
May enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Management: Due to a risk of serotonin syndrome/serotonin toxicity, discontinue serotonin modulators 2 weeks prior to the administration of linezolid. If urgent initiation of linezolid is needed, discontinue serotonin modulators immediately and monitor closely. |
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Obinutuzumab |
May enhance the hypotensive effect of Blood Pressure Lowering Agents. Management: Consider temporarily withholding blood pressure lowering medications beginning 12 hours prior to obinutuzumab infusion and continuing until 1 hour after the end of the infusion. |
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Stiripentol |
May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Use of stiripentol with CYP3A4 substrates that are considered to have a narrow therapeutic index should be avoided due to the increased risk for adverse effects and toxicity. Any CYP3A4 substrate used with stiripentol requires closer monitoring. |
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Risk Factor X (Avoid combination) |
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Alizapride |
May diminish the therapeutic effect of Anti-Parkinson Agents (Dopamine Agonist). |
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Alpha-/Beta-Agonists |
Ergot Derivatives may enhance the hypertensive effect of Alpha-/BetaAgonists. Ergot Derivatives may enhance the vasoconstricting effect of Alpha-/Beta-Agonists. |
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Alpha1-Agonists |
Ergot Derivatives may enhance the hypertensive effect of Alpha1-Agonists. Ergot Derivatives may enhance the vasoconstricting effect of Alpha1-Agonists. |
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Amisulpride |
May diminish the therapeutic effect of Anti-Parkinson Agents (Dopamine Agonist). Anti-Parkinson Agents (Dopamine Agonist) may diminish the therapeutic effect of Amisulpride. |
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Bromperidol |
Blood Pressure Lowering Agents may enhance the hypotensive effect of Bromperidol. Bromperidol may diminish the hypotensive effect of Blood Pressure Lowering Agents. |
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Conivaptan |
May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). |
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CYP3A4 Inhibitors (Strong) |
May increase the serum concentration of Bromocriptine. |
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Dapoxetine |
May enhance the adverse/toxic effect of Serotonin Modulators. |
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Fusidic Acid (Systemic) |
May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). |
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Idelalisib |
May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). |
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Lorcaserin |
May enhance the adverse/toxic effect of Ergot Derivatives. Specifically, use of these drugs together may increase the risk of developing valvular heart disease. Lorcaserin may enhance the serotonergic effect of Ergot Derivatives. This could result in serotonin syndrome. |
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Methylene Blue |
May enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. |
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Nitroglycerin |
Ergot Derivatives may diminish the vasodilatory effect of Nitroglycerin. This is of particular concern in patients being treated for angina. Nitroglycerin may increase the serum concentration of Ergot Derivatives. |
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Protease Inhibitors |
May increase the serum concentration of Ergot Derivatives. |
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Roxithromycin |
May increase the serum concentration of Ergot Derivatives. |
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Serotonin 5-HT1D Receptor Agonists |
Ergot Derivatives may enhance the vasoconstricting effect of Serotonin 5-HT1D Receptor Agonists. Serotonin 5-HT1D Receptor Agonists may enhance the vasoconstricting effect of Ergot Derivatives. |
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Sulpiride |
May diminish the therapeutic effect of Anti-Parkinson Agents (Dopamine Agonist). |
Monitor:
- Vital signs including the blood pressure and heart rate at baseline and then periodically.
- Liver function tests
- Renal functions
- CBC
- Cardiac status
- Visual fields (in patients with prolactinoma)
- Pregnancy test during the amenorrheic period
- Growth hormone (in patients with acromegaly)
- Prolactin levels
- Gastrointestinal bleeding (in patients with a history of peptic ulcer disease)
- Melanoma skin examinations
- Serum glucose and Glycate hemoglobin.
How to take Bromocriptine?
- It should be administered with meals to reduce the gastrointestinal upset.
- Cycloset should be taken within 2 hours of waking in the morning. If the morning dose is missed, resume with the usual dose the next morning.
Mechanism of action of Bromocriptine:
- It is a semisynthetic ergot alkaloid derivative with a sympatholytic activity at acting at the post-synaptic dopamine D-2 receptors in the tuberoinfundibular and nigrostriatal pathways.
- Activation by the dopamine receptors of the tuberoinfundibular pathways results in inhibition of pituitary hormone secretion, while it increases coordinated motor activity through the nigrostriatal channels.
- Unknown mechanisms also allow it to be used in the treatment of type 2 diabetes mellitus.
- Its effects on the circadian rhythm could be a factor in insulin resistance and obesity.
- Bromocriptine can reset the hypothalamic circadian rhythm of patients with insulin resistance and obesity, and lower glucose output without affecting insulin secretion.
90 - 96% of the drug is protein-bound and is metabolized primarily in the liver via CYP3A.
It undergoes extensive first-pass hepatic metabolism. It has been abioavailability65-95 % and aplasma half-life eliminationBetween 5 and 6 hours. Time to reachpeak plasma concentrationIt takes between 1 and 2.5 hours.excretedPrimarily via feces
International brands of Bromocriptine:
- Bromocriptine
- DOM-Bromocriptine
- NU-Bromocriptine
- PMS-Bromocriptine
- Antiprotin
- Apo-Bromocriptine
- Aspen Bromocriptine
- Barlolin
- Brameston
- Brom
- Bromergon
- Bromo-Kin
- Bromocriptin-Richter
- Bromocriptina
- Bromolac
- Butin
- Cripsa
- Criptine
- Criten
- Demil
- Deprolac
- Dopagon
- Kripton
- Lactodel
- Medocriptine
- Parlodel
- Pravidel
- Protinal
- Ronalin
- Serocryptin
- Suplac
- Umprel
Bromocriptine brand names in Pakistan:
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Bromocriptine (Mesylate) [Tabs 10 mg] |
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| Brolib | Libra Pharmaceuticals (Pvt) Ltd |
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Bromocriptine (Mesylate) [Tabs 2.5 mg] |
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| Bromicon | Helicon Pharmaceutek Pakistan (Pvt) Ltd. |
| Bromotin | Caraway Pharmaceuticals |
| Brotin | Shaigan Pharmaceuticals (Pvt) Ltd |
| Cripton | Evron (Pvt) Ltd. |
| Cripton | Evron (Pvt) Ltd. |
| Parlodel | Novartis Pharma (Pak) Ltd |
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