Bromocriptine

Overview

Bromocriptine (Cycloset®, Parlodel®) is a synthetic ergot derivative and dopamine (D2) receptor agonist that acts primarily as a prolactin inhibitor. It has historically been used in dogs and cats for selected reproductive and endocrine disorders, but its use has largely declined due to the availability of safer and more effective dopamine agonists such as cabergoline.

In dogs, bromocriptine has been used for pseudocyesis, suppression of lactation, pregnancy termination, estrus induction, and as an adjunct in pyometra management. In cats, it has been used for acromegaly and mammary fibroadenomatous hyperplasia. However, adverse effects are relatively common, and alternative agents are generally preferred in small animal practice.

Mechanism of Action (MOA): Bromocriptine stimulates dopamine (D2) receptors, resulting in inhibition of prolactin release from the anterior pituitary. It may also reduce growth hormone concentrations in patients with acromegaly. By suppressing prolactin, bromocriptine interferes with lactation and alters reproductive hormone dynamics.

Indications

In dogs and cats, bromocriptine has been used for selected reproductive and endocrine disorders. Its use is largely extra-label and has decreased in favor of other dopamine agonists with improved safety profiles; however, it may still be considered in specific clinical situations.

• Pseudocyesis (pseudopregnancy) in dogs: Used to suppress prolactin secretion and reduce lactation and maternal behaviors associated with pseudocyesis.
• Suppression of lactation (dogs): May be used to inhibit inappropriate or unwanted lactation.
• Pregnancy termination (dogs): Administered in conjunction with a prostaglandin for termination of pregnancy; not commonly recommended due to adverse effects and availability of alternatives.
• Adjunctive treatment of pyometra (dogs): Used in combination with prostaglandins in selected cases.
• Estrus induction (dogs): Historically used for induction of estrus, although this indication is not commonly recommended.
• Acromegaly (cats): Used as adjunctive therapy to reduce growth hormone concentrations and potentially decrease insulin requirements.
• Mammary fibroadenomatous hyperplasia (cats): Reported use as adjunctive therapy; not commonly recommended.

Dosage (Reference)

Dog

In dogs, bromocriptine is used extra-label for reproductive and endocrine indications. Adverse effects are common, and dosing should be carefully monitored.

Cat

In cats, bromocriptine is used extra-label for selected endocrine and mammary conditions. Compounding may be required for accurate dosing.

Warnings & Precautions

Bromocriptine is an ergot-derived dopamine agonist with a wide range of potential adverse effects. Careful patient selection and monitoring are essential when used in dogs and cats, particularly because safer alternatives are often available.

• Hypersensitivity to ergot derivatives: Contraindicated in patients with known hypersensitivity to ergot alkaloids (e.g., cabergoline). Patients intolerant of cabergoline may also not tolerate bromocriptine.
• Pregnancy: Generally contraindicated during pregnancy unless termination is desired. Ergot alkaloid effects may increase the risk of reproductive complications.
• Hypertension: Use cautiously in patients with hypertension, particularly those receiving antihypertensive therapy, as syncope or additive hypotension may occur.
• Hepatic disease: Use with caution in patients with liver dysfunction, as hepatic metabolism may be reduced, increasing the risk of adverse effects.
• Lactation suppression: Bromocriptine interferes with prolactin secretion and inhibits lactation; administration to nursing animals is not recommended unless suppression of lactation is the intended therapeutic goal.
• Dose-related adverse effects: Many adverse reactions are dose-dependent; gradual dose adjustment and administration with food may improve tolerance.

Drug Interactions

Bromocriptine has numerous potential drug interactions related to its dopaminergic activity, hepatic metabolism (CYP3A4), and cardiovascular effects. When used in dogs and cats, concurrent medications should be reviewed carefully and monitoring adjusted as needed.

• Azole antifungals (e.g., itraconazole, ketoconazole): May increase bromocriptine plasma concentrations by inhibiting hepatic metabolism, increasing the risk of adverse effects.
• Macrolide antibiotics (e.g., erythromycin, clarithromycin): May increase bromocriptine concentrations via CYP3A4 inhibition.
• Other ergot alkaloids (e.g., cabergoline, metergoline, pergolide): Concomitant use is not recommended due to increased risk of severe adverse reactions, including hypertension and cardiovascular complications.
• Hypotensive medications (e.g., amlodipine, enalapril, opioids): May cause additive hypotension when administered with bromocriptine.
• Metoclopramide: May stimulate prolactin release in dogs, potentially counteracting the intended prolactin-inhibiting effects of bromocriptine.
• Monoamine oxidase inhibitors (MAOIs; e.g., amitraz, selegiline, linezolid): Concurrent use should be avoided due to the risk of significant adverse neurologic or cardiovascular effects.
• Estrogens and progestins: May interfere with the intended endocrine effects of bromocriptine.
• Phenothiazines (e.g., acepromazine, chlorpromazine) and butyrophenones (e.g., haloperidol): May increase prolactin concentrations, potentially necessitating dose adjustment of bromocriptine.
• Cyclosporine: May increase cyclosporine concentrations; monitoring is recommended.
• Octreotide: May increase bromocriptine concentrations.
• Reserpine and amitriptyline: May increase prolactin concentrations, potentially reducing bromocriptine effectiveness.
• Sympathomimetics (e.g., phenylpropanolamine): Rarely associated with enhanced bromocriptine effects, including potential cardiac complications.
• Ethanol: May produce a disulfiram-type reaction (e.g., nausea, vomiting) when used concurrently.

Side Effects & Overdose

Side Effects

Adverse effects of bromocriptine in dogs and cats are common and generally dose-related. Many reactions improve with dose reduction or administration with food.

• Gastrointestinal effects: Nausea and vomiting are among the most frequently observed adverse effects, particularly in dogs.
• CNS depression: Sedation, lethargy, and fatigue may occur during therapy.
• Hypotension: May be most pronounced after the first dose but can persist with continued treatment.
• Behavioral or psychoactive changes (cats): Long-term administration in cats may result in abnormal behaviors such as head or body movements.
• Hypoglycemia: Documented in humans; incidence in veterinary patients is unknown but should be considered in at-risk animals.

Overdose

Overdose of bromocriptine may result in marked gastrointestinal, neurologic, and cardiovascular signs. There is no specific antidote; treatment is supportive and based on clinical presentation.

• Clinical signs: Severe nausea, vomiting, lethargy, hypothermia, tachycardia, and profound hypotension.
• Gastrointestinal decontamination: Emesis may occur spontaneously; induction of emesis or administration of activated charcoal may be considered if appropriate and early after ingestion.
• Cardiovascular monitoring: Blood pressure and heart rate should be closely monitored.
• Supportive care: Provide fluid therapy and symptomatic treatment as needed.

Key Notes

Practical clinical considerations for the use of bromocriptine in dogs and cats:

• Alternative agents preferred: Cabergoline is generally favored in dogs and cats due to improved safety and tolerability compared with bromocriptine.
• Limited modern use: Bromocriptine is now infrequently used in small animal practice and is typically reserved for cases where other dopamine agonists are unavailable or unsuitable.
• Insulin requirements in cats: In feline acromegaly, therapy may reduce insulin requirements; periodic reassessment of insulin dosing may be necessary.
• Compounding considerations: Feline dosing may require compounding to achieve accurate microgram-level administration.
• First-pass metabolism: Due to significant hepatic first-pass effect, only a small fraction of the administered dose reaches systemic circulation.
• Owner counseling: Inform owners that therapy may not be well tolerated and that close communication is important if appetite, behavior, or activity level changes.