Metergoline — Veterinary Vademecum Drug Reference

Dosage & Administration Guidelines

Species	Route	Dose	Frequency	Duration & Clinical Notes
Dog	PO	0.2-0.5 mg/kg	q12h (every 12 hours)	Duration: 5-8 days for pseudopregnancy; 4-7 days for lactation suppression Notes: Administer with food to reduce gastrointestinal upset. For pseudopregnancy, treatment is usually continued until clinical signs resolve.
Cat	PO	0.2-0.5 mg/kg	q12h	Duration: 5-7 days for lactation suppression; longer for fibroadenomatous hyperplasia (up to 2-3 weeks) Notes: Use cautiously in cats with hepatic disease. Monitor for signs of serotonin syndrome if used with other serotonergic drugs.
Horse	PO	0.01-0.02 mg/kg	q24h	Duration: 3-5 days Notes: Limited data; use only when benefit outweighs risk. Not approved for horses.

Clinical Indications & Species Uses

General Indications

Suppression of prolactin secretion
Treatment of hyperprolactinemia-related conditions

Dog (Canine)

Treatment of pseudopregnancy (false pregnancy)
Suppression of lactation
Management of behavioral disorders associated with pseudopregnancy

Cat (Feline)

Suppression of lactation
Treatment of fibroadenomatous hyperplasia (mammary hypertrophy) when associated with hyperprolactinemia

Pharmacology & Mechanism of Action

Drug Class: Ergot alkaloid derivative | Pharmacological Group: Serotonin (5-HT) receptor antagonist; prolactin inhibitor

Mechanism of Action: Metergoline is a semisynthetic ergot alkaloid that acts primarily as a competitive antagonist at serotonin (5-HT) receptors, particularly 5-HT2A and 5-HT2C subtypes, and also exhibits partial agonist activity at 5-HT1 receptors. It also has dopamine D2 receptor agonist activity, which contributes to its prolactin-lowering effect. By blocking serotonin receptors and stimulating dopamine receptors, metergoline inhibits the release of prolactin from the anterior pituitary gland. In veterinary medicine, it is used to suppress lactation and treat conditions associated with hyperprolactinemia, such as pseudopregnancy in dogs and inappropriate lactation in cats.

Pharmacodynamics: Metergoline reduces serum prolactin levels, leading to decreased mammary gland stimulation and milk production. It also modulates serotonergic neurotransmission, which may influence behavior and appetite. In dogs, it has been shown to reduce signs of pseudopregnancy, including behavioral changes and mammary gland enlargement. In cats, it suppresses lactation and can be used to treat fibroadenomatous hyperplasia (mammary hypertrophy) associated with high progesterone and prolactin levels. Its effects on serotonin receptors may also contribute to anti-anxiety and anti-aggressive properties, though these are not primary clinical uses.

⚡ Pharmacokinetics Summary

Absorption: Metergoline is well absorbed after oral administration. Peak plasma concentrations are reached within 2-4 hours in dogs. Food may slightly delay absorption but does not significantly affect overall bioavailability.

Distribution: Metergoline is widely distributed in tissues. It crosses the blood-brain barrier and acts on central serotonin and dopamine receptors. It is also distributed into milk, which is relevant for lactating animals.

Metabolism: Metergoline undergoes extensive hepatic metabolism, primarily via oxidation and conjugation. Several metabolites are formed, some of which may retain pharmacological activity.

Excretion: Metergoline and its metabolites are excreted primarily in the feces via biliary elimination, with a smaller amount excreted in urine. In dogs, the elimination half-life is approximately 8-10 hours.

Half-Life: Dogs: ~8-10 hours; Cats: ~6-8 hours (estimated); Other species: not well documented.

Bioavailability: Oral bioavailability is approximately 60-70% in dogs, with first-pass metabolism reducing systemic exposure.

Protein Binding: Approximately 80-90% bound to plasma proteins.

Available Formulations & Strengths

Oral Tablet 4 mg, 8 mg (available in some countries; not FDA-approved in the US) (PO)

Contraindications & Clinical Warnings

Contraindications:

Hypersensitivity to metergoline or other ergot derivatives
Pregnancy (unless used for termination of pregnancy under veterinary supervision)
Lactating animals when suppression is not desired
Concurrent use with other ergot alkaloids or drugs that cause vasoconstriction
Severe hepatic impairment

Warnings & Clinical Precautions:

Use with caution in animals with cardiovascular disease, as ergot derivatives can cause vasoconstriction.
Monitor for signs of serotonin syndrome (agitation, tremors, hyperthermia) when used with other serotonergic drugs (e.g., SSRIs, TCAs, tramadol).
Safety in pregnant animals has not been established; use only when clearly needed.
In food animals, withdrawal times have not been established; do not use in animals intended for food production.
May cause gastrointestinal upset; administer with food.
Use with caution in animals with renal or hepatic impairment.

Adverse Effects & Reactions

Common:

Vomiting
Diarrhea
Loss of appetite
Lethargy
Mild sedation

Serious / Severe:

Vasoconstriction leading to tissue ischemia
Serotonin syndrome (when combined with other serotonergic drugs)
Hypotension or hypertension
Seizures (rare)

Rare:

Allergic reactions (rash, urticaria)
Hepatotoxicity
Blood dyscrasias

Key Drug Interactions

Interacting Drug / Class	Clinical Effect & Mechanism	Severity
Serotonergic drugs (SSRIs, SNRIs, TCAs, tramadol, MAO inhibitors)	Increased risk of serotonin syndrome (agitation, tremors, hyperthermia, seizures).	High
Ergot alkaloids (e.g., ergotamine, bromocriptine)	Additive vasoconstrictive effects, risk of ischemia and gangrene.	High
Dopamine antagonists (e.g., metoclopramide, phenothiazines)	May reduce the prolactin-lowering effect of metergoline.	Moderate
Antihypertensive agents	May enhance hypotensive effects.	Moderate
CYP3A4 inhibitors (e.g., ketoconazole, erythromycin)	May increase metergoline plasma levels, increasing risk of adverse effects.	Moderate

Overdose & Toxicity Management

Signs of Toxicity:

Severe vomiting
Diarrhea
Agitation
Tremors
Hyperthermia
Seizures
Cardiovascular collapse
Respiratory depression

Emergency Treatment Protocol: Treatment is symptomatic and supportive. Induce emesis if recent ingestion and animal is conscious. Administer activated charcoal to reduce absorption. Provide intravenous fluids for cardiovascular support. Control seizures with diazepam or barbiturates. Monitor for signs of serotonin syndrome and treat with cyproheptadine (1.1 mg/kg in dogs, 2-4 mg total per cat) if severe. Provide supportive care including temperature regulation and respiratory support as needed.

Food Animal Withdrawal Times

Metergoline is not approved for use in food animals. No withdrawal times have been established. Do not use in animals intended for food production.

Storage, Handling & Regulatory Information

Storage Temperature: Store at controlled room temperature, 20-25°C (68-77°F).

Light Sensitivity: Light-sensitive — protect from direct exposure.

Handling & Special Conditions: Protect from light and moisture. Keep in a tightly closed container.

Dispensing Status: Prescription Required (Rx Only)

Approval Status: Not FDA-approved for veterinary use in the US. Available in some other countries (e.g., Italy) for veterinary use.

Extra-Label (Off-Label) Use: In the US, metergoline is not FDA-approved for veterinary use. It may be used extra-label under the Animal Medicinal Drug Use Clarification Act (AMDUCA) when a valid veterinarian-client-patient relationship exists and when no approved drug is available. For food animals, extra-label use is prohibited if no withdrawal times are established.

Clinical Pearls & Practice Notes

💡 Clinical Insights: Metergoline is a valuable drug for managing pseudopregnancy in dogs and suppressing lactation in dogs and cats. It is particularly useful when rapid cessation of milk production is desired, such as after weaning or in cases of false pregnancy. In cats, it may be used to treat fibroadenomatous hyperplasia, a progesterone-induced condition often associated with elevated prolactin. The drug's dual action as a serotonin antagonist and dopamine agonist makes it effective in reducing prolactin levels. However, its use is limited by availability and lack of regulatory approval in many countries. Clinicians should be aware of potential drug interactions, especially with serotonergic agents, and monitor for adverse effects. In food animals, metergoline should never be used due to lack of withdrawal data. Overall, metergoline is a useful adjunct in reproductive management, but its use should be based on careful risk-benefit analysis.

References & Literature

📚 Plumb's Veterinary Drug Handbook
📚 Papich Veterinary Pharmacology and Therapeutics
📚 Compendium of Veterinary Products (CVP)