PERGOLIDE MESYLATE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for PERGOLIDE MESYLATE (PERGOLIDE MESYLATE).
Ergoline-derived dopamine D2 receptor agonist; also activates D1 and D3 receptors, and has antagonist activity at α2-adrenergic and 5-HT2B receptors.
| Metabolism | Hepatic metabolism via CYP3A4 and CYP2D6; first-pass effect; major metabolites include N-despropylpergolide and pergolide sulfoxide. |
| Excretion | Renal: 50-60% as metabolites; Fecal: 40-50%; Biliary: minor (<5%) |
| Half-life | Terminal elimination half-life: 15-27 hours (mean 21 hours); clinically relevant for once-daily dosing |
| Protein binding | 90-95% bound to albumin |
| Volume of Distribution | 0.6-1.2 L/kg (mean 1.0 L/kg); extensive tissue distribution |
| Bioavailability | Oral: approximately 20% due to extensive first-pass metabolism |
| Onset of Action | Oral: 30-60 minutes; peak effect at 1-2 hours |
| Duration of Action | Oral: 6-8 hours (dopaminergic effects), up to 24 hours (prolactin suppression) |
0.05 mg orally once daily for first 2 days, then increase by 0.1-0.15 mg/day every 3 days over 12 days, then by 0.25 mg/day every 3 days until optimal response; usual therapeutic range 2-3 mg/day divided 3 times daily; maximum 5 mg/day.
| Dosage form | TABLET |
| Renal impairment | No specific dose adjustment recommendations; use with caution in severe renal impairment (CrCl < 30 mL/min) due to limited data. |
| Liver impairment | No specific dose adjustment guidelines; contraindicated in Child-Pugh class C cirrhosis due to risk of hepatic encephalopathy; use with caution in Child-Pugh class A or B. |
| Pediatric use | Safety and efficacy not established; no approved pediatric dosing recommendations. |
| Geriatric use | Initiate at 0.05 mg once daily; titrate more slowly due to increased sensitivity and higher risk of hallucinations, hypotension, and confusion. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for PERGOLIDE MESYLATE (PERGOLIDE MESYLATE).
| Breastfeeding | Pergolide inhibits prolactin secretion and may suppress lactation. It is excreted in rat milk; human data are absent. M/P ratio unknown. Use during breastfeeding is contraindicated as it may interfere with milk production and expose the infant to unknown risks. |
| Teratogenic Risk | Pergolide is a dopamine agonist with limited human pregnancy data. In animal studies, doses up to 2 mg/kg/day showed no teratogenicity but increased post-implantation loss and decreased fetal weight. Human reports from inadvertent use suggest no major malformations, but the risk of first-trimester exposure cannot be excluded. Second and third trimester: No specific fetal risks documented. Overall, avoid in pregnancy unless benefit outweighs potential risk. |
■ FDA Black Box Warning
Risk of cardiac valvulopathy associated with 5-HT2B receptor agonism; use contraindicated in patients with history of cardiac valvulopathy.
| Serious Effects |
Hypersensitivity to ergot derivatives; history of cardiac valvulopathy; ergot alkaloid-related fibrotic disorders; concomitant use with dopamine antagonists.
| Precautions | Cardiac valvulopathy; fibrotic complications (pleuropulmonary, pericardial, retroperitoneal); neuroleptic malignant syndrome-like symptoms; dopamine agonist withdrawal syndrome; somnolence/sudden sleep onset; hypotension; hallucinations; dyskinesias; impulse control disorders. |
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| Fetal Monitoring | Monitor maternal blood pressure and signs of hypotension or dyskinesia. Fetal monitoring includes ultrasound for growth and amniotic fluid volume if used during pregnancy. Heart rate and movement monitoring is advised. |
| Fertility Effects | Pergolide can normalize prolactin levels, potentially restoring ovulation and fertility in hyperprolactinemic patients. No direct adverse effects on fertility have been reported. |