PROPULSID
Clinical safety rating: caution
Comprehensive clinical and safety monograph for PROPULSID (PROPULSID).
Selective serotonin 5-HT4 receptor agonist that enhances release of acetylcholine in the myenteric plexus of the gastrointestinal tract, increasing gastrointestinal motility.
| Metabolism | Extensively metabolized by CYP3A4; also undergoes oxidative N-dealkylation and aromatic hydroxylation. No significant CYP2D6 involvement. |
| Excretion | Primarily metabolized in the liver via CYP3A4; approximately 35-45% excreted in urine as metabolites and unchanged drug (<10% unchanged), and 45-60% in feces via biliary elimination. |
| Half-life | Terminal elimination half-life is 6-12 hours (mean 7-10 hours) in healthy individuals; prolonged to 15-20 hours in hepatic impairment or with CYP3A4 inhibitors. |
| Protein binding | 97-98% bound, primarily to albumin; also to alpha1-acid glycoprotein. |
| Volume of Distribution | 3.0-5.0 L/kg; extensive tissue distribution, indicating high extravascular penetration. |
| Bioavailability | Oral bioavailability is approximately 35-45% due to extensive first-pass metabolism; variable depending on CYP3A4 activity. |
| Onset of Action | Oral: Onset of gastric emptying effect within 30-60 minutes; peak effect at 1-2 hours. |
| Duration of Action | Duration of action is 3-4 hours for gastric emptying effects; clinical effects may persist for up to 8 hours due to active metabolites (norcisapride). |
10 mg orally three times daily, 15 minutes before meals and at bedtime. Maximum dose 20 mg four times daily.
| Dosage form | SUSPENSION |
| Renal impairment | GFR 20-40 mL/min: reduce dose by 50%; GFR <20 mL/min: contraindicated. |
| Liver impairment | Child-Pugh Class B: reduce dose by 50%; Child-Pugh Class C: contraindicated. |
| Pediatric use | 0.2-0.3 mg/kg/dose orally three to four times daily; maximum 10 mg per dose. |
| Geriatric use | Initiate at 5 mg three times daily; titrate cautiously due to risk of QT prolongation and drug interactions. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for PROPULSID (PROPULSID).
| Breastfeeding | Excreted into breast milk; M/P ratio approximately 0.5. Limited data suggest low infant exposure. Use with caution, monitor infant for potential proarrhythmic effects. |
| Teratogenic Risk | Insufficient human data. Animal studies show no evidence of teratogenicity at clinically relevant doses. No increased risk of major malformations reported in limited postmarketing surveillance. Theoretical risk of QT prolongation in fetus if maternal use near term. |
| Fetal Monitoring |
■ FDA Black Box Warning
WARNING: QT prolongation, torsade de pointes, and sudden death have been reported, particularly in patients with predisposing conditions. PROPULSID is contraindicated with certain drugs and medical conditions that increase the risk of these events.
| Serious Effects |
["Concurrent use of CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, erythromycin, clarithromycin, troleandomycin, fluconazole, and grapefruit juice).","Concurrent use of drugs that prolong QT interval (e.g., quinidine, procainamide, amiodarone, sotalol, and certain antipsychotics).","History of long QT syndrome or congenital QT prolongation.","Clinically significant bradycardia, hypokalemia, or hypomagnesemia.","Known hypersensitivity to cisapride or any component."]
| Precautions | ["Risk of QT interval prolongation and cardiac arrhythmias; avoid in patients with a history of long QT syndrome, electrolyte disturbances, or bradycardia.","Concomitant use with CYP3A4 inhibitors (e.g., ketoconazole, erythromycin) or drugs that prolong QT interval is contraindicated.","Use with caution in patients with hepatic impairment due to risk of elevated drug levels.","Monitor for diarrhea, which may indicate overdose or toxicity."] |
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| Monitor ECG for QT interval prolongation. Assess electrolyte levels (K+, Mg2+). Fetal ultrasound for growth and anatomy if used in first trimester. Monitor for maternal arrhythmias. |
| Fertility Effects | No known adverse effects on fertility in humans. Animal studies show no impairment of fertility at therapeutic doses. |