DROPERIDOL
Clinical safety rating: safe
Animal studies have demonstrated safety
Droperidol is a butyrophenone antipsychotic that acts primarily as a dopamine D2 receptor antagonist. It also exhibits antiemetic effects via blockade of dopamine D2 receptors in the chemoreceptor trigger zone. Additionally, it has alpha-adrenergic blocking properties and can prolong the QT interval by blocking cardiac potassium channels (hERG).
| Metabolism | Primarily metabolized by CYP3A4 and to a lesser extent by CYP2D6; also undergoes N-dealkylation and hydroxylation. Metabolites include p-fluorobenzoylpropionic acid and droperidol N-oxide. |
| Excretion | Renal (75% as metabolites, <1% unchanged); fecal (22%); biliary excretion contributes to enterohepatic circulation. |
| Half-life | Terminal elimination half-life: 2.3 hours (range 1.5–4.7 hours). Clinical context: Short half-life allows rapid titration but requires repeated dosing or continuous infusion for sustained effect; accumulation with hepatic impairment. |
| Protein binding | ~90% bound to albumin and α1-acid glycoprotein. |
| Volume of Distribution | 2–3 L/kg (mean 2.5 L/kg). Clinical meaning: Extensive tissue distribution, with high affinity for CNS and peripheral tissues. |
| Bioavailability | IM: 60–80% (due to first-pass metabolism); oral: approximately 60% (significant first-pass effect; oral use not common in clinical practice). |
| Onset of Action | IV: 3–10 minutes; IM: 10–30 minutes. Peak effect: IV within 10 minutes; IM within 30–60 minutes. |
| Duration of Action | Duration: 2–4 hours for sedative and antipsychotic effects; antiemetic effect may persist up to 6–12 hours. Clinical notes: Prolonged duration in elderly, hepatic impairment, or with higher doses. |
| Molecular Weight | 379.43 |
2.5-10 mg IV/IM every 3-4 hours as needed for nausea and vomiting; for agitation or psychosis in perioperative settings: 0.625-1.25 mg IV/IM, may repeat every 6 hours.
| Dosage form | INJECTABLE |
| Renal impairment | No dose adjustment required for renal impairment per FDA labeling; use caution in severe renal disease due to potential accumulation of metabolite. |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B: use 50% of normal dose; Child-Pugh C: avoid use due to risk of QT prolongation and hepatic metabolism. |
| Pediatric use | For postoperative nausea/vomiting: 0.05-0.06 mg/kg IV/IM (maximum 1 mg) for children >2 years; for agitation: 0.01-0.03 mg/kg IV/IM every 4-6 hours as needed (max 2.5 mg). |
| Geriatric use | Start at 50% of adult dose (e.g., 0.625-1.25 mg IV/IM); titrate slowly due to increased sensitivity to QT prolongation, extrapyramidal symptoms, and hypotension. |
| 1st trimester | Avoid. Studies suggest possible teratogenic effects in animal models; limited human data. Use only if benefit outweighs risk for severe nausea/vomiting. |
| 2nd trimester | Avoid. Increased risk of maternal QT prolongation and possible fetal effects; use only if clearly needed and no safer alternatives. |
| 3rd trimester | Avoid near term. May cause neonatal QT prolongation, extrapyramidal symptoms, or respiratory depression; use only if benefit clearly outweighs risk. |
Clinical note
Other QT-prolonging agents increase risk of torsades de pointes Can cause QT prolongation and severe hypotension.
| Placental transfer | Crosses placenta. Measured cord blood levels approximately 50% of maternal serum levels; fetal exposure can cause neonatal effects. |
| Breastfeeding | Present in breast milk in low concentrations; likely compatible with breastfeeding, but monitor infant for sedation, extrapyramidal symptoms, or QT prolongation. American Academy of Pediatrics considers it compatible. |
■ FDA Black Box Warning
WARNING: QT PROLONGATION AND TORSADES DE POINTES. Droperidol can cause QT interval prolongation and torsades de pointes, which can be fatal. Use is contraindicated in patients with known QT prolongation or concurrent use of QT-prolonging drugs. ECG monitoring is recommended before and during administration.
| Common Effects | sedation |
| Serious Effects |
Known hypersensitivity to droperidol or butyrophenonesProlonged QT interval (QTc > 450 ms in men or > 460 ms in women)History of torsades de pointesConcurrent use of drugs that prolong QT intervalClinically significant bradycardiaElectrolyte disturbances (hypokalemia, hypomagnesemia)Severe hepatic impairment
| Precautions | Risk of QT prolongation and torsades de pointes; monitor ECG and electrolytes, Extrapyramidal symptoms (dystonia, akathisia, parkinsonism), Neuroleptic malignant syndrome (NMS), Hypotension and tachycardia, Central nervous system depression and respiratory depression when combined with opioids, Increased risk of falls in elderly patients, Potential for paradoxical excitement or agitation |
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| Lactation Rating | L3 (Moderately Safe) |
| Teratogenic Risk | FDA Pregnancy Category C. First trimester: Limited human data; animal studies show embryotoxicity but not teratogenicity at high doses. Second and third trimesters: Avoid near term due to risk of neonatal extrapyramidal symptoms, sedation, and respiratory depression. |
| Fetal Monitoring | Monitor maternal blood pressure, heart rate, ECG for QT prolongation. Fetal monitoring for heart rate variability and signs of distress during labor. |
| Fertility Effects | May cause transient hyperprolactinemia, potentially impairing fertility by disrupting luteal phase and ovulation. Reversible upon discontinuation. |
| Food/Dietary | No specific food interactions are documented. However, avoid excessive intake of caffeine or other stimulants, as they may exacerbate CNS stimulation or cardiac effects. Maintain adequate hydration and electrolyte balance; hypokalemia and hypomagnesemia increase risk of QT prolongation. |
| Clinical Pearls | Droperidol has a black box warning for QT prolongation and torsade de pointes; obtain baseline ECG and monitor QTc interval, especially in patients with electrolyte abnormalities, bradycardia, or concurrent use of other QT-prolonging drugs. Metabolized via CYP3A4; avoid in patients with known or suspected pheochromocytoma. Onset of action is 3-10 minutes IV, duration 2-4 hours. May cause significant hypotension in hypovolemic patients; ensure adequate hydration. Use with caution in elderly due to anticholinergic effects and risk of falls. |
| Patient Advice | Droperidol can cause serious heart rhythm changes; you will need an ECG before and during treatment. · Report any fainting, palpitations, or irregular heartbeat immediately. · Avoid alcohol and other CNS depressants while taking this medication. · You may feel drowsy or dizzy; do not drive or operate heavy machinery until you know how the drug affects you. · Inform your doctor if you have a history of heart disease, electrolyte imbalance, or if you are taking other medications that affect heart rhythm. · Take exactly as prescribed; do not change dose or stop without consulting your doctor. |