MEPERGAN
Clinical safety rating: caution
Comprehensive clinical and safety monograph for MEPERGAN (MEPERGAN).
Meperidine is a synthetic opioid agonist that binds to mu-opioid receptors in the central nervous system, mimicking endogenous endorphins to produce analgesia. Promethazine is a phenothiazine antipsychotic that antagonizes histamine H1, dopamine D2, muscarinic acetylcholine, and alpha-adrenergic receptors, providing sedation and antiemetic effects.
| Metabolism | Meperidine is primarily metabolized by hepatic CYP3A4 and CYP2B6 to normeperidine (active metabolite with lower analgesic potency but longer half-life). Promethazine is metabolized in the liver via CYP2D6 and glucuronidation. |
| Excretion | Renal elimination of metabolites (meperidine: ~90% as metabolites, <5% unchanged; promethazine: ~70-80% as metabolites, <1% unchanged). Biliary/fecal excretion is minimal (<10% for both). |
| Half-life | Meperidine: 3-4 hours (terminal; increased in hepatic impairment). Promethazine: 9-16 hours (terminal; prolonged in elderly). |
| Protein binding | Meperidine: 65-75% (primarily alpha1-acid glycoprotein and albumin). Promethazine: 90-93% (primarily albumin). |
| Volume of Distribution | Meperidine: 4-5 L/kg (large, indicates extensive tissue distribution). Promethazine: 9-20 L/kg (very large, extensive tissue binding). |
| Bioavailability | Meperidine: Oral ~50% (first-pass metabolism); IM/IV 100%. Promethazine: Oral ~25% (extensive first-pass); IM/IV 100%. |
| Onset of Action | IM: 10-15 min; IV: immediate (within 5 min); Oral: 30-60 min. |
| Duration of Action | Meperidine: 2-4 hours (analgesic). Promethazine: 4-6 hours (sedative). Combined product: clinical effects last 3-6 hours. |
Meperidine 50-100 mg and promethazine 25-50 mg IM/IV every 3-4 hours as needed. Maximum meperidine dose: 600 mg/day.
| Dosage form | INJECTABLE |
| Renal impairment | CrCl 10-50 mL/min: Administer 75% of normal dose at normal intervals. CrCl <10 mL/min: Administer 50% of normal dose at normal intervals; avoid in renal impairment due to normeperidine accumulation. |
| Liver impairment | Child-Pugh Class A: No adjustment. Child-Pugh Class B: Reduce dose by 50%. Child-Pugh Class C: Avoid use; meperidine is contraindicated in severe hepatic impairment. |
| Pediatric use | Meperidine 1-2 mg/kg and promethazine 0.5-1 mg/kg IM/IV every 3-4 hours. Maximum single dose: meperidine 100 mg; promethazine 50 mg. Not recommended in children <2 years due to risk of respiratory depression. |
| Geriatric use | Avoid use in elderly due to risk of normeperidine accumulation and CNS excitation. If unavoidable, use lowest effective dose (e.g., meperidine 25 mg) with extended intervals, and monitor for respiratory depression, delirium, and seizures. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for MEPERGAN (MEPERGAN).
| Breastfeeding | Meperidine: Excreted into breast milk (M/P ratio approximately 1.1). Accumulation of normeperidine may occur in breastfeeding infants, especially with repeated dosing, causing neurobehavioral depression. Promethazine: Excreted into breast milk in small amounts; not expected to cause adverse effects in infants. Use caution: avoid repeated doses of meperidine; consider alternative analgesics. |
| Teratogenic Risk | Mepergan (meperidine and promethazine) is classified as FDA Pregnancy Category C. Meperidine: Inadequate studies in pregnant women; animal studies show teratogenic effects at high doses. Risk of neonatal respiratory depression with chronic use or high doses near term. Promethazine: No well-controlled human studies; animal studies not teratogenic but may cause extrapyramidal symptoms in neonates if used in third trimester. |
■ FDA Black Box Warning
Meperidine has boxed warnings for risk of medication errors (confusion with other concentrations), respiratory depression, neonatal opioid withdrawal syndrome with prolonged use during pregnancy, and risks from concomitant use with benzodiazepines or other CNS depressants. Promethazine has a boxed warning for severe tissue injury (including gangrene) with intravenous administration.
| Serious Effects |
Hypersensitivity to meperidine or promethazine, significant respiratory depression, acute or severe bronchial asthma, upper airway obstruction, monoamine oxidase inhibitor use within 14 days, gastrointestinal obstruction, suspected surgical abdomen, and pediatric age less than 2 years (promethazine).
| Precautions | Respiratory depression, CNS depression, hypotension, seizures (especially with normeperidine accumulation in renal impairment), serotonin syndrome with serotonergic drugs, tolerance/dependence, severe tissue injury with promethazine injection, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, and disulfiram-like reaction with alcohol. |
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| Fetal Monitoring | Monitor maternal respiratory rate, sedation level, and blood pressure. Fetal monitoring for heart rate variability if used during labor. Neonatal monitoring for respiratory depression, sedation, and withdrawal symptoms if used near delivery or chronically. |
| Fertility Effects | Meperidine may impair fertility in females by decreasing gonadotropin secretion and altering menstrual cycle. Promethazine may cause false positive pregnancy tests by interacting with hCG assays. No known direct effect on male fertility. |