MEPERGAN
Clinical safety rating
cautionComprehensive 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. |
| Molecular Weight | 347.5 |
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 | Avoid due to potential teratogenic effects (promethazine is a phenothiazine; meperidine may cause fetal dependence). |
| 2nd trimester | Use only if clearly needed; risk of fetal respiratory depression and maternal seizures with meperidine. |
| 3rd trimester | Avoid near term due to risk of neonatal respiratory depression, withdrawal, and altered fetal heart rate patterns. |
Clinical note
Comprehensive clinical and safety monograph for MEPERGAN (MEPERGAN).
| Placental transfer | Both meperidine and promethazine readily cross the placenta. Meperidine achieves fetal concentrations similar to maternal; promethazine appears in fetal blood within minutes of maternal administration. |
| Breastfeeding | Both meperidine and promethazine are excreted into breast milk. Meperidine and its active metabolite normeperidine accumulate in infants, potentially causing respiratory depression and sedation. Avoid breastfeeding if possible; if used, monitor infant for sedation, poor feeding, and respiratory depression. The American Academy of Pediatrics considers meperidine to be usually compatible but recommends caution. |
| Lactation Rating | L3 (Moderately Safe) - Limited data; potential for adverse effects in infant. |
| 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. |
| 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. |
■ 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, promethazine, or any phenothiazineConcurrent use of MAO inhibitors or within 14 days of such therapySevere respiratory depressionAcute or severe bronchial asthmaUpper airway obstructionKnown or suspected mechanical gastrointestinal obstructionConcurrent use of linezolid or methylene blue (serotonin syndrome risk)
| 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. |
| Food/Dietary | Avoid alcohol and any foods or beverages that could potentiate CNS depression. No specific food interactions; maintain normal diet unless instructed otherwise. Grapefruit juice may alter meperidine metabolism; avoid excessive consumption. |
| Clinical Pearls | Mepergan is a fixed combination of meperidine (opioid analgesic) and promethazine (phenothiazine antiemetic). Use with caution in elderly due to increased risk of respiratory depression, sedation, and anticholinergic effects. Avoid in patients with severe respiratory insufficiency, paralytic ileus, or acute asthma. Promethazine can cause severe tissue necrosis if extravasation occurs; ensure proper IV access. Meperidine accumulates normeperidine, a neurotoxic metabolite with proconvulsant activity; avoid prolonged use (>48 hours) and in patients with renal impairment. Monitor for hypotension and QT prolongation, especially with concurrent use of other QT-prolonging agents. |
| Patient Advice | This medication can cause drowsiness, dizziness, or blurred vision; avoid driving or operating machinery until you know how it affects you. · Do not consume alcohol or other central nervous system depressants while taking this medicine. · Take exactly as prescribed; do not increase dose or frequency without consulting your doctor due to risk of dependence and serious side effects. · If you have difficulty breathing, severe constipation, or signs of serotonin syndrome (agitation, hallucinations, fever, sweating, shivering, fast heart rate, muscle stiffnes, twitching, loss of coordination), seek emergency medical attention. · Store at room temperature away from moisture and heat. Keep out of reach of children. |
Loading safety data…