MEPERIDINE HYDROCHLORIDE
Clinical safety rating: avoid
MAOIs can cause serotonin syndrome and hyperpyrexia Life-threatening respiratory depression may occur.
Meperidine is a synthetic opioid agonist that binds to mu-opioid receptors in the central nervous system, mimicking endogenous endorphins to produce analgesia. It also has weak serotonergic activity.
| Metabolism | Primarily hepatic via hydrolysis to meperidinic acid and N-demethylation to normeperidine (active metabolite with neurotoxic potential). CYP3A4 and CYP2B6 are involved in N-demethylation. |
| Excretion | Renal: 70-80% as metabolites (normeperidine ~20%, meperidinic acid ~50%) and <5% unchanged; biliary/fecal: <10% |
| Half-life | 3-4 hours in normal renal function; prolonged to >12 hours in hepatic impairment (cirrhosis) or renal failure (normeperidine accumulates) |
| Protein binding | 60-80% bound primarily to albumin, also alpha-1-acid glycoprotein |
| Volume of Distribution | 3-5 L/kg; extensive tissue distribution, higher than morphine |
| Bioavailability | Oral: 50-60% (due to first-pass metabolism); IM/SC: ~100% |
| Onset of Action | IV: 1–3 min; IM: 10–15 min; SC: 15–20 min; Oral: 30–60 min |
| Duration of Action | Analgesia: 2–4 hours; clinical note: normeperidine has half-life 15-30 hours, causing CNS excitation with repeated dosing |
| Molecular Weight | 283.8 |
50-150 mg orally or intramuscularly every 3-4 hours as needed for pain. Maximum single dose: 150 mg. Maximum daily dose: 600 mg.
| Dosage form | INJECTABLE |
| Renal impairment | GFR 10-50 mL/min: administer 75% of normal dose; GFR <10 mL/min: administer 50% of normal dose; Hemodialysis: not significantly removed, administer 50% of normal dose. |
| Liver impairment | Child-Pugh Class A: no adjustment; Child-Pugh Class B: reduce dose by 50%; Child-Pugh Class C: avoid use or administer 25% of normal dose. |
| Pediatric use | Oral/IM: 1-2 mg/kg/dose every 3-4 hours as needed; maximum single dose: 100 mg; not recommended for prolonged use due to normeperidine accumulation. |
| Geriatric use | Initiate at 50% of adult dose; maximum single dose: 50 mg; monitor for CNS and respiratory depression; avoid in renal impairment. |
| 1st trimester | Avoid; use only if clearly needed. Associated with neural tube defects in animal studies. Limited human data; risk cannot be excluded. |
| 2nd trimester | Use with caution; potential for fetal respiratory depression and dependence. May cause premature contractions. |
| 3rd trimester | Avoid; prolonged use may lead to neonatal opioid withdrawal syndrome and respiratory depression. Use only if benefit outweighs risk. |
Clinical note
MAOIs can cause serotonin syndrome and hyperpyrexia Life-threatening respiratory depression may occur.
| FDA category | Positive |
| Placental transfer | Rapidly crosses placenta; approximately 100% within minutes. Fetal plasma concentrations may exceed maternal levels. |
| Breastfeeding |
■ FDA Black Box Warning
Concomitant use with CNS depressants (e.g., other opioids, benzodiazepines, alcohol) may cause profound sedation, respiratory depression, coma, and death. Use with CYP3A4 inhibitors or discontinuation of CYP3A4 inducers may increase meperidine exposure and risk of toxicity.
| Common Effects | Sedation |
| Serious Effects |
Hypersensitivity to meperidine or any componentConcurrent use with MAOIs or within 14 daysSevere respiratory depressionAcute or severe bronchial asthmaUpper airway obstructionSuspected surgical abdomenUse of MAOIs within 14 daysSevere hypotensionHead injury or increased intracranial pressureSeizure disorderConcurrent use with serotonergic drugs (risk of serotonin syndrome)
| Precautions | Risk of respiratory depression, particularly in elderly, debilitated, or COPD patients. Normeperidine accumulation can cause seizures, especially in renal impairment. Serotonin syndrome risk when used with serotonergic drugs. Physical dependence and tolerance develop with prolonged use. Avoid in patients with MAOIs use within 14 days. |
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| Small amounts excreted into breast milk. Monitor infant for drowsiness and respiratory depression. The American Academy of Pediatrics considers use compatible with breastfeeding with caution. Avoid in mothers with history of substance abuse. |
| Lactation Rating | L2 (Safer) |
| Teratogenic Risk | Limited human data; meperidine crosses placenta. First trimester: potential neural tube defects (observational, weak association). Second trimester: no specific malformations reported. Third trimester: risk of neonatal respiratory depression, decreased fetal heart rate variability, and neonatal withdrawal syndrome with chronic use. Avoid in prolonged labor due to accumulation of normeperidine (active metabolite) causing seizures. |
| Fetal Monitoring | Maternal: monitor respiratory rate, sedation level, oxygen saturation, blood pressure, and fetal heart rate (continuous electronic fetal monitoring recommended during labor). Fetal: assess for heart rate variability and decelerations. Neonatal: observe for respiratory depression, hypotonia, bradycardia, and withdrawal symptoms (jitteriness, poor feeding) for 24-48 hours after delivery. |
| Fertility Effects | No established adverse effects on human fertility. Animal studies: no impairment of fertility at clinical doses. However, chronic opioid use can disrupt hypothalamic-pituitary-gonadal axis, potentially causing menstrual irregularities or anovulation. Data specific to meperidine insufficient. |
| Food/Dietary | Avoid grapefruit juice as it may increase meperidine levels. High-fat meals may delay absorption. No other significant food interactions. |
| Clinical Pearls | Avoid concurrent use with MAOIs due to risk of serotonin syndrome. Use with caution in patients with renal impairment as normeperidine accumulation can cause seizures. Oral bioavailability is ~50-60% due to first-pass metabolism. Duration of action is 2-4 hours. Not preferred for chronic pain due to toxicity concerns. |
| Patient Advice | Take exactly as prescribed; do not increase dose or frequency. · Avoid alcohol and other CNS depressants. · Do not drive or operate machinery until you know how meperidine affects you. · Report severe constipation, nausea, or difficulty urinating. · Do not stop abruptly after prolonged use to avoid withdrawal symptoms. · Seek emergency care if you experience slow breathing, severe dizziness, or seizures. |