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 |
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 | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
MAOIs can cause serotonin syndrome and hyperpyrexia Life-threatening respiratory depression may occur.
| FDA category | Positive |
| Breastfeeding | Meperidine is excreted into breast milk. M/P ratio approximately 0.7-1.0. Relative infant dose estimated <4% of maternal weight-adjusted dose. However, normeperidine accumulates in neonates with potential for neurobehavioral depression and seizures. American Academy of Pediatrics recommends caution; safer alternatives (e.g., morphine) are preferred. Avoid in breastfeeding women, especially with multiple doses or extended use. |
| Teratogenic Risk |
■ 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, significant respiratory depression, acute or severe bronchial asthma, upper airway obstruction, concurrent use or within 14 days of MAOIs, gastrointestinal obstruction (e.g., paralytic ileus), and suspected or known head injury with elevated intracranial pressure.
| 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. |
Loading safety data…
| 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. |