MEPERIDINE HYDROCHLORIDE PRESERVATIVE FREE
Clinical safety rating: avoid
Positive evidence of fetus risks but benefits may outweigh risks in some cases
Meperidine is a synthetic opioid agonist that exerts its analgesic effects by binding to mu-opioid receptors in the central nervous system, thereby mimicking the actions of endogenous opioids. It also has some kappa-opioid receptor activity and weak serotonergic effects.
| Metabolism | Meperidine is primarily metabolized in the liver via hydrolysis to meperidinic acid and via N-demethylation to normeperidine (an active metabolite with proconvulsant properties), mainly by CYP3A4 and CYP2B6. |
| Excretion | Primarily renal (90% as metabolites, ~5-30% unchanged); biliary/fecal excretion accounts for <10%. Urinary excretion is pH-dependent; acidic urine increases elimination. |
| Half-life | Terminal elimination half-life: 2.5–4 hours (mean 3.2 h). In cirrhosis, half-life prolonged to 7–11 hours; in elderly, half-life extends up to 8 hours. Normeperidine (active metabolite) half-life: 15–30 hours (accumulates with renal impairment). |
| Protein binding | 65–75% bound primarily to alpha-1-acid glycoprotein (AAG) and albumin. |
| Volume of Distribution | 2.7–4.2 L/kg. High Vd indicates extensive tissue distribution, including CNS. |
| Bioavailability | Oral: approximately 50–60% (first-pass metabolism); IM/IV: 100%. |
| Onset of Action | IV: 1–2 minutes; IM: 10–15 minutes; Oral: 30–60 minutes (but oral bioavailability is low). |
| Duration of Action | IV/IM: 2–4 hours (analgesia); Oral: 2–4 hours. Normeperidine accumulation may cause prolonged CNS excitation. |
| Molecular Weight | 283.8 |
50-100 mg IM/SC every 3-4 hours as needed; 25-50 mg IV slowly every 3-4 hours as needed.
| Dosage form | INJECTABLE |
| Renal impairment | GFR 10-50 mL/min: administer 75% of normal dose every 4-6 hours. GFR <10 mL/min: administer 50% of normal dose every 6 hours. Monitor for neurotoxicity. |
| Liver impairment | Child-Pugh A: no adjustment. Child-Pugh B: reduce dose by 50%. Child-Pugh C: avoid use or reduce dose by 75% with extended interval. |
| Pediatric use | 1-1.5 mg/kg IM/SC/IV every 3-4 hours as needed; maximum single dose 100 mg. Not recommended for prolonged use. |
| Geriatric use | Initiate at 25 mg IM/SC/IV every 4 hours; titrate cautiously due to increased risk of CNS and respiratory depression. Avoid, if possible, due to risk of delirium and falls. |
| 1st trimester | Avoid unless absolutely necessary; limited data, potential teratogenicity in animal studies. |
| 2nd trimester | Use with caution; may cause fetal respiratory depression if given near delivery. |
| 3rd trimester | Avoid prolonged use or high doses near term; risk of neonatal respiratory depression and opioid withdrawal. |
Clinical note
MAOIs can cause serotonin syndrome and hyperpyrexia Life-threatening respiratory depression may occur.
| Placental transfer | Rapid placental transfer; fetal concentrations may approach maternal levels. |
| Breastfeeding | Small amounts enter breast milk; monitor infant for sedation and respiratory depression. Avoid in mothers with opioid dependency or if infant is premature. |
| Lactation Rating |
■ FDA Black Box Warning
Meperidine carries a risk of respiratory depression, particularly in elderly, cachectic, or debilitated patients, and when used in high doses or with other CNS depressants. Concomitant use with CYP3A4 inhibitors or discontinuation of CYP3A4 inducers may increase meperidine exposure. Accidental ingestion, especially in children, can be fatal.
| Common Effects | Sedation |
| Serious Effects |
Concurrent MAOI therapy (or within 14 days)Severe respiratory depressionAcute or severe bronchial asthmaKnown hypersensitivity to meperidineUse of linezolid or methylene blue
| Precautions | Risk of respiratory depression; use with caution in patients with head injury, increased intracranial pressure, or impaired respiratory function., Serotonin syndrome risk when used with serotonergic drugs (e.g., SSRIs, MAOIs)., Normeperidine accumulation can cause CNS excitation, seizures, and anxiety; avoid prolonged use or high doses., Risk of opioid use disorder, abuse, and addiction; monitor for signs of misuse., Neonatal opioid withdrawal syndrome with prolonged use during pregnancy., Adrenal insufficiency and androgen deficiency with chronic use., Severe hypotension in patients with compromised ability to maintain blood pressure., Use with caution in renal or hepatic impairment, elderly, and cachectic patients., May impair mental or physical abilities; caution during driving or hazardous tasks. |
Loading safety data…
| L3 - Moderately Safe |
| Teratogenic Risk | FDA Category C. First trimester: limited human data; animal studies show no clear teratogenicity but fetal effects at high doses. Second/third trimester: risk of neonatal respiratory depression, withdrawal, and neurobehavioral effects with chronic or high-dose use near term. |
| Fetal Monitoring | Monitor maternal respiratory rate, sedation, and pain scores. Fetal heart rate monitoring during labor; assess neonatal Apgar scores, respiratory effort, and signs of opioid withdrawal. |
| Fertility Effects | May impair fertility in females via inhibition of GnRH and gonadotropin release; chronic use may cause oligomenorrhea or anovulation. Reversible upon cessation. |
| Food/Dietary | Avoid alcohol; may enhance CNS depression. Grapefruit juice may increase meperidine levels (moderate interaction). No other significant food interactions. |
| Clinical Pearls | Preservative-free formulation is indicated for epidural or intrathecal administration to avoid neurotoxicity. Meperidine has a unique metabolite, normeperidine, which can accumulate with repeated dosing, especially in renal impairment, causing CNS excitation (tremor, seizures). Avoid use with MAOIs due to risk of serotonin syndrome. Do not use for chronic pain due to short duration and toxicity concerns. Use with caution in patients with head injuries, asthma, or seizure disorders. |
| Patient Advice | This medication is for short-term pain relief only, not for long-term use. · Do not drink alcohol while taking meperidine; it increases sedation and risk of side effects. · Report any signs of serotonin syndrome: agitation, hallucinations, rapid heart rate, fever, muscle stiffness. · Avoid driving or operating machinery until you know how this drug affects you. · Do not take with other sedatives or antidepressants without consulting your doctor. · If you have kidney problems, inform your doctor as the dose may need adjustment. |