Opioid analgesic, phenylpiperidine class
Brand names: Demerol
Updated · Methodology
Second line
Meperidine is used for acute postoperative pain and renal colic when morphine is contraindicated. In Spain Dolantina is historically used in obstetrics and perioperative care. SED has since 2020 recommended restricting use due to normeperidine neurotoxicity on repeated doses and high risk of fatal serotonin syndrome with MAO inhibitors and SSRIs.
ICD-10: R52.0 · ICD-11: MG31.2
Mu-opioid receptor agonist in the CNS. Also inhibits serotonin reuptake and binds alpha-2 adrenoceptors. Metabolised by CYP3A4 and CYP2B6 to active normeperidine with long half-life (15–20 hours) and neurotoxicity on accumulation (seizures, delirium). 10-fold weaker analgesic than morphine. Widely used perioperatively in Spain as Dolantina.
In Spain Dolantina is used in labour. Long-term third-trimester use risks neonatal withdrawal syndrome.
Passes into milk. After single labour dose breastfeeding is possible with infant drowsiness monitoring.
Reference information, not a clinical decision. Discuss feeding pauses or changes with your physician or an IBCLC.
5 pairs found. Sorted from critical to minor.
Mechanism
Linezolid is a reversible MAO inhibitor. With meperidine – serotonin syndrome.
Symptoms
Hyperthermia, myoclonus.
Management
Combination contraindicated.
Sources
Mechanism
Meperidine inhibits serotonin reuptake. With phenelzine (MAOI) causes fatal serotonin syndrome. boxed warning.
Symptoms
Hyperthermia above 39°C, myoclonus, coma within hours.
Management
Combination contraindicated. At least 14 days between MAOI withdrawal and meperidine. Alternative – morphine or fentanyl.
Sources
Mechanism
Selegiline irreversibly inhibits monoamine oxidase (MAO), the enzyme that breaks down catecholamines and serotonin. At recommended doses it acts mainly on MAO type B (MAO-B) and loses this selectivity above 10 mg a day (selegiline SmPC; US Food and Drug Administration () selegiline label). In patients taking MAO inhibitors, therapeutic doses of meperidine have occasionally caused unpredictable, severe and sometimes fatal reactions, and the mechanism is unclear (FDA meperidine label). The combination can cause acute excitation or depression of the central nervous system, with high or low blood pressure (meperidine SmPC). Because MAO inhibition is irreversible, the risk persists after stopping selegiline until the body makes new enzyme. Liver enzymes play no part here: selegiline does not inhibit CYP3A4 or CYP2B6, which break down meperidine (FDA selegiline and meperidine labels).
Symptoms
The reaction takes two forms. One resembles acute opioid overdose, with coma, severe respiratory depression, cyanosis and hypotension; the other shows hyperexcitability, seizures, tachycardia, hyperpyrexia and hypertension, sometimes as serotonin syndrome with agitation, hyperthermia, diarrhoea, sweating, tremor and impaired consciousness (US Food and Drug Administration () meperidine label). Patients given selegiline with meperidine have had stupor, muscle rigidity, severe agitation, hallucinations and raised temperature, and deaths have occurred; symptoms usually resolve over days once the combination is stopped (FDA selegiline label). Serotonin syndrome usually starts within several hours to a few days of combined use but can appear later (FDA meperidine label).
Management
The combination is contraindicated (selegiline SmPC, sections 4.3 and 4.5; meperidine SmPC, sections 4.3 and 4.5; US Food and Drug Administration () selegiline and meperidine labels, section 4). Start meperidine no earlier than 14 days after the last dose of selegiline (meperidine SmPC, section 4.3; FDA selegiline and meperidine labels, section 4). Switching to another opioid does not lift the ban: selegiline is contraindicated with opioids as a class (selegiline SmPC, section 4.3), with tramadol and methadone among the examples (FDA selegiline label). General anaesthesia in a patient taking selegiline calls for caution. Monoamine oxidase inhibitors, selegiline included, can potentiate the central nervous system depressants used in anaesthesia, with reports of transient respiratory and cardiovascular depression, hypotension and coma (selegiline SmPC, section 4.4). If serotonin syndrome is suspected, stop meperidine (FDA meperidine label). Symptoms usually resolve over days once the combination is stopped (FDA selegiline label). Intravenous hydrocortisone or prednisolone have been used for severe reactions, with intravenous chlorpromazine added for hypertension and hyperpyrexia; the usefulness and safety of opioid overdose reversal agents in this reaction are unknown (FDA meperidine label).
Sources
Mechanism
Same pharmacodynamics – fatal serotonin syndrome.
Symptoms
Hyperthermia, myoclonus, coma.
Management
Combination contraindicated.
Sources
Verbatim lines from the interaction sections, in the language of the label
«Antidepresivos, ansiolíticos, hipnóticos: la administración concomitante de petidina e IMAOs está contraindicada (ver sección 4.3). Los efectos depresores de la petidina pueden verse aumentados y…»AEMPS, section 4.5 · Open on CIMA
«CONTRAINDICATIONS: • Concurrent use of monoamine oxidase inhibitors (MAOIs) or use of MAOIs within the last 14 days [see Warnings and Precautions (5.6) , Drug Interactions (7) ]»FDA, section 4 · Open on DailyMed
«Uso concurrente de inhibidores de la monoaminooxidasa (IMAOs) no selectivos (iproniazida, nialamida y fenelzina), selectivos A (moclobemida, toloxatona), selectivos B (selegilina)…»AEMPS, section 4.3 · Open on CIMA
«Uso concurrente de inhibidores de la monoaminooxidasa (IMAOs) no selectivos (iproniazida, nialamida y fenelzina), selectivos A (moclobemida, toloxatona), selectivos B (selegilina)…»AEMPS, section 4.3 · Open on CIMA
«Antivirales: ritonavir aumenta significativamente las concentraciones plasmáticas de norpetidina, por lo que está contraindicada la administración concomitante de petidina y ritonavir (ver sección…»AEMPS, section 4.5 · Open on CIMA
«Dopaminérgicos: está contraindicada la administración concomitante de selegilina (ver sección 4.3).»AEMPS, section 4.5 · Open on CIMA
«Trastornos hepatobiliares: El uso concomitante de hidrocloruro de petidina y medicamentos sedantes como las benzodiacepinas o medicamentos relacionados puede provocar sedación, depresión…»AEMPS, section 4.4 · Open on CIMA
«La administración concomitante de Petidina Basi con gabapentinoides (gabapentina y pregabalina) puede provocar depresión respiratoria, hipotensión, sedación profunda, coma o la muerte (véase la…»AEMPS, section 4.5 · Open on CIMA
«La administración concomitante de Petidina Basi con gabapentinoides (gabapentina y pregabalina) puede provocar depresión respiratoria, hipotensión, sedación profunda, coma o la muerte (véase la…»AEMPS, section 4.5 · Open on CIMA
«DRUG INTERACTIONS: Intervention: Monitor patients for signs of diminished diuresis and/FDA, section 7 · Open on DailyMed
«DRUG INTERACTIONS: Intervention: Monitor patients for signs of respiratory depression that may be greater than otherwise expected and decrease the dosage of DEMEROL Injection and/FDA, section 7 · Open on DailyMed
«Antivirales: ritonavir aumenta significativamente las concentraciones plasmáticas de norpetidina, por lo que está contraindicada la administración concomitante de petidina y ritonavir (ver sección…»AEMPS, section 4.5 · Open on CIMA
«DRUG INTERACTIONS: Examples: Benzodiazepines and other sedatives/FDA, section 7 · Open on DailyMed
«DRUG INTERACTIONS: Examples: Macrolide antibiotics (e.g., erythromycin), azole-antifungal agents (e.g., ketoconizole), protease inhibitors (e.g., ritonavir)»FDA, section 7 · Open on DailyMed
«DRUG INTERACTIONS: Benzodiazepines and Other Central Nervous System (CNS) Depressants»FDA, section 7 · Open on DailyMed
«DRUG INTERACTIONS: Examples: Rifampin, carbamazepine, phenytoin»FDA, section 7 · Open on DailyMed
«DRUG INTERACTIONS: Clinical Impact: The concomitant use of DEMEROL Injection and CYP3A4 inducers or CYP2B6 inducers can decrease the plasma concentration of meperidine [see Clinical Pharmacology…»FDA, section 7 · Open on DailyMed
«DRUG INTERACTIONS: Clinical Impact: The concomitant use of DEMEROL Injection and CYP3A4 or CYP2B6 inhibitors can increase the plasma concentration of meperidine, resulting in increased or prolonged…»FDA, section 7 · Open on DailyMed
«Estimulantes de la motilidad: petidina tiene un efecto antagónico sobre metoclopramida y domperidona.»AEMPS, section 4.5 · Open on CIMA
«DRUG INTERACTIONS: Examples: Macrolide antibiotics (e.g., erythromycin), azole-antifungal agents (e.g., ketoconizole), protease inhibitors (e.g., ritonavir)»FDA, section 7 · Open on DailyMed
«DRUG INTERACTIONS: Examples: Benzodiazepines and other sedatives/FDA, section 7 · Open on DailyMed
«DRUG INTERACTIONS: Examples: Phenelzine, tranylcypromine, linezolid»FDA, section 7 · Open on DailyMed
«Antidiarreicos y agentes antiperistálticos (tales como loperamida y caolín): su uso simultáneo puede aumentar el riesgo de un estreñimiento severo.»AEMPS, section 4.5 · Open on CIMA
«DRUG INTERACTIONS: Examples: Macrolide antibiotics (e.g., erythromycin), azole-antifungal agents (e.g., ketoconizole), protease inhibitors (e.g., ritonavir)»FDA, section 7 · Open on DailyMed
«Petidina,»AEMPS, section 4.3 · Open on CIMA
«CONTRAINDICATIONS: Phenelzine sulfate should not be used in combination with dextromethorphan or with CNS depressants such as alcohol and certain narcotics. Excitation, seizures, delirium…»FDA, section 4 · Open on DailyMed
«Tratamiento concomitante con otros inhibidores de la monoamino-oxidasa (MAO) (incluyendo medicamentos y productos naturales sin prescripción, p. ej.: Hierba de San Juan) o petidina (ver sección 4.5)…»AEMPS, section 4.3 · Open on CIMA
«CONTRAINDICATIONS: Rasagiline is contraindicated for use with meperidine, tramadol, methadone, propoxyphene and MAO inhibitors (MAOIs), including other selective MAO-B inhibitors, because of risk of…»FDA, section 4 · Open on DailyMed
«Aumento o disminución de los niveles del medicamento concomitante: Petidina,propoxifeno»AEMPS, section 4.3 · Open on CIMA
«Selegilina no debe usarse en combinación con inhibidores selectivos de la recaptación de serotonina (ISRS) (fluoxetina), inhibidores de la recaptación de la serotonina y noradrenalina (ISRN) (p.ej…»AEMPS, section 4.3 · Open on CIMA
«CONTRAINDICATIONS: • EMSAM (selegiline transdermal system) is contraindicated with selective serotonin reuptake inhibitors (SSRIs, e.g., fluoxetine, sertraline, and paroxetine); serotonin and…»FDA, section 4 · Open on DailyMed
«petidina, tramadol, dextrometorfano (dextrometorfano contenido en antitusivos);»AEMPS, section 4.3 · Open on CIMA
«Combination with Certain Drugs: carbamazepine meperidine tapentadol»FDA, section 4 · Open on DailyMed
«Pacientes que tomen cualquiera de estos medicamentos: inhibidores de la recaptación de serotonina (ver sección 4.4), antidepresivos tricíclicos, agonistas del receptor 5 HT 1 de serotonina…»AEMPS, section 4.3 · Open on CIMA
«Fármacos serotoninérgicos: Se aconseja precaución y un estrecho control del paciente cuando se combinan fármacos con actividad serotoninérgica (incluyendo L-triptófano, triptanes, tramadol…»AEMPS, section 4.5 · Open on CIMA
«Established and Other Potentially Significant Drug Interactions: Anesthetic: meperidine ↓ meperidine/FDA, section 7 · Open on DailyMed
«Agentes serotoninérgicos: En raras ocasiones, se ha notificado síndrome serotoninérgico en pacientes en tratamiento concomitante de ISRS/AEMPS, section 4.5 · Open on CIMA
«Drugs Having Clinically Important Interactions with Alprazolam: Examples Morphine, buprenorphine, hydromorphone, oxymorphone, oxycodone, fentanyl, methadone, alfentanil, butorpenol, codeine…»FDA, section 7 · Open on DailyMed
«Los narcóticos (morfina, petidina) disminuyen la velocidad de absorción y disminuyen las concentraciones máximas de diazepam administrado por vía oral.»AEMPS, section 4.5 · Open on CIMA
«Fármacos serotoninérgicos: El síndrome serotoninérgico puede producirse con la administración simultánea de metadona con petidina, inhibidores de la monoaminooxidasa (MAO) y fármacos con serotonina…»AEMPS, section 4.5 · Open on CIMA
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Meperidine is evaluated for the following indications with varying evidence strength: Postoperative pain (evidence tier B). See the full indication matrix with dosing and citations above on this page.
Common side effects of Meperidine (≥ 1 in 100): Nausea, vomiting, Sedation, Constipation, Dizziness, Dry mouth. See the Safety section for uncommon and serious reactions.
In Spain Dolantina is used in labour. Long-term third-trimester use risks neonatal withdrawal syndrome.
Passes into milk. After single labour dose breastfeeding is possible with infant drowsiness monitoring.
Meperidine is contraindicated in: MAO inhibitors (phenelzine, tranylcypromine) and within 14 days of withdrawal – fatal serotonin syndrome; Linezolid, methylene blue; Selegiline; Severe renal impairment (normeperidine accumulation); Prior seizures. Full list in the Safety section.
Direct links to regulator labels. Open in a new tab.
Metamizole sodium, Morphine, Naratriptan, Oxycodone, Rizatriptan, Tramadol + Paracetamol, Dihydroergotamine, Oxycodone + Naloxone