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Meperidine (pethidine): Drug information

Meperidine (pethidine): Drug information
(For additional information see "Meperidine (pethidine): Patient drug information" and see "Meperidine (pethidine): Pediatric drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)
ALERT: US Boxed Warning
Risk of medication errors (oral solution):

Ensure accuracy when prescribing, dispensing, and administering meperidine oral solution. Dosing errors due to confusion between mg and mL, and other meperidine oral solutions of different concentrations, can result in accidental overdose and death.

Addiction, abuse, and misuse:

Meperidine exposes patients and other users to the risks of opioid addiction, abuse, and misuse, which can lead to overdose and death. Assess each patient's risk prior to prescribing meperidine, and monitor all patients regularly for the development of these behaviors and conditions.

Opioid analgesic risk evaluation and mitigation strategy (REMS):

To ensure that the benefits of opioid analgesics outweigh the risks of addiction, abuse, and misuse, the FDA has required a REMS for these products. Under the requirements of the REMS, drug companies with approved opioid analgesic products must make REMS-compliant education programs available to health care providers. Health care providers are strongly encouraged to complete a REMS-compliant education program and counsel patients and/or their caregivers, with every prescription, on safe use, serious risks, storage, and disposal of these products; emphasize to patients and their caregivers the importance of reading the Medication Guide every time it is provided by their pharmacist, and consider other tools to improve patient, household, and community safety.

Life-threatening respiratory depression:

Serious, life-threatening, or fatal respiratory depression may occur with use of meperidine. Monitor for respiratory depression, especially during initiation of meperidine or following a dose increase.

Accidental ingestion:

Accidental ingestion of meperidine, especially by children, can result in a fatal overdose of meperidine.

Neonatal opioid withdrawal syndrome:

Prolonged use of meperidine during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life-threatening if not recognized and treated, and requires management according to protocols developed by neonatology experts. If opioid use is required for a prolonged period in a pregnant woman, advise the patient of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available.

Cytochrome P450 3A4 interaction:

The concomitant use of meperidine with all cytochrome P450 3A4 inhibitors may result in an increase in meperidine plasma concentrations, which could increase or prolong adverse reactions and may cause potentially fatal respiratory depression. In addition, discontinuation of a concomitantly used cytochrome P450 3A4 inducer may result in an increase in meperidine plasma concentration. Monitor patients receiving meperidine and any CYP3A4 inhibitor or inducer.

Risks from concomitant use with benzodiazepines or other CNS depressants:

Concomitant use of opioids with benzodiazepines or other CNS depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death. Reserve concomitant prescribing of meperidine and benzodiazepines or other CNS depressants for use in patients for whom alternative treatment options are inadequate. Limit dosage and duration to the minimum required. Follow patients for signs and symptoms of respiratory depression and sedation.

Concomitant use of meperidine with MAOIs:

Concomitant use of meperidine with MAOIs can result in coma, severe respiratory depression, cyanosis, and hypotension. Use of meperidine with MAOIs within last 14 days is contraindicated.

Brand Names: US
  • Demerol
Brand Names: Canada
  • Demerol [DSC]
Pharmacologic Category
  • Analgesic, Opioid
Dosing: Adult
Acute pain

Acute pain (alternative therapy):

Note: Other than in rare situations, NOT recommended for the treatment of pain due to potential neurotoxicity and availability of safer alternatives, especially in patients with kidney disease or elderly patients. Oral route and patient-controlled analgesia (PCA) use are NOT recommended (APS 2016; ISMP 2007; Mariano 2021). Reserve for patients who do not tolerate or have no access to other options.

IM (preferred route), IV: 50 to 150 mg every 3 to 4 hours as needed; maximum daily dose: 600 mg; limit duration to ≤48 hours (APS 2016; manufacturer's labeling). If IV administration is required, administer diluted and at a slow rate. Dosing based on severity of pain; start at the lower end of dosing range.

Obstetrical analgesia: IM, SUBQ: 50 to 100 mg when pain becomes regular; may repeat at 1- to 3-hour intervals.

Preoperative: IM, SUBQ: 50 to 100 mg administered 30 to 90 minutes before the beginning of anesthesia.

Postoperative shivering

Postoperative shivering (off-label use): IV: 12.5 to 50 mg once (Crowley 2008; Kranke 2002; Mercandante 1994; Miller 2010; Wang 1999) or 0.2 mg/kg with adjunctive dexamethasone (Solhpour 2016).

Rigors from amphotericin B

Rigors from amphotericin B (conventional) (off-label use): IV: 25 to 50 mg once (Burks 1980; Ellis 1992; Nucci 1999).

Discontinuation or tapering of therapy: When discontinuing or tapering chronic opioid therapy, the dose should be gradually tapered. An optimal tapering schedule has not been established (CDC [Dowell 2016]). Proposed schedules range from slow (eg, 10% reduction per week or 10% reduction per month depending on duration of chronic therapy) to rapid (eg, 25% to 50% reduction every few days) (CDC 2015). Individualize based on discussions with patient to minimize withdrawal while considering patient-specific goals and concerns as well as the opioid's pharmacokinetics. Slower tapers may be appropriate after long-term use (eg, years), particularly in the final stage of tapering, whereas more rapid tapers may be appropriate in patients experiencing severe adverse effects (CDC [Dowell 2016]). Monitor carefully for signs/symptoms of withdrawal. If the patient displays withdrawal symptoms, consider slowing the taper schedule; alterations may include increasing the interval between dose reductions, decreasing amount of daily dose reduction, pausing the taper and restarting when the patient is ready, and/or coadministration of an alpha-2 agonist (eg, clonidine) to blunt withdrawal symptoms (Berna 2015; CDC [Dowell 2016]). Continue to offer nonopioid analgesics as needed for pain management during the taper; consider nonopioid adjunctive treatments for withdrawal symptoms (eg, GI complaints, muscle spasm) as needed (Berna 2015; Sevarino 2018).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Adult

Avoid use as an analgesic in renal impairment (American Pain Society 2016; ISMP 2007).

Dosing: Hepatic Impairment: Adult

There are no dosage adjustments provided in the manufacturer's labeling; use with caution and titrate slowly; monitor closely for signs of CNS excitation (eg, seizure activity) and CNS and respiratory depression. In patients with severe impairment, consider a lower dose when initiating therapy; an increased opioid effect may be seen in patients with cirrhosis; dose reduction is more important for the oral (route not recommended [APS 2016]) than IV route (Tegeder 1999).

Dosing: Pediatric

(For additional information see "Meperidine (pethidine): Pediatric drug information")

Acute pain

Acute pain (analgesic): Limited data available:

Note: Although FDA approved, the American Pain Society (2016) and ISMP (2007) do not recommend meperidine use as an analgesic. If use for acute pain (in patients without renal or CNS disease) cannot be avoided, treatment should be limited to ≤48 hours and doses should not exceed 600 mg per 24 hours in adults. Oral route is not recommended for treatment of acute or chronic pain. If IV route is required, consider a reduced dose. Patients with prior opioid exposure may require higher initial doses. Should not be used for chronic pain. Doses should be titrated to appropriate analgesic effect; when changing route of administration, note that oral doses are about half as effective as parenteral dose.

Infants >6 months, Children, and Adolescents:

IM, IV, or SUBQ: Initial: 0.8 to 2 mg/kg/dose every 3 to 4 hours as needed; maximum dose range: 50 to 75 mg/dose; consider dose reduction in critically ill (Berde 2002; Coté 2019; manufacturer's labeling).

Oral: Initial: 1.1 to 3 mg/kg/dose every 3 to 4 hours as needed; maximum dose range: 50 to 100 mg/dose (Berde 2002; manufacturer's labeling).

Sedation, preoperative

Sedation, preoperative: Limited data available: Infants, Children, and Adolescents: IM, IV, SUBQ: 0.5 to 2 mg/kg administered 30 to 90 minutes before the beginning of anesthesia; maximum dose: 2 mg/kg or 100 mg/dose, whichever is less (Coté 2019; Zeltzer 1990; manufacturer's labeling).

Sickle cell disease, acute crisis

Sickle cell disease, acute crisis: Limited data available: Note: Due to risk of adverse effects from metabolite (normeperidine) accumulation, meperidine is unlikely first-line agent and generally not recommended for use unless it is the only opioid effective for the patient or the patient has uncorrectable intolerances or allergies to other opioid options (APS 1999; NHLBI 2014).

Infants ≥6 months, Children, and Adolescents:

Patient weight <50 kg: IV: Initial: 0.75 to 1 mg/kg every 3 to 4 hours as needed (APS 1999).

Patient weight ≥50 kg: IV: Initial: 50 to 150 mg every 3 hours as needed (APS 1999).

Shivering, postoperative

Shivering, postoperative: Limited data available: Infants, Children, and Adolescents: IV: 1 to 2 mg/kg/dose once; maximum dose range: 50 to 75 mg/dose; consider dose reduction in critically ill (Berde 2002; Coté 2019).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Pediatric

Avoid use as an analgesic in renal impairment (APS 2016; ISMP 2007).

Dosing: Hepatic Impairment: Pediatric

There are no dosage adjustments provided in the manufacturer's labeling; use with caution and titrate slowly; monitor closely for signs of CNS excitation (eg, seizure activity) and CNS and respiratory depression. In patients with severe impairment, consider a lower dose when initiating therapy; an increased opioid effect may be seen in patients with cirrhosis; dose reduction is more important for the oral route (due to increased bioavailability) than IV route based on experience in adults (Tegeder 1999).

Dosing: Older Adult

Avoid use as an analgesic (American Pain Society 2016; Beers Criteria [AGS 2019]; ISMP 2007).

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Solution, Injection, as hydrochloride:

Demerol: 25 mg/mL (1 mL); 50 mg/mL (1 mL)

Demerol: 50 mg/mL (30 mL); 100 mg/mL (20 mL [DSC]) [contains metacresol]

Solution, Injection, as hydrochloride [preservative free]:

Demerol: 25 mg/mL (1 mL); 25 mg/0.5 mL (0.5 mL [DSC]); 50 mg/mL (1 mL); 75 mg/1.5 mL (1.5 mL [DSC]); 100 mg/2 mL (2 mL [DSC]); 75 mg/mL (1 mL); 100 mg/mL (1 mL)

Generic: 25 mg/mL (1 mL); 50 mg/mL (1 mL); 100 mg/mL (1 mL)

Solution, Oral, as hydrochloride:

Generic: 50 mg/5 mL (500 mL)

Tablet, Oral, as hydrochloride:

Generic: 50 mg, 100 mg [DSC]

Generic Equivalent Available: US

Yes

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Solution, Injection, as hydrochloride:

Generic: 50 mg/mL (1 mL); 75 mg/mL ([DSC]); 100 mg/mL ([DSC])

Tablet, Oral, as hydrochloride:

Demerol: 50 mg [DSC]

Controlled Substance

C-II

Medication Guide and/or Vaccine Information Statement (VIS)

An FDA-approved patient medication guide, which is available with the product information and as follows, must be dispensed with this medication:

Demerol tablets, oral solution: https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/005010s059lbl.pdf#page=32

Administration: Adult

Injection: Administer IM, SubQ, or IV (patient should be lying down during administration); IV push should be administered slowly using a diluted solution, use of a 10 mg/mL concentration has been recommended. IM administration is preferred when repeated doses are required.

Oral solution: Administer each dose in 1/2 glass of water (undiluted solution may exert topical anesthetic effect on mucous membranes). Use a calibrated measuring device to measure dosage; do not use a teaspoon or a tablespoon. Use extreme caution; dosing errors can result in accidental overdose and death.

Administration: Pediatric

Oral: Oral solution: Administer each dose in 1/2 glass of water; undiluted solution may cause topical anesthetic effect on mucous membranes. Use a calibrated measuring device to measure dosage; do not use a teaspoon or a tablespoon. Use extreme caution; dosing errors can result in accidental overdose and death.

Parenteral:

IM: Preferred route when repeat doses required; inject undiluted into a large muscle.

IV: Administer slowly over at least 4 to 5 minutes as a diluted solution (≤10 mg/mL); patients should be lying down; do not administer rapid IV (Dobbins 2010; Gahart 2020; manufacturer's labeling).

SUBQ: Administer undiluted.

Use: Labeled Indications

Acute pain: Management of acute pain severe enough to require an opioid analgesic and for which alternative treatments are inadequate; obstetrical analgesia, preoperative medication (IV only).

Limitations of use: The American Pain Society and Institute for Safe Medication Practices do not recommend meperidine's use as an analgesic. If use in acute pain (in patients without renal or CNS disease) cannot be avoided, treatment should be limited to ≤48 hours and doses should not exceed 600 mg per 24 hours (APS 2016; ISMP 2007).

Use: Off-Label: Adult

Postoperative shivering; Rigors from amphotericin B (conventional); Targeted temperature management-related shivering

Medication Safety Issues
Sound-alike/look-alike issues:

Meperidine may be confused with meprobamate

Demerol may be confused with Demulen, Desyrel, Dilaudid, Pamelor

High alert medication:

The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drug classes which have a heightened risk of causing significant patient harm when used in error.

Older Adult: High-Risk Medication:

Beers Criteria: Meperidine is identified in the Beers Criteria as a potentially inappropriate medication to be avoided in patients 65 years and older (independent of diagnosis or condition) due to a potentially higher risk of neurotoxicity, including delirium, compared with other opioids; safer alternatives are available. In addition, oral meperidine lacks analgesic efficacy in dosages commonly used (Beers Criteria [AGS 2019]).

Pharmacy Quality Alliance (PQA): Meperidine is identified as a high-risk medication in patients 65 years and older on the PQA’s Use of High-Risk Medications in the Elderly (HRM) performance measure, a safety measure used by the Centers for Medicare and Medicaid Services (CMS) for Medicare plans (PQA 2017).

Pediatric patients: High-risk medication:

KIDs List: Meperidine, when used in neonatal and pediatric patients <18 years of age, is identified on the Key Potentially Inappropriate Drugs in Pediatrics (KIDs) list and use should be avoided in neonates and used with caution in pediatric patients <18 years of age due to risk of respiratory depression (strong recommendation; high quality of evidence) (PPA [Meyers 2020]).

Other safety concerns:

Avoid the use of meperidine for pain control, especially in elderly and renally compromised patients because of the risk of neurotoxicity (APS 2016; ISMP 2007).

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.

Frequency not defined:

Cardiovascular: Bradycardia, cardiac arrest, circulatory depression, flushing, hypotension, palpitations, shock, syncope, tachycardia

Central nervous system: Agitation, confusion, delirium, disorientation, dizziness, drug dependence (physical dependence), habituation, hallucination, headache, increased intracranial pressure, involuntary muscle movements (including muscle twitching, myoclonus), mood changes (including euphoria, dysphoria), sedation, seizure (associated with metabolite accumulation), serotonin syndrome

Dermatologic: Diaphoresis, pruritus, skin rash, urticaria

Gastrointestinal: Biliary colic, constipation, nausea, spasm of sphincter of Oddi, vomiting, xerostomia

Genitourinary: Urinary retention

Hypersensitivity: Anaphylaxis, histamine release, hypersensitivity reaction

Local: Injection site reaction (including pain, wheal, and flare)

Neuromuscular & skeletal: Tremor, weakness

Ophthalmic: Visual disturbance

Respiratory: Dyspnea, respiratory arrest, respiratory depression

<1%, postmarketing, and/or case reports: Hypogonadism (Brennan 2013; Debono 2011)

Contraindications

Hypersensitivity (eg, anaphylaxis) to meperidine or any component of the formulation; use with or within 14 days of MAO inhibitors; significant respiratory depression; acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment; GI obstruction, including paralytic ileus (known or suspected).

Canadian labeling: Additional contraindications (not in US labeling): Known or suspected mechanical GI obstruction (eg, bowel obstruction or strictures) or any diseases/conditions that affect bowel transit (eg, ileus of any type); suspected surgical abdomen (eg, acute appendicitis or pancreatitis); mild pain that can be managed with other pain medications; acute or severe bronchial asthma, chronic obstructive airway, status asthmaticus; acute respiratory depression; hypoxia; hypercapnia; cor pulmonale; acute alcoholism, delirium tremens, and convulsive disorders; severe CNS depression, increased cerebrospinal or intracranial pressure and head injury; concurrent use or use within 14 days of an MAOI

Documentation of allergenic cross-reactivity for opioids is limited. However, because of similarities in chemical structure and/or pharmacologic actions, the possibility of cross-sensitivity cannot be ruled out with certainty.

Warnings/Precautions

Concerns related to adverse effects:

• CNS depression: May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving).

• CNS events: Normeperidine (an active metabolite and CNS stimulant) may accumulate and precipitate anxiety, tremors, or seizures; risk increases with preexisting CNS or renal dysfunction, prolonged use (>48 hours), and cumulative dose (>600 mg/24 hours in adults). Oral meperidine should not be used since first-pass metabolism decreases efficacy while increasing normeperidine concentrations (APS 2016). Note: Naloxone does not reverse, and may even worsen, neurotoxicity.

• Constipation: May cause constipation which may be problematic in patients with unstable angina and patients post-myocardial infarction (MI). Consider preventive measures (eg, stimulant laxative) to reduce the potential for constipation.

• Hypotension: May cause severe hypotension (including orthostatic hypotension and syncope); use with caution in patients with hypovolemia, cardiovascular disease (including acute MI), or drugs which may exaggerate hypotensive effects (including phenothiazines or general anesthetics). Monitor for symptoms of hypotension following initiation or dose titration. Avoid use in patients with circulatory shock.

• Respiratory depression: [US Boxed Warning]: Serious, life-threatening, or fatal respiratory depression may occur. Monitor closely for respiratory depression, especially during initiation or dose escalation. Carbon dioxide retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids. Patients and caregivers should be educated on how to recognize respiratory depression and the importance of getting emergency assistance immediately (eg, calling 911) in the event of known or suspected overdose.

• Serotonin syndrome: May occur with concomitant use of serotonergic agents (eg, selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, triptans, tricyclic antidepressants), lithium, St. John's wort, agents that impair metabolism of serotonin (eg, monoamine oxidase inhibitors [MAOIs]). Monitor patients for serotonin syndrome such as mental status changes (eg, agitation, hallucinations, coma); autonomic instability (eg, tachycardia, labile blood pressure, hyperthermia); neuromuscular changes (eg, hyperreflexia, incoordination); and/or GI symptoms (eg, nausea, vomiting, diarrhea).

Disease-related concerns:

• Abdominal conditions: May obscure diagnosis or clinical course of patients with acute abdominal conditions.

• Adrenocortical insufficiency: Use with caution and reduce initial dosage in patients with adrenal insufficiency, including Addison disease. Long-term opioid use may cause secondary hypogonadism, which may lead to mood disorders and osteoporosis (Brennan 2013).

• Biliary tract impairment: Use with caution in patients with biliary tract dysfunction, including acute pancreatitis; opioids may cause constriction of sphincter of Oddi.

• CNS depression/coma: Avoid use in patients with impaired consciousness or coma as these patients are susceptible to intracranial effects of carbon dioxide retention.

• Delirium tremens: Use with caution in patients with delirium tremens.

• Head trauma: Use with extreme caution in patients with head injury, intracranial lesions, or elevated intracranial pressure (ICP); exaggerated elevation of ICP may occur.

• Hepatic impairment: Use with caution in patients with hepatic disorders; meperidine and to a lesser degree normeperidine may accumulate and precipitate either CNS depression or CNS excitation (eg, anxiety, tremors, or seizures) (Danzinger 1994; Tegeder 1999).

• Obesity: Use with caution in patients who are morbidly obese.

• Pheochromocytoma: Use with caution in patients with pheochromocytoma.

• Prostatic hyperplasia/urinary stricture: Use with caution and reduce initial dosage in patients with prostatic hyperplasia and/or urinary stricture.

• Psychosis: Use with caution in patients with toxic psychosis.

• Renal impairment: Avoid use in patients with renal impairment (APS 2016; ISMP 2007); normeperidine may accumulate and precipitate anxiety, tremors, or seizures.

• Respiratory disease: Use with caution and monitor for respiratory depression in patients with significant chronic obstructive pulmonary disease or cor pulmonale, and those with a substantially decreased respiratory reserve, hypoxia, hypercapnia, or preexisting respiratory depression, particularly when initiating and titrating therapy; critical respiratory depression may occur, even at therapeutic dosages. Consider the use of alternative nonopioid analgesics in these patients.

• Seizure disorders: Use with caution in patients with seizure disorders, may cause or aggravate seizures if high doses used or from prolonged use (accumulation of metabolite).

• Sickle-cell disease: In patients with sickle cell disease, use with caution; normeperidine (active metabolite) may accumulate and induce seizures in these patients. Meperidine is not recommended for use in sickle cell patients by the American Pain Society and should only be used in sickle cell patients with a vaso-occlusive crisis if it is the only effective opioid for an individual patient, as normeperidine (active metabolite) may accumulate and induce seizures (APS 2016; NHLBI 2014).

• Sleep-related disorders: Opioid use increases the risk for sleep-related disorders (eg, central sleep apnea, hypoxemia) in a dose-dependent fashion; use with caution.

• Tachycardia: Use with caution in patients with atrial flutter and other supraventricular tachycardias; use may increase ventricular response rate possibly due to a vagolytic effect.

• Thyroid dysfunction: Use with caution in patients with thyroid dysfunction, including hypothyroidism.

Concurrent drug therapy issues:

• Benzodiazepines or other CNS depressants: [US Boxed Warning]: Concomitant use of opioids with benzodiazepines or other CNS depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death. Reserve concomitant prescribing of meperidine and benzodiazepines or other CNS depressants for use in patients for whom alternative treatment options are inadequate. Limit dosage and durations to the minimum required and follow patients for signs and symptoms of respiratory depression and sedation. Consider prescribing naloxone for emergency treatment of opioid overdose in patients taking benzodiazepines or other CNS depressants concomitantly with opioids.

• CYP3A4 interactions: [US Boxed Warning]: Use with all CYP3A4 inhibitors may result in an increase in meperidine plasma concentrations, which could increase or prolong adverse drug effects and may cause potentially fatal respiratory depression. In addition, discontinuation of a concomitant CYP3A4 inducer may result in increased meperidine concentrations. Monitor patients receiving meperidine and any CYP3A4 inhibitor or inducer.

• Monoamine oxidase inhibitors interactions: [US Boxed Warning]: Concomitant use of meperidine with MAOIs can result in coma, severe respiratory depression, cyanosis, and hypotension. Use of meperidine with MAOIs within last 14 days is contraindicated.

Special populations:

• Cachectic or debilitated patients: Use with caution in cachectic or debilitated patients; there is a greater potential for critical respiratory depression, even at therapeutic dosages; reduce initial dosage. Consider the use of alternative nonopioid analgesics in these patients.

• Older adult: Avoid the use of meperidine for pain control, especially in older adults and renally compromised patients because of the risk of neurotoxicity (APS 2016; ISMP 2007). Meperidine should be avoided in those older adults with, or at risk for, delirium because of the potential to cause or worsen delirium.

• Neonates: Neonatal withdrawal syndrome: [US Boxed Warning]: Prolonged use of opioids during pregnancy can cause neonatal withdrawal syndrome, which may be life-threatening if not recognized and treated according to protocols developed by neonatology experts. If opioid use is required for a prolonged period in a pregnant woman, advise the patient of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available. Signs and symptoms include irritability, hyperactivity and abnormal sleep pattern, high pitched cry, tremor, vomiting, diarrhea, and failure to gain weight. Onset, duration, and severity depend on the drug used, duration of use, maternal dose, and rate of drug elimination by the newborn.

Dosage form specific issues:

• Benzyl alcohol and derivatives: Some dosage forms may contain sodium benzoate/benzoic acid; benzoic acid (benzoate) is a metabolite of benzyl alcohol; large amounts of benzyl alcohol (≥99 mg/kg/day) have been associated with a potentially fatal toxicity (“gasping syndrome”) in neonates; the “gasping syndrome” consists of metabolic acidosis, respiratory distress, gasping respirations, CNS dysfunction (including convulsions, intracranial hemorrhage), hypotension, and cardiovascular collapse (AAP ["Inactive" 1997]; CDC 1982); some data suggests that benzoate displaces bilirubin from protein binding sites (Ahlfors 2001); avoid or use dosage forms containing benzyl alcohol derivative with caution in neonates. See manufacturer's labeling.

• Oral solution: Risk of medication errors: [US Boxed Warning]: Ensure accuracy when prescribing, dispensing, and administering meperidine oral solution. Dosing errors due to confusion between mg and mL, and other meperidine solutions of different concentrations, can result in accidental overdose and death. Do not use a teaspoon or a tablespoon to measure a dose; use a calibrated measuring device. Use extreme caution in measuring the dosage.

• Parenteral: Administer IV injections very slowly, preferably in the form of a diluted solution. Do not administer IV unless a opioid antagonist and the facilities for assisted or controlled respiration are immediately available. When meperidine is given parenterally, especially IV, the patient should be lying down.

• Sulfites: Some preparations may contain sulfites which may cause allergic reaction.

Other warnings/precautions:

• Abrupt discontinuation/withdrawal: Abrupt discontinuation in patients who are physically dependent on opioids has been associated with serious withdrawal symptoms, uncontrolled pain, attempts to find other opioids (including illicit), and suicide. Use a collaborative, patient-specific taper schedule that minimizes the risk of withdrawal, considering factors such as current opioid dose, duration of use, type of pain, and physical and psychological factors. Monitor pain control, withdrawal symptoms, mood changes, suicidal ideation, and for use of other substances and provide care as needed. Concurrent use of mixed agonist/antagonist analgesics (eg, pentazocine, nalbuphine, butorphanol) or partial agonist (eg, buprenorphine) analgesics may also precipitate withdrawal symptoms and/or reduced analgesic efficacy in patients following prolonged therapy with mu opioid agonists.

• Abuse/misuse/diversion: [US Boxed Warning]: Meperidine exposes patients and other users to the risks of addiction, abuse, and misuse, potentially leading to overdose and death. Assess each patient's risk prior to prescribing; monitor all patients regularly for development of these behaviors or conditions. Use with caution in patients with a history of drug abuse or acute alcoholism; potential for drug dependency exists. Other factors associated with increased risk for misuse include younger age, concomitant depression (major), and psychotropic medication use.

• Accidental ingestion: [US Boxed Warning]: Accidental ingestion of even one dose, especially in children, can result in a fatal overdose of meperidine.

• Acute and/or cancer pain management: Meperidine offers no advantage over other opioids as an analgesic and has unique neurotoxicity. The use of meperidine in this setting should be avoided (APS 2016; ISMP 2007).

• Chronic pain management: Use is not recommended for the management of chronic pain.

• Naloxone access: Discuss the availability of naloxone with all patients who are prescribed opioid analgesics, as well as their caregivers, and consider prescribing it to patients who are at increased risk of opioid overdose. These include patients who are also taking benzodiazepines or other CNS depressants, have an opioid use disorder (OUD) (current or history of), or have experienced a previous opioid overdose. Additionally, health care providers should consider prescribing naloxone to patients prescribed medications to treat OUD; patients at risk of opioid overdose even if they are not taking an opioid analgesic or medication to treat OUD; and patients taking opioids, including methadone or buprenorphine for OUD, if they have household members, including children, or other close contacts at risk for accidental ingestion or opioid overdose. Inform patients and caregivers on options for obtaining naloxone (eg, by prescription, directly from a pharmacist, a community-based program) as permitted by state dispensing and prescribing guidelines. Educate patients and caregivers on how to recognize respiratory depression, proper administration of naloxone, and getting emergency help.

• Optimal regimen: An opioid-containing analgesic regimen should be tailored to each patient's needs and based upon the route of administration, degree of tolerance for opioids (naive versus chronic user), age, weight, and medical condition. The optimal analgesic dose varies widely among patients; doses should be titrated to pain relief/prevention.

• REMS program: [US Boxed Warning]: To ensure that the benefits of opioid analgesics outweigh the risks of addiction, abuse, and misuse, a REMS is required. Drug companies with approved opioid analgesic products must make REMS-compliant education programs available to health care providers. Health care providers are encouraged to complete a REMS-compliant education program; counsel patients and/or their caregivers, with every prescription, on safe use, serious risks, storage, and disposal of these products; emphasize to patients and their caregivers the importance of reading the Medication Guide every time it is provided by their pharmacist; and consider other tools to improve patient, household, and community safety.

• Surgery: Opioids decrease bowel motility; monitor for decreased bowel motility in postop patients receiving opioids. Use with caution in the perioperative setting; individualize treatment when transitioning from parenteral to oral analgesics.

Warnings: Additional Pediatric Considerations

Due to decreased elimination rate, neonates and young infants may be at higher risk for adverse effects, especially respiratory depression; use with extreme caution and in reduced doses in this age group.

Metabolism/Transport Effects

Substrate of CYP3A4 (major); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.

Alizapride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Almotriptan: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy

Alosetron: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy

Alvimopan: Opioid Agonists may enhance the adverse/toxic effect of Alvimopan. This is most notable for patients receiving long-term (i.e., more than 7 days) opiates prior to alvimopan initiation. Management: Alvimopan is contraindicated in patients receiving therapeutic doses of opioids for more than 7 consecutive days immediately prior to alvimopan initiation. Risk D: Consider therapy modification

Amifampridine: Agents With Seizure Threshold Lowering Potential may enhance the neuroexcitatory and/or seizure-potentiating effect of Amifampridine. Risk C: Monitor therapy

Amphetamines: May enhance the analgesic effect of Opioid Agonists. Risk C: Monitor therapy

Amphetamines: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability). Initiate amphetamines at lower doses, monitor frequently, and adjust doses as needed. Risk C: Monitor therapy

Anticholinergic Agents: May enhance the adverse/toxic effect of Opioid Agonists. Specifically, the risk for constipation and urinary retention may be increased with this combination. Risk C: Monitor therapy

Antiemetics (5HT3 Antagonists): May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy

Azelastine (Nasal): May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination

Blonanserin: CNS Depressants may enhance the CNS depressant effect of Blonanserin. Management: Use caution if coadministering blonanserin and CNS depressants; dose reduction of the other CNS depressant may be required. Strong CNS depressants should not be coadministered with blonanserin. Risk D: Consider therapy modification

Brimonidine (Topical): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Bromopride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Bromperidol: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination

BuPROPion: May enhance the neuroexcitatory and/or seizure-potentiating effect of Agents With Seizure Threshold Lowering Potential. Risk C: Monitor therapy

BusPIRone: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy

Cannabinoid-Containing Products: CNS Depressants may enhance the CNS depressant effect of Cannabinoid-Containing Products. Risk C: Monitor therapy

Chlormethiazole: May enhance the CNS depressant effect of CNS Depressants. Management: Monitor closely for evidence of excessive CNS depression. The chlormethiazole labeling states that an appropriately reduced dose should be used if such a combination must be used. Risk D: Consider therapy modification

Chlorphenesin Carbamate: May enhance the adverse/toxic effect of CNS Depressants. Risk C: Monitor therapy

Cimetidine: May increase the serum concentration of Meperidine. Risk C: Monitor therapy

Clofazimine: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

CNS Depressants: May enhance the CNS depressant effect of Opioid Agonists. Management: Avoid concomitant use of opioid agonists and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Risk D: Consider therapy modification

CYP3A4 Inducers (Moderate): May decrease the serum concentration of Meperidine. Risk C: Monitor therapy

CYP3A4 Inducers (Strong): May decrease the serum concentration of Meperidine. Risk C: Monitor therapy

CYP3A4 Inhibitors (Moderate): May increase the serum concentration of Meperidine. Risk C: Monitor therapy

CYP3A4 Inhibitors (Strong): May increase the serum concentration of Meperidine. Risk C: Monitor therapy

Dapoxetine: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Do not use serotonergic agents (high risk) with dapoxetine or within 7 days of serotonergic agent discontinuation. Do not use dapoxetine within 14 days of monoamine oxidase inhibitor use. Dapoxetine labeling lists this combination as contraindicated. Risk X: Avoid combination

Daridorexant: May enhance the CNS depressant effect of CNS Depressants. Management: Dose reduction of daridorexant and/or any other CNS depressant may be necessary. Use of daridorexant with alcohol is not recommended, and the use of daridorexant with any other drug to treat insomnia is not recommended. Risk D: Consider therapy modification

Desmopressin: Opioid Agonists may enhance the hyponatremic effect of Desmopressin. Risk C: Monitor therapy

DexmedeTOMIDine: CNS Depressants may enhance the CNS depressant effect of DexmedeTOMIDine. Management: Monitor for increased CNS depression during coadministration of dexmedetomidine and CNS depressants, and consider dose reductions of either agent to avoid excessive CNS depression. Risk D: Consider therapy modification

Dexmethylphenidate-Methylphenidate: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy

Dextromethorphan: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy

Difelikefalin: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Dimethindene (Topical): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Diuretics: Opioid Agonists may enhance the adverse/toxic effect of Diuretics. Opioid Agonists may diminish the therapeutic effect of Diuretics. Risk C: Monitor therapy

Droperidol: May enhance the CNS depressant effect of CNS Depressants. Management: Consider dose reductions of droperidol or of other CNS agents (eg, opioids, barbiturates) with concomitant use. Risk D: Consider therapy modification

Eletriptan: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy

Eluxadoline: Opioid Agonists may enhance the constipating effect of Eluxadoline. Risk X: Avoid combination

Ergot Derivatives: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy

FentaNYL: Meperidine may enhance the CNS depressant effect of FentaNYL. Meperidine may enhance the serotonergic effect of FentaNYL. This could result in serotonin syndrome. Management: Consider alternatives to this combination. If use is necessary, monitor for signs and symptoms of serotonin syndrome/serotonin toxicity and CNS depression. Risk D: Consider therapy modification

Fexinidazole: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination

Flunarizine: CNS Depressants may enhance the CNS depressant effect of Flunarizine. Risk X: Avoid combination

Flunitrazepam: CNS Depressants may enhance the CNS depressant effect of Flunitrazepam. Management: Reduce the dose of CNS depressants when combined with flunitrazepam and monitor patients for evidence of CNS depression (eg, sedation, respiratory depression). Use non-CNS depressant alternatives when available. Risk D: Consider therapy modification

Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination

Gastrointestinal Agents (Prokinetic): Opioid Agonists may diminish the therapeutic effect of Gastrointestinal Agents (Prokinetic). Risk C: Monitor therapy

HydrOXYzine: May enhance the CNS depressant effect of CNS Depressants. Management: Consider a decrease in the CNS depressant dose, as appropriate, when used together with hydroxyzine. Increase monitoring of signs/symptoms of CNS depression in any patient receiving hydroxyzine together with another CNS depressant. Risk D: Consider therapy modification

Iohexol: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Iohexol. Specifically, the risk for seizures may be increased. Management: Discontinue agents that may lower the seizure threshold 48 hours prior to intrathecal use of iohexol. Wait at least 24 hours after the procedure to resume such agents. In nonelective procedures, consider use of prophylactic antiseizure drugs. Risk D: Consider therapy modification

Iomeprol: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Iomeprol. Specifically, the risk for seizures may be increased. Management: Discontinue agents that may lower the seizure threshold 48 hours prior to intrathecal use of iomeprol. Wait at least 24 hours after the procedure to resume such agents. In nonelective procedures, consider use of prophylactic antiseizure drugs. Risk D: Consider therapy modification

Iopamidol: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Iopamidol. Specifically, the risk for seizures may be increased. Management: Discontinue agents that may lower the seizure threshold 48 hours prior to intrathecal use of iopamidol. Wait at least 24 hours after the procedure to resume such agents. In nonelective procedures, consider use of prophylactic antiseizure drugs. Risk D: Consider therapy modification

Kava Kava: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Kratom: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination

Lemborexant: May enhance the CNS depressant effect of CNS Depressants. Management: Dosage adjustments of lemborexant and of concomitant CNS depressants may be necessary when administered together because of potentially additive CNS depressant effects. Close monitoring for CNS depressant effects is necessary. Risk D: Consider therapy modification

Linezolid: May enhance the serotonergic effect of Serotonergic Opioids (High Risk). This could result in serotonin syndrome. Management: Consider alternatives to this drug combination. If combined, monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes). Risk D: Consider therapy modification

Lisuride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Lofexidine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Lorcaserin (Withdrawn From US Market): May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy

Magnesium Sulfate: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Methotrimeprazine: CNS Depressants may enhance the CNS depressant effect of Methotrimeprazine. Methotrimeprazine may enhance the CNS depressant effect of CNS Depressants. Management: Reduce the usual dose of CNS depressants by 50% if starting methotrimeprazine until the dose of methotrimeprazine is stable. Monitor patient closely for evidence of CNS depression. Risk D: Consider therapy modification

Methylene Blue: May enhance the serotonergic effect of Serotonergic Opioids (High Risk). This could result in serotonin syndrome. Management: Consider alternatives to this drug combination. If combined, monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes). Risk D: Consider therapy modification

Metoclopramide: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Metoclopramide: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Consider monitoring for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy

MetyroSINE: CNS Depressants may enhance the sedative effect of MetyroSINE. Risk C: Monitor therapy

Minocycline (Systemic): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Monoamine Oxidase Inhibitors (Antidepressant): Meperidine may enhance the serotonergic effect of Monoamine Oxidase Inhibitors (Antidepressant). This could result in serotonin syndrome. Risk X: Avoid combination

Monoamine Oxidase Inhibitors (Type B): Serotonergic Opioids (High Risk) may enhance the serotonergic effect of Monoamine Oxidase Inhibitors (Type B). This could result in serotonin syndrome. Risk X: Avoid combination

Nalfurafine: Opioid Agonists may enhance the adverse/toxic effect of Nalfurafine. Opioid Agonists may diminish the therapeutic effect of Nalfurafine. Risk C: Monitor therapy

Nalmefene: May diminish the therapeutic effect of Opioid Agonists. Management: Avoid the concomitant use of oral nalmefene and opioid agonists. Discontinue oral nalmefene 1 week prior to any anticipated use of opioid agonists. If combined, larger doses of opioid agonists will likely be required. Risk D: Consider therapy modification

Naltrexone: May diminish the therapeutic effect of Opioid Agonists. Management: Seek therapeutic alternatives to opioids. See full drug interaction monograph for detailed recommendations. Risk X: Avoid combination

Nefazodone: May enhance the serotonergic effect of Meperidine. This could result in serotonin syndrome. Nefazodone may increase the serum concentration of Meperidine. Management: Consider reducing meperidine dose. Monitor for signs and symptoms of respiratory depression, sedation, and serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia) when these agents are combined. Risk D: Consider therapy modification

Olopatadine (Nasal): May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination

Ondansetron: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy

Opioid Agonists: CNS Depressants may enhance the CNS depressant effect of Opioid Agonists. Management: Avoid concomitant use of opioid agonists and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Risk D: Consider therapy modification

Opioids (Mixed Agonist / Antagonist): May diminish the analgesic effect of Opioid Agonists. Management: Seek alternatives to mixed agonist/antagonist opioids in patients receiving pure opioid agonists, and monitor for symptoms of therapeutic failure/high dose requirements (or withdrawal in opioid-dependent patients) if patients receive these combinations. Risk X: Avoid combination

Orphenadrine: CNS Depressants may enhance the CNS depressant effect of Orphenadrine. Risk X: Avoid combination

Oxitriptan: Serotonergic Agents (High Risk) may enhance the serotonergic effect of Oxitriptan. This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy

Oxomemazine: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination

Oxybate Salt Products: CNS Depressants may enhance the CNS depressant effect of Oxybate Salt Products. Management: Consider alternatives to this combination when possible. If combined, dose reduction or discontinuation of one or more CNS depressants (including the oxybate salt product) should be considered. Interrupt oxybate salt treatment during short-term opioid use Risk D: Consider therapy modification

OxyCODONE: CNS Depressants may enhance the CNS depressant effect of OxyCODONE. Management: Avoid concomitant use of oxycodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Risk D: Consider therapy modification

Ozanimod: May enhance the adverse/toxic effect of Serotonergic Agents (High Risk). Risk C: Monitor therapy

Paraldehyde: CNS Depressants may enhance the CNS depressant effect of Paraldehyde. Risk X: Avoid combination

Pegvisomant: Opioid Agonists may diminish the therapeutic effect of Pegvisomant. Risk C: Monitor therapy

PHENobarbital: May enhance the CNS depressant effect of Meperidine. PHENobarbital may increase serum concentrations of the active metabolite(s) of Meperidine. Management: Avoid concomitant use of meperidine and phenobarbital when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Risk D: Consider therapy modification

Piribedil: CNS Depressants may enhance the CNS depressant effect of Piribedil. Risk C: Monitor therapy

Pramipexole: CNS Depressants may enhance the sedative effect of Pramipexole. Risk C: Monitor therapy

Primidone: May enhance the CNS depressant effect of Meperidine. Primidone may increase serum concentrations of the active metabolite(s) of Meperidine. Management: Avoid concomitant use of meperidine and primidone when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Risk D: Consider therapy modification

Procarbazine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Ramosetron: Opioid Agonists may enhance the constipating effect of Ramosetron. Risk C: Monitor therapy

Ramosetron: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy

Ropeginterferon Alfa-2b: CNS Depressants may enhance the adverse/toxic effect of Ropeginterferon Alfa-2b. Specifically, the risk of neuropsychiatric adverse effects may be increased. Management: Avoid coadministration of ropeginterferon alfa-2b and other CNS depressants. If this combination cannot be avoided, monitor patients for neuropsychiatric adverse effects (eg, depression, suicidal ideation, aggression, mania). Risk D: Consider therapy modification

ROPINIRole: CNS Depressants may enhance the sedative effect of ROPINIRole. Risk C: Monitor therapy

Rotigotine: CNS Depressants may enhance the sedative effect of Rotigotine. Risk C: Monitor therapy

Rufinamide: May enhance the adverse/toxic effect of CNS Depressants. Specifically, sleepiness and dizziness may be enhanced. Risk C: Monitor therapy

Samidorphan: May diminish the therapeutic effect of Opioid Agonists. Risk X: Avoid combination

Selective Serotonin Reuptake Inhibitors: Serotonergic Opioids (High Risk) may enhance the serotonergic effect of Selective Serotonin Reuptake Inhibitors. This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) if these agents are combined. Risk C: Monitor therapy

Serotonergic Agents (High Risk, Miscellaneous): Serotonergic Opioids (High Risk) may enhance the serotonergic effect of Serotonergic Agents (High Risk, Miscellaneous). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) if these agents are combined. Risk C: Monitor therapy

Serotonergic Non-Opioid CNS Depressants: May enhance the CNS depressant effect of Serotonergic Opioids (High Risk). Serotonergic Non-Opioid CNS Depressants may enhance the serotonergic effect of Serotonergic Opioids (High Risk). This could result in serotonin syndrome. Management: Consider alternatives to this drug combination. If combined, monitor for signs and symptoms of serotonin syndrome/serotonin toxicity and CNS depression. Risk D: Consider therapy modification

Serotonin 5-HT1D Receptor Agonists (Triptans): May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy

Serotonin/Norepinephrine Reuptake Inhibitors: Meperidine may enhance the serotonergic effect of Serotonin/Norepinephrine Reuptake Inhibitors. This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) if these agents are combined. Risk C: Monitor therapy

Sincalide: Drugs that Affect Gallbladder Function may diminish the therapeutic effect of Sincalide. Management: Consider discontinuing drugs that may affect gallbladder motility prior to the use of sincalide to stimulate gallbladder contraction. Risk D: Consider therapy modification

Sodium Phosphates: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Sodium Phosphates. Specifically, the risk of seizure or loss of consciousness may be increased in patients with significant sodium phosphate-induced fluid or electrolyte abnormalities. Risk C: Monitor therapy

Somatostatin Analogs: Opioid Agonists may diminish the analgesic effect of Somatostatin Analogs. Opioid Agonists may enhance the analgesic effect of Somatostatin Analogs. Risk C: Monitor therapy

St John's Wort: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. St John's Wort may decrease the serum concentration of Serotonergic Agents (High Risk). Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy

Succinylcholine: May enhance the bradycardic effect of Opioid Agonists. Risk C: Monitor therapy

Suvorexant: CNS Depressants may enhance the CNS depressant effect of Suvorexant. Management: Dose reduction of suvorexant and/or any other CNS depressant may be necessary. Use of suvorexant with alcohol is not recommended, and the use of suvorexant with any other drug to treat insomnia is not recommended. Risk D: Consider therapy modification

Syrian Rue: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy

Thalidomide: CNS Depressants may enhance the CNS depressant effect of Thalidomide. Risk X: Avoid combination

TraMADol: Serotonergic Opioids (High Risk) may enhance the CNS depressant effect of TraMADol. Serotonergic Opioids (High Risk) may enhance the serotonergic effect of TraMADol. This could result in serotonin syndrome. Management: Consider alternatives to this drug combination. If combined, monitor for signs and symptoms of serotonin syndrome/serotonin toxicity and CNS depression. Risk D: Consider therapy modification

Tricyclic Antidepressants: May enhance the CNS depressant effect of Serotonergic Opioids (High Risk). Serotonergic Opioids (High Risk) may enhance the serotonergic effect of Tricyclic Antidepressants. This could result in serotonin syndrome. Management: Consider alternatives to this drug combination. If combined, monitor for signs and symptoms of serotonin syndrome/serotonin toxicity and CNS depression. Risk D: Consider therapy modification

Valerian: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Zolpidem: CNS Depressants may enhance the CNS depressant effect of Zolpidem. Management: Reduce the Intermezzo brand sublingual zolpidem adult dose to 1.75 mg for men who are also receiving other CNS depressants. No such dose change is recommended for women. Avoid use with other CNS depressants at bedtime; avoid use with alcohol. Risk D: Consider therapy modification

Reproductive Considerations

Long-term opioid use may cause secondary hypogonadism, which may lead to sexual dysfunction or infertility in men and women (Brennan 2013).

Pregnancy Considerations

Opioids cross the placenta.

According to some studies, maternal use of opioids may be associated with birth defects (including neural tube defects, congenital heart defects, and gastroschisis), poor fetal growth, stillbirth, and preterm delivery (CDC [Dowell 2016]).

[US Boxed Warning]: Prolonged use of meperidine during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life-threatening if not recognized and treated, and requires management according to protocols developed by neonatology experts. If opioid use is required for a prolonged period in a pregnant woman, advise the patient of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available. If chronic opioid exposure occurs in pregnancy, adverse events in the newborn (including withdrawal) may occur (Chou 2009). Symptoms of neonatal abstinence syndrome (NAS) following opioid exposure may be autonomic (eg, fever, temperature instability), gastrointestinal (eg, diarrhea, vomiting, poor feeding/weight gain), or neurologic (eg, high-pitched crying, hyperactivity, increased muscle tone, increased wakefulness/abnormal sleep pattern, irritability, sneezing, seizure, tremor, yawning) (Dow 2012; Hudak 2012). Mothers who are physically dependent on opioids may give birth to infants who are also physically dependent. Opioids may cause respiratory depression and psycho-physiologic effects in the neonate; newborns of mothers receiving opioids during labor should be monitored.

Although approved for use in obstetrical analgesia, meperidine is not recommended for peripartum analgesia due to the prolonged half-life of the active metabolite in the mother and neonate (ACOG 209 2019), and it is not recommended to treat chronic noncancer pain in pregnant women or those who may become pregnant (CDC [Dowell 2016]; Chou 2009).

Breastfeeding Considerations

Meperidine is present in breast milk.

Breast milk exposure to meperidine and normeperidine is consistently associated with neonatal sedation and may interfere with breastfeeding. Nonopioid analgesics are preferred for breastfeeding females who require pain control peripartum or for surgery outside of the postpartum period; meperidine is not recommended if an opioid is needed. Although a single dose is likely to be acceptable, close monitoring of the infant is required following multiple doses (ABM [Martin 2018]; ABM [Reece-Stremtan 2017]; Sachs 2013).

When opioids are needed in breastfeeding women, the lowest effective dose for the shortest duration of time should be used to limit adverse events in the mother and breastfeeding infant (ABM [Martin 2018]; ABM [Reece-Stremtan 2017]). Breastfeeding women using opioids for postpartum pain should monitor their infants for drowsiness, sedation, feeding difficulties, or limpness (ACOG 209 2019). Withdrawal symptoms may occur when maternal use is discontinued or breastfeeding is stopped. According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and benefits of treatment to the mother.

Monitoring Parameters

Pain relief, respiratory and mental status, blood pressure; bowel function; signs/symptoms of misuse, abuse and addiction; signs or symptoms of hypogonadism or hypoadrenalism (Brennan 2013) or serotonin syndrome in patient receiving other medications that enhance serotonergic activity (Gillman 2005)

Mechanism of Action

Binds to opioid receptors in the CNS, causing inhibition of ascending pain pathways, altering the perception of and response to pain; produces generalized CNS depression

Pharmacokinetics

Onset of action: Analgesic: Oral, IM, SubQ: 10 to 15 minutes; IV: ~5 minutes

Peak effect: IV: 5 to 7 minutes; IM, SubQ: ~1 hour; Oral: 2 hours

Duration: Oral, IM, SubQ: 2 to 4 hours; IV: 2 to 3 hours

Absorption: IM, Oral: Erratic and highly variable

Distribution: Vdss:

Neonates: Preterm 1 to 7 days: 8.8 L/kg; Term 1 to 7 days: 5.6 L/kg

Infants 1 week to 2 months: 8 L/kg

Infants and Children 3 to 18 months: 5 L/kg

Children 5 to 8 years: 2.8 L/kg

Adults: 3 to 4 L/kg

Protein binding (to alpha 1-acid glycoprotein): Neonates: 52%; Infants: 3 to 18 months: 85%; Adults: 65% to 75%

Metabolism: Hepatic; hydrolyzed to meperidinic acid (inactive) or undergoes N-demethylation to normeperidine (active; has 1/2 the analgesic effect and 2 to 3 times the CNS effects of meperidine)

Bioavailability: ~50% to 60%; increased with liver disease

Half-life elimination:

Parent drug: Terminal phase:

Preterm infants 3.6 to 65 days of age: 11.9 hours (range: 3.3 to 59.4 hours)

Term infants: 0.3 to 4 days of age: 10.7 hours (range: 4.9 to 16.8 hours); 26 to 73 days of age: 8.2 hours (range: 5.7 to 31.7 hours)

Neonates: 23 hours (range: 12 to 39 hours)

Infants 3 to 18 months: 2.3 hours

Children 5 to 8 years: 3 hours

Adults: 2.5 to 4 hours, Liver disease: 7 to 11 hours

Normeperidine (active metabolite): Neonates: 30 to 85 hours; Adults: 8 to 16 hours; normeperidine half-life is dependent on renal function and can accumulate with high doses or in patients with decreased renal function; normeperidine may precipitate tremors or seizures

Excretion: Urine (as metabolites; ~5% as unchanged drug)

Pharmacokinetics: Additional Considerations

Altered kidney function: Accumulation of meperidine and/or normeperidine may occur.

Hepatic function impairment: Accumulation of meperidine and/or normeperidine may occur. Half-life is 1.3 to 2 times greater in cirrhotic patients.

Older adult: Elderly patients have a slower elimination rate.

Postoperative patients: The half-life is 1.3 to 2 times greater in these patients.

Pricing: US

Solution (Demerol Injection)

25 mg/mL (per mL): $7.25

50 mg/mL (per mL): $7.49

75 mg/mL (per mL): $7.68

100 mg/mL (per mL): $7.68

Solution (Meperidine HCl Injection)

25 mg/mL (per mL): $3.04 - $3.05

50 mg/mL (per mL): $3.17

100 mg/mL (per mL): $3.47 - $3.48

Solution (Meperidine HCl Oral)

50 mg/5 mL (per mL): $0.32

Tablets (Meperidine HCl Oral)

50 mg (per each): $47.39

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Brand Names: International
  • Aldolan (TR);
  • Alodan "Gerot" (AT);
  • Cluyer (AR);
  • Deme (PH);
  • Demero (VE);
  • Demerol HCl (MX, PH);
  • Dolantina (BR, ES);
  • Dolcontral (DE);
  • Dolestine (IL);
  • Doloblok (LV);
  • Dolosal (BR);
  • Dolsin (CZ);
  • Dornot (BR);
  • Lydol (BG);
  • Meperdol (PY);
  • Meperidol (UY);
  • Pethidine (BD, GB, HK, KR, PK, TW);
  • Pethidine Injection (AU);
  • Pethidine-Hameln (SG);
  • Pethisom (BE);
  • Verpat (LK)


For country code abbreviations (show table)
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