Pethidine (Meperidine)

Pharmacologic Category

Analgesic, Opioid

Dosing: Adult

Note: The American Pain Society and ISMP 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. Oral administration is not recommended for treatment of acute or chronic pain. If IV administration is required, consider a reduced dose. When treating pain, patients with prior opioid exposure may require higher initial doses (APS 2016; ISMP 2007).

Pain management:

Acute pain: IM, SubQ: 50 to 150 mg every 3 to 4 hours as needed.

Discontinuation of therapy: When discontinuing chronic opioid therapy, the dose should be gradually tapered down. An optimal universal tapering schedule for all patients has not been established (CDC [Dowell 2016]). Proposed schedules range from slow (eg, 10% reductions per week) to rapid (eg, 25% to 50% reduction every few days) (CDC 2015). Tapering schedules should be individualized to minimize opioid withdrawal while considering patient-specific goals and concerns as well as the pharmacokinetics of the opioid being tapered. An even slower taper may be appropriate in patients who have been receiving opioids for a long duration (eg, years), particularly in the final stage of tapering, whereas more rapid tapers may be appropriate in patients experiencing severe adverse events (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).

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.

Dosage adjustment for concomitant therapy: Concomitant phenothiazines/tranquilizers: Reduce meperidine dose by 25% to 50% when administered concomitantly with phenothiazines and other tranquilizers.

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

* See Dosage and Administration in AHFS Essentials for additional information.

Dosing: Geriatric

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

Dosing: Renal 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

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.

Note: The American Pain Society (2008) 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/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.

Acute pain (analgesic) (Berde 2002): Initial:

Infants ≤6 months:

IM, IV, SubQ: 0.2 to 0.25 mg/kg/dose every 2 to 3 hours

Oral: 0.5 to 0.75 mg/kg/dose every 3 to 4 hours

Infants >6 months, Children, and Adolescents:

IM, IV, or SubQ; intermittent dosing:

Patient weight <50 kg: 0.8 to 1 mg/kg/dose every 2 to 3 hours as needed; maximum dose: 75 mg/dose

Patient weight ≥50 kg: 50 to 75 mg every 2 to 3 hours as needed

Oral:

Patient weight <50 kg: 2 to 3 mg/kg/dose every 3 to 4 hours as needed; maximum dose: 150 mg/dose

Patient weight ≥50 kg: 100 to 150 mg every 3 to 4 hours as needed

Analgesia for minor procedures/sedation; preoperative: Infants, Children, and Adolescents:

IM, IV, SubQ: 0.5 to 1 mg/kg given 30 to 90 minutes before the beginning of anesthesia; maximum dose: 2 mg/kg or 150 mg/dose (Zeltzer 1990)

Oral: 2 to 4 mg/kg given 30 to 90 minutes before the beginning of anesthesia; maximum dose: 150 mg/dose

Sickle cell disease, acute crisis; opioid naïve patients: (APS 1999): Infants ≥6 months, Children, and Adolescents: Note: Not recommended for use unless it is the only opioid effective for the patient (NHLBI 2014). Initial:

Patient weight <50 kg: IV: 0.75 to 1 mg/kg every 3 to 4 hours as needed; maximum dose: 1.75 mg/kg/dose or 100 mg/dose

Patient weight ≥50 kg: IV: 50 to 150 mg every 3 hours as needed

Dosing: Renal Impairment: Pediatric

The manufacturer recommends to use with caution and reduce dose; accumulation of meperidine and its active metabolite (normeperidine) may occur. The American Pain Society and ISMP recommend to avoid use in renal impairment. (American Pain Society 2008; ISMP 2007).

Dosing: Hepatic Impairment: Pediatric

Use with caution and reduce dose; accumulation of meperidine and its active metabolite (normeperidine) may occur.

Calculations

• Fentanyl Transdermal Conversion
• Opioid Agonist Conversion

Use: Labeled Indications

Pain management: 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).

* See Uses in AHFS Essentials for additional information.

Use: Off-Label: Adult

Postoperative shiveringLevel of Evidence [C, G]

Data from a limited number of patients studied suggest that short-term use of meperidine may be beneficial in reducing postoperative shivering Ref. Clinical experience also suggests the utility of meperidine to reduce shivering from general and epidural anesthesia Ref. Additional data may be necessary to further define the role of meperidine in this setting.

Based on the American Society of Anesthesiologists practice guidelines for postanesthetic care, meperidine, unless contraindicated or unavailable, is recommended for the treatment of shivering during emergence and recovery when clinically necessary.

Rigors from amphotericin B (conventional)Level of Evidence [C]

Data from a limited number of patients studied suggest that meperidine may be beneficial in reducing rigors lasting longer than 3 to 5 minutes from conventional amphotericin B Ref. Additional data may be necessary to further define the role of meperidine for the treatment of rigors associated with conventional amphotericin B.

Targeted temperature management-related shiveringLevel of Evidence [C]

Data from a limited number of patients studied suggest that meperidine may be beneficial in reducing shivering in patients undergoing targeted temperature management (aka, therapeutically induced hypothermia) Ref. Clinical experience also suggests the utility of meperidine to safely and effectively prevent or treat shivering after induction of targeted temperature management Ref. Additional data may be necessary to further define the role of meperidine in this setting.

Of note, the active metabolite of meperidine, normeperidine, is a CNS excitotoxin and may cause seizures, especially in patients with renal insufficiency; if used, consider restricting high-dose use to a short time period (eg, ≤24 hours) to prevent this from occurring Ref. Overall, the optimal dose for meperidine in this setting is not well-established. Therefore, no specific dosing recommendations can be made at this time.

Level of Evidence Definitions

Level of Evidence Scale

Use: Unsupported: Adult

Pain management (oral)

The American Pain Society (APS) does not recommend the use of oral meperidine for treatment of acute or chronic pain since oral meperidine undergoes extensive first-pass metabolism to form excessive amounts of normeperidine (a CNS excitotoxin) that are not relative to the dose administered (APS 2016). Overall, the APS and Institute for Safe Medication Practices do not recommend meperidine’s use as an analgesic (APS 2016; ISMP 2007).

Class and Related Monographs

Opioid Analgesics

Clinical Practice Guidelines

Patient Safety:

“CDC Guideline for Prescribing Opioids for Chronic Pain,” 2016

Administration: IV

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.

Administration: Injectable Detail

pH: 3.5 to 6

Administration: Oral

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

Parenteral:

IM: Preferred route; inject undiluted into a large muscle

IV:

Slow IV push: Do not administer rapid IV, dilute and administer over at least 5 minutes

Intermittent IV infusion: Dilute and administer over 15 to 30 minutes

SubQ: Suitable for occasional use; when repeated doses are required, the IM route of administration is preferred; administer undiluted

Storage/Stability

Injection: Store at 20°C to 25°C (68°F to 77°F).

Oral solution, tablets: Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F).

Preparation for Administration: Pediatric

Oral: Oral solution: Dilute dose in 1/2 glass of water prior to use

Parenteral:

Slow IV push: Dilute solution to ≤10 mg/mL

Intermittent IV infusion: Dilute to 1 mg/mL

Compatibility

See Trissel’s IV Compatibility Database

Open Trissel's IV Compatibility

Medication Patient Education with HCAHPS Considerations

What is this drug used for?

• It is used to ease pain.

• It is used during surgery.

• It may be given to you for other reasons. Talk with the doctor.

Frequently reported side effects of this drug

• Loss of strength and energy

• Flushing

• Nausea

• Vomiting

• Dry mouth

• Sweating a lot

• Headache

Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:

• Severe fatigue

• Severe dizziness

• Passing out

• Confusion

• Severe constipation

• Seizures

• Chest pain

• Fast heartbeat

• Slow heartbeat

• Abnormal heartbeat

• Trouble urinating

• Sensing things that seem real but are not

• Mood changes

• Severe abdominal pain

• Trouble breathing

• Slow breathing

• Shallow breathing

• Noisy breathing

• Sexual dysfunction (males)

• Decreased sex drive

• Trouble getting pregnant

• No menstrual periods

• Tremors

• Abnormal movements

• Vision changes

• Adrenal gland problems like severe nausea, vomiting, severe dizziness, passing out, muscle weakness, severe fatigue, mood changes, lack of appetite, or weight loss.

• Serotonin syndrome like dizziness, severe headache, agitation, sensing things that seem real but are not, fast heartbeat, abnormal heartbeat, flushing, tremors, sweating a lot, change in balance, severe nausea, or severe diarrhea.

• Signs of a significant reaction like wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.

Medication Safety Issues

Sound-alike/look-alike issues:

High alert medication:

Geriatric Patients: High-Risk Medication:

Other safety concerns:

REMS Components

Opioids for analgesic use: Elements to Assure Safe Use; Medication Guide

REMS Programs

• Opioid Analgesic

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.

• 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]), or agents that impair metabolism of tramadol (eg, CYP2D6 and 3A4 inhibitors). 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 anemia, use with caution and decrease initial dose; normeperidine (active metabolite) may accumulate and induce seizures in these patients; Note: Meperidine is not recommended for use in sickle cell patients by the American Pain Society (APS 2016) 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 (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.

• 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.

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

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.

• Elderly: 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). 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.

• 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.

* See Cautions in AHFS Essentials for additional information.

Geriatric Considerations

Meperidine is not recommended as a drug of first choice for the treatment of pain in the elderly due to the accumulation of its metabolite, normeperidine, which can lead to serious CNS side effects (eg, tremor, seizures). The Beers Criteria recommends avoiding use of meperidine completely, as the doses typically needed for analgesia are too high to use in an older adult, especially in the setting of diminished renal function. Meperidine should also be avoided in those with, or at risk for, delirium due to its ability to cause or worsen this syndrome (Beers Criteria [AGS 2019]).

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.

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).

Breast-Feeding 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.

Lexicomp Pregnancy & Lactation, In-Depth

• Meperidine

Briggs' Drugs in Pregnancy & Lactation

• Meperidine

Adverse Reactions

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)

* See Cautions in AHFS Essentials for additional information.

Allergy and Idiosyncratic Reactions

• Opioid Allergy/Hypersensitivity

Toxicology

• Opioids

Metabolism/Transport Effects

None known.

Drug Interactions Open Interactions

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, mental status changes) when these agents are combined. 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. Exceptions: Alosetron; Ondansetron; Ramosetron. Risk C: Monitor therapy

Azelastine (Nasal): CNS Depressants may enhance the CNS depressant effect of Azelastine (Nasal). 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

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

Cannabis: May enhance the CNS depressant effect of CNS Depressants. 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

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. Exceptions: Nefazodone. 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

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

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

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

Dronabinol: May enhance the CNS depressant effect of CNS Depressants. 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. Exceptions to this monograph are discussed in further detail in separate drug interaction monographs. 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. Exceptions: Lisuride; Nicergoline. 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

Flunitrazepam: CNS Depressants may enhance the CNS depressant effect of Flunitrazepam. Risk D: Consider therapy modification

Fosphenytoin: May decrease the serum concentration of Meperidine. Risk C: Monitor therapy

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 Meperidine. Management: Consider a decrease in meperidine dose, as appropriate, when used together with hydroxyzine. With concurrent use, monitor patients closely for excessive response to the combination. 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 anticonvulsants. 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 anticonvulsants. 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 anticonvulsants. Risk D: Consider therapy modification

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

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. Management: Drugs listed as exceptions to this monograph are discussed in further detail in separate drug interaction monographs. 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 adult dose of CNS depressant agents by 50% with initiation of concomitant methotrimeprazine therapy. Further CNS depressant dosage adjustments should be initiated only after clinically effective methotrimeprazine dose is established. 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

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

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

Nalmefene: May diminish the therapeutic effect of Opioid Agonists. Management: Avoid the concomitant use of nalmefene and opioid agonists. Discontinue nalmefene 1 week prior to any anticipated use of opioid agonistss. 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 D: Consider therapy modification

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

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

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). Management: Concomitant use of ozanimod with serotonergic agents is not recommended. If combined, monitor patients closely for the development of hypertension, including hypertensive crises. Risk D: Consider therapy modification

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

Perampanel: May enhance the CNS depressant effect of CNS Depressants. Management: Patients taking perampanel with any other drug that has CNS depressant activities should avoid complex and high-risk activities, particularly those such as driving that require alertness and coordination, until they have experience using the combination. Risk D: Consider therapy modification

Phenytoin: May decrease the serum concentration of Meperidine. Risk C: Monitor therapy

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

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

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

Selective Serotonin Reuptake Inhibitors: CNS Depressants may enhance the adverse/toxic effect of Selective Serotonin Reuptake Inhibitors. Specifically, the risk of psychomotor impairment may be enhanced. Risk C: Monitor therapy

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. Exceptions: Dapoxetine. 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. Exceptions: Almotriptan; Eletriptan. 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 Oxybate: May enhance the CNS depressant effect of CNS Depressants. Management: Consider alternatives to combined use. When combined use is needed, consider minimizing doses of one or more drugs. Use of sodium oxybate with alcohol or sedative hypnotics is contraindicated. Risk D: Consider therapy modification

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

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

Tetrahydrocannabinol and Cannabidiol: May enhance the CNS depressant effect of CNS Depressants. 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

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

Test Interactions

Increased amylase (S), increased BSP retention, increased CPK (IM injections)

Genes of Interest

• Catechol-O-Methyltransferase

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)

Advanced Practitioners Physical Assessment/Monitoring

Monitor frequently for need; assess patient's physical and/or psychological dependence. For inpatients, implement safety measures to prevent falls. Discontinue slowly after prolonged use.

Nursing Physical Assessment/Monitoring

Monitor for effectiveness of pain relief. Monitor blood pressure, CNS and respiratory status, and degree of sedation at beginning of therapy and periodically thereafter. Assess patient's physical and/or psychological dependence. For inpatients, implement safety measures (eg, side rails up, call light within reach, instructions to call for assistance). Discontinue slowly after prolonged use.

Controlled Substance

C-II

Dosage Forms: US

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

Solution, Injection, as hydrochloride:

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

Generic: 10 mg/mL (30 mL [DSC])

Solution, Injection, as hydrochloride [preservative free]:

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

Demerol: 50 mg [DSC], 100 mg [DSC]

Generic: 50 mg, 100 mg

Dosage Forms: Canada

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

Solution, Injection, as hydrochloride:

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

Generic: 10 mg/mL ([DSC]); 50 mg/mL (1 mL); 75 mg/mL (1 mL); 100 mg/mL (1 mL)

Tablet, Oral, as hydrochloride:

Demerol: 50 mg

Anatomic Therapeutic Chemical (ATC) Classification

• N02AB02

Generic Available (US)

Yes

Pricing: US

Solution (Demerol Injection)

25 mg/0.5 mL (per 0.5 mL): $2.69

25 mg/mL (per mL): $7.14

50 mg/mL (per mL): $4.80

75 mg/1.5 mL (per mL): $3.09

75 mg/mL (per mL): $7.56

100 mg/2 mL (per mL): $2.52

100 mg/mL (per mL): $4.63

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): $33.17

100 mg (per each): $2.72

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.

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

Pharmacodynamics/Kinetics

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)

Pharmacodynamics/Kinetics: Additional Considerations

Renal function impairment: 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.

Geriatric: Elderly patients have a slower elimination rate.

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

Dental Use

Adjunct in preoperative intravenous conscious sedation in patients undergoing dental surgery; alternate oral opioid in patients allergic to codeine to treat moderate to moderate-severe pain

* See Uses in AHFS Essentials for additional information.

Local Anesthetic/Vasoconstrictor Precautions

No information available to require special precautions

Dental Health Professional Considerations

Meperidine is not to be used as the opioid drug of first choice. It is recommended only to be used in codeine-allergic patients when an opioid analgesic is indicated. Meperidine is not an anti-inflammatory agent. Meperidine, as with other opioid analgesics, is recommended only for limited acute dosing (ie, 3 days or less); common adverse effects in the dental patient are nausea, sedation, and constipation. Meperidine has a significant addiction liability, especially when given long-term.

Effects on Dental Treatment

Key adverse event(s) related to dental treatment: Xerostomia (normal salivary flow resumes upon discontinuation). See Dental Health Professional Considerations.

Effects on Bleeding

No information available to require special precautions

Dental Usual Dosing

Note: The American Pain Society (2008) and ISMP (2007) 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/24 hours. 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.

Pain (analgesic): Adults: Oral: Initial: Opioid-naive: 50 mg every 3 to 4 hours as needed; usual dosage range: 50 to 150 mg every 3 to 4 hours as needed (manufacturer's recommendation; oral route is not recommended for acute pain)

Related Information

• Beers Criteria 2019: Potentially Inappropriate Medication Use in Older Adults ≥65 Years of Age
• Opioid Conversion Table and Morphine Equivalent Dose Table
• Patient Information for Disposal of Unused Medications

Index Terms

Isonipecaine Hydrochloride; Meperidine Hydrochloride; Pethidine Hydrochloride

References

Ahlfors CE. Benzyl alcohol, kernicterus, and unbound bilirubin. J Pediatr. 2001;139(2):317-319.[PubMed 11487763]

2019 American Geriatrics Society Beers Criteria Update Expert Panel. American Geriatrics Society 2019 updated AGS Beers Criteria for Potentially Inappropriate Medication Use in Older Adults. J Am Geriatr Soc. 2019;67(4):674-694. doi: 10.1111/jgs.15767.[PubMed 30693946]

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Brand Names: International

Aldolan (TR); Alodan "Gerot" (AT); Cluyer (AR); Deme (PH); Demero (VE); Demerol HCl (MX, PH); Dolantin (DE); Dolantina (BR, ES); Doloblok (LV); Dolosal (BR); Dolsin (CZ); Dornot (BR); Lydol (BG); Meperdol (PY); Meperidol (UY); Pethidin (CH); Pethidine (BD, GB, HK, IN, KR, PK, TW); Pethidine Injection (AU, NZ); Pethidine Roche (ZA); Pethidine Tablet (NZ); Pethidine-Hameln (SG); Petidin (DK, NO, SE); Petidina (CL); Verpat (LK)

Last Updated 5/2/20