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.
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.
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.
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 of meperidine, especially by children, can result in a fatal overdose of meperidine.
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.
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.
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 can result in coma, severe respiratory depression, cyanosis, and hypotension. Use of meperidine with MAOIs within last 14 days is contraindicated.
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 (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).
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.
Avoid use as an analgesic in renal impairment (American Pain Society 2016; ISMP 2007).
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).
(For additional information see "Meperidine (pethidine): Pediatric drug information")
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: 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: 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: 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.
Avoid use as an analgesic in renal impairment (APS 2016; ISMP 2007).
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).
Avoid use as an analgesic (American Pain Society 2016; Beers Criteria [AGS 2019]; ISMP 2007).
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]
Yes
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]
C-II
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
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.
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.
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).
Postoperative shivering; Rigors from amphotericin B (conventional); Targeted temperature management-related shivering
Meperidine may be confused with meprobamate
Demerol may be confused with Demulen, Desyrel, Dilaudid, Pamelor
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.
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).
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]).
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).
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)
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.
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.
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.
Substrate of CYP3A4 (major); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential
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
Long-term opioid use may cause secondary hypogonadism, which may lead to sexual dysfunction or infertility in men and women (Brennan 2013).
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).
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.
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)
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
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)
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.
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
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