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Meperidine

Medical and Pharmacy Editor:

Brand Name: Demerol, Pethidine

Generic Name: Meperidine

Drug Class: Synthetic, Opioids; Opioid Analgesics

What Is Meperidine and How Does It Work?

Meperidine is used to help relieve moderate to severe pain. It may also be used before and during surgery or other procedures. Meperidine belongs to a class of drugs known as opioid (narcotic) analgesics and is similar to morphine. It works in the brain to change how your body feels and responds to pain.

Meperidine should not be used to treat long-term or ongoing pain. It should only be used to treat sudden episodes of moderate to severe pain. See also Warnings and Precautions section.

Meperidine is available under the following different brand names: Demerol and pethidine.

Dosages of Meperidine

Dosage Forms and Strengths

Syrup: Schedule II

  • 50 mg/5 mL

Tablet: Schedule II

  • 50 mg
  • 100 mg

Injectable solution: Schedule II

  • 25 mg/mL
  • 50 mg/mL
  • 75 mg/mL
  • 100 mg/mL

Dosage Considerations – Should be Given as Follows:

Therapy exposes users to the risks of addiction, abuse and misuse; because extended-release products deliver opioid over extended period of time, there is a greater risk for overdose and death due to the larger amount of tramadol present; addiction can occur at recommended dosages and if drug is misused or abused; assess each patient's risk for opioid addiction, abuse or misuse prior to prescribing therapy; risks are increased in patients with personal or family history of substance abuse (including drug or alcohol abuse or addiction) or mental illness (e.g., major depression); patients at risk may be prescribed opioids but use in such patients necessitates intensive counseling about risks and proper use along with intensive monitoring for signs of addiction, abuse and misuse; strategies to reduce these risks include prescribing drug in smallest appropriate quantity and advising patient on proper disposal of unused drug.

Pain

  • Meperidine is not recommended as a first choice analgesic by The American Pain Society and ISMP (2007); if no other options, limit use in acute pain to up to 48 hours; doses should not exceed 600 mg/24 hours; oral route is not recommended for treatment of acute or chronic pain
  • Pain: 50-150 mg orally/intramuscularly/subcutaneously every 3-4 hours as needed; adjust dose-based degree of response
  • Preoperatively: 50-150 mg intramuscularly/subcutaneously (IM/SC) every 3-4 hours as needed
  • Continuous infusion: 15-35 mg/hour
  • Obstetrical analgesia: 50-100 mg intramuscularly/subcutaneously (IM/SC); repeated every 1-3 hours as needed
  • Pediatric: 1-1.8 mg/kg orally/intramuscularly/subcutaneously every 3-4 hours as needed; individual dose not to exceed 100 mg
  • Pediatric, preoperatively: 1.1-2.2 mg/kg intramuscularly/subcutaneously (IM/SC) 30-90 minutes before initiation of anesthesia
  • Geriatric: 50 mg orally every 4 hours or 25 mg intramuscularly (IM) every 4 hours; treatment for acute pain should be limited to 1-2 doses

Dosage Modifications

  • Renal impairment: Avoid use
  • Hepatic impairment: Consider lower initial dose initially; increased opioid effect possible in cirrhosis

Dosing Considerations

  • Not drug of choice in elderly patients, because of accumulation of metabolite normeperidine, causing increased central nervous system (CNS) effects
  • Reduce total daily dose in elderly patients
RxList

What Are Side Effects Associated with Using Meperidine?

Common side effects of meperidine include:

Postmarketing side effects of meperidine reported include:

This is not a complete list of side effects and other serious side effects may occur. Call your doctor for information and medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

What Other Drugs Interact with Meperidine?

If your doctor has directed you to use this medication for your condition, your doctor or pharmacist may already be aware of any possible drug interactions or side effects and may be monitoring you for them. Do not start, stop, or change the dosage of this medicine or any medicine before getting further information from your doctor, healthcare provider or pharmacist first.

Severe interactions of meperidine include:

  • alvimopan

Severe interactions of meperidine include:

  • alvimopan
  • isocarboxazid
  • linezolid
  • phenelzine
  • procarbazine
  • rasagiline
  • safinamide
  • selegiline
  • selegiline transdermal
  • tranylcypromine

Meperidine has serious interactions with at least 54 different drugs.

Meperidine has moderate interactions with at least 219 different drugs.

Mild interactions of meperidine include:

This document does not contain all possible interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you, and share the list with your doctor and pharmacist. Check with your physician if you have health questions or concerns.

RxList

What Are Warnings and Precautions for Meperidine?

Warnings

Addiction, abuse, and misuse

  • Risk of opioid addiction, abuse, and misuse, which can lead to overdose and death; assess each patient's risk prior to prescribing and monitor all patients regularly for the development of these behaviors or conditions

Life-threatening respiratory depression

  • Serious, life-threatening, or fatal respiratory depression may occur
  • Monitor for respiratory depression, especially during initiation or following a dose increase

Neonatal opioid withdrawal syndrome

  • Prolonged use 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

Interactions with Drugs Affecting Cytochrome P450 Isoenzymes

  • Concomitant use with cytochrome P450 3A4 inhibitors or discontinuation of inducers can result in fatal overdose of meperidine

Risks From Concomitant Use With Benzodiazepines Or Other CNS Depressants

  • Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death; reserve concomitant prescribing for use in patients for whom alternative treatment options are inadequate; limit dosages and durations to minimum required; follow patients for signs and symptoms of respiratory depression and sedation

Concomitant Use of Meperidine with Monoamine Oxidase (MAO) Inhibitors

  • Concomitant use of with monoamine oxidase (MAO) inhibitors can result in coma, severe respiratory depression, cyanosis and hypotension; use with MAO inhibitors is contraindicated

This medication contains meperidine. Do not take Demerol or pethidine if you are allergic to meperidine or any ingredients contained in this drug.

Keep out of reach of children. In case of overdose, get medical help or contact a Poison Control Center immediately.

Contraindications

  • Hypersensitivity to drug or component of the formulation
  • Acute or severe bronchial asthma in an unmonitored setting or in absence of resuscitative equipment
  • Known or suspected gastrointestinal obstruction, including paralytic ileus
  • Within 14 days of taking monoamine oxidase (MAO) inhibitors; if linezolid or intravenous (IV) methylene blue (MAOIs) must be administered, discontinue serotonergic drug immediately and monitor for central nervous system (CNS) toxicity; may resume 24 hours after last linezolid or methylene blue dose, or after 2 weeks of monitoring, whichever comes first

Effects of Drug Abuse

Therapy exposes users to the risks of addiction, abuse and misuse; because extended-release products deliver opioid over extended period of time, there is a greater risk for overdose and death due to the larger amount of tramadol present; addiction can occur at recommended dosages and if drug is misused or abused; assess each patient's risk for opioid addiction, abuse or misuse prior to prescribing therapy; risks are increased in patients with personal or family history of substance abuse (including drug or alcohol abuse or addiction) or mental illness (e.g., major depression); patients at risk may be prescribed opioids but use in such patients necessitates intensive counseling about risks and proper use along with intensive monitoring for signs of addiction, abuse and misuse; strategies to reduce these risks include prescribing drug in smallest appropriate quantity and advising patient on proper disposal of unused drug.

Short-Term Effects

  • While serious, life-threatening, or fatal respiratory depression can occur at any time during therapy, the risk is greatest during the initiation of therapy or following a dosage increase; monitor patients closely for respiratory depression, especially within the first 24-72 hours of initiating therapy with and following dosage increases; to reduce risk of respiratory depression, proper dosing and titration are essential; overestimating dosage when converting patients from another opioid product can result in a fatal overdose with the first dose.
  • See "What Are Side Effects Associated with Using Meperidine?"

Long-Term Effects

  • 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.
  • Chronic use of opioids may cause reduced fertility in females and males of reproductive potential; it is not known whether effects on fertility are reversible.
  • Chronic high-dose therapy or administration to patients with renal impairment may result in accumulation of active metabolite normeperidine, leading to agitation and seizures.
  • See "What Are Side Effects Associated with Using Meperidine?"

Cautions

  • Therapy exposes users to the risks of addiction, abuse and misuse; because extended-release products deliver opioid over extended period of time, there is a greater risk for overdose and death due to the larger amount of tramadol present; addiction can occur at recommended dosages and if drug is misused or abused; assess each patient's risk for opioid addiction, abuse or misuse prior to prescribing therapy; risks are increased in patients with personal or family history of substance abuse (including drug or alcohol abuse or addiction) or mental illness (e.g., major depression); patients at risk may be prescribed opioids but use in such patients necessitates intensive counseling about risks and proper use along with intensive monitoring for signs of addiction, abuse and misuse; strategies to reduce these risks include prescribing drug in smallest appropriate quantity and advising patient on proper disposal of unused drug.
  • Therapy may cause severe low blood pressure (hypotension) including orthostatic hypotension and syncope in ambulatory patients; there is increased risk in patients whose ability to maintain blood pressure has already been compromised by a reduced blood volume or concurrent administration of certain CNS depressant drugs (e.g., phenothiazines or general anesthetics); monitor patients for signs of hypotension after initiating or titrating dosage; in patients with circulatory shock, therapy may cause vasodilation that can further reduce cardiac output and blood pressure; avoid therapy in patients with circulatory shock.
  • In patients who may be susceptible to intracranial effects of CO2 retention (e.g., those with evidence of increased intracranial pressure or brain tumors), therapy may reduce respiratory drive, and resultant CO2 retention can further increase intracranial pressure; monitor such patients for signs of sedation and respiratory depression, particularly when initiating therapy; opioids may obscure clinical course in a patient with a head injury; avoid the use in patients with impaired consciousness or coma.
  • Contraindicated in patients with known or suspected gastrointestinal obstruction, including paralytic ileus; may cause spasm of sphincter of Oddi; opioids may cause increases in serum amylase; monitor patients with biliary tract disease, including acute pancreatitis, for worsening symptoms.
  • Use in patients with acute or severe bronchial asthma in unmonitored setting or in absence of resuscitative equipment is contraindicated; patients with significant chronic obstructive pulmonary disease or cor pulmonale, and those with a substantially decreased respiratory reserve, hypoxia, hypercapnia, or pre-existing respiratory depression are at increased risk of decreased respiratory drive including apnea, even at recommended dosages.
  • Caution in acute abdominal conditions (may obscure diagnosis or clinical course of patient), pseudomembranous colitis, toxin-mediated diarrhea.
  • Narrow therapeutic index in certain patient populations, particularly in combination with central nervous system (CNS)-depressant drugs.
  • Cardiac arrhythmias, drug abuse or dependence, emotional lability, gallbladder disease, head injury, increased intracranial pressure, benign prostatic hyperplasia, hepatic or renal impairment, seizures with epilepsy, urethral stricture, urinary tract surgery.
  • Use with caution in following conditions: Sickle cell anemia; acute alcoholism; adrenocortical insufficiency (e.g., Addison disease); CNS depression or coma; delirium tremens; debilitated patients; kyphoscoliosis associated with respiratory depression; myxedema or hypothyroidism; prostatic hypertrophy or urethral stricture; head trauma; biliary tract impairment; severe impairment of hepatic, pulmonary, or renal function; toxic psychosis.
  • Warn patients not to drive or operate dangerous machinery unless they are tolerant to therapy and know how they will react to medication.
  • While serious, life-threatening, or fatal respiratory depression can occur at any time during therapy, the risk is greatest during the initiation of therapy or following a dosage increase; monitor patients closely for respiratory depression, especially within the first 24-72 hours of initiating therapy with and following dosage increases; to reduce risk of respiratory depression, proper dosing and titration are essential; overestimating dosage when converting patients from another opioid product can result in a fatal overdose with the first dose.
  • Prolonged use 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.
  • In patients with pheochromocytoma, meperidine has been reported to provoke hypertension.
  • If necessary, meperidine may be given intravenously, but injection should be given very slowly, preferably as diluted solution; rapid intravenous injection of narcotic analgesics, including meperidine, increases incidence of adverse reactions; severe respiratory depression, apnea, hypotension, peripheral circulatory collapse, and cardiac arrest have occurred; meperidine should not be administered intravenously unless a narcotic antagonist and facilities for assisted or controlled respiration are immediately available; when meperidine is given parenterally, especially intravenously, the patient should be lying down.
  • Chronic use of opioids may cause reduced fertility in females and males of reproductive potential; it is not known whether effects on fertility are reversible.
  • Avoid use of mixed agonist/antagonist (e.g., pentazocine, nalbuphine, and butorphanol) or partial agonist (e.g., buprenorphine) analgesics in patients who are receiving a full opioid agonist analgesic; mixed agonist/antagonist and partial agonist analgesics may reduce analgesic effect and/or may precipitate withdrawal symptoms; when discontinuing therapy, gradually taper dosage; do not abruptly discontinue therapy.
  • May cause less smooth muscle spasm and constipation than equipotent doses of morphine.
  • Cases of adrenal insufficiency reported with opioid use, more often following greater than one month of use; symptoms may include nausea, vomiting, anorexia, fatigue, weakness, dizziness, and low blood pressure; if adrenal insufficiency is diagnosed, treat with physiologic replacement doses of corticosteroids; wean patient off of opioid to allow adrenal function to recover and continue corticosteroid treatment until adrenal function recovers; other opioids may be tried as some cases reported use of a different opioid without recurrence of adrenal insufficiency.
  • Chronic high-dose therapy or administration to patients with renal impairment may result in accumulation of active metabolite normeperidine, leading to agitation and seizures.
  • Drug interaction overview:
    • Concomitant use with a CYP3A4 inhibitor, such as macrolide antibiotics (e.g., erythromycin), azole-antifungal agents (e.g., ketoconazole), and protease inhibitors (e.g., ritonavir), may increase plasma concentrations of meperidine and prolong opioid adverse reactions, which may cause potentially fatal respiratory depression, particularly when an inhibitor is added after a stable dose of meperidine injection is achieved; similarly, discontinuation of a CYP3A4 inducer, such as rifampin, carbamazepine, and phenytoin, in meperidine-injection treated patients may increase meperidine plasma concentrations and prolong opioid adverse reactions; when using meperidine Injection with CYP3A4 inhibitors or discontinuing CYP3A4 inducers in meperidine-Injection treated patients, monitor patients closely at frequent intervals and consider dosage reduction of meperidine injection until stable drug effects are achieved
    • Concomitant use of meperidine injection with CYP3A4 inducers or discontinuation of a CYP3A4 inhibitor could decrease meperidine plasma concentrations, decrease opioid efficacy or, possibly, lead to a withdrawal syndrome in a patient who had developed physical dependence to meperidine; when using meperidine injection with CYP3A4 inducers or discontinuing CYP3A4 inhibitors, monitor patients closely at frequent intervals and consider increasing opioid dosage if needed to maintain adequate analgesia or if symptoms of opioid withdrawal occur
    • Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death; reserve concomitant prescribing for use in patients for whom alternative treatment options are inadequate; limit dosages and durations to minimum required; follow patients for signs and symptoms of respiratory depression and sedation
    • Cases of serotonin syndrome, a potentially life-threatening condition, reported, particularly during concomitant use with serotonergic drugs. Serotonergic drugs include selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), triptans, 5-HT3 receptor antagonists, drugs that affect the serotonergic neurotransmitter system (e.g., mirtazapine, trazodone, tramadol), and drugs that impair metabolism of serotonin (including MAO inhibitors, both those intended to treat psychiatric disorders and also others, such as linezolid and intravenous methylene blue); may occur within recommended dosage range; symptoms may include mental status changes (e.g., agitation, hallucinations, coma), autonomic instability (e.g., tachycardia, labile blood pressure, hyperthermia), neuromuscular aberrations (e.g., hyperreflexia, incoordination, rigidity), and/or gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea); onset of symptoms generally occurs within several hours to a few days of concomitant use, but may occur later than that; discontinue therapy if serotonin syndrome is suspected
    • Meperidine is contraindicated in patients who have received MAO inhibitors within the last 14 days; therapeutic doses of meperidine have occasionally precipitated unpredictable, severe, and occasionally fatal reactions in patients who have received such agents within 14 days; intravenous hydrocortisone or prednisolone have been used to treat severe reactions, with the addition of intravenous chlorpromazine in those cases exhibiting hypertension and hyperpyrexia

Pregnancy and Lactation

  • Prolonged use of opioid analgesics such as meperidine during pregnancy for medical or nonmedical purposes can result in physical dependence in neonate and neonatal opioid withdrawal syndrome shortly after birth. The onset, duration, and severity of neonatal opioid withdrawal syndrome vary based on the specific opioid used, duration of use, timing and amount of last maternal use, and the rate of elimination of drug by newborn. Observe newborns for symptoms of neonatal opioid withdrawal syndrome and manage accordingly.
  • Meperidine appears in milk of nursing mothers receiving the drug. The developmental and health benefits of breastfeeding should be considered along with mother's clinical need for therapy and any potential adverse effects on breastfed infant or from underlying maternal condition.
Reviewed on 1/24/2018

References:
Medscape. Meperidine.
https://reference.medscape.com/drug/demerol-meperidine-343315
RxList. Demerol Side Effects Center.
https://www.rxlist.com/demerol-side-effects-drug-center.htm

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