meperidine

General

High Alert Medication: This medication bears a heightened risk of causing significant patient harm when it is used in error.

**REMS Drug**

**BEERS Drug**

Pronunciation:
me-per-i-deen


Trade Name(s)

  • Demerol

Ther. Class.

opioid analgesics

Pharm. Class.

opioid agonists

Controlled Substance Schedule: II

Indications

  • Moderate or severe pain (alone or with nonopioid agents).
  • Anesthesia adjunct.
  • Analgesic during labor.
  • Preoperative sedation.

Unlabeled Use(s):

Rigors.

Action

Binds to opiate receptors in the CNS. Alters the perception of and response to painful stimuli, while producing generalized CNS depression.

Therapeutic Effect(s):

Decrease in severity of pain.

Pharmacokinetics

Absorption: 50% from the GI tract; well absorbed from IM sites. Oral doses are about half as effective as parenteral doses.

Distribution: Widely distributed. Crosses the placenta; enters breast milk.

Protein Binding: Neonates: 52%; Infants 3–18 mo: 85%; Adults: 60–80%.

Metabolism and Excretion: Mostly metabolized by the liver; some converted to normeperidine, which may accumulate and cause seizures. 5% excreted unchanged by the kidneys.

Half-life: Neonates: 12–39 hr; Infants 3–18 mo: 2.3 hr; Children 5–8 yr: 3 hr; Adults: 2.5–4 hr (↑ in impaired renal or hepatic function [7–11 hr]).

TIME/ACTION PROFILE (analgesia)

ROUTEONSETPEAKDURATION
PO15 min 60 min2–4 hr
IM10–15 min30–50 min2–4 hr
Subcut10–15 min40–60 min2–4 hr
IVimmediate5–7 min2–3 hr

Contraindication/Precautions

Contraindicated in:

  • Hypersensitivity;
  • Hypersensitivity to bisulfites (some injectable products);
  • Recent (within 14 days) MAO inhibitor therapy;
  • Severe respiratory insufficiency;
  • OB:  Labor and delivery;
  •  Lactation:  Lactation.

Use Cautiously in:

  • Head trauma;
  • ↑ intracranial pressure;
  • Severe renal or hepatic impairment;
  • Acute asthma attack, COPD, hypoxia, or hypercapnea;
  • Hypothyroidism;
  • Adrenal insufficiency;
  • Alcoholism;
  • Debilitated patients (dose ↓ suggested);
  • Undiagnosed abdominal pain or prostatic hyperplasia;
  • Patients with renal impairment, or extensive burns;
  • High-dose or prolonged therapy (>600 mg/day or >2 days; ↑ risk of CNS stimulation and seizures due to accumulation of normeperidine);
  • Sickle cell anemia (may require ↓ initial doses);
  • OB:   Avoid chronic use during pregnancy as can result in neonatal opioid withdrawal syndrome;
  • Pedi:  Syrup contains benzyl alcohol, which can cause "gasping syndrome" in neonates. Children have ↑ risk of seizures due to accumulation of normeperidine;
  • Geri:  Appears on Beers list; morphine recommended.

Adverse Reactions/Side Effects

CV: hypotension, bradycardia

Derm: flushing, sweating

EENT: blurred vision, diplopia, miosis

Endo: adrenal insufficiency

GI: constipation, nausea, vomiting

GU: urinary retention

Neuro: SEIZURES, confusion, sedation, dysphoria, euphoria, floating feeling, hallucinations, headache, unusual dreams

Resp: RESPIRATORY DEPRESSION (including central sleep apnea or sleep-related hypoxemia)

Misc: HYPERSENSITIVITY REACTIONS (including anaphylaxis), physical dependence, psychological dependence, tolerance

* CAPITALS indicate life-threatening.
Underline indicate most frequent.

Interactions

Drug-Drug

  • Do not use in patients receiving  MAO inhibitors  or  procarbazine  (may cause fatal reaction–contraindicated within 14 days of MAO inhibitor therapy).
  • Use with  benzodiazepines  or other  CNS depressants  including other  opioids,  non-benzodiazepine sedative/hypnotics,  anxiolytics,  general anesthetics,  muscle relaxants,  antipsychotics, and  alcohol  may cause profound sedation, respiratory depression, coma, and death; reserve concurrent use for when alternative treatment options are inadequate.
  • Administration of  mixed agonist/antagonist analgesics, including  nalbuphine  or  butorphanol  or  partial agonist analgesics, including  buprenorphine , may ↓ meperidine's analgesic effects and/or precipitate opioid withdrawal in physically dependent patients.
  • Concurrent use of  CYP3A4 inhibitors  including  ritonavir,  ketoconazole,  itraconazole,  fluconazole,  clarithromycin,  erythromycin,  nefazodone,  diltiazem,  verapamil,  nelfinavir, and  fosamprenavir  ↑ levels and risk of opioid toxicity; careful monitoring during initiation, dose changes, or discontinuation of the inhibitor is recommended.
  • Concurrent use with  CYP3A4 inducers  including  barbiturates,  carbamazepine,  efavirenz,  corticosteroids,  modafinil,  nevirapine,  oxcarbazepine,  phenobarbital,  phenytoin,  rifabutin, or  rifampin  may ↓ levels and analgesia; if inducers are discontinued or dosage ↓, patients should be monitored for signs of opioid toxicity and necessary dose adjustments should be made.
  •  Nalbuphine  may ↓ analgesia.
  •  Protease inhibitors  may ↑ effects and adverse reactions (concurrent use should be avoided).
  •  Phenytoin  ↑ metabolism and may ↓ effects.
  •  Chlorpromazine  and  thioridazine  may ↑ the risk of adverse reactions (concurrent use should be avoided).
  • May aggravate side effects of  isoniazid.
  •  Acyclovir  may ↑ plasma concentrations of meperidine and normeperidine.
  • Drugs that affect serotonergic neurotransmitter systems, including  tricyclic antidepressants,  SSRIs,  SNRIs,  MAO inhibitors,  TCAs,  tramadol,  trazodone,  mirtazapine,  5–HT3  receptor antagonists,  linezolid,  methylene blue, and  triptans  ↑ risk of serotonin syndrome.

Drug-Natural Products:

  • Concomitant use of  kava-kava,  valerian, or  chamomile  can ↓ CNS depression.
  •  St. John's wort  may ↑ serious side effects, concurrent use is not recommended.

Route/Dosage

PO (Adults): Analgesia– 50–150 mg every 3–4 hr; may ↑ as needed (not to exceed 600 mg/24 hr).

IM Subcut (Adults): Analgesia– 50–150 mg every 3–4 hr; may ↑ as needed (not to exceed 600 mg/24 hr).  Analgesia during labor– 50–100 mg when contractions become regular; may repeat every 1–3 hr.  Preoperative sedation– 50–100 mg 30–90 min before anesthesia.

PO (Children): Analgesia– 1.1–1.8 mg/kg every 3–4 hr (max = 100 mg/dose).

IM Subcut (Children): Analgesia– 1.1–1.8 mg/kg every 3–4 hr (max = 100 mg/dose).  Preoperative sedation– 1.1–2.2 mg/kg 30–90 min before anesthesia (not to exceed adult dose).

IV (Adults): 15–35 mg/hr as a continuous infusion;  PCA– 10 mg initially; with a range of 1–5 mg/incremental dose, recommended lockout interval is 6–10 min (minimum 5 min).

IV (Children): Continuous infusion– 0.5–1 mg/kg loading dose followed by 0.3 mg/kg/hr, titrate to effect up to 0.5–0.7 mg/kg/hr.

Availability (generic available)

Tablets: 50 mg, 100 mg

Oral solution (banana flavor): 50 mg/5 mL

Solution for injection : 25 mg/mL, 50 mg/mL, 75 mg/mL, 100 mg/mL

Assessment

  • Assess type, location, and intensity of pain prior to and 1 hr following PO, subcut, and IM doses and 5 min (peak) following IV administration. When titrating opioid doses, increases of 25–50% should be administered until there is either a 50% reduction in the patient's pain rating on a numerical or visual analogue scale or the patient reports satisfactory pain relief. A repeat dose can be safely administered at the time of the peak if previous dose is ineffective and side effects are minimal.
  • An equianalgesic chart (see equianalgesic dosing guidelines) should be used when changing routes or when changing from one opioid to another.
  • Assess BP, pulse, and respirations before and periodically during administration. If respiratory rate is <10/min, assess level of sedation. Dose may need to be decreased by 25–50%. Initial drowsiness will diminish with continued use. Monitor for respiratory depression, especially during initiation or following dose increase; serious, life-threatening, or fatal respiratory depression may occur. May cause sleep-related breathing disorders (central sleep apnea [CSA], sleep-related hypoxemia).
  • Assess bowel function routinely. Prevention of constipation should be instituted with increased intake of fluids and bulk and with laxatives to minimize constipating effects. Stimulant laxatives should be administered routinely if opioid use exceeds 2–3 days, unless contraindicated. Consider drugs for opioid induced constipation.
  • Prolonged use may lead to physical and psychological dependence and tolerance. This should not prevent patient from receiving adequate analgesia. Patients who receive meperidine for pain rarely develop psychological dependence. Progressively higher doses may be required to relieve pain with long-term therapy.
  • Monitor patients on chronic or high-dose therapy for CNS stimulation (restlessness, irritability, seizures) due to accumulation of normeperidine metabolite. Risk of toxicity increases with doses >600 mg/24 hr, chronic administration (>2 days), and renal impairment.
  • Assess risk for opioid addiction, abuse, or misuse prior to administration.
  • Geri:  Meperidine has been reported to cause delirium in the elderly; older adults are at increased risk for normeperidine toxicity. Monitor frequently.
  • Pedi:  Assess pediatric patient frequently; neonates, infants, and children are more sensitive to the effects of opioid analgesics and may experience respiratory complications, excitability, and restlessness more frequently.

Lab Test Considerations:

May ↑ plasma amylase and lipase concentrations.

Toxicity and Overdose:

If an opioid antagonist is required to reverse respiratory depression or coma, naloxone (Narcan) is the antidote. Dilute the 0.4-mg ampule of naloxone in 10 mL of 0.9% NaCl and administer 0.5 mL (0.02 mg) by IV push every 2 min. For children and patients weighing <40 kg, dilute 0.1 mg of naloxone in 10 mL of 0.9% NaCl for a concentration of 10 mcg/mL and administer 0.5 mcg/kg every 2 min. Titrate dose to avoid withdrawal, seizures, and severe pain. In patients receiving meperidine chronically, naloxone may precipitate seizures by eliminating the CNS depressant effects of meperidine, allowing the convulsant activity of normeperidine to predominate. Monitor patient closely.

Implementation

  • High Alert: Accidental overdose of opioid analgesics has resulted in fatalities. Before administering, clarify all ambiguous orders; have second practitioner independently check original order, dose calculations, and infusion pump settings. Pedi:  Medication errors with opioid analgesics are common in the pediatric population and include misinterpretation or miscalculation of doses and use of inappropriate measuring devices.
  • Explain therapeutic value of medication prior to administration to enhance the analgesic effect.

    • Regularly administered doses may be more effective than prn administration. Analgesic is more effective if given before pain becomes severe.
    • Coadministration with nonopioid analgesics may have additive analgesic effects and permit lower doses.
    • Oral dose is <50% as effective as parenteral. When changing to oral administration, dose may need to be increased (see equianalgesic dosing guidelines).
    • Medication should be discontinued gradually after long-term use to prevent withdrawal symptoms. For patients who are physically opioid dependent, initiate the taper by a small enough increment (no greater than 10% to 25% of total daily dose) to avoid withdrawal symptoms, and proceed with dose-lowering at an interval of every 2 to 4 wk. Patients who have been taking opioids for briefer periods of time may tolerate a more rapid taper. Monitor frequently to manage pain and withdrawal symptoms (restlessness, lacrimation, rhinorrhea, yawning, perspiration, chills, myalgia, mydriasis, irritability, anxiety, backache, joint pain, weakness, abdominal cramps, insomnia, nausea, anorexia, vomiting, diarrhea, or increased blood pressure, respiratory rate, or heart rate). If withdrawal symptoms occur, pause the taper for a period of time or raise dose of opioid analgesic to previous dose, and then proceed with a slower taper. Also, monitor patients for changes in mood, emergence of suicidal thoughts, or use of other substances. A multimodal approach to pain management may optimize the treatment of chronic pain, as well as assist with the successful tapering of the opioid analgesic.
    • May be administered via PCA pump.
  • PO Doses may be administered with food or milk to minimize GI irritation. Syrup should be diluted in half-full glass of water.
  • IM Administration of repeated subcut doses may cause local irritation.
  •  REMS: FDA strongly encourages health care professionals to complete a REMS-compliant education program that includes all the elements of the FDA Education  Blueprint for Health Care Providers Involved in the Management or Support of Patients with Pain,  available at www.fda.gov/OpioidAnalgesicREMSBlueprint. Information on programs can be found at 1-800-503-0784 or www.opioidanalgesicrems.com.
  • Discuss availability of naloxone for emergency treatment of opioid overdose with the patient and caregiver and assess the potential need for access to naloxone, both when initiating and renewing therapy, especially if patient has household members (including children) or other close contacts at risk for accidental exposure or overdose. Consider prescribing naloxone, based on the patient's risk factors for overdose, such as concomitant use of CNS depressants, a history of opioid use disorder, or prior opioid overdose. However, the presence of risk factors for overdose should not prevent the proper management of pain in any patient.

IV Administration

  • IV Push:  Administer undiluted.
  • Rate: High Alert: Administer slowly over at least 5 min. Rapid administration may lead to increased respiratory depression, hypotension, and circulatory collapse.
  • Intermittent Infusion:   Dilution:  Dilute with D5W, D10W, dextrose/saline combinations, dextrose/Ringer's or lactated Ringer's injection combinations, 0.45% NaCl, 0.9% NaCl, or Ringer's or LR. Administer via infusion pump. Concentration:  1 mg/mL.
  • Rate: Administer over 15–30 min
  • Y-Site Compatibility:
    • acetaminophen
    • alemtuzumab
    • alfentanil
    • MORE...
      • amifostine
      • amikacin
      • aminocaproic acid
      • aminophylline
      • amiodarone
      • amphotericin B lipid complex
      • anidulafungin
      • argatroban
      • arsenic trioxide
      • ascorbic acid
      • atracurium
      • atropine
      • azithromycin
      • aztreonam
      • benztropine
      • bivalirudin
      • bleomycin
      • bumetanide
      • buprenorphine
      • busulfan
      • calcium chloride
      • calcium gluconate
      • cangrelor
      • carboplatin
      • carmustine
      • caspofungin
      • cefazolin
      • cefotaxime
      • cefoxitin
      • ceftaroline
      • ceftazidime
      • ceftolozane/tazobactam
      • ceftriaxone
      • cefuroxime
      • chlorpromazine
      • ciprofloxacin
      • cisatracurium
      • cisplatin
      • cladribine
      • clindamycin
      • cyanocobalamin
      • cyclophosphamide
      • cyclosporine
      • cytarabine
      • dacarbazine
      • dactinomycin
      • daptomycin
      • daunorubicin hydrochloride
      • daunorubicin liposome
      • dexmedetomidine
      • dexrazoxane
      • digoxin
      • diltiazem
      • diphenhydramine
      • dobutamine
      • docetaxel
      • dopamine
      • doxorubicin hydrochloride
      • doxycycline
      • droperidol
      • enalaprilat
      • ephedrine
      • epinephrine
      • epirubicin
      • epoetin alfa
      • eptifibatide
      • ertapenem
      • erythromycin
      • esmolol
      • etoposide
      • etoposide phosphate
      • famotidine
      • fenoldopam
      • fentanyl
      • filgrastim
      • floxuridine
      • fluconazole
      • fludarabine
      • fluorouracil
      • folic acid
      • foscarnet
      • fosphenytoin
      • gemcitabine
      • gentamicin
      • glycopyrrolate
      • granisetron
      • hetastarch
      • hydrocortisone
      • ifosfamide
      • insulin, regular
      • irinotecan
      • isavuconazonium
      • isoproterenol
      • ketamine
      • ketorolac
      • labetalol
      • lactated Ringer's
      • leucovorin calcium
      • levofloxacin
      • lidocaine
      • linezolid
      • mannitol
      • melphalan
      • meropenem/vaborbactam
      • mesna
      • methotrexate
      • metoclopramide
      • metoprolol
      • metronidazole
      • midazolam
      • milrinone
      • mitomycin
      • mitoxantrone
      • morphine
      • multivitamins
      • mycophenolate
      • naloxone
      • nicardipine
      • nitroglycerin
      • nitroprusside
      • norepinephrine
      • octreotide
      • ondansetron
      • oxacillin
      • oxaliplatin
      • oxytocin
      • paclitaxel
      • palonosetron
      • pamidronate
      • pancuronium
      • papaverine
      • pemetrexed
      • penicillin G
      • pentamidine
      • phentolamine
      • phenylephrine
      • phytonadione
      • piperacillin/tazobactam
      • plazomicin
      • potassium acetate
      • potassium chloride
      • procainamide
      • prochlorperazine
      • promethazine
      • propofol
      • propranolol
      • protamine
      • pyridoxine
      • quinupristin/dalfopristin
      • remifentanil
      • rituximab
      • rocuronium
      • sargramostim
      • sodium acetate
      • streptozocin
      • succinylcholine
      • sufentanil
      • tacrolimus
      • tedizolid
      • theophylline
      • thiamine
      • thiotepa
      • tigecycline
      • tirofiban
      • tobramycin
      • topotecan
      • trastuzumab
      • vancomycin
      • vasopressin
      • vecuronium
      • verapamil
      • vinblastine
      • vincristine
      • vinorelbine
      • voriconazole
      • zidovudine
      • zoledronic acid
  • Y-Site Incompatibility:
    • allopurinol
    • amphotericin B deoxycholate
    • amphotericin B liposome
    • MORE...
      • azathioprine
      • cefepime
      • dantrolene
      • diazepam
      • diazoxide
      • ganciclovir
      • gemtuzumab ozogamicin
      • idarubicin
      • indomethacin
      • lorazepam
      • micafungin
      • nafcillin
      • pantoprazole
      • pentobarbital
      • phenobarbital
      • phenytoin
      • sodium bicarbonate
      • thiopental

Patient/Family Teaching

  • Instruct patient on how and when to ask for and take pain medication.
  •  REMS: Instruct patient to take meperidine as directed. If dose is less effective after a few wk, do not increase dose without consulting health care professional. Discuss safe use, risks, and proper storage and disposal of opioid analgesics with patients and caregivers with each Rx. The Patient Counseling Guide (PCG) is available at www.fda.gov/OpioidAnalgesicREMSPCG. Pedi:  Teach parents or caregivers how to accurately measure liquid medication and to use only the measuring device dispensed with the medication.
  • May cause drowsiness or dizziness. Advise patient to call for assistance when ambulating or smoking. Caution patient to avoid driving or other activities requiring alertness until response to medication is known.
  • Advise patient that meperidine is a drug with known abuse potential. Protect it from theft, and never give to anyone other than the individual for whom it was prescribed. Store out of sight and reach of children, and in a location not accessible by others.
  • Educate patients and caregivers on how to recognize respiratory depression and emphasize the importance of calling 911 or getting emergency medical help right away in the event of a known or suspected overdose. Inform patients and caregivers about various ways to obtain naloxone as permitted by individual state naloxone dispensing and prescribing requirements or guidelines (by prescription, directly from a pharmacist, or as part of a community-based program).
  • Advise patient to change positions slowly to minimize orthostatic hypotension.
  • Instruct patient to avoid concurrent use of alcohol or other CNS depressants.
  • Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and consult health care professional before taking any new medications.
  • Advise ambulatory patients that nausea and vomiting may be decreased by lying down.
  • Encourage patient to turn, cough, and breathe deeply every 2 hr to prevent atelectasis.
  • Rep:  Advise patient to notify health care professional if pregnancy is planned or suspected, or if breast feeding. Inform patient of potential for neonatal opioid withdrawal syndrome with prolonged use during pregnancy. Monitor neonate for signs and symptoms of withdrawal symptoms (irritability, hyperactivity and abnormal sleep pattern, high pitched cry, tremor, vomiting, diarrhea, and/or failure to gain weight); usually occur the first days after birth. Monitor infants exposed to meperidine through breast milk for excess sedation and respiratory depression. Chronic use may reduce fertility in females and males.

Evaluation/Desired Outcomes

  • Decrease in severity of pain without a significant alteration in level of consciousness or respiratory status.
  • Resolution of rigors.

meperidineis the Emergency Central Word of the day!