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Pronunciation
(me PER i deen)
Generic Available (U.S.)
Yes
Index Terms
Controlled Substance
C-II
U.S. Brand Names
Canadian Brand Names
Pharmacologic Category
Pharmacologic Category Synonyms
Use: Labeled Indications
Management of moderate-to-severe pain; adjunct to anesthesia and preoperative sedation
Use: Dental
Adjunct in preoperative intravenous conscious sedation in patients undergoing dental surgery; alternate oral narcotic in patients allergic to codeine to treat moderate to moderate-severe pain
Use: Unlabeled/Investigational
Reduce postoperative shivering; reduce rigors from amphotericin B (conventional)
Pregnancy Risk Factor
C
Pregnancy Considerations
Animal reproduction studies have not been conducted. Meperidine is known to cross the placenta, which may result in respiratory or CNS depression in the newborn.
Lactation
Enters breast milk/not recommended (AAP rates “compatible”; AAP 2001 update pending)
Breast-Feeding Considerations
Meperidine is excreted in breast milk and may cause CNS and/or respiratory depression in the nursing infant.
Contraindications
Hypersensitivity to meperidine or any component of the formulation; use with or within 14 days of MAO inhibitors; pregnancy (prolonged use or high doses near term)
Warnings/Precautions
Concerns related to adverse effects:
• CNS depression: May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving).
• CNS events: Normeperidine (an active metabolite and CNS stimulant) may accumulate and precipitate anxiety, tremors, or seizures; risk increases with preexisting CNS or renal dysfunction, prolonged use (>48 hours), and cumulative dose (>600 mg/24 hours). Oral meperidine should not be used since first-pass metabolism decreases efficacy while increasing normeperidine concentrations. Note: Naloxone does not reverse, and may even worsen, neurotoxicity.
• Hypotension: May cause hypotension; use with caution in patients with hypovolemia, cardiovascular disease (including acute MI), or drugs which may exaggerate hypotensive effects (including phenothiazines or general anesthetics).
Disease-related concerns:
• Abdominal conditions: May obscure diagnosis or clinical course of patients with acute abdominal conditions.
• Adrenal insufficiency: Use with caution in patients with adrenal insufficiency, including Addison's disease.
• Biliary tract impairment: Use with caution in patients with biliary tract dysfunction; acute pancreatitis may cause constriction of sphincter of Oddi.
• CNS depression/coma: Use with caution in patients with CNS depression or coma.
• Drug abuse: Use with caution in patients with a history of drug abuse or acute alcoholism; potential for drug dependency exists. Tolerance, psychological and physical dependence may occur with prolonged use.
• Head trauma: Use with extreme caution in patients with head injury, intracranial lesions, or elevated intracranial pressure; exaggerated elevation of ICP may occur.
• Hepatic impairment: Use with caution in patients with hepatic disorders.
• Obesity: Use with caution in patients who are morbidly obese.
• Prostatic hyperplasia/urinary stricture: Use with caution in patients with prostatic hyperplasia and/or urinary stricture.
• Psychoses: Use with caution in patients with toxic psychoses.
• Renal impairment: Avoid use in patients with renal impairment.
• Respiratory disease: Use with caution in patients with pre-existing respiratory compromise (hypoxia and/or hypercapnia), COPD or other obstructive pulmonary disease, and kyphoscoliosis or other skeletal disorder which may alter respiratory function; critical respiratory depression may occur, even at therapeutic dosages.
• Sickle-cell disease: Use is not recommended; increased risk of normeperidine-induced seizures.
• Tachycardias: Use with caution in patients with supraventricular tachycardias.
• Thyroid dysfunction: Use with caution in patients with thyroid dysfunction.
Concurrent drug therapy issues:
• Sedatives: Effects may be potentiated when used with other sedative drugs or ethanol.
Special populations:
• Debilitated patients: Use with caution in debilitated patients; there is a greater potential for critical respiratory depression, even at therapeutic dosages.
• Elderly: Avoid use in the elderly; meperidine is not an effective oral analgesic at commonly used doses. May cause confusion; other opioids are preferred in the elderly (Beers Criteria).
Dosage form specific issues:
• Sulfites: Some preparations contain sulfites which may cause allergic reaction.
Other warnings/precautions:
• Abuse/misuse/diversion: Healthcare provider should be alert to problems of abuse, misuse, and diversion.
• 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 (American Pain Society [APS], 2008; ISMP, 2007).
• Chronic pain management: Use is not recommended for the management of chronic pain.
• Withdrawal: Concurrent use of agonist/antagonist analgesics may precipitate withdrawal symptoms and/or reduced analgesic efficacy in patients following prolonged therapy with mu opioid agonists. Abrupt discontinuation following prolonged use may also lead to withdrawal symptoms.
Adverse Reactions
Frequency not defined.
Cardiovascular: Hypotension
Central nervous system: Fatigue, drowsiness, dizziness, nervousness, headache, restlessness, malaise, confusion, mental depression, hallucinations, paradoxical CNS stimulation, increased intracranial pressure, seizure (associated with metabolite accumulation), serotonin syndrome
Dermatologic: Rash, urticaria
Gastrointestinal: Nausea, vomiting, constipation, anorexia, stomach cramps, xerostomia, biliary spasm, paralytic ileus, sphincter of Oddi spasm
Genitourinary: Ureteral spasms, decreased urination
Local: Pain at injection site
Neuromuscular & skeletal: Weakness
Respiratory: Dyspnea
Miscellaneous: Anaphylaxis, histamine release, hypersensitivity reactions, physical and psychological dependence
Metabolism/Transport Effects
Substrate (minor) of CYP2B6, 2C19, 3A4
Drug Interactions
Alcohol (Ethyl): CNS Depressants may enhance the CNS depressant effect of Alcohol (Ethyl). Risk C: Monitor therapy
Alvimopan: Analgesics (Opioid) 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
Ammonium Chloride: May increase the excretion of Analgesics (Opioid). Risk C: Monitor therapy
Amphetamines: May enhance the analgesic effect of Analgesics (Opioid). Risk C: Monitor therapy
Antipsychotic Agents (Phenothiazines): May enhance the hypotensive effect of Analgesics (Opioid). Risk C: Monitor therapy
Barbiturates: May enhance the CNS depressant effect of Meperidine. Barbiturates may increase serum concentrations of the active metabolite(s) of Meperidine. Risk C: Monitor therapy
CNS Depressants: May enhance the adverse/toxic effect of other CNS Depressants. Exceptions: Levocabastine (Nasal). Risk C: Monitor therapy
Desmopressin: Analgesics (Opioid) may enhance the adverse/toxic effect of Desmopressin. 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 (e.g., opioids, barbiturates) with concomitant use. Risk D: Consider therapy modification
Fosphenytoin: May decrease the serum concentration of Meperidine. Risk C: Monitor therapy
HydrOXYzine: May enhance the CNS depressant effect of Meperidine. Management: Consider a decrease in meperidine dose, as appropriate, when used together with hydroxyzine. With concurrent use, monitor patients closely for excessive response to the combination. Risk D: Consider therapy modification
MAO Inhibitors: May enhance the serotonergic effect of Meperidine. This may cause serotonin syndrome. Risk X: Avoid combination
Mixed Agonist / Antagonist Opioids: May diminish the analgesic effect of Analgesics (Opioid). 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 D: Consider therapy modification
Pegvisomant: Analgesics (Opioid) may diminish the therapeutic effect of Pegvisomant. Risk C: Monitor therapy
Phenytoin: May decrease the serum concentration of Meperidine. Risk C: Monitor therapy
Protease Inhibitors: May enhance the adverse/toxic effect of Meperidine. Protease Inhibitors may decrease the serum concentration of Meperidine. Concentrations of the toxic Normeperidine metabolite may be increased. Risk D: Consider therapy modification
Selective Serotonin Reuptake Inhibitors: Analgesics (Opioid) may enhance the serotonergic effect of Selective Serotonin Reuptake Inhibitors. This may cause serotonin syndrome. Risk C: Monitor therapy
Serotonin Modulators: May enhance the adverse/toxic effect of other Serotonin Modulators. The development of serotonin syndrome may occur. Risk D: Consider therapy modification
Sibutramine: May enhance the serotonergic effect of Serotonin Modulators. This may cause serotonin syndrome. Risk X: Avoid combination
Succinylcholine: May enhance the bradycardic effect of Analgesics (Opioid). Risk C: Monitor therapy
Thiazide Diuretics: Analgesics (Opioid) may enhance the orthostatic hypotensive effect of Thiazide Diuretics. Risk C: Monitor therapy
Ethanol/Nutrition/Herb Interactions
Ethanol: May increase CNS depression; monitor for increased effects with coadministration. Caution patients about effects.
Herb/Nutraceutical: Avoid valerian, St John's wort, kava kava, gotu kola (may increase CNS depression).
Storage
Meperidine injection should be stored at room temperature; do not freeze. Protect from light. Protect oral dosage forms from light.
Compatibility
Stable in dextran 6% in dextrose, dextran 6% in NS, D5LR, D51/4NS, D51/2NS, D5NS, D5W, D10W, LR, 1/2NS, NS.
Y-site administration: Compatible: Amifostine, amikacin, ampicillin, ampicillin/sulbactam, atenolol, aztreonam, bumetanide, cefamandole, cefazolin, cefotaxime, cefotetan, cefoxitin, ceftazidime, ceftizoxime, ceftriaxone, cefuroxime, chloramphenicol, cisatracurium, cladribine, clindamycin, co-trimoxazole, dexamethasone sodium phosphate, diltiazem, diphenhydramine, dobutamine, docetaxel, dopamine, doxycycline, droperidol, erythromycin lactobionate, etoposide phosphate, famotidine, filgrastim, fluconazole, fludarabine, gatifloxacin, gemcitabine, gentamicin, granisetron, heparin, hydrocortisone sodium succinate, insulin (regular), kanamycin, labetalol, lidocaine, linezolid, magnesium sulfate, melphalan, methyldopate, methylprednisolone sodium succinate, metoclopramide, metoprolol, metronidazole, ondansetron, oxacillin, oxytocin, paclitaxel, penicillin G potassium, piperacillin, piperacillin/tazobactam, potassium chloride, propofol, propranolol, ranitidine, remifentanil, sargramostim, teniposide, thiotepa, ticarcillin, ticarcillin/clavulanate, tobramycin, vancomycin, verapamil, vinorelbine. Incompatible: Allopurinol, amphotericin B cholesteryl sulfate complex, cefepime, cefoperazone, doxorubicin liposome, idarubicin, imipenem/cilastatin, minocycline. Variable (consult detailed reference): Acyclovir, furosemide, nafcillin.
Compatibility in syringe: Compatible: Atropine, atropine with hydroxyzine, atropine with promethazine, butorphanol, chlorpromazine, cimetidine, dimenhydrinate, diphenhydramine, droperidol, fentanyl, glycopyrrolate, hydroxyzine, ketamine, metoclopramide, midazolam, ondansetron, pentazocine, pentazocine with perphenazine, perphenazine, prochlorperazine edisylate, promazine, promethazine, ranitidine, scopolamine. Incompatible: Heparin, morphine, pentobarbital.
Compatibility when admixed: Compatible: Cefazolin, dobutamine, metoclopramide, ondansetron, scopolamine, succinylcholine, triflupromazine, verapamil. Incompatible: Aminophylline, amobarbital, floxacillin, furosemide, heparin, morphine, phenobarbital, phenytoin, thiopental. Variable (consult detailed reference): Sodium bicarbonate.
Mechanism of Action
Binds to opiate receptors in the CNS, causing inhibition of ascending pain pathways, altering the perception of and response to pain; produces generalized CNS depression
Pharmacodynamics/Kinetics
Onset of action: Analgesic: Oral, SubQ: 10-15 minutes; I.V.: ~5 minutes
Peak effect: SubQ.: ~1 hour; Oral: 2 hours
Duration: Oral, SubQ.: 2-4 hours
Absorption: I.M.: Erratic and highly variable
Protein binding: 65% to 75%
Metabolism: Hepatic; hydrolyzed to meperidinic acid (inactive) or undergoes N-demethylation to normeperidine (active; has 1/2 the analgesic effect and 2-3 times the CNS effects of meperidine)
Bioavailability: ~50% to 60%; increased with liver disease
Half-life elimination:
Parent drug: Terminal phase: Adults: 2.5-4 hours, Liver disease: 7-11 hours
Normeperidine (active metabolite): 15-30 hours; can accumulate with high doses (>600 mg/day) or with decreased renal function
Excretion: Urine (as metabolites)
Dosage
Note: The American Pain Society (2008) and ISMP (2007) do not recommend meperidine's use as an analgesic.
Children: Pain: Oral, I.M., I.V., SubQ: 1-1.5 mg/kg/dose every 3-4 hours as needed; 1-2 mg/kg as a single dose preoperative medication may be used; maximum: 100 mg/dose (Note: Oral route is not recommended for acute pain.)
Adults: Pain:
Oral: Initial: Opiate-naive: 50 mg every 3-4 hours as needed; usual dosage range: 50-150 mg every 2-4 hours as needed (manufacturers recommendation; oral route is not recommended for acute pain)
I.M., SubQ: Initial: Opiate-naive: 50-75 mg every 3-4 hours as needed; patients with prior opiate exposure may require higher initial doses
Slow I.V.: Initial: 5-10 mg every 5 minutes as needed
Preoperatively: 50-100 mg given 30-90 minutes before the beginning of anesthesia
Postoperative shivering (unlabeled use): 25-50 mg once (Crowley, 2008; Kranke, 2002; Mercandante, 1994; Wang, 1999)
Note: If use in acute pain (in patients without renal or CNS disease) cannot be avoided, treatment should be limited to ≤48 hours and doses should not exceed 600 mg/24 hours.
Elderly:
Oral: 50 mg every 4 hours
I.M.: 25 mg every 4 hours
Dosing adjustment in renal impairment: Avoid use in renal impairment
Dosing adjustment/comments in hepatic disease: Increased narcotic effect in cirrhosis; reduction in dose more important for oral than I.V. route
Dental Usual Dosing
Pain (analgesic): Adults: Oral: Initial: Opiate-naive: 50 mg every 3-4 hours as needed; usual dosage range: 50-150 mg every 2-4 hours as needed (manufacturers recommendation; oral route is not recommended for acute pain)
Administration: Oral
Oral solution: Administer solution in 1/2 glass of water; undiluted solution may exert topical anesthetic effect on mucous membranes
Administration: I.V.
Meperidine may be administered I.M., SubQ, or I.V. IVP should be given slowly, use of a 10 mg/mL concentration has been recommended. For continuous I.V. infusions, a more dilute solution (eg, 1 mg/mL) should be used.
Administration: I.V. Detail
pH: 3.5-6.0 (adjusted)
Monitoring Parameters
Pain relief, respiratory and mental status, blood pressure; observe patient for excessive sedation, CNS depression, seizures, respiratory depression
Reference Range
Therapeutic: 70-500 ng/mL (SI: 283-2020 nmol/L); Toxic: >1000 ng/mL (SI: >4043 nmol/L)
Test Interactions
Increased amylase (S), increased BSP retention, increased CPK (I.M. injections)
Patient Education
Drug may cause physical and/or psychological dependence. While using this medication, do not use alcohol and other prescription or OTC medications (especially sedatives, tranquilizers, antihistamines, or pain medications) without consulting prescriber. Maintain adequate hydration, unless instructed to restrict fluid intake. May cause hypotension, dizziness, drowsiness, impaired coordination, or blurred vision; loss of appetite, nausea, or vomiting; or constipation. Report chest pain, slow or rapid heartbeat, dizziness, or persistent headache; changes in mental status; seizures; changes in renal function; skin rash; or shortness of breath.
Geriatric Considerations
Meperidine is not recommended as a drug of first choice for the treatment of chronic pain in the elderly due to the accumulation of its metabolite, normeperidine, which leads to serious CNS side effects (eg, tremor, seizures). If used for acute pain, its use should be limited to 1-2 doses.
This medication is considered to be potentially inappropriate in this patient population (Beers Criteria severity: High).
Anesthesia and Critical Care Concerns/Other Considerations
Clinical Pearls/Comments: Accumulation of normeperidine can cause anxiety, tremors, or seizures. Meperidine inhibits serotonin reuptake; potential for serotonin syndrome when administered with other serotonergic agents (eg, SSRI, MAO inhibitor). Combination of meperidine and an MAO inhibitor is an absolute contraindication. Euphoria is more common with meperidine than with other opioids.
Evidence-Based Information: The 2002 ACCM/SCCM guidelines for analgesia (critically-ill adult) recommend against using meperidine repetitively.
Dental Health: Effects on Dental Treatment
Key adverse event(s) related to dental treatment: Xerostomia (normal salivary flow resumes upon discontinuation). See Dental Health Professional Considerations.
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Dental Comment
Meperidine is not to be used as the narcotic drug of first choice. It is recommended only to be used in codeine-allergic patients when a narcotic analgesic is indicated. Meperidine is not an anti-inflammatory agent. Meperidine, as with other narcotic analgesics, is recommended only for limited acute dosing (ie, 3 days or less); common adverse effects in the dental patient are nausea, sedation, and constipation. Meperidine has a significant addiction liability, especially when given long-term.
Mental Health: Effects on Mental Status
Sedation is common; may cause nervousness or confusion; may rarely produce depression, hallucinations, or paradoxical CNS stimulation
Mental Health: Effects on Psychiatric Treatment
Sedation is common; may cause nervousness or confusion; may rarely produce depression, hallucinations, or paradoxical CNS stimulation
Nursing: Physical Assessment/Monitoring
Monitor frequently for need; assess patient's physical and/or psychological dependence. For inpatients, implement safety measures to prevent falls. Discontinue slowly after prolonged use.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, solution, as hydrochloride: 25 mg/mL (1 mL); 50 mg/mL (1 mL); 100 mg/mL (1 mL)
Demerol®: 25 mg/mL (1 mL); 25 mg/0.5 mL (0.5 mL); 50 mg/mL (1 mL, 1.5 mL, 2 mL, 30 mL); 75 mg/mL (1 mL); 100 mg/mL (1 mL, 20 mL)
Injection, solution, as hydrochloride [for PCA pump]: 10 mg/mL (30 mL)
Solution, oral, as hydrochloride: 50 mg/5 mL (500 mL)
Tablet, oral, as hydrochloride: 50 mg, 100 mg
Demerol®: 50 mg [scored]
Demerol®: 100 mg
Pricing: U.S. (www.drugstore.com)
Solution (Meperidine HCl)
50 mg/5 mL (500): $69.99
100 mg/mL (1): $33.99
Tablets (Demerol)
50 mg (30): $50.99
100 mg (20): $70.62
Tablets (Meperidine HCl)
50 mg (20): $18.66
50 mg (20): $19.99
100 mg (20): $26.66
References
American Academy of Pediatrics Committee on Drugs, “Reappraisal of Lytic Cocktail/Demerol®, Phenergan®, and Thorazine® (DPT) for the Sedation of Children,” Pediatrics, 1995, 95(4):598-602.
American Academy of Pediatrics Committee on Drugs, "Transfer of Drugs and Other Chemicals Into Human Milk," Pediatrics, 2001, 108(3):776-89.
Armstrong PJ and Bersten A, “Normeperidine Toxicity,” Anesth Analg, 1986, 65(5):536-8.
Buchanan JF and Brown CR, “Designer Drugs: A Problem in Clinical Toxicology,” Med Toxicol Adverse Drug Exp, 1988, 3(1):1-17.
Clark RF, Wei EM, and Anderson PO, “Meperidine: Therapeutic Use and Toxicity,” J Emerg Med, 1995,13(6):797-802.
Cole TB, Sprinkle RH, Smith SJ, et al, “Intravenous Narcotic Therapy for Children With Severe Sickle Cell Pain Crisis,” Am J Dis Child, 1986, 140(12):1255-9.
Crowley LJ and Buggy DJ, “Shivering and Neuraxial Anesthesia,” Reg Anesth Pain Med, 2008, 33(3):241-52.
Ferrell BA, “Pain Management in Elderly People,” J Am Geriatr Soc, 1991, 39(1):64-73.
Golembiewski J, “Safety Concerns With Meperidine,” J Perianesth Nurs, 2002, 17(2):123-5.
Institute for Safe Medication Practice, “High Alert Medication Feature: Reducing Patient Harm From Opiates,” ISMP Medication Safety Alert, February 22, 2007. Available at http://www.ismp.org/Newsletters/acutecare/articles/20070222.asp
Jacobi J, Fraser GL, Coursin DB, et al, “Clinical Practice Guidelines for the Sustained Use of Sedatives and Analgesics in the Critically Ill Adult,” Crit Care Med, 2002, 30(1):119-41. Available at http://www.sccm.org/pdf/sedatives.pdf
Kranke P, Eberhart LH, Roewer N, et al, “Pharmacologic Treatment of Postoperative Shivering: A Quantitative Systematic Review of Randomized Controlled Trials,” Anesth Analg, 2002, 94(2):543-60.
Kyff JV and Rice TL, “Meperidine-Associated Seizures in a Child,” Clin Pharm, 1990, 9(5):337-8.
Latta KS, Ginsberg B, and Barkin RL, “Meperidine: A Critical Review,” Am J Ther, 2002, 9(1):53-68.
Mercadante S, De Michele P, Letterio G, et al, “Effect of Clonidine on Postpartum Shivering After Epidural Analgesia: A Randomized, Controlled, Double-Blind Study,” J Pain Symptom Manage, 1994, 9(5):294-7.
Miller RR and Jick H, “Clinical Effects of Meperidine in Hospitalized Medical Patients,” J Clin Pharmacol, 1978, 18(4):180-9.
Olkkola KT, Hamunen K, and Maunuksela EL, “Clinical Pharmacokinetics and Pharmacodynamics of Opioid Analgesics in Infants and Children,” Clin Pharmacokinet, 1995, 28(5):385-404.
Pokela ML, Olkkola KT, Koivisto ME, et al, “Pharmacokinetics and Pharmacodynamics of Intravenous Meperidine in Neonates and Infants,” Clin Pharmacol Ther, 1992, 52(4):342-9.
“Principles of Analgesic Use in the Treatment of Acute Pain and Cancer Pain,” 6th ed, Glenview, IL: American Pain Society, 2008.
Stone PA, Macintyre PE, and Jarvis DA, “Norpethidine Toxicity and Patient Controlled Analgesia,” Br J Anaesth, 1993, 71(5):738-40.
Wang JJ, Ho ST, Lee SC, et al, “A Comparison Among Nalbuphine, Meperidine, and Placebo for Treating Postanesthetic Shivering,” Anesth Analg, 1999, 88(3):686-9.
International Brand Names
Lexi-Comp.com
Last full review/revision May 2011
Content last modified May 2011
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