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Pronunciation:

(me PER i deen)

U.S. Brand Names:

Demerol®; Meperitab®

Synonyms:

Isonipecaine Hydrochloride; Meperidine Hydrochloride; Pethidine Hydrochloride

Generic Available:

Yes

Canadian Brand Names:

Demerol®

Use:

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

Restrictions:

C-II

Pregnancy Risk Factor:

C/D (prolonged use or high doses at term)

Pregnancy Implications:

Meperidine is known to cross the placenta, which may result in respiratory or CNS depression in the newborn.

Lactation:

Enters breast milk/contraindicated (AAP rates "compatible")

Contraindications:

Hypersensitivity to meperidine or any component of the formulation; patients receiving MAO inhibitors presently or in the past 14 days; pregnancy (prolonged use or high doses near term)

Warnings/Precautions:

An opioid-containing analgesic regimen should be tailored to each patient's needs and based upon the type of pain being treated (acute versus chronic), 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. Use for chronic pain management not recommended. Oral meperidine not recommended for acute pain management.

Use with caution in patients with pulmonary, hepatic, renal disorders, or increased intracranial pressure; use with caution in patients with renal failure or seizure disorders or those receiving high-dose meperidine; normeperidine (an active metabolite and CNS stimulant) may accumulate and precipitate twitches, tremors, or seizures; some preparations contain sulfites which may cause allergic reaction; not recommended as a drug of first choice for the treatment of chronic pain in the elderly due to the accumulation of normeperidine; for acute pain, its use should be limited to 1-2 doses; tolerance or drug dependence may result from extended use. Use only with extreme caution (if at all) in patients with head injury or increased intracranial pressure (ICP); potential to elevate ICP may be greatly exaggerated in these patients.

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)

Dermatologic: Rash, urticaria

Gastrointestinal: Nausea, vomiting, constipation, anorexia, stomach cramps, xerostomia, biliary spasm, paralytic ileus

Genitourinary: Ureteral spasms, decreased urination

Local: Pain at injection site

Neuromuscular & skeletal: Weakness

Respiratory: Dyspnea

Miscellaneous: Histamine release, physical and psychological dependence

Overdosage/Toxicology:

Symptoms of overdose include CNS depression, respiratory depression, mydriasis, bradycardia, pulmonary edema, chronic tremor, CNS excitability, and seizures. Treatment is symptomatic. Naloxone, 2 mg I.V. with repeat administration as necessary up to a total dose of 10 mg, can be used to reverse opiate effects. Naloxone should not be used to treat meperidine-induced seizures.

Drug Interactions:

Acyclovir: May increase meperidine metabolite concentrations. Use caution.

Barbiturates: May decrease analgesic efficacy and increase sedative and/or respiratory depressive effects of meperidine.

Cimetidine: May increase meperidine metabolite concentrations; use caution.

CNS depressants (including benzodiazepines): May potentiate the sedative and/or respiratory depressive effects of meperidine.

MAO inhibitors: Greatly potentiate the effects of meperidine; acute opioid overdosage symptoms can be seen, including severe toxic reactions. Concurrent use within 14 days of an MAO inhibitor is contraindicated.

Phenothiazines: May potentiate the sedative and/or respiratory depressive effects of meperidine; may increase the incidence of hypotension.

Phenytoin: May decrease the analgesic effects of meperidine

Ritonavir: May increase meperidine metabolite concentrations; use caution.

Serotonin agonists: Serotonin agonists may enhance the adverse/toxic effect of meperidine. Serotonin syndrome may occur.

Serotonin reuptake inhibitors: May potentiate the effects of meperidine; including severe toxic reactions

Tricyclic antidepressants: May potentiate the sedative and/or respiratory depressive effects of meperidine. In addition, potentially may increase the risk of serotonin syndrome.

Ethanol/Nutrition/Herb Interactions:

Ethanol: Avoid or limit ethanol (may increase CNS depression). Watch for sedation.

Food: Glucose may cause hyperglycemia; monitor blood glucose concentrations.

Herb/Nutraceutical: Avoid valerian, St John's wort, kava kava, gotu kola (may increase CNS depression).

Stability:

Meperidine injection should be stored at room temperature and protected from light and freezing; protect oral dosage forms from light

Incompatible with aminophylline, heparin, phenobarbital, phenytoin, and sodium bicarbonate

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, I.M.: 10-15 minutes; I.V.: ~5 minutes

Peak effect: Oral, SubQ, I.M.: ~1 hour

Duration: Oral, SubQ, I.M.: 2-4 hours

Distribution: Crosses placenta; enters breast milk

Protein binding: 65% to 75%

Metabolism: Hepatic; active metabolite (normeperidine)

Bioavailability: ~50% to 60%; increased with liver disease

Half-life elimination:

Parent drug: Terminal phase: Neonates: 23 hours (range: 12-39 hours); Adults: 2.5-4 hours, Liver disease: 7-11 hours

Normeperidine (active metabolite): 15-30 hours; can accumulate with high doses or with decreased renal function

Dosage:

Note: Doses should be titrated to necessary analgesic effect. When changing route of administration, note that oral doses are about half as effective as parenteral dose. Oral route not recommended for chronic pain. These are guidelines and do not represent the maximum doses that may be required in all patients.

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

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

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; usual dosage range: 50-150 mg every 2-4 hours as needed

Preoperatively: 50-100 mg given 30-90 minutes before the beginning of anesthesia

Slow I.V.: Initial: 5-10 mg every 5 minutes as needed

Patient-controlled analgesia (PCA): Usual concentration: 10 mg/mL

Initial dose: 10 mg

Demand dose: 1-5 mg (manufacturer recommendations); range 5-25 mg (American Pain Society, 1999).

Lockout interval: 5-10 minutes

Elderly:

Oral: 50 mg every 4 hours

I.M.: 25 mg every 4 hours

Dosing adjustment in renal impairment: Avoid repeated administration of meperidine in renal dysfunction:

Clcr 10-50 mL/minute: Administer at 75% of normal dose

Clcr<10 mL/minute: Administer at 50% of normal dose

Dosing adjustment/comments in hepatic disease: Increased narcotic effect in cirrhosis; reduction in dose more important for oral than I.V. route

Administration:

Meperidine may be administered I.M. (preferably), SubQ, or I.V.; I.V. push should be administered 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.

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:

If self-administered, use exactly as directed; do not increase dose or frequency. 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 (2-3 L/day of fluids) unless instructed to restrict fluid intake. May cause hypotension, dizziness, drowsiness, impaired coordination, or blurred vision (use caution when driving, climbing stairs, or changing position - rising from sitting or lying to standing, or when engaging in tasks requiring alertness until response to drug is known); loss of appetite, nausea, or vomiting (frequent mouth care, small, frequent meals, chewing gum, or sucking lozenges may help); or constipation (increased exercise, fluids, fruit, or fiber may help; if unresolved, consult prescriber about use of stool softeners). Report chest pain, slow or rapid heartbeat, acute dizziness or persistent headache; changes in mental status; swelling of extremities or unusual weight gain; changes in urinary elimination; acute headache; back or flank pain or muscle spasms; blurred vision; skin rash; or shortness of breath. Pregnancy/breast-feeding precautions: Inform prescriber if you are or intend to become pregnant. Consult prescriber if breast-feeding.

Anesthesia and Critical Care Concerns/Other Considerations:

The 2002 ACCM/SCCM guidelines for analgesia (critically-ill adult) recommend against using meperidine repetitively. The guidelines recommend fentanyl in patients who need immediate pain relief because of its rapid onset of action; fentanyl or hydromorphone is preferred in patients who are hypotensive or have renal dysfunction. Morphine or hydromorphone is recommended for intermittent, scheduled therapy. Both have a longer duration of action requiring less frequent administration.

Dental Health: Effects on Dental Treatment:

Key adverse event(s) related to dental treatment: Xerostomia (normal salivary flow resumes upon discontinuation).

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

Oncology: Vesicant:

No

Dosage Forms:

Injection, solution, as hydrochloride [ampul]: 25 mg/0.5 mL (0.5 mL); 25 mg/mL (1 mL); 50 mg/mL (1 mL, 1.5 mL, 2 mL); 75 mg/mL (1 mL); 100 mg/mL (1 mL)

Injection, solution, as hydrochloride [prefilled syringe]: 25 mg/mL (1 mL); 50 mg/mL (1 mL); 75 mg/mL (1 mL); 100 mg/mL (1 mL)

Injection, solution, as hydrochloride [for PCA pump]: 10 mg/mL (30 mL, 50 mL, 60 mL)

Injection, solution, as hydrochloride [vial]: 25 mg/mL (1 mL); 50 mg/mL (1 mL, 30 mL); 75 mg/mL (1 mL); 100 mg/mL (1 mL, 20 mL) [may contain sodium metabisulfite]

Syrup, as hydrochloride: 50 mg/5 mL (500 mL) [contains sodium benzoate]

Demerol®: 50 mg/5 mL (480 mL) [contains benzoic acid; banana flavor]

Tablet, as hydrochloride (Demerol®, Meperitab®): 50 mg, 100 mg

International Brand Names:

Demerol® (CA)

References

"American Academy of Pediatrics Committee on Drugs. The Transfer of Drugs and Other Chemicals Into Human Milk,"Pediatrics, 2001, 108(3):776-89.

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.

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.

Carr DB, Jacox AK, Chapman RC, et al, "Acute Pain Management," Guideline Technical Report, No. 1. Rockville, MD: U.S. Department of Health and Human Services, Public Health Service, Agency for Health Care Policy and Research. AHCPR Publication No. 95-0034. February 1995.

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.

"Drugs for Pain,"Med Lett Drugs Ther, 2000, 42(1085):73-8.

Ferrell BA, "Pain Management in Elderly People,"J Am Geriatr Soc, 1991, 39(1):64-73.

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. Accessed August 2, 2003.

Kyff JV and Rice TL, "Meperidine-Associated Seizures in a Child,"Clin Pharm, 1990, 9(5):337-8.

Miller RR and Jick H, "Clinical Effects of Meperidine in Hospitalized Medical Patients,"J Clin Pharmacol, 1978, 18(4):180-9.

Mokhlesi B, Leikin JB, Murray P, et al, "Adult Toxicology in Critical Care: Part II: Specific Poisonings,"Chest, 2003, 123(3):897-922.

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 Chronic Cancer Pain," 4th ed, Glenview, IL: American Pain Society, 1999.

Stone PA, Macintyre PE, and Jarvis DA, "Norpethidine Toxicity and Patient Controlled Analgesia,"Br J Anaesth, 1993, 71(5):738-40.

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