What are the contraindications for meperidine (Demerol)?

Meperidine Contraindications

Meperidine is absolutely contraindicated in patients with hypersensitivity to the drug and in those receiving monoamine oxidase inhibitors (MAOIs) or who have received MAOIs within 14 days, as this combination can precipitate life-threatening reactions including severe respiratory depression, coma, hyperpyrexia, seizures, and death. 1

Absolute Contraindications

Hypersensitivity

• Meperidine must not be administered to patients with known hypersensitivity to meperidine 1

Monoamine Oxidase Inhibitor (MAOI) Use

• Meperidine is absolutely contraindicated in patients currently taking MAOIs or who have received MAOIs within the past 14 days 1
• This interaction can produce unpredictable, severe, and occasionally fatal reactions 2
• Life-threatening complications manifest in two distinct patterns 2:
  • Depressive reactions: coma, severe respiratory depression, cyanosis, and hypotension resembling acute narcotic overdose
  • Excitatory reactions: hyperexcitability, convulsions, tachycardia, hyperpyrexia, hypertension, agitation, headache, hemodynamic instability, rigidity, seizures, and death
• Unlike other opioids (morphine, codeine, oxycodone, buprenorphine), meperidine acts as a weak serotonin reuptake inhibitor and can precipitate serotonin toxicity when combined with MAOIs 3
• Phentolamine is specifically used in hypertensive emergencies induced by interactions between MAOIs and other drugs 2

Critical Clinical Pitfall: If an opioid is urgently needed in a patient on MAOIs, consider morphine, codeine, oxycodone, or buprenorphine instead, as these are not serotonin reuptake inhibitors and do not precipitate serotonin toxicity with MAOIs 3

Relative Contraindications and Major Precautions

Renal Insufficiency

• Meperidine should be avoided in patients with renal insufficiency (GFR <30 mL/min/1.73 m²) and end-stage renal disease (ESRD) 2
• The half-life of meperidine is prolonged significantly with renal insufficiency, increasing the potential for neurotoxicity from accumulation of normeperidine, an active metabolite with potent central excitatory toxicity 2
• Neurotoxic reactions include irritability, tremor, myoclonus, and seizures caused by normeperidine accumulation 2

Concurrent CNS Depressants

• Use with extreme caution in patients receiving other central nervous system depressants including sedatives, hypnotics, general anesthetics, phenothiazines, tranquilizers, and alcohol 1
• The concomitant use of benzodiazepines or barbiturates with meperidine has a synergistic effect on respiratory depression risk 2
• Drug-drug interactions may result in respiratory depression, hypotension, profound sedation, or coma 1

Cardiovascular Conditions

• Use with caution in patients with atrial flutter and other supraventricular tachycardias due to possible vagolytic action that may significantly increase ventricular response rate 1

Seizure Disorders

• Meperidine may aggravate preexisting convulsions in patients with convulsive disorders 1
• If dosage is escalated substantially above recommended levels due to tolerance, convulsions may occur even in individuals without a history of convulsive disorders 1

Other Conditions Requiring Caution

• Addison's disease 1
• CNS depression or coma 1
• Delirium tremens 1
• Debilitated patients 1
• Kyphoscoliosis associated with respiratory depression 1
• Myxedema or hypothyroidism 1
• Prostatic hypertrophy or urethral stricture 1
• Severe impairment of hepatic or pulmonary function 1
• Toxic psychosis 1
• Acute abdominal conditions (may obscure diagnosis or clinical course) 1

Drug Interactions Beyond MAOIs

• Acyclovir: Plasma concentrations of meperidine and normeperidine may be increased, requiring caution with concomitant administration 1
• Mixed agonist/antagonist opioids (pentazocine, nalbuphine, butorphanol, buprenorphine): May reduce meperidine's analgesic effect or precipitate withdrawal symptoms 1

Special Populations

• Pregnancy and lactation: Requires careful risk-benefit assessment 1
• Elderly patients: Dose reduction may be necessary 1
• Patients with drug or alcohol dependence: Use with caution due to increased frequency of narcotic tolerance, dependence, and addiction risk 1

Important Note: Given meperidine's inferior or similar analgesic efficacy compared to other opioids, association with more sedation and respiratory depression, and the serious risks from normeperidine accumulation and MAOI interactions, many experts recommend it should not be used as a first-line analgesic and consideration should be given to removing it from formularies or restricting its use 4, 5, 6