What are the precautions and contraindications for pethidine (meperidine) 50mg?

Pethidine (Meperidine) 50mg: Precautions and Contraindications

Pethidine should be avoided as a first-line analgesic due to significant safety concerns, particularly its contraindication in renal insufficiency, risk of serotonin syndrome with multiple drug interactions, and accumulation of toxic metabolites. 1

Absolute Contraindications

Renal Impairment:

• Contraindicated in patients with GFR <30 mL/min/1.73 m² and end-stage renal disease due to accumulation of normeperidine, an active metabolite that causes seizures and CNS toxicity 1, 2
• Even in moderate renal disease, metabolites accumulate and cause significant side effects 2

Drug Interactions:

• Absolutely contraindicated with monoamine oxidase inhibitors (MAOIs) - must avoid use within 14-15 days of MAOI therapy due to risk of fatal serotonergic reactions 3, 4
• Contraindicated with other serotonergic medications due to increased risk of serotonin syndrome 1

Other Absolute Contraindications:

• Suspected opiate addiction 5
• Undiagnosed acute abdominal pain 5

Major Precautions and Relative Contraindications

Hepatic Disease:

• Use with extreme caution as pethidine undergoes extensive hepatic metabolism; altered disposition occurs in liver disease requiring dose adjustment and plasma concentration monitoring 2

Elderly Patients:

• Significant changes in drug disposition occur in the elderly, requiring careful dose reduction and monitoring 2

Cardiovascular Conditions:

• Avoid in heart failure 5
• Can cause hypotension, particularly with rapid IV administration 3

Neurological Conditions:

• Contraindicated in head injury 5
• Risk of CNS toxicity from normeperidine accumulation, including seizures 1, 4

Pregnancy and Lactation:

• Contraindicated in pregnancy and lactation according to standard opioid precautions 3
• However, meperidine and propofol have been used safely in specific pregnancy contexts when benefits outweigh risks 3

Critical Safety Concerns

Metabolite Toxicity:

• Normeperidine, the demethylated metabolite, has significant CNS toxicity including seizure risk 1, 4
• This metabolite accumulates particularly in renal impairment and with repeated dosing 2, 4

Respiratory Depression:

• Standard opioid precaution: monitor oxygen saturation and be prepared to support ventilation 3
• Risk increases when combined with other CNS depressants (benzodiazepines, antihistamines, alcohol) 3
• Naloxone should be available for reversal 3

Serotonin Syndrome Risk:

• Pethidine has serotonergic effects that increase toxicity risk when combined with other serotonergic medications 1
• Monitor for mental status changes (confusion, agitation), neuromuscular hyperactivity (tremors, clonus, hyperreflexia), and autonomic instability (hypertension, tachycardia, hyperthermia) 6

Administration-Specific Precautions

Route of Administration:

• Should be used by intramuscular injection, not orally, due to poor oral bioavailability 5, 4
• IV administration carries higher risk of hypotension and requires slower infusion 3
• Typical dose: 50-150 mg IM, repeated every 3-4 hours as needed 3

Duration of Use:

• Should NOT be used for chronic pain or malignancy 5
• Appropriate only for acute pain situations (trauma, renal/biliary colic) 5
• Analgesic effects last only 3-4 hours with parenteral administration 4

Common Adverse Effects Requiring Monitoring

• Hypotension, particularly with rapid administration 3
• Nausea and vomiting (may be reduced with antiemetic co-administration) 3, 4
• Fatigue and drowsiness 3, 7
• Dizziness 3
• Constipation 3
• Muscle weakness 3
• Histamine release 3

Superior Alternatives

For moderate to severe pain, use instead:

• Morphine, hydromorphone, oxycodone, or fentanyl - these provide more reliable analgesia with better safety profiles 1

For patients with renal impairment specifically:

• Fentanyl, sufentanil, or methadone (under experienced supervision) as they have no active metabolites 1

Clinical Bottom Line

Pethidine 50mg should be considered a second-line agent only for acute pain when other opioids are unavailable or contraindicated 4. The combination of poor efficacy, multiple drug interactions, toxic metabolite accumulation, and increased risk of serotonin syndrome makes it an inferior choice compared to modern alternatives 1. If it must be used, ensure normal renal function, absence of MAOI therapy, short-term use only, and close monitoring for respiratory depression and CNS toxicity 1, 2, 4.