Is pethidine (meperidine) obsolete as an analgesic?

Is Pethidine (Meperidine) Obsolete?

Yes, pethidine (meperidine) is effectively obsolete for most clinical indications and should be avoided in modern analgesic practice. 1, 2

Guideline-Based Recommendations Against Pethidine

Pethidine has no place as a WHO level 3 opioid since other opioids have become available. 1 This represents the clearest guideline statement on the drug's obsolescence, coming from cancer pain management standards where opioid selection is critical.

The evidence supporting abandonment of pethidine is multifaceted:

Major Safety Concerns

Neurotoxic Metabolite Accumulation

• Pethidine produces normeperidine, a neurotoxic metabolite with a long half-life (15-30 hours) that accumulates with repeated dosing 3, 4, 5
• Normeperidine causes central nervous system excitation ranging from nervousness and tremors to multifocal myoclonus and seizures 5
• Pethidine is contraindicated in patients with renal insufficiency (GFR <30 mL/min/1.73 m²) and end-stage renal disease due to metabolite accumulation 2
• Even patients without overt renal dysfunction can accumulate normeperidine with repeated administration 5

Dangerous Drug Interactions

• Life-threatening interactions occur with monoamine oxidase inhibitors (MAOIs), causing agitation, hemodynamic instability, rigidity, seizures, and death 1
• Serotonergic effects increase toxicity risk when combined with other serotonergic medications 2
• Unlike other opioids (fentanyl, morphine), pethidine uniquely poses this MAOI interaction risk 1

Limited Efficacy Profile

Inferior Analgesic Properties

• Pethidine offers limited potency and short duration of action compared to alternatives 3, 6
• Clinical trials demonstrate similar or inferior analgesic efficacy compared to morphine, fentanyl, tramadol, and even NSAIDs for postoperative and labor pain 7
• No advantage exists over other opioids for biliary colic or pancreatitis, despite historical beliefs 6

Problematic Dosing Characteristics

• Intermittent administration produces plasma concentration fluctuations associated with incomplete pain relief and side effects 4
• While only 3.7% of prescriptions exceed the 600 mg maximum daily dose, 96.7% exceed the recommended 2-day duration limit 3

Superior Alternatives Exist

For Moderate to Severe Pain:

• Morphine, hydromorphone, oxycodone, or fentanyl provide more reliable analgesia with better safety profiles 2
• These agents lack the neurotoxic metabolite concerns of pethidine 2

For Patients with Renal Impairment:

• Fentanyl, sufentanil, or methadone (under experienced supervision) have no active metabolites and are safer choices 2

For Postoperative Shivering (The One Remaining Indication):

• Pethidine remains more effective than other opioid agonists or agonist-antagonists for treating postoperative shivering 1
• However, this narrow indication does not justify routine formulary inclusion 1
• Hypothermia (the common cause of shivering) should be treated by rewarming, not pharmacologically 1

Historical Context

The 2023 British Journal of Anaesthesia narrative review traces pethidine's rise and fall 1:

• Emerged during World War II as a synthetic opioid alternative 1
• Featured prominently in the 1946 Liverpool anaesthetic technique (balanced anaesthesia) 1
• By 1962, fentanyl was developed and recognized for superior hemodynamic stability 1
• Modern practice uses shorter, stronger-acting drugs like remifentanil 1

Prescribing Trends Confirm Obsolescence

Declining but Concerning Use Patterns:

• Marked decline in pethidine users and prescriptions from 2001-2014 among older adults 3
• However, remaining users receive increasing amounts (18.98 to 56.14 defined daily doses per user per year), suggesting concentrated use by a small group of prescribers 3
• This pattern indicates the drug persists primarily through prescriber habit rather than clinical merit 3

Common Pitfalls to Avoid

• Do not use pethidine for chronic pain management due to normeperidine accumulation risk with repeated dosing 3, 5
• Never prescribe pethidine to patients taking MAOIs due to life-threatening interaction risk 1
• Avoid in older adults who are more sensitive to side effects and often have diminished renal function 3
• Do not assume pethidine is safer for biliary or pancreatic pain—this is a myth without supporting evidence 6
• Recognize that sedation and respiratory depression occur more frequently with pethidine than with alternative opioids 7

Practical Implementation

For institutions still carrying pethidine:

• Remove from formulary or implement strict restrictions 6
• Target educational initiatives at the small group of high-volume prescribers 3
• Removing from medication insurance schemes provides additional incentive to discontinue use 3

The evidence overwhelmingly supports that pethidine is obsolete for analgesic purposes, with the sole exception of treating postoperative shivering when other measures fail. 1, 2, 7