Pethidine

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).

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 in adults). Oral meperidine should not be used since first-pass metabolism decreases efficacy while increasing normeperidine concentrations (APS 2016). Note: Naloxone does not reverse, and may even worsen, neurotoxicity.

May cause constipation which may be problematic in patients with unstable angina and patients post-myocardial infarction. Consider preventive measures (eg, stimulant laxative) to reduce the potential for constipation.

May cause severe hypotension (including orthostatic hypotension and syncope); use with caution in patients with hypovolemia, cardiovascular disease (including acute MI), or drugs which may exaggerate hypotensive effects (including phenothiazines or general anesthetics). Monitor for symptoms of hypotension following initiation or dose titration. Avoid use in patients with circulatory shock.

Serious, life-threatening, or fatal respiratory depression may occur. Monitor closely for respiratory depression, especially during initiation or dose escalation. Carbon dioxide retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids.

May occur with concomitant use of serotonergic agents (eg, SSRIs, SNRIs, triptans, TCAs), lithium, St. John's wort, agents that impair metabolism of serotonin (eg, MAO inhibitors), or agents that impair metabolism of tramadol (eg, CYP2D6 and 3A4 inhibitors). Monitor patients for serotonin syndrome such as mental status changes (eg, agitation, hallucinations, coma); autonomic instability (eg, tachycardia, labile blood pressure, hyperthermia); neuromuscular changes (eg, hyperreflexia, incoordination); and/or GI symptoms (eg, nausea, vomiting, diarrhea). Disease-related concerns:

May obscure diagnosis or clinical course of patients with acute abdominal conditions.

Use with caution and reduce initial dosage in patients with adrenal insufficiency, including Addison disease. Long-term opioid use may cause secondary hypogonadism, which may lead to sexual dysfunction, infertility, mood disorders, and osteoporosis (Brennan 2013).

Use with caution in patients with biliary tract dysfunction, including acute pancreatitis; opioids may cause constriction of sphincter of Oddi.

Avoid use in patients with impaired consciousness or coma as these patients are susceptible to intracranial effects of carbon dioxide retention.

Use with caution in patients with delirium tremens.

Use with extreme caution in patients with head injury, intracranial lesions, or elevated intracranial pressure (ICP); exaggerated elevation of ICP may occur.

Use with caution in patients with hepatic disorders; meperidine and to a lesser degree normeperidine may accumulate and precipitate either CNS depression or CNS excitation (eg, anxiety, tremors, or seizures) (Danzinger 1994; Tegeder 1999).

Use with caution in patients who are morbidly obese.

Use with caution in patients with pheochromocytoma.

Use with caution and reduce initial dosage in patients with prostatic hyperplasia and/or urinary stricture.

Use with caution in patients with toxic psychosis.

Avoid use in patients with renal impairment (APS 2016; ISMP 2007); normeperidine may accumulate and precipitate anxiety, tremors, or seizures.

Use with caution and monitor for respiratory depression in patients with significant chronic obstructive pulmonary disease or cor pulmonale, and those with a substantially decreased respiratory reserve, hypoxia, hypercapnia, or preexisting respiratory depression, particularly when initiating and titrating therapy; critical respiratory depression may occur, even at therapeutic dosages. Consider the use of alternative nonopioid analgesics in these patients.

Use with caution in patients with seizure disorders, may cause or aggravate seizures if high doses used or from prolonged use (accumulation of metabolite).

In patients with sickle cell anemia, use with caution and decrease initial dose; normeperidine (active metabolite) may accumulate and induce seizures in these patients; Note: Meperidine is not recommended for use in sickle cell patients by the American Pain Society (APS 2016) and should only be used in sickle cell patients with a vaso-occlusive crisis (VOC) if it is the only effective opioid for an individual patient (NHLBI 2014).

Use with caution in patients with atrial flutter and other supraventricular tachycardias; use may increase ventricular response rate possibly due to a vagolytic effect.

Use with caution in patients with thyroid dysfunction, including hypothyroidism. Concurrent drug therapy issues:

Concomitant use of opioids with benzodiazepines or other CNS depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death. Reserve concomitant prescribing of meperidine and benzodiazepines or other CNS depressants for use in patients for whom alternative treatment options are inadequate. Limit dosage and durations to the minimum required and follow patients for signs and symptoms of respiratory depression and sedation.

Use with all CYP3A4 inhibitors may result in an increase in meperidine plasma concentrations, which could increase or prolong adverse drug effects and may cause potentially fatal respiratory depression. In addition, discontinuation of a concomitant CYP3A4 inducer may result in increased meperidine concentrations. Monitor patients receiving meperidine and any CYP3A4 inhibitor or inducer.

Concomitant use of meperidine with MAOIs can result in coma, severe respiratory depression, cyanosis, and hypotension. Use of meperidine with MAOIs within last 14 days is contraindicated.

Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information. Special populations:

Use with caution in cachectic or debilitated patients; there is a greater potential for critical respiratory depression, even at therapeutic dosages; reduce initial dosage. Consider the use of alternative nonopioid analgesics in these patients.

Avoid the use of meperidine for pain control, especially in elderly and renally compromised patients because of the risk of neurotoxicity (APS 2016; ISMP 2007). Meperidine should be avoided in those older adults with, or at risk for, delirium because of the potential to cause or worsen delirium.

Neonatal withdrawal syndrome: [US Boxed Warning]: Prolonged use of opioids during pregnancy can cause neonatal withdrawal syndrome, which may be life-threatening if not recognized and treated according to protocols developed by neonatology experts. If opioid use is required for a prolonged period in a pregnant woman, advise the patient of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available. Signs and symptoms include irritability, hyperactivity and abnormal sleep pattern, high pitched cry, tremor, vomiting, diarrhea, and failure to gain weight. Onset, duration, and severity depend on the drug used, duration of use, maternal dose, and rate of drug elimination by the newborn. Dosage form specific issues:

Some dosage forms may contain sodium benzoate/benzoic acid; benzoic acid (benzoate) is a metabolite of benzyl alcohol; large amounts of benzyl alcohol (≥99 mg/kg/day) have been associated with a potentially fatal toxicity (“gasping syndrome”) in neonates; the “gasping syndrome” consists of metabolic acidosis, respiratory distress, gasping respirations, CNS dysfunction (including convulsions, intracranial hemorrhage), hypotension, and cardiovascular collapse (AAP ["Inactive" 1997]; CDC 1982); some data suggests that benzoate displaces bilirubin from protein binding sites (Ahlfors 2001); avoid or use dosage forms containing benzyl alcohol derivative with caution in neonates. See manufacturer's labeling.

Risk of medication errors: [US Boxed Warning]: Ensure accuracy when prescribing, dispensing, and administering meperidine oral solution. Dosing errors due to confusion between mg and mL, and other meperidine solutions of different concentrations, can result in accidental overdose and death. Do not use a teaspoon or a tablespoon to measure a dose; use a calibrated measuring device. Use extreme caution in measuring the dosage.

Administer IV injections very slowly, preferably in the form of a diluted solution. Do not administer IV unless a opioid antagonist and the facilities for assisted or controlled respiration are immediately available. When meperidine is given parenterally, especially IV, the patient should be lying down.

Some preparations may contain sulfites which may cause allergic reaction. Other warnings/precautions:

Meperidine exposes patients and other users to the risks of addiction, abuse, and misuse, potentially leading to overdose and death. Assess each patient's risk prior to prescribing; monitor all patients regularly for development of these behaviors or conditions. Use with caution in patients with a history of drug abuse or acute alcoholism; potential for drug dependency exists. Other factors associated with increased risk for misuse include younger age, concomitant depression (major), and psychotropic medication use.

Accidental ingestion of even one dose, especially in children, can result in a fatal overdose of meperidine.

Meperidine offers no advantage over other opioids as an analgesic and has unique neurotoxicity. The use of meperidine in this setting should be avoided (APS 2016; ISMP 2007).

Use is not recommended for the management of chronic pain.

An opioid-containing analgesic regimen should be tailored to each patient's needs and based upon 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.

Opioids decrease bowel motility; monitor for decreased bowel motility in postop patients receiving opioids. Use with caution in the perioperative setting; individualize treatment when transitioning from parenteral to oral analgesics.

Concurrent use of mixed agonist/antagonist analgesics (eg, pentazocine, nalbuphine, butorphanol) or partial agonist (eg, buprenorphine) analgesics may precipitate withdrawal symptoms and/or reduced analgesic efficacy in patients following prolonged therapy with mu opioid agonists. Taper dose gradually when discontinuing.