What are the contraindications to prescribing tramadol?

Contraindications to Tramadol

Tramadol is absolutely contraindicated in patients with acute intoxication with alcohol, hypnotics, narcotics, centrally acting analgesics, other opioids, or psychotropic drugs, as well as in patients with hypersensitivity to tramadol or other opioids. 1

Absolute Contraindications

• Acute intoxication with any of the following: 1

  • Alcohol
  • Hypnotics
  • Narcotics
  • Centrally acting analgesics
  • Opioids
  • Psychotropic drugs

• Hypersensitivity to tramadol, any component of the product, or other opioids 1

• Patients with a history of anaphylactoid reactions to codeine and other opioids should not receive tramadol 1

Strong Contraindications (Do Not Combine)

• Monoamine oxidase inhibitors (MAOIs): Tramadol should not be combined with MAOIs due to increased risk of adverse events including seizures and serotonin syndrome; animal studies have shown increased deaths with combined administration 2, 1

Age-Related Contraindications

• Children under 12 years of age: The FDA issued a black-box warning in 2017 contraindicating tramadol in children <12 years 3, 4

• Children under 18 years following tonsillectomy and adenoidectomy: This contraindication was established in 2013 and expanded in 2017 4

High-Risk Situations Requiring Extreme Caution or Avoidance

Serotonin Syndrome Risk

Tramadol should be used with great caution or avoided in patients taking serotonergic drugs due to potentially life-threatening serotonin syndrome: 5, 1

• Selective serotonin reuptake inhibitors (SSRIs)
• Serotonin-norepinephrine reuptake inhibitors (SNRIs)
• Tricyclic antidepressants (TCAs)
• Triptans
• Other drugs that impair serotonin metabolism

The risk is amplified in patients on multiple serotonergic medications 5

Seizure Risk

Tramadol should be avoided or used with extreme caution in patients with: 2, 6, 1

• Epilepsy or history of seizures
• Recognized risk factors for seizures (head trauma, metabolic disorders, alcohol and drug withdrawal, CNS infections)
• Patients taking medications that lower seizure threshold:
  • Neuroleptics
  • Other drugs that reduce seizure threshold

Tramadol lowers the seizure threshold, especially at high doses 5, 1

Respiratory Depression Risk

Tramadol should be avoided or used with extreme caution in patients at risk for respiratory depression: 1

• Patients with compromised respiratory function
• When combined with CNS depressants (alcohol, opioids, anesthetic agents, phenothiazines, tranquilizers, sedative-hypnotics)
• Patients with increased intracranial pressure or head injury (respiratory depressant effects include CO₂ retention and secondary elevation of cerebrospinal fluid pressure) 1

Renal Impairment

Tramadol should be avoided in patients with renal impairment unless there are no alternatives 7

Morphine, meperidine, codeine, and tramadol should be avoided in this population; if opioids are needed, methadone (excreted fecally) or carefully titrated fentanyl, oxycodone, or hydromorphone are preferred 7

Genetic Polymorphism

Tramadol has reduced or no analgesic effect in CYP2D6 poor metabolizers (more common among Asians), though this is not an absolute contraindication 7, 6, 8

Tramadol is a prodrug requiring CYP2D6 metabolism to achieve analgesic effects 7, 6

Drug Interactions Requiring Avoidance

Tramadol should not be combined with or requires extreme caution with: 1

• CYP2D6 inhibitors (reduce analgesic effect)
• CYP3A4 inhibitors (impair tramadol metabolism)
• Drugs that compete for CYP2D6 (may reduce analgesic effects)

Psychiatric and Substance Use Disorders

Do not prescribe tramadol for patients who are: 1

• Suicidal or addiction-prone
• Taking tranquilizers or antidepressants with excessive alcohol use
• Suffering from emotional disturbance or depression (consider non-narcotic analgesics instead)

Tramadol-related deaths have occurred in patients with histories of emotional disturbances, suicidal ideation/attempts, and misuse of tranquilizers, alcohol, and other CNS-active drugs 1

Special Populations Requiring Caution

• Elderly patients (≥75 years): Require reduced tramadol dosing to mitigate seizure risk 5

• Ambulatory patients: Tramadol may impair mental and physical abilities required for driving or operating machinery 1

Clinical Pitfalls

• Naloxone administration in tramadol overdose may increase seizure risk 1

• Tramadol has limitations in dose titration related to a low threshold for neurotoxicity 7

• Tramadol may be less effective than morphine for moderate cancer pain based on very low certainty evidence 7

• Serious anaphylactoid reactions, though rare, have been reported, often following the first dose 1