What are the contraindications for tramadol (ultram)?

Contraindications for Tramadol

Tramadol is absolutely contraindicated in children under 12 years of age, in all patients under 18 years undergoing tonsillectomy/adenoidectomy, in adolescents 12-18 years with obesity or respiratory risk factors (obstructive sleep apnea, severe lung disease), and in patients with acute intoxication with alcohol, hypnotics, narcotics, centrally acting analgesics, or psychotropic drugs. 1, 2, 3

Absolute Contraindications

Pediatric Population

• Children younger than 12 years: Tramadol is FDA-contraindicated for any indication in this age group due to respiratory depression risk 1, 2
• All patients under 18 years post-tonsillectomy/adenoidectomy: This surgical population has demonstrated fatal respiratory complications, leading to an FDA black box warning 1, 2
• Adolescents 12-18 years with risk factors: Those who are obese or have conditions increasing breathing problems (obstructive sleep apnea, severe lung disease) are contraindicated from receiving tramadol 1, 2

Acute Intoxication States

• Acute intoxication with alcohol, hypnotics, narcotics, centrally acting analgesics, opioids, or psychotropic drugs: Tramadol worsens central nervous system and respiratory depression in these patients 3

Hypersensitivity

• Previous hypersensitivity to tramadol, any component of the product, or other opioids 3

Relative Contraindications and High-Risk Situations

Hepatic Dysfunction

• Liver cirrhosis: Limit tramadol to 50 mg every 12 hours (not more frequently) due to significantly increased bioavailability and risk of accumulation 2, 4
• General hepatic impairment: Requires dose adjustment due to increased risk of adverse effects from impaired metabolism 2

Renal Dysfunction

• Renal impairment: Requires dose adjustment as tramadol and its active metabolite (M1) accumulate, increasing toxicity risk 2

Concomitant Medications Creating High Risk

• CYP2D6 inhibitors: Increase production of the active M1 metabolite, raising respiratory depression risk 5
• Benzodiazepines: Significantly increase respiratory depression and CNS depression risk; if unavoidable, use lowest effective doses with intensive monitoring 6, 5
• Other opioids: Additive respiratory depression effects make combination particularly dangerous 6, 5
• Antidepressants (SSRIs, SNRIs, tricyclics): Create risk of serotonin syndrome due to tramadol's serotonin reuptake inhibition properties 6, 5, 7
• MAO inhibitors: Should not be administered with tramadol 8

Seizure Risk Populations

• Epileptics: Tramadol lowers seizure threshold and should be avoided or used with extreme caution 7, 9
• Patients on seizure-threshold lowering drugs: Increased risk of tramadol-induced seizures 7, 9

Elderly Patients

• Age over 75 years: Higher risk for adverse effects from CNS depression; dose adjustment required due to age-related changes in metabolism 2

Critical Clinical Pitfalls

Drug Abuse Context

• Active substance abuse: Tramadol-related respiratory depression is strongly associated with drug abuse patterns, with higher mortality risk 5

Respiratory Compromise

• Sleep apnea, obesity, or pre-existing respiratory conditions: These patients face particularly high risk for fatal respiratory complications 6

Serotonin Syndrome Risk

• Concomitant serotonergic agents: The combination of tramadol's serotonin reuptake inhibition with other serotonergic drugs (SSRIs, SNRIs, tricyclics) creates significant risk of serotonin syndrome, which can be fatal if untreated 7
• Monitor for agitation, confusion, tachycardia, hypertension, hyperthermia, hyperreflexia, and clonus 7

Pharmacogenetic Considerations

• CYP2D6 polymorphism: Patients who are ultra-rapid metabolizers convert tramadol to its active M1 metabolite more quickly, creating higher opioid receptor activity and increased respiratory depression risk—this was the basis for the initial FDA pediatric warnings 1, 8