Tramadol

Relative contraindication. Concurrent use with alcohol, benzodiazepines, other opioids, or GHB/GBL significantly enhances respiratory depression risk. The tramadol-benzodiazepine combination carries paradoxical danger: seizure protection is eliminated while respiratory depression worsens.

Relative contraindication. Tramadol's proconvulsant activity at supratherapeutic doses makes it inappropriate for patients with epilepsy or other conditions lowering seizure threshold. If used, careful dose monitoring and seizure precautions are required.

Absolute contraindication. Concurrent or recent MAOI use with tramadol may cause life-threatening serotonin syndrome. A 14-day washout period from MAOIs is required before tramadol initiation.

Relative contraindication. Concurrent use of tramadol with SSRIs, SNRIs, TCAs, or other serotonergic medications increases serotonin syndrome risk. If combination is clinically necessary, lowest effective doses and close monitoring are required.

Relative contraindication. Hepatic impairment alters tramadol metabolism unpredictably — potentially both reducing analgesic efficacy (impaired M1 production) and increasing toxicity from parent compound accumulation.

Absolute contraindication per CPIC guidelines and FDA labeling. CYP2D6 ultrarapid metabolizers produce excess active metabolite M1, resulting in opioid toxicity at standard doses. At least one pediatric death reported.

Relative contraindication. Tramadol misuse in pregnancy is associated with neonatal abstinence syndrome. Risk-benefit assessment required when considering use during pregnancy.

Relative contraindication. Not recommended in nursing mothers due to risk of M1 exposure to the infant via breast milk. Risk is greatest in CYP2D6 ultrarapid metabolizer mothers.

Absolute contraindication. Life-threatening respiratory depression and death have been reported in children under 12 receiving tramadol. FDA labeling explicitly contraindicates use in this age group.

Absolute contraindication per FDA labeling. Tramadol must not be used for post-tonsillectomy or post-adenoidectomy analgesia in patients under 18 years.