tramadol/ acetaminophen

Appropriate Use

should only be prescribed by healthcare professionals knowledgeable about opioid use and how to mitigate associated risks; reserve opioid analgesics for patients with inadequate tx alternatives; proper dosing and titration essential to decr. resp. depression risk

Addiction, Abuse, and Misuse

opioid agonist Schedule IV controlled substance with risk of addiction, abuse, and misuse, which can lead to overdose and death; assess opioid abuse or addiction risk prior to prescribing; regularly reassess all patients for misuse, abuse, and addiction

Respiratory Depression

serious, life-threatening, or fatal cases may occur even with recommended use, especially during tx start or after dose incr; to decr. risk, initiate and titrate dose appropriately

Accidental Ingestion

accidental ingestion of even one dose, especially by children, can result in fatal tramadol overdose

Risks from Concomitant Use with Benzodiazepines, CNS Depressants

concomitant opioid use with benzodiazepines or other CNS depressants, including alcohol, may result in profound sedation, resp. depression, coma, and death; reserve concomitant use for patients with inadequate alternative tx options

Neonatal Opioid Withdrawal Syndrome

advise pregnant patients with extended opioid use of risk of potentially life-threatening neonatal opioid withdrawal syndrome; ensure tx by neonatology experts available at delivery

Opioid Analgesic REMS

providers are strongly encouraged to complete risk evaluation and mitigation strategy (REMS)-compliant education program, counsel patients and/or caregivers with each Rx on serious risks, safe use, and importance of reading medication guide

Ultra-Rapid Metabolism of Tramadol and Other Respiratory Depression Risk in Children

resp. depression and death have occurred in children; some cases involved tramadol use post-tonsillectomy and/or adenoidectomy and at least one case had evidence of being a CYP2D6 ultra-rapid metabolizer; contraindicated in patients <12 yo and in patients <18 yo post-tonsillectomy and/or adenoidectomy; avoid use in patients 12-18 yo with risk factors that incr. sensitivity to resp. depressant effects of tramadol

CYP450 3A4 Interaction

concomitant use or D/C of concomitant CYP450 3A4 inducers, 3A4 inhibitors, or 2D6 inhibitors are complex requiring careful consideration of the effects on tramadol and its active metabolite

Hepatotoxicity

acetaminophen associated with acute liver failure including cases of liver transplant and death; most liver injury associated with acetaminophen doses >4000 mg per day and >1 acetaminophen-containing product