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 w/ inadequate tx alternatives; proper dosing and titration essential to decr. resp. depression risk

Addiction, Abuse, and Misuse

opioid agonist Schedule IV controlled substance w/ 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 w/ recommended use, esp. during tx start or after dose incr; to decr. risk, initiate and titrate dose appropriately

Accidental Ingestion

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

Risks from Concomitant Use w/ Benzodiazepines, CNS Depressants

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

Neonatal Opioid Withdrawal Syndrome

advise pregnant patients w/ extended opioid use of risk of potentially life-threatening neonatal opioid withdrawal syndrome; ensure tx by neonatology experts avail. 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 w/ 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 w/ 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 w/ acute liver failure incl. cases of liver transplant and death; most liver injury associated w/ acetaminophen doses >4000 mg per day and >1 acetaminophen-containing product