Tramadol: Difference between revisions
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MDElliottMD (talk | contribs) parser-claude: Tramadol MedTemplate refill, Top 300 stub upgrade |
Safety wave: 2017 FDA boxed warning + pediatric/breastfeeding contraindications (FDA DSC April 20 2017); M1 affinity framing + CPIC 2021 cite |
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| pregnancy = Chronic third-trimester exposure produces neonatal opioid withdrawal syndrome and respiratory depression at delivery.{{citation needed}} | | pregnancy = Chronic third-trimester exposure produces neonatal opioid withdrawal syndrome and respiratory depression at delivery.{{citation needed}} | ||
| legal = [[USLegal:Schedule IV|Schedule IV controlled substance]] in US (federally scheduled 2014); some states schedule higher<ref name="ultram-label" /> | | legal = [[USLegal:Schedule IV|Schedule IV controlled substance]] in US (federally scheduled 2014); some states schedule higher<ref name="ultram-label" /> | ||
| mechanism = <vote slug="tramadol-mech-claim"> | | mechanism = <vote slug="tramadol-mech-claim">Tramadol acts partly as a prodrug for opioid effect: CYP2D6 converts it to O-desmethyltramadol (M1), which binds the mu-opioid receptor with substantially higher affinity than the parent compound (reported on the order of 200-fold, with estimates varying by assay), so M1 is the dominant opioid-active moiety while parent tramadol contributes serotonin and norepinephrine reuptake inhibition.<ref>Grond S, Sablotzki A. Clinical pharmacology of tramadol. Clin Pharmacokinet. 2004;43(13):879-923.</ref> Pharmacogenomic guidance on CYP2D6 metabolizer status for opioid selection is provided by the Clinical Pharmacogenetics Implementation Consortium.<ref>Crews KR, Monte AA, Huddart R, et al. Clinical Pharmacogenetics Implementation Consortium Guideline for CYP2D6, OPRM1, and COMT Genotypes and Select Opioid Therapy. Clin Pharmacol Ther. 2021;110(4):888-896.</ref></vote> CYP2D6 ultra-rapid metabolizers produce dangerously high M1 levels with risk of fatal respiratory depression, particularly in children; CYP2D6 poor metabolizers get reduced opioid analgesic benefit and rely on the serotonin/norepinephrine reuptake component. '''Serotonin syndrome''' risk with SSRIs, SNRIs, MAOIs, and other serotonergic agents. '''Seizure''' risk is dose-dependent and elevated in patients with epilepsy, head trauma, or concurrent serotonergic medicines. | ||
| monitoring = '''Boxed warning:''' tramadol carries an FDA boxed warning for life-threatening respiratory depression arising from ultra-rapid CYP2D6 metabolism to the active metabolite O-desmethyltramadol (M1), alongside the opioid-class warnings for addiction, abuse, and misuse and for fatal interaction with benzodiazepines and other CNS depressants.<ref>U.S. Food and Drug Administration. Drug Safety Communication: FDA restricts use of prescription codeine pain and cough medicines and tramadol pain medicines in children; recommends against use in breastfeeding women. April 20, 2017.</ref> Tramadol is contraindicated for any use in children younger than 12 years, and contraindicated in children younger than 18 years to treat pain after tonsillectomy and/or adenoidectomy; use in adolescents 12 to 18 years is not recommended when they have obesity, obstructive sleep apnea, or severe lung disease.<ref>FDA Drug Safety Communication, April 20, 2017 (as above); tramadol prescribing information, Boxed Warning.</ref> Use is not recommended in breastfeeding women because M1 passes into breast milk and can cause sedation and life-threatening respiratory depression in the infant, especially of an ultra-rapid metabolizer.<ref>American College of Obstetricians and Gynecologists. Committee Opinion No. 711: Opioid Use and Opioid Use Disorder in Pregnancy. Obstet Gynecol. 2017;130(2):e81-e94.</ref> | |||
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Latest revision as of 18:33, 29 June 2026
Opioid analgesic (atypical, weak μ-agonist with serotonin/norepinephrine reuptake inhibition), Schedule IV controlled substance, Analgesic
Tramadol
Ultram (IR), Ultram ER, ConZip ER
Experience
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Problems
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Effects
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Monitoring
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Relevant Literature
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Pharmacy
Starting dose
IR: 25-50 mg PO every 4-6 hours as needed, titrate as tolerated. ER: 100 mg PO once daily, titrate by 100 mg every 5 days
Preparations
IR tablets 50 mg; ER tablets 100, 200, 300 mg (Ultram ER, ConZip); oral solution 5 mg/mL; combination products with acetaminophen (Ultracet)
US FDA Max
400 mg/day (IR, adult); 300 mg/day (ER); 300 mg/day in elderly >75 years
Common uses
Classification(s)
Pharmacology
Routes
Oral
Onset
30-60 minutes (IR)
Duration
4-6 hours (IR); 24 hours (ER)
Half-life
Tramadol 6-7 hours; M1 active metabolite 7-9 hours[3]
Bioavailability
~75% (IR, rises with multi-dose administration due to saturable first-pass)[3]
Pregnancy
Chronic third-trimester exposure produces neonatal opioid withdrawal syndrome and respiratory depression at delivery.[citation needed]
Legal status
Schedule IV controlled substance in US (federally scheduled 2014); some states schedule higher[3]
Purported mechanism
Tramadol acts partly as a prodrug for opioid effect: CYP2D6 converts it to O-desmethyltramadol (M1), which binds the mu-opioid receptor with substantially higher affinity than the parent compound (reported on the order of 200-fold, with estimates varying by assay), so M1 is the dominant opioid-active moiety while parent tramadol contributes serotonin and norepinephrine reuptake inhibition.[1] Pharmacogenomic guidance on CYP2D6 metabolizer status for opioid selection is provided by the Clinical Pharmacogenetics Implementation Consortium.[2]0 CYP2D6 ultra-rapid metabolizers produce dangerously high M1 levels with risk of fatal respiratory depression, particularly in children; CYP2D6 poor metabolizers get reduced opioid analgesic benefit and rely on the serotonin/norepinephrine reuptake component. Serotonin syndrome risk with SSRIs, SNRIs, MAOIs, and other serotonergic agents. Seizure risk is dose-dependent and elevated in patients with epilepsy, head trauma, or concurrent serotonergic medicines.
Pharmacopedia is intended for reference. Nothing here is advice. In an emergency call 911; US Poison Control 1-800-222-1222. See the full disclaimer.
References
- ↑ Grond S, Sablotzki A. Clinical pharmacology of tramadol. Clin Pharmacokinet. 2004;43(13):879-923.
- ↑ Crews KR, Monte AA, Huddart R, et al. Clinical Pharmacogenetics Implementation Consortium Guideline for CYP2D6, OPRM1, and COMT Genotypes and Select Opioid Therapy. Clin Pharmacol Ther. 2021;110(4):888-896.
- ↑ 3.0 3.1 3.2 FDA Prescribing Information, Ultram (tramadol hydrochloride), Janssen, current revision. https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/020281s048lbl.pdf
- ↑ U.S. Food and Drug Administration. Drug Safety Communication: FDA restricts use of prescription codeine pain and cough medicines and tramadol pain medicines in children; recommends against use in breastfeeding women. April 20, 2017.
- ↑ FDA Drug Safety Communication, April 20, 2017 (as above); tramadol prescribing information, Boxed Warning.
- ↑ American College of Obstetricians and Gynecologists. Committee Opinion No. 711: Opioid Use and Opioid Use Disorder in Pregnancy. Obstet Gynecol. 2017;130(2):e81-e94.