Tramadol
Opioid analgesic (atypical, weak μ-agonist with serotonin/norepinephrine reuptake inhibition), Schedule IV controlled substance, Analgesic
Tramadol
Ultram (IR), Ultram ER, ConZip ER
Experience
No personal reports yet
No clinical reports yet
Log in to add your own experience.
Problems
No problems yet. Be the first to suggest one.
+ Add a problemTitration strategies
No titration strategies yet. Be the first to suggest one.
Effects
No effects listed yet. Be the first to suggest one.
Monitoring
Relevant anecdote
No anecdotes yet. Share a relevant one.
Relevant Literature
No literature entries yet.
Log in to submit relevant literature.
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.