Chemical: Drug
tramadol

last updated 05/02/2017

1. Annotation of DPWG Guideline for tramadol and CYP2D6

Summary

For CYP2D6 poor metabolizers (PM), select an alternative to tramadol (not oxycodone or codeine) and be alert for symptoms of insufficient pain relief. For CYP2D6 intermediate metabolizers (IM), be alert for symptoms of insufficient pain relief, and consider dose increase or select an alternative to tramadol (not oxycodone or codeine). For CYP2D6 ultrarapid metabolizers, use a 30% decreased dose and be alert for ADEs, or use an alternative to tramadol (not oxycodone or codeine).

Annotation

Note that the FDA released a safety announcement on 4/20/2017 stating that codeine and tramadol should not be used in children under 12 years.

The Royal Dutch Pharmacists Association - Pharmacogenetics Working Group has evaluated therapeutic dose recommendations for tramadol based on CYP2D6 genotypes [Article:21412232]. For PM and IM genotypes, they recommend selecting an alternative drug (not oxycodone or codeine) and/or being extra alert to symptoms of insufficient pain relief. For UM genotypes, they recommend using a 30% decreased dose and being alert for ADEs, or using an alternative drug (not oxycodone or codeine).

Phenotype (Genotype)Therapeutic Dose RecommendationLevel of EvidenceClinical Relevance
PM (two inactive (*3-*8, *11-*16, *19-*21, *38, *40, *42) alleles)Select alternative drug-not oxycodone or codeine- or be alert to symptoms of insufficient pain relief.Published controlled studies of good quality* relating to phenotyped and/or genotyped patients or healthy volunteers, and having relevant pharmacokinetic or clinical endpoints.Clinical effect (S): short-lived discomfort (< 48 hr) without permanent injury: e.g. reduced decrease in resting heart rate; reduction in exercise tachycardia; decreased pain relief from oxycodone; ADE resulting from increased bioavailability of atomoxetine (decreased appetite, insomnia, sleep disturbance etc.); neutropenia > 1.5x109/l; leucopenia > 3.0x109/l; thrombocytopenia > 75x109/l; moderate diarrhea not affecting daily activities; reduced glucose increase following oral glucose tolerance test.
IM (two decreased-activity (*9, *10, *17, *29, *36, *41) alleles or carrying one active (*1, *2, *33, *35) and one inactive (*3-*8, *11-*16, *19-*21, *38, *40, *42) allele, or carrying one decreased-activity (*9, *10, *17, *29, *36, *41) allele and one inactive (*3-*8, *11-*16, *19-*21, *38, *40, *42) allele)Be alert to decreased efficacy. Consider dose increase. If response is still inadequate, select alternative drug- not oxycodone or codeine-or be alert to symptoms of insufficient pain relief.Published controlled studies of good quality* relating to phenotyped and/or genotyped patients or healthy volunteers, and having relevant pharmacokinetic or clinical endpoints.Clinical effect (S): short-lived discomfort (< 48 hr) without permanent injury: e.g. reduced decrease in resting heart rate; reduction in exercise tachycardia; decreased pain relief from oxycodone; ADE resulting from increased bioavailability of atomoxetine (decreased appetite, insomnia, sleep disturbance etc); neutropenia > 1.5x109/l; leucopenia > 3.0x109/l; thrombocytopenia > 75x109/l; moderate diarrhea not affecting daily activities; reduced glucose increase following oral glucose tolerance test.
UM (a gene duplication in absence of inactive (*3-*8, *11-*16, *19-*21, *38, *40, *42) or decreased-activity (*9, *10, *17, *29, *36, *41) alleles)Reduce dose by 30% and be alert to ADEs (e.g., nausea, vomiting, constipation, respiratory depression, confusion, urinary retention) or select alternative drug (e.g., acetaminophen, NSAID, morphine-not oxycodone or codeine).Published controlled studies of moderate quality* relating to phenotyped and/or genotyped patients or healthy volunteers, and having relevant pharmacokinetic or clinical endpoints.Clinical effect (S): long-standing discomfort (48-168 hr) without permanent injury e.g. failure of therapy with tricyclic antidepressants, atypical antipsychotic drugs; extrapyramidal side effects; parkinsonism; ADE resulting from increased bioavailability of tricyclic antidepressants, metoprolol, propafenone (central effects e.g. dizziness); INR 4.5-6.0; neutropenia 1.0-1.5x109/l; leucopenia 2.0-3.0x109/l; thrombocytopenia 50-75x109/l.
  • *See Methods or [Article:18253145] for definition of "good" and "moderate" quality.
  • S: statistically significant difference.

Annotated Labels

  1. Annotation of FDA Label for tramadol and CYP2D6
  2. Annotation of HCSC Label for acetaminophen,tramadol and CYP2D6
last updated 05/01/2017

1. Annotation of FDA Label for tramadol and CYP2D6

On FDA Biomarker List
Actionable PGx

Summary

The FDA-approved label for tramadol (ULTRAM) states that it is metabolized by CYP2D6 and CYP3A4, and that CYP2D6 poor metabolizers had approximately 20% higher concentrations of the drug as compared to extensive metabolizers. Additionally, concentrations of the metabolite M1 (O-desmethyltramadol; pharmacologically active) were 40% lower in CYP2D6 poor metabolizers as compared to extensive metabolizers.

Annotation

On April 20th 2017, the FDA released a safety announcement stating that they are restricting the use of codeine and tramadol in children, and recommending against the use of codeine and tramadol in breastfeeding mothers due to possible harm to their infants. Please refer to the link above for full details on the safety announcement.

Tramadol is an opioid and metabolized mainly via CYP2D6. Excerpts from the tramadol (ULTRAM) drug label:

Tramadol is extensively metabolized after oral administration by a number of pathways, including CYP2D6 and CYP3A4, as well as by conjugation of parent and metabolites...One metabolite (O-desmethyltramadol, denoted M1) is pharmacologically active in animal models. Formation of M1 is dependent on CYP2D6 and as such is subject to inhibition, which may affect the therapeutic response.

Approximately 7% of the population has reduced activity of the CYP2D6 isoenzyme of cytochrome P-450. These individuals are “poor metabolizers” of debrisoquine, dextromethorphan, tricyclic antidepressants, among other drugs. Based on a population PK analysis of Phase I studies in healthy subjects, concentrations of tramadol were approximately 20% higher in “poor metabolizers” versus “extensive metabolizers”, while M1 concentrations were 40% lower. Concomitant therapy with inhibitors of CYP2D6 such as fluoxetine, paroxetine and quinidine could result in significant drug interactions. In vitro drug interaction studies in human liver microsomes indicate that inhibitors of CYP2D6 such as fluoxetine and its metabolite norfluoxetine, amitriptyline and quinidine inhibit the metabolism of tramadol to various degrees, suggesting that concomitant administration of these compounds could result in increases in tramadol concentrations and decreased concentrations of M1. The full pharmacological impact of these alterations in terms of either efficacy or safety is unknown. Concomitant use of SEROTONIN re-uptake INHIBITORS and MAO INHIBITORS may enhance the risk of adverse events, including seizure and serotonin syndrome.

For the complete drug label text with sections containing pharmacogenetic information highlighted, see the tramadol drug label.

*Disclaimer: The contents of this page have not been endorsed by the FDA and are the sole responsibility of PharmGKB.

Full label available at DailyMed

Genes and/or phenotypes found in this label

  • Epidermal Necrolysis, Toxic
    • Warnings section, Adverse reactions section, Precautions section
    • source: PHONT
  • Pain
    • Warnings section, Adverse reactions section, Precautions section
    • source: PHONT
  • Stevens-Johnson Syndrome
    • Warnings section
    • source: PHONT
  • CYP1A2
    • metabolism/PK, Clinical pharmacology section, Pharmacokinetics section
    • source: U.S. Food and Drug Administration
  • CYP2D6
    • metabolism/PK, Drug interactions section, Clinical pharmacology section, Pharmacokinetics section
    • source: U.S. Food and Drug Administration
  • CYP2E1
    • metabolism/PK, Clinical pharmacology section, Pharmacokinetics section
    • source: U.S. Food and Drug Administration
  • CYP3A4
    • metabolism/PK, Drug interactions section, Clinical pharmacology section, Pharmacokinetics section
    • source: U.S. Food and Drug Administration

2. Annotation of HCSC Label for acetaminophen,tramadol and CYP2D6

Actionable PGx

Summary

The product monographs for tramadol and acetaminophen (APO-TRAMADOL/ACET) and tramadol (APO-TRAMADOL) note that patients who are CYP2D6 poor metabolizers may have increased tramadol concentrations as compared to those who are CYP2D6 extensive metabolizers.

Annotation

Tramadol/acetaminophen (APO-TRAMADOL/ACET) and tramadol (APO-TRAMADOL) are used to manage moderate to moderately severe pain in adults. Excerpt from the APO-TRAMADOL/ACET and APO-TRAMADOL product monographs:

Approximately 7% of the population has reduced activity of the CYP2D6 isoenzyme of cytochrome P450. These individuals are "poor metabolizers"... Based on a population PK analysis of Phase I studies in healthy subjects, concentrations of tramadol were approximately 20% higher in "poor metabolizers" versus "extensive metabolizers", while M1 concentrations were 40% lower... The full pharmacological impact of these alterations in terms of either efficacy or safety is unknown.

For the complete product monograph text with sections containing pharmacogenetic information highlighted, see the tramadol and acetaminophen product monograph and the tramadol product monograph

*Disclaimer: The contents of this page have not been endorsed by HCSC and are the sole responsibility of PharmGKB.

Clinical Variants that meet the highest level of criteria, manually curated by PharmGKB, are shown below.

To see more Clinical Variants with lower levels of criteria, click the button at the bottom of the page.

Clinical Annotation for rs1799971 (OPRM1), alfentanil, Drugs used in opioid dependence, fentanyl, heroin, morphine, naltrexone, opioids, tramadol, Heroin Dependence, Opioid-Related Disorders, Pain and Pain, Postoperative (level 2B Metabolism/PK)

Level of Evidence
Level 2B
Type
Metabolism/PK
Variant
rs1799971
Genes
OPRM1
Phenotypes
Heroin Dependence, Opioid-Related Disorders, Pain, Pain, Postoperative
OMB Race
Mixed Population

To see the rest of this clinical annotation please register or sign in.

Disclaimer: The PharmGKB's clinical annotations reflect expert consensus based on clinical evidence and peer-reviewed literature available at the time they are written and are intended only to assist clinicians in decision-making and to identify questions for further research. New evidence may have emerged since the time an annotation was submitted to the PharmGKB. The annotations are limited in scope and are not applicable to interventions or diseases that are not specifically identified.

The annotations do not account for individual variations among patients, and cannot be considered inclusive of all proper methods of care or exclusive of other treatments. It remains the responsibility of the health-care provider to determine the best course of treatment for a patient. Adherence to any guideline is voluntary, with the ultimate determination regarding its application to be made solely by the clinician and the patient. PharmGKB assumes no responsibility for any injury or damage to persons or property arising out of or related to any use of the PharmGKB clinical annotations, or for any errors or omissions.

? = Mouse-over for quick help

The table below contains information about pharmacogenomic variants on PharmGKB. Please follow the link in the "Variant" column for more information about a particular variant. Each link in the "Variant" column leads to the corresponding PharmGKB Variant Page. The Variant Page contains summary data, including PharmGKB manually curated information about variant-drug pairs based on individual PubMed publications. The PMIDs for these PubMed publications can be found on the Variant Page.

The tags in the first column of the table indicate what type of information can be found on the corresponding Variant Page.

Links in the "Gene" column lead to PharmGKB Gene Pages.

List of all variant annotations for tramadol

Gene ? Variant?
(147) 		Alternate Names ? Chemicals ? Alleles ?
(+ chr strand) 		Function ? Amino Acid?
Translation
VIP CA VA CYP2D6 *1 N/A N/A N/A
No VIP available CA VA CYP2D6 *1xN N/A N/A N/A
VIP CA VA CYP2D6 *2 N/A N/A N/A
No VIP available CA VA CYP2D6 *2xN N/A N/A N/A
VIP CA VA CYP2D6 *3 N/A N/A N/A
VIP CA VA CYP2D6 *4 N/A N/A N/A
No VIP available CA VA CYP2D6 *5 N/A N/A N/A
VIP CA VA CYP2D6 *6 N/A N/A N/A
VIP No VIP available No VIP available CYP2D6 *9 N/A N/A N/A
VIP CA VA CYP2D6 *10 N/A N/A N/A
VIP No VIP available VA CYP2D6 *17 N/A N/A N/A
VIP No VIP available No VIP available CYP2D6 *29 N/A N/A N/A
VIP No VIP available No VIP available CYP2D6 *41 N/A N/A N/A
No VIP available CA VA
rs1045642 NC_000007.13:g.87138645A>G, NC_000007.14:g.87509329A>G, NG_011513.1:g.208920T>C, NM_000927.4:c.3435T>C, NP_000918.2:p.Ile1145=, rs10239679, rs11568726, rs117328163, rs17210003, rs2229108, rs386513066, rs60023214, rs9690664
A > G
 SNP
I1145I
VIP No Clinical Annotations available No Variant Annotations available
rs1065852 NC_000022.10:g.42526694G=, NC_000022.10:g.42526694G>A, NC_000022.11:g.42130692G=, NC_000022.11:g.42130692G>A, NG_008376.3:g.4300C=, NG_008376.3:g.4300C>T, NM_000106.5:c.100C=, NM_000106.5:c.100C>T, NM_001025161.2:c.100C=, NM_001025161.2:c.100C>T, NP_000097.3:p.Pro34=, NP_000097.3:p.Pro34Ser, NP_001020332.2:p.Pro34=, NP_001020332.2:p.Pro34Ser, NT_187682.1:g.53033G=, NT_187682.1:g.53033G>A, NW_004504305.1:g.53019A=, NW_004504305.1:g.53019A>G, NW_009646208.1:g.16258A=, NW_009646208.1:g.16258A>G, XM_005278353.1:c.100T=, XM_005278353.1:c.100T>C, XM_005278354.1:c.-1454C>T, XM_005278354.1:c.-1454T>C, XM_005278354.3:c.-1454C>T, XM_005278354.3:c.-1454T>C, XM_011529966.1:c.100C=, XM_011529966.1:c.100C>T, XM_011529967.1:c.100C=, XM_011529967.1:c.100C>T, XM_011529968.1:c.100C=, XM_011529968.1:c.100C>T, XM_011529969.1:c.37+605C>T, XM_011529969.1:c.37+605T>C, XM_011529970.1:c.100C=, XM_011529970.1:c.100C>T, XM_011529971.1:c.37+605C>T, XM_011529971.1:c.37+605T>C, XM_011529972.1:c.100C=, XM_011529972.1:c.100C>T, XM_011547541.1:c.-1454C>T, XM_011547541.1:c.-1454T>C, XM_011547750.1:c.37+605C>T, XM_011547750.1:c.37+605T>C, XM_011547751.1:c.-1114C>T, XM_011547751.1:c.-1114T>C, XM_011547756.1:c.42+469A>G, XM_011547756.1:c.42+469G>A, XM_011548819.1:c.-1454C>T, XM_011548819.1:c.-1454T>C, XP_005278410.1:p.Ser34=, XP_005278410.1:p.Ser34Pro, XP_011528268.1:p.Pro34=, XP_011528268.1:p.Pro34Ser, XP_011528269.1:p.Pro34=, XP_011528269.1:p.Pro34Ser, XP_011528270.1:p.Pro34=, XP_011528270.1:p.Pro34Ser, XP_011528272.1:p.Pro34=, XP_011528272.1:p.Pro34Ser, XP_011528274.1:p.Pro34=, XP_011528274.1:p.Pro34Ser, XR_430455.2:n.328+4A>G, XR_430455.2:n.328+4G>A, XR_952536.1:n.-1751A>G, XR_952536.1:n.-1751G>A, XR_952537.1:n.-1751A>G, XR_952537.1:n.-1751G>A, XR_952538.1:n.-1751A>G, XR_952538.1:n.-1751G>A, XR_952539.1:n.-1462A>G, XR_952539.1:n.-1462G>A, XR_952745.1:n.1257C=, XR_952745.1:n.1257C>T, rs117813846, rs58862176
G > A
 SNP
P34S
rs12208357 NC_000006.11:g.160543148C>T, NC_000006.12:g.160122116C>T, NM_003057.2:c.181C>T, NM_153187.1:c.181C>T, NP_003048.1:p.Arg61Cys, NP_694857.1:p.Arg61Cys, XM_005267102.1:c.181C>T, XM_005267102.3:c.181C>T, XM_005267103.1:c.181C>T, XM_005267105.1:c.-485C>T, XM_005267105.3:c.-485C>T, XM_006715552.1:c.181C>T, XM_011536074.1:c.-895C>T, XP_005267159.1:p.Arg61Cys, XP_005267160.1:p.Arg61Cys, XP_006715615.1:p.Arg61Cys, rs56982873
C > T
 SNP
R61C
VIP No Clinical Annotations available No Variant Annotations available
rs16947 NC_000022.10:g.42523943A=, NC_000022.10:g.42523943A>G, NC_000022.11:g.42127941G=, NC_000022.11:g.42127941G>A, NG_008376.3:g.7051C=, NG_008376.3:g.7051C>T, NM_000106.5:c.886C=, NM_000106.5:c.886C>T, NM_001025161.2:c.733C=, NM_001025161.2:c.733C>T, NP_000097.3:p.Arg296=, NP_000097.3:p.Arg296Cys, NP_001020332.2:p.Arg245=, NP_001020332.2:p.Arg245Cys, NT_187682.1:g.50282A=, NT_187682.1:g.50282A>G, NW_004504305.1:g.50268G=, NW_004504305.1:g.50268G>A, NW_009646208.1:g.13507G=, NW_009646208.1:g.13507G>A, XM_005278353.1:c.742C=, XM_005278353.1:c.742C>T, XM_005278354.1:c.586C=, XM_005278354.1:c.586C>T, XM_005278354.3:c.586C=, XM_005278354.3:c.586C>T, XM_011529966.1:c.886C=, XM_011529966.1:c.886C>T, XM_011529967.1:c.886C=, XM_011529967.1:c.886C>T, XM_011529968.1:c.886C=, XM_011529968.1:c.886C>T, XM_011529969.1:c.742C=, XM_011529969.1:c.742C>T, XM_011529970.1:c.733C=, XM_011529970.1:c.733C>T, XM_011529971.1:c.742C=, XM_011529971.1:c.742C>T, XM_011529972.1:c.843+233C>T, XM_011529972.1:c.843+233T>C, XM_011547541.1:c.586C=, XM_011547541.1:c.586C>T, XM_011547750.1:c.742T=, XM_011547750.1:c.742T>C, XM_011547751.1:c.670T=, XM_011547751.1:c.670T>C, XM_011547756.1:c.-2094A>G, XM_011547756.1:c.-2094G>A, XM_011548819.1:c.586C=, XM_011548819.1:c.586C>T, XP_005278410.1:p.Arg248=, XP_005278410.1:p.Arg248Cys, XP_005278411.1:p.Arg196=, XP_005278411.1:p.Arg196Cys, XP_011528268.1:p.Arg296=, XP_011528268.1:p.Arg296Cys, XP_011528269.1:p.Arg296=, XP_011528269.1:p.Arg296Cys, XP_011528270.1:p.Arg296=, XP_011528270.1:p.Arg296Cys, XP_011528271.1:p.Arg248=, XP_011528271.1:p.Arg248Cys, XP_011528272.1:p.Arg245=, XP_011528272.1:p.Arg245Cys, XP_011528273.1:p.Arg248=, XP_011528273.1:p.Arg248Cys, XP_011545843.1:p.Arg196=, XP_011545843.1:p.Arg196Cys, XP_011546052.1:p.Cys248=, XP_011546052.1:p.Cys248Arg, XP_011546053.1:p.Cys224=, XP_011546053.1:p.Cys224Arg, XP_011547121.1:p.Arg196=, XP_011547121.1:p.Arg196Cys, XR_430455.2:n.-1930A>G, XR_430455.2:n.-1930G>A, XR_952745.1:n.2000+233C>T, XR_952745.1:n.2000+233T>C, rs117039205, rs57836231
A > G
 SNP
R296C
No VIP available CA VA
rs1799971 NC_000006.11:g.154360797A>G, NC_000006.12:g.154039662A>G, NG_021208.1:g.34162A>G, NM_000914.4:c.118A>G, NM_001008503.2:c.118A>G, NM_001008504.3:c.118A>G, NM_001008505.2:c.118A>G, NM_001145279.3:c.397A>G, NM_001145280.3:c.-11+28644A>G, NM_001145281.2:c.47+29103A>G, NM_001145282.2:c.118A>G, NM_001145283.2:c.118A>G, NM_001145284.3:c.118A>G, NM_001145285.2:c.118A>G, NM_001145286.2:c.118A>G, NM_001285522.1:c.118A>G, NM_001285523.1:c.118A>G, NM_001285524.1:c.397A>G, NP_000905.3:p.Asn40Asp, NP_001008503.2:p.Asn40Asp, NP_001008504.2:p.Asn40Asp, NP_001008505.2:p.Asn40Asp, NP_001138751.1:p.Asn133Asp, NP_001138754.1:p.Asn40Asp, NP_001138755.1:p.Asn40Asp, NP_001138756.1:p.Asn40Asp, NP_001138757.1:p.Asn40Asp, NP_001138758.1:p.Asn40Asp, NP_001272451.1:p.Asn40Asp, NP_001272452.1:p.Asn40Asp, NP_001272453.1:p.Asn133Asp, NR_104348.1:n.252A>G, NR_104349.1:n.252A>G, NR_104350.1:n.252A>G, NR_104351.1:n.252A>G, XM_005267002.1:c.304A>G, XM_006715497.2:c.304A>G, XM_011535849.1:c.397A>G, XP_005267059.1:p.Asn102Asp, XP_006715560.1:p.Asn102Asp, XP_011534151.1:p.Asn133Asp, XR_245534.1:n.304A>G, XR_245535.1:n.304A>G, XR_245536.1:n.304A>G, XR_245537.1:n.304A>G, rs17181017, rs52818856, rs61596185
A > G
 SNP
N40D
No VIP available CA VA
rs2032582 NC_000007.13:g.87160618A>C, NC_000007.13:g.87160618A>T, NC_000007.14:g.87531302A>C, NC_000007.14:g.87531302A>T, NG_011513.1:g.186947T>A, NG_011513.1:g.186947T>G, NM_000927.4:c.2677T>A, NM_000927.4:c.2677T>G, NP_000918.2:p.Ser893Ala, NP_000918.2:p.Ser893Thr, rs10228331, rs2229106, rs386553610, rs57135550, rs9641018
A > C
A > T
 SNP
S893A
VIP No Clinical Annotations available No Variant Annotations available
rs28371706 NC_000022.10:g.42525772G>A, NC_000022.11:g.42129770G>A, NG_008376.3:g.5222C>T, NM_000106.5:c.320C>T, NM_001025161.2:c.320C>T, NP_000097.3:p.Thr107Ile, NP_001020332.2:p.Thr107Ile, NT_187682.1:g.52111G>A, NW_004504305.1:g.52097G>A, NW_009646208.1:g.15336G>A, XM_005278353.1:c.320C>T, XM_005278354.1:c.-532C>T, XM_005278354.3:c.-532C>T, XM_011529966.1:c.320C>T, XM_011529967.1:c.320C>T, XM_011529968.1:c.320C>T, XM_011529969.1:c.177C>T, XM_011529970.1:c.320C>T, XM_011529971.1:c.177C>T, XM_011529972.1:c.320C>T, XM_011547541.1:c.-532C>T, XM_011547750.1:c.177C>T, XM_011547751.1:c.-192C>T, XM_011547756.1:c.-265G>A, XM_011548819.1:c.-532C>T, XP_005278410.1:p.Thr107Ile, XP_011528268.1:p.Thr107Ile, XP_011528269.1:p.Thr107Ile, XP_011528270.1:p.Thr107Ile, XP_011528271.1:p.His59=, XP_011528272.1:p.Thr107Ile, XP_011528273.1:p.His59=, XP_011528274.1:p.Thr107Ile, XP_011546052.1:p.His59=, XR_430455.2:n.-101G>A, XR_952745.1:n.1477C>T, rs587777915, rs59604033
G > A
 SNP
T107I
VIP No Clinical Annotations available No Variant Annotations available
rs28371725 NC_000022.10:g.42523805C>T, NC_000022.11:g.42127803C>T, NG_008376.3:g.7189G>A, NM_000106.5:c.985+39G>A, NM_001025161.2:c.832+39G>A, NT_187682.1:g.50144C>T, NW_004504305.1:g.50130C>T, NW_009646208.1:g.13369C>T, XM_005278353.1:c.841+39G>A, XM_005278354.1:c.685+39G>A, XM_005278354.3:c.685+39G>A, XM_011529966.1:c.985+39G>A, XM_011529967.1:c.985+39G>A, XM_011529968.1:c.985+39G>A, XM_011529969.1:c.841+39G>A, XM_011529970.1:c.832+39G>A, XM_011529971.1:c.841+39G>A, XM_011529972.1:c.844-169G>A, XM_011547541.1:c.724G>A, XM_011547750.1:c.841+39G>A, XM_011547751.1:c.769+39G>A, XM_011548819.1:c.724G>A, XP_011545843.1:p.Glu242Lys, XP_011547121.1:p.Glu242Lys, XR_952745.1:n.2001-169G>A, rs57124011, rs587777916
C > T
 SNP
rs34130495 NC_000006.11:g.160560824G>A, NC_000006.12:g.160139792G>A, NM_003057.2:c.1201G>A, NM_153187.1:c.1201G>A, NP_003048.1:p.Gly401Ser, NP_694857.1:p.Gly401Ser, XM_005267102.1:c.1201G>A, XM_005267102.3:c.1201G>A, XM_005267103.1:c.1201G>A, XM_005267104.1:c.625G>A, XM_005267104.3:c.625G>A, XM_005267105.1:c.625G>A, XM_005267105.3:c.625G>A, XM_006715552.1:c.1201G>A, XM_011536074.1:c.625G>A, XP_005267159.1:p.Gly401Ser, XP_005267160.1:p.Gly401Ser, XP_005267161.1:p.Gly209Ser, XP_005267162.1:p.Gly209Ser, XP_006715615.1:p.Gly401Ser, XP_011534376.1:p.Gly209Ser, rs45512393
G > A
 SNP
G401S
No VIP available CA VA
rs35167514 NC_000006.11:g.160560881delA, NC_000006.12:g.160139849delA, NM_003057.2:c.1258delA, NM_153187.1:c.1258delA, NP_003048.1:p.Met420Terfs, NP_694857.1:p.Met420Terfs, XM_005267102.1:c.1258delA, XM_005267102.3:c.1258delA, XM_005267103.1:c.1258delA, XM_005267104.1:c.682delA, XM_005267104.3:c.682delA, XM_005267105.1:c.682delA, XM_005267105.3:c.682delA, XM_006715552.1:c.1258delA, XM_011536074.1:c.682delA, XP_005267159.1:p.Met420Terfs, XP_005267160.1:p.Met420Terfs, XP_005267161.1:p.Met228Terfs, XP_005267162.1:p.Met228Terfs, XP_006715615.1:p.Met420Terfs, XP_011534376.1:p.Met228Terfs, rs45542538
A > -
 indel
M420*
VIP No Clinical Annotations available No Variant Annotations available
rs35742686 NC_000022.10:g.42524244delT, NC_000022.11:g.42128242delT, NG_008376.3:g.6750delA, NM_000106.5:c.775delA, NM_001025161.2:c.622delA, NP_000097.3:p.Arg259Glyfs, NP_001020332.2:p.Arg208Glyfs, NT_187682.1:g.50583delT, NW_004504305.1:g.50569delT, NW_009646208.1:g.13808delT, XM_005278353.1:c.631delA, XM_005278354.1:c.475delA, XM_005278354.3:c.475delA, XM_011529966.1:c.775delA, XM_011529967.1:c.775delA, XM_011529968.1:c.775delA, XM_011529969.1:c.631delA, XM_011529970.1:c.622delA, XM_011529971.1:c.631delA, XM_011529972.1:c.775delA, XM_011547541.1:c.475delA, XM_011547750.1:c.631delA, XM_011547751.1:c.559delA, XM_011547756.1:c.-1793delT, XM_011548819.1:c.475delA, XP_005278410.1:p.Arg211Glyfs, XP_005278411.1:p.Arg159Glyfs, XP_011528268.1:p.Arg259Glyfs, XP_011528269.1:p.Arg259Glyfs, XP_011528270.1:p.Arg259Glyfs, XP_011528271.1:p.Arg211Glyfs, XP_011528272.1:p.Arg208Glyfs, XP_011528273.1:p.Arg211Glyfs, XP_011528274.1:p.Arg259Glyfs, XP_011545843.1:p.Arg159Glyfs, XP_011546052.1:p.Arg211Glyfs, XP_011546053.1:p.Arg187Glyfs, XP_011547121.1:p.Arg159Glyfs, XR_430455.2:n.-1629delT, XR_952745.1:n.1932delA, rs45593132, rs60790764
T > -
T > T
 indel
R259G
VIP No Clinical Annotations available No Variant Annotations available
rs3892097 NC_000022.10:g.42524947C=, NC_000022.10:g.42524947C>T, NC_000022.11:g.42128945C=, NC_000022.11:g.42128945C>T, NG_008376.3:g.6047G=, NG_008376.3:g.6047G>A, NM_000106.5:c.506-1A>G, NM_000106.5:c.506-1G>A, NM_001025161.2:c.353-1A>G, NM_001025161.2:c.353-1G>A, NT_187682.1:g.51286C=, NT_187682.1:g.51286C>T, NW_004504305.1:g.51272T=, NW_004504305.1:g.51272T>C, NW_009646208.1:g.14511C=, NW_009646208.1:g.14511C>T, XM_005278353.1:c.363-2A>G, XM_005278353.1:c.363-2G>A, XM_005278354.1:c.207-2A>G, XM_005278354.1:c.207-2G>A, XM_005278354.3:c.207-2A>G, XM_005278354.3:c.207-2G>A, XM_011529966.1:c.506-1A>G, XM_011529966.1:c.506-1G>A, XM_011529967.1:c.506-1A>G, XM_011529967.1:c.506-1G>A, XM_011529968.1:c.506-1A>G, XM_011529968.1:c.506-1G>A, XM_011529969.1:c.363-2A>G, XM_011529969.1:c.363-2G>A, XM_011529970.1:c.353-1A>G, XM_011529970.1:c.353-1G>A, XM_011529971.1:c.363-2A>G, XM_011529971.1:c.363-2G>A, XM_011529972.1:c.506-1A>G, XM_011529972.1:c.506-1G>A, XM_011547541.1:c.207-2A>G, XM_011547541.1:c.207-2G>A, XM_011547750.1:c.363-2A>G, XM_011547750.1:c.363-2G>A, XM_011547751.1:c.290-1A>G, XM_011547751.1:c.290-1G>A, XM_011547756.1:c.-1090C>T, XM_011547756.1:c.-1090T>C, XM_011548819.1:c.207-2A>G, XM_011548819.1:c.207-2G>A, XR_430455.2:n.-926C>T, XR_430455.2:n.-926T>C, XR_952745.1:n.1663-1A>G, XR_952745.1:n.1663-1G>A, rs1800716, rs28371711, rs60082401, rs606231227
C > T
 SNP
No VIP available No Clinical Annotations available VA
rs4680 NC_000022.10:g.19951271G>A, NC_000022.11:g.19963748G>A, NG_011526.1:g.27009G>A, NM_000754.3:c.472G>A, NM_001135161.1:c.472G>A, NM_001135162.1:c.472G>A, NM_007310.2:c.322G>A, NP_000745.1:p.Val158Met, NP_001128633.1:p.Val158Met, NP_001128634.1:p.Val158Met, NP_009294.1:p.Val108Met, NR_039918.1:n.-5G>A, XM_005261229.1:c.472G>A, XM_011529885.1:c.586G>A, XM_011529886.1:c.586G>A, XM_011529887.1:c.472G>A, XM_011529888.1:c.472G>A, XM_011529889.1:c.472G>A, XM_011529890.1:c.472G>A, XM_011529891.1:c.472G>A, XP_005261286.1:p.Val158Met, XP_011528187.1:p.Val196Met, XP_011528188.1:p.Val196Met, XP_011528189.1:p.Val158Met, XP_011528190.1:p.Val158Met, XP_011528191.1:p.Val158Met, XP_011528192.1:p.Val158Met, XP_011528193.1:p.Val158Met, rs1131157, rs11544671, rs165688, rs17295216, rs17349704, rs17818178, rs17849308, rs17850006, rs2070104, rs3177905, rs3190784, rs3747070, rs58002978
G > A
 SNP
V158M
VIP No Clinical Annotations available No Variant Annotations available
rs5030655 NC_000022.10:g.42525086delA, NC_000022.11:g.42129084delA, NG_008376.3:g.5908delT, NM_000106.5:c.454delT, NM_001025161.2:c.353-140delT, NP_000097.3:p.Trp152Glyfs, NT_187682.1:g.51425delA, NW_004504305.1:g.51411delA, NW_009646208.1:g.14650delA, XM_005278353.1:c.363-141delT, XM_005278354.1:c.155delT, XM_005278354.3:c.155delT, XM_011529966.1:c.454delT, XM_011529967.1:c.454delT, XM_011529968.1:c.454delT, XM_011529969.1:c.311delT, XM_011529970.1:c.353-140delT, XM_011529971.1:c.311delT, XM_011529972.1:c.454delT, XM_011547541.1:c.155delT, XM_011547750.1:c.311delT, XM_011547751.1:c.238delT, XM_011547756.1:c.-951delA, XM_011548819.1:c.155delT, XP_005278411.1:p.Val52Glyfs, XP_011528268.1:p.Trp152Glyfs, XP_011528269.1:p.Trp152Glyfs, XP_011528270.1:p.Trp152Glyfs, XP_011528271.1:p.Val104Glyfs, XP_011528273.1:p.Val104Glyfs, XP_011528274.1:p.Trp152Glyfs, XP_011545843.1:p.Val52Glyfs, XP_011546052.1:p.Val104Glyfs, XP_011546053.1:p.Trp80Glyfs, XP_011547121.1:p.Val52Glyfs, XR_430455.2:n.-787delA, XR_952745.1:n.1611delT, rs11568727, rs28371709
A > -
A > A
 indel
W152G
VIP No Clinical Annotations available No Variant Annotations available
rs5030656 NC_000022.10:g.42524176_42524178delCTT, NC_000022.11:g.42128174_42128176delCTT, NG_008376.3:g.6816_6818delAAG, NM_000106.5:c.841_843delAAG, NM_001025161.2:c.688_690delAAG, NP_000097.3:p.Lys281del, NP_001020332.2:p.Lys230del, NT_187682.1:g.50515_50517delCTT, NW_004504305.1:g.50501_50503delCTT, NW_009646208.1:g.13740_13742delCTT, XM_005278353.1:c.697_699delAAG, XM_005278354.1:c.541_543delAAG, XM_005278354.3:c.541_543delAAG, XM_011529966.1:c.841_843delAAG, XM_011529967.1:c.841_843delAAG, XM_011529968.1:c.841_843delAAG, XM_011529969.1:c.697_699delAAG, XM_011529970.1:c.688_690delAAG, XM_011529971.1:c.697_699delAAG, XM_011529972.1:c.841_843delAAG, XM_011547541.1:c.541_543delAAG, XM_011547750.1:c.697_699delAAG, XM_011547751.1:c.625_627delAAG, XM_011547756.1:c.-1861_-1859del, XM_011548819.1:c.541_543delAAG, XP_005278410.1:p.Lys233del, XP_005278411.1:p.Lys181del, XP_011528268.1:p.Lys281del, XP_011528269.1:p.Lys281del, XP_011528270.1:p.Lys281del, XP_011528271.1:p.Lys233del, XP_011528272.1:p.Lys230del, XP_011528273.1:p.Lys233del, XP_011528274.1:p.Lys281del, XP_011545843.1:p.Lys181del, XP_011546052.1:p.Lys233del, XP_011546053.1:p.Lys209del, XP_011547121.1:p.Lys181del, XR_430455.2:n.-1697_-1695del, XR_952745.1:n.1998_2000delAAG, rs587777919
CTT > -
CTT > CTT
 indel
VIP No Clinical Annotations available No Variant Annotations available
rs59421388 NC_000022.10:g.42523610C>T, NC_000022.11:g.42127608C>T, NG_008376.3:g.7384G>A, NM_000106.5:c.1012G>A, NM_001025161.2:c.859G>A, NP_000097.3:p.Val338Met, NP_001020332.2:p.Val287Met, NT_187682.1:g.49949C>T, NW_004504305.1:g.49935C>T, NW_009646208.1:g.13174C>T, XM_005278353.1:c.868G>A, XM_005278354.1:c.712G>A, XM_005278354.3:c.712G>A, XM_011529966.1:c.1012G>A, XM_011529967.1:c.1012G>A, XM_011529968.1:c.1012G>A, XM_011529969.1:c.868G>A, XM_011529970.1:c.859G>A, XM_011529971.1:c.868G>A, XM_011529972.1:c.870G>A, XM_011547541.1:c.*118G>A, XM_011547750.1:c.868G>A, XM_011547751.1:c.796G>A, XM_011548819.1:c.*118G>A, XP_005278410.1:p.Val290Met, XP_005278411.1:p.Val238Met, XP_011528268.1:p.Val338Met, XP_011528269.1:p.Val338Met, XP_011528270.1:p.Val338Met, XP_011528271.1:p.Val290Met, XP_011528272.1:p.Val287Met, XP_011528273.1:p.Val290Met, XP_011528274.1:p.Thr290=, XP_011546052.1:p.Val290Met, XP_011546053.1:p.Val266Met, XR_952745.1:n.2027G>A
C > T
 SNP
V338M
VIP No Clinical Annotations available No Variant Annotations available
rs61736512 NC_000022.10:g.42525134C>T, NC_000022.11:g.42129132C>T, NG_008376.3:g.5860G>A, NM_000106.5:c.406G>A, NM_001025161.2:c.353-188G>A, NP_000097.3:p.Val136Met, NT_187682.1:g.51473C>T, NW_004504305.1:g.51459C>T, NW_009646208.1:g.14698C>T, XM_005278353.1:c.363-189G>A, XM_005278354.1:c.107G>A, XM_005278354.3:c.107G>A, XM_011529966.1:c.406G>A, XM_011529967.1:c.406G>A, XM_011529968.1:c.406G>A, XM_011529969.1:c.263G>A, XM_011529970.1:c.353-188G>A, XM_011529971.1:c.263G>A, XM_011529972.1:c.406G>A, XM_011547541.1:c.107G>A, XM_011547750.1:c.263G>A, XM_011547751.1:c.190G>A, XM_011547756.1:c.-903C>T, XM_011548819.1:c.107G>A, XP_005278411.1:p.Arg36His, XP_011528268.1:p.Val136Met, XP_011528269.1:p.Val136Met, XP_011528270.1:p.Val136Met, XP_011528271.1:p.Arg88His, XP_011528273.1:p.Arg88His, XP_011528274.1:p.Val136Met, XP_011545843.1:p.Arg36His, XP_011546052.1:p.Arg88His, XP_011546053.1:p.Val64Ile, XP_011547121.1:p.Arg36His, XR_430455.2:n.-739C>T, XR_952745.1:n.1563G>A
C > T
 SNP
V136M
VIP No Clinical Annotations available No Variant Annotations available
rs72552763 NC_000006.11:g.160560883_160560885delGAT, NC_000006.12:g.160139851_160139853delGAT, NM_003057.2:c.1260_1262delGAT, NM_153187.1:c.1260_1262delGAT, NP_003048.1:p.Met420del, NP_694857.1:p.Met420del, XM_005267102.1:c.1260_1262delGAT, XM_005267102.3:c.1260_1262delGAT, XM_005267103.1:c.1260_1262delGAT, XM_005267104.1:c.684_686delGAT, XM_005267104.3:c.684_686delGAT, XM_005267105.1:c.684_686delGAT, XM_005267105.3:c.684_686delGAT, XM_006715552.1:c.1260_1262delGAT, XM_011536074.1:c.684_686delGAT, XP_005267159.1:p.Met420del, XP_005267160.1:p.Met420del, XP_005267161.1:p.Met228del, XP_005267162.1:p.Met228del, XP_006715615.1:p.Met420del, XP_011534376.1:p.Met228del
GAT > -
 indel
Alleles, Functions, and Amino Acid Translations are all sourced from dbSNP 147
2D structure from PubChem
provided by PubChem

Overview

Generic Names
  • Tramadol HCl
  • Tramadol hydrochloride
  • Tramadolum [INN-Latin]
  • Tramodol Hcl
  • tramadol
Trade Names
  • Crispin
  • Ralivia ER
  • Ralivia Flashtab
  • Tramadol HCl BP/EP
  • Tramal
  • Tridural
  • Ultram
  • Ultram ER
  • Zydol
Brand Mixture Names

PharmGKB Accession Id

PA451735

Type(s):

Drug

Description

A narcotic analgesic proposed for moderate to severe pain. It may be habituating.

Source: Drug Bank

Pharmacogenetics

Pharmacokinetics

Tramadol can be O-demethylated to the active metabolite O-desmethyltramadol (M1) by CYP2D6 [Article:19180260] and N-demethylated to M2 by CYP3A4 [Articles:15530129, 19180260] and CYP2B6 [Article:19180260].

CYP2D6*10 was associated with altered pharmacokinetics of tramadol in healthy Chinese subjects but CYP2D6*2 had no effect [Article:20456744].

Transport

ABCB1 did not transport of tramadol or metabolites in vitro [Article:19496778] although the ABCB1 variant [RSID:rs1045642] (3435C>T) has been associated with tramadol pharmacokinetics in vivo [Article:17265061]. Kanaan et al suggest that the PEPT1 transporter SLC15A1 may transport tramadol and although did not demonstrate this conclusively [Article:19496778].

Pharmacodynamics

Tramadol is a synthetic opioid that acts at OPRM1 (mu opioid receptor) [Article:20179508]. The M1 metabolite has a higher affinity for OPRM1 than the parent drug [Article:20179508]. Additional analgesic effects of tramadol occur via seratonergic pathways involving HTR7 in mice [Article:20179508] and HTR3 in human [Article:12032025] and norepinephrine neurotransmission [Article:19180260]. Tramadol is a racemic mixture where (+)tramadol inhibits serotonin reuptake and (-)tramadol inhibits norepinephrine reuptake [Article:15509185]. Serotonin syndrome may occur in patients taking combinations of tramadol and other agents that increase serotonin activity [Article:19180260].

Source: PharmGKB

Indication

Indicated in the treatment of moderate to severe pain. Consider for those prone to constipation or respiratory depression. Tramadol is used to treat postoperative, dental, cancer, and acute musculosketetal pain and as an adjuvant to NSAID therapy in patients with osteoarthritis.

Source: Drug Bank

Other Vocabularies

Information pulled from DrugBank has not been reviewed by PharmGKB.

Pharmacology, Interactions, and Contraindications

Mechanism of Action

Tramadol and its O-desmethyl metabolite (M1) are selective, weak OP3-receptor agonists. Opiate receptors are coupled with G-protein receptors and function as both positive and negative regulators of synaptic transmission via G-proteins that activate effector proteins. As the effector system is adenylate cyclase and cAMP located at the inner surface of the plasma membrane, opioids decrease intracellular cAMP by inhibiting adenylate cyclase. Subsequently, the release of nociceptive neurotransmitters such as substance P, GABA, dopamine, acetylcholine and noradrenaline is inhibited. The analgesic properties of Tramadol can be attributed to norepinephrine and serotonin reuptake blockade in the CNS, which inhibits pain transmission in the spinal cord. The (+) enantiomer has higher affinity for the OP3 receptor and preferentially inhibits serotonin uptake and enhances serotonin release. The (-) enantiomer preferentially inhibits norepinephrine reuptake by stimulating alpha(2)-adrenergic receptors.

Source: Drug Bank

Pharmacology

Tramadol, a centrally-acting analgesic, exists as a racemic mixture of the _trans_ isomer, with important differences in binding, activity, and metabolism associated with the two enantiomers. Although Tramadol is a synthetic analog of codeine, it has a significantly lower affinity for opioid receptors than codeine.

Source: Drug Bank

Absorption, Distribution, Metabolism, Elimination & Toxicity

Biotransformation

The major metabolic pathways appear to be N- and O- demethylation and glucuronidation or sulfation in the liver. One metabolite (O-desmethyltramadol, denoted M1) is pharmacologically active in animal models.

Source: Drug Bank

Protein Binding

20%

Source: Drug Bank

Absorption

Racemic tramadol is rapidly and almost completely absorbed after oral administration. The mean absolute bioavailability of a 100 mg oral dose is approximately 75%.The mean peak plasma concentration of racemic tramadol and M1 occurs at two and three hours, respectively, after administration in healthy adults.

Source: Drug Bank

Half-Life

23 +/- 10 minutes

Source: Drug Bank

Toxicity

LD ~50~=350mg/kg (orally in mice)

Source: Drug Bank

Clearance

* 5.9 mL/min/Kg [Healthy Adults, 100 mg qid, MD p.o] * 8.5 mL/min/Kg [Healthy Adults, 100 mg SD p.o] * 6.89 mL/min/Kg [Geriatric, (<75 yr), 50 mg SD p.o.] * 4.23 mL/min/Kg [Hepatic Impaired, 50 mg SD p.o.] * 4.23 mL/min/Kg [Renal Impaired, Clcr10-3mL/min, 100 mg SD i.v.] * 3.73 mL/min/Kg [Renal Impaired, CLcr<5 mL/min, 100 mg SD i.v.] * 6.4 mL/min/Kg [Male following a 100 mg IV dose] * 5.7 mL/min/Kg [Female following a 100 mg IV dose]

Source: Drug Bank

Route of Elimination

Tramadol is eliminated primarily through metabolism by the liver and the metabolites are eliminated primarily by the kidneys. Tramadol and its metabolites are excreted primarily in the urine with observed plasma half-lives of 6.3 and 7.4 hours for tramadol and M1, respectively. Approximately 30% of the dose is excreted in the urine as unchanged drug, whereas 60% of the dose is excreted as metabolites.

Source: Drug Bank

Volume of Distribution

* 2.6 L/kg [male 100 mg intravenous dose] * 2.9 L/kg [female 100 mg intravenous dose]

Source: Drug Bank

Chemical Properties

Chemical Formula

C16H25NO2

Source: Drug Bank

Average Molecular Weight

263.3752

Source: Drug Bank

Monoisotopic Molecular Weight

263.188529049

Source: Drug Bank

SMILES

CN(C)C[C@H]1CCCC[C@@]1(C2=CC(=CC=C2)OC)O

Source: PubChem

InChI String

InChI=1S/C16H25NO2/c1-17(2)12-14-7-4-5-10-16(14,18)13-8-6-9-15(11-13)19-3/h6,8-9,11,14,18H,4-5,7,10,12H2,1-3H3/t14-,16+/m1/s1

Source: PubChem

PharmGKB Curated Pathways

Pathways created internally by PharmGKB based primarily on literature evidence.

  1. Tramadol Pharmacokinetics
    Schematic representation of tramadol metabolism in human liver cell.

Genes that are associated with this drug in PharmGKB's database based on (1) variant annotations, (2) literature review, (3) pathways or (4) information automatically retrieved from DrugBank, depending on the "evidence" and "source" listed below.

Curated Information ?

EvidenceGene
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
ABCB1
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
COMT
No Dosing Guideline available DL No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
CYP1A2
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available PW
CYP2B6
DG DL CA VA VIP PW
CYP2D6
No Dosing Guideline available DL No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
CYP2E1
No Dosing Guideline available DL No Clinical Annotation available No Variant Annotation available No VIP available PW
CYP3A4
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
OPRM1
No Dosing Guideline available No Drug Label available CA VA VIP No VIP available
SLC22A1

Drug Targets

Gene Description
CHRM3 (source: Drug Bank )
GRIN3A (source: Drug Bank )
HTR2C (source: Drug Bank )
OPRD1 (source: Drug Bank )
OPRK1 (source: Drug Bank )
OPRM1 (source: Drug Bank )
SLC6A2 (source: Drug Bank )
SLC6A4 (source: Drug Bank )

Drug Interactions

Interaction Description
carbamazepine - tramadol Reduces the efficacy of tramadol (source: Drug Bank )
carbamazepine - tramadol Reduces the efficacy of tramadol (source: Drug Bank )
escitalopram - tramadol Increased risk of serotonin syndrome (source: Drug Bank )
escitalopram - tramadol Increased risk of serotonin syndrome (source: Drug Bank )
fluoxetine - tramadol Increased risk of serotonin syndrome (source: Drug Bank )
fluoxetine - tramadol Increased risk of serotonin syndrome (source: Drug Bank )
isocarboxazid - tramadol Increased risk of seizures and serotonin syndrome (source: Drug Bank )
isocarboxazid - tramadol Increased risk of seizures and serotonin syndrome (source: Drug Bank )
moclobemide - tramadol Increased risk of seizures and serotonin syndrome (source: Drug Bank )
moclobemide - tramadol Increased risk of seizures and serotonin syndrome (source: Drug Bank )
moclobemide - tramadol Increased risk of seizures and serotonin syndrome (source: Drug Bank )
nefazodone - tramadol Increased risk of serotonin syndrome (source: Drug Bank )
nefazodone - tramadol Increased risk of serotonin syndrome (source: Drug Bank )
phenelzine - tramadol Increased risk of seizures and serotonin syndrome (source: Drug Bank )
phenelzine - tramadol Increased risk of seizures and serotonin syndrome (source: Drug Bank )
rasagiline - tramadol Increased risk of seizures and serotonin syndrome (source: Drug Bank )
telithromycin - tramadol Telithromycin may reduce clearance of Tramadol. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Tramadol if Telithromycin is initiated, discontinued or dose changed. (source: Drug Bank )
tramadol - almotriptan Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome. (source: Drug Bank )
tramadol - aminoglutethimide Aminoglutethimide may decrease the effect of Tramadol by increasing Tramadol metabolism and clearance. (source: Drug Bank )
tramadol - amiodarone Amiodarone may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance. Amiodarone may decrease the effect of Tramadol by decreasing active metabolite production. (source: Drug Bank )
tramadol - amitriptyline Tramadol increases the risk of serotonin syndrome and seizures. (source: Drug Bank )
tramadol - amoxapine Tramadol increases the risk of serotonin syndrome and seizures. (source: Drug Bank )
tramadol - amprenavir Amprenavir may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance. (source: Drug Bank )
tramadol - aprepitant Aprepitant may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance. (source: Drug Bank )
tramadol - atazanavir Atazanavir may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance. (source: Drug Bank )
tramadol - benzphetamine Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome. (source: Drug Bank )
tramadol - bosentan Bosentan may decrease the effect of Tramadol by increasing Tramadol metabolism and clearance. (source: Drug Bank )
tramadol - bromocriptine Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome. (source: Drug Bank )
tramadol - cabergoline Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome. (source: Drug Bank )
tramadol - carbamazepine Carbamazepine may decrease the effect of Tramadol by increasing Tramadol metabolism and clearance. (source: Drug Bank )
tramadol - chloroquine Chloroquine may decrease the effect of Tramadol by decreasing active metabolite production. (source: Drug Bank )
tramadol - chlorpromazine Chlorpromazine may decrease the effect of Tramadol by decreasing active metabolite production. (source: Drug Bank )
tramadol - cimetidine Cimetidine may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance. Cimetidine may decrease the effect of Tramadol by decreasing active metabolite production. (source: Drug Bank )
tramadol - cinacalcet Cinacalcet may decrease the effect of Tramadol by decreasing active metabolite production. (source: Drug Bank )
tramadol - citalopram Tramadol increases the risk of serotonin syndrome and seizures. (source: Drug Bank )
tramadol - clarithromycin Clarithromycin may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance. (source: Drug Bank )
tramadol - clomipramine Tramadol increases the risk of serotonin syndrome and seizures. Clomipramine may decrease the effect of Tramadol by decreasing active metabolite production. (source: Drug Bank )
tramadol - clotrimazole Clotrimazole may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance. (source: Drug Bank )
tramadol - clozapine Clozapine may decrease the effect of Tramadol by decreasing active metabolite production. (source: Drug Bank )
tramadol - cocaine Cocaine may decrease the effect of Tramadol by decreasing active metabolite production. (source: Drug Bank )
tramadol - conivaptan Conivaptan may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance. (source: Drug Bank )
tramadol - cyclobenzaprine Increases risk of seizure. (source: Drug Bank )
tramadol - cyclosporine Cyclosporine may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance. (source: Drug Bank )
tramadol - darifenacin Darifenacin may decrease the effect of Tramadol by decreasing active metabolite production. (source: Drug Bank )
tramadol - darunavir Darunavir may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance. (source: Drug Bank )
tramadol - delavirdine Delavirdine may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance. Delavirdine may decrease the effect of Tramadol by decreasing active metabolite production. (source: Drug Bank )
tramadol - desipramine Tramadol increases the risk of serotonin syndrome and seizures. Desipramine may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance. Desipramine may decrease the effect of Tramadol by decreasing active metabolite production. (source: Drug Bank )
tramadol - dexamethasone Dexamethasone may decrease the effect of Tramadol by increasing Tramadol metabolism and clearance. (source: Drug Bank )
tramadol - dextroamphetamine Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome. (source: Drug Bank )
tramadol - dextromethorphan Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome. (source: Drug Bank )
tramadol - dihydroergotamine Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome. (source: Drug Bank )
tramadol - diltiazem Diltiazem may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance. (source: Drug Bank )
tramadol - diphenhydramine Diphenhydramine may decrease the effect of Tramadol by decreasing active metabolite production. (source: Drug Bank )
tramadol - doxepin Tramadol increases the risk of serotonin syndrome and seizures. (source: Drug Bank )
tramadol - duloxetine Duloxetine may decrease the effect of Tramadol by decreasing active metabolite production. Increased risk of serotonin syndrome. Monitor for Tramadol efficacy and symptoms of serotonin syndrome. (source: Drug Bank )
tramadol - efavirenz Efavirenz may decrease the effect of Tramadol by increasing Tramadol metabolism and clearance. (source: Drug Bank )
tramadol - eletriptan Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome. (source: Drug Bank )
tramadol - ergonovine Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome. (source: Drug Bank )
tramadol - ergotamine Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome. (source: Drug Bank )
tramadol - erythromycin Erythromycin may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance. (source: Drug Bank )
tramadol - escitalopram Tramadol increases the risk of serotonin syndrome and seizures. (source: Drug Bank )
tramadol - fluconazole Fluconazole may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance. (source: Drug Bank )
tramadol - fluoxetine Tramadol increases the risk of serotonin syndrome and seizures. Fluoxetine may decrease the effect of Tramadol by decreasing active metabolite production. (source: Drug Bank )
tramadol - fluvoxamine Tramadol increases the risk of serotonin syndrome and seizures. (source: Drug Bank )
tramadol - fosamprenavir Fosamprenavir may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance. (source: Drug Bank )
tramadol - fosphenytoin Fosphenytoin may decrease the effect of Tramadol by increasing Tramadol metabolism and clearance. (source: Drug Bank )
tramadol - frovatriptan Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome. (source: Drug Bank )
tramadol - furazolidone Tramadol increases the risk of serotonin syndrome and seizure induction by the MAO inhibitor, Furazolidone. (source: Drug Bank )
tramadol - haloperidol Haloperidol may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance. Haloperidol may decrease the effect of Tramadol by decreasing active metabolite production. (source: Drug Bank )
tramadol - imatinib Imatinib may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance. Imatinib may decrease the effect of Tramadol by decreasing active metabolite production. (source: Drug Bank )
tramadol - imipramine Tramadol increases the risk of serotonin syndrome and seizures. Imipramine may decrease the effect of Tramadol by decreasing active metabolite production. (source: Drug Bank )
tramadol - indinavir Indinavir may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance. (source: Drug Bank )
tramadol - isocarboxazid Tramadol increases the risk of serotonin syndrome and seizure induction by the MAO inhibitor, Isocarboxazid. (source: Drug Bank )
tramadol - isoniazid Isoniazid may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance. Isoniazid may decrease the effect of Tramadol by decreasing active metabolite production. (source: Drug Bank )
tramadol - itraconazole Itraconazole may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance. (source: Drug Bank )
tramadol - ketoconazole Ketoconazole may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance. Ketoconazole may decrease the effect of Tramadol by decreasing active metabolite production. (source: Drug Bank )
tramadol - lapatinib Lapatinib may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance. (source: Drug Bank )
tramadol - lidocaine Lidocaine may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance. Lidocaine may decrease the effect of Tramadol by decreasing active metabolite production. (source: Drug Bank )
tramadol - linezolid Tramadol increases the risk of serotonin syndrome and seizure induction by the MAO inhibitor, Linezolid. (source: Drug Bank )
tramadol - lisdexamfetamine Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome. (source: Drug Bank )
tramadol - lopinavir Lopinavir may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance. Lopinavir may decrease the effect of Tramadol by decreasing active metabolite production. (source: Drug Bank )
tramadol - maprotiline Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome. (source: Drug Bank )
tramadol - meperidine Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome. (source: Drug Bank )
tramadol - methadone Methadone may decrease the effect of Tramadol by decreasing active metabolite production. (source: Drug Bank )
tramadol - methamphetamine Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome. (source: Drug Bank )
tramadol - methotrimeprazine Additive CNS depressant effects. Decrease dose of tramadol by 50% if initiating methotrimeprazine therapy. Monitor for increased CNS depression and apply further dosage adjustments as required. (source: Drug Bank )
tramadol - methylergonovine Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome. (source: Drug Bank )
tramadol - metronidazole Metronidazole may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance. (source: Drug Bank )
tramadol - miconazole Miconazole may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance. Miconazole may decrease the effect of Tramadol by decreasing active metabolite production. (source: Drug Bank )
tramadol - mirtazapine Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome. (source: Drug Bank )
tramadol - moclobemide Tramadol increases the risk of serotonin syndrome and seizure induction by the MAO inhibitor, Moclobemide. (source: Drug Bank )
tramadol - nafcillin Nafcillin may decrease the effect of Tramadol by increasing Tramadol metabolism and clearance. (source: Drug Bank )
tramadol - naratriptan Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome. (source: Drug Bank )
tramadol - nefazodone Nefazodone may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance. Increased risk of serotonin syndrome. Monitor for Tramadol toxicity and symptoms of serotonin syndrome. (source: Drug Bank )
tramadol - nelfinavir Nelfinavir may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance. (source: Drug Bank )
tramadol - nevirapine Nevirapine may decrease the effect of Tramadol by increasing Tramadol metabolism and clearance. (source: Drug Bank )
tramadol - nicardipine Nicardipine may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance. Nicardipine may decrease the effect of Tramadol by decreasing active metabolite production. (source: Drug Bank )
tramadol - nilotinib Nilotinib may decrease the effect of Tramadol by decreasing active metabolite production. (source: Drug Bank )
tramadol - norfloxacin Norfloxacin may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance. (source: Drug Bank )
tramadol - nortriptyline Tramadol increases the risk of serotonin syndrome and seizures. (source: Drug Bank )
tramadol - oxcarbazepine Oxcarbazepine may decrease the effect of Tramadol by increasing Tramadol metabolism and clearance. (source: Drug Bank )
tramadol - paroxetine Tramadol increases the risk of serotonin syndrome and seizures. Paroxetine may decrease the effect of Tramadol by decreasing active metabolite production. (source: Drug Bank )
tramadol - pentobarbital Pentobarbital may decrease the effect of Tramadol by increasing Tramadol metabolism and clearance. (source: Drug Bank )
tramadol - pergolide Pergolide may decrease the effect of Tramadol by decreasing active metabolite production. Increased risk of serotonin syndrome. Monitor for Tramadol efficacy and symptoms of serotonin syndrome. (source: Drug Bank )
tramadol - phendimetrazine Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome. (source: Drug Bank )
tramadol - phenelzine Tramadol increases the risk of serotonin syndrome and seizure induction by the MAO inhibitor, Phenelzine. (source: Drug Bank )
tramadol - phenobarbital Phenobarbital may decrease the effect of Tramadol by increasing Tramadol metabolism and clearance. (source: Drug Bank )
tramadol - phentermine Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome. (source: Drug Bank )
tramadol - phenytoin Phenytoin may decrease the effect of Tramadol by increasing Tramadol metabolism and clearance. (source: Drug Bank )
tramadol - pioglitazone Pioglitazone may decrease the effect of Tramadol by decreasing active metabolite production. (source: Drug Bank )
tramadol - posaconazole Posaconazole may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance. (source: Drug Bank )
tramadol - primidone Primidone may decrease the effect of Tramadol by increasing Tramadol metabolism and clearance. (source: Drug Bank )
tramadol - procarbazine Tramadol increases the risk of serotonin syndrome and seizure induction by the MAO inhibitor, Procarbazine. (source: Drug Bank )
tramadol - promethazine Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome. (source: Drug Bank )
tramadol - protriptyline Tramadol increases the risk of serotonin syndrome and seizures. (source: Drug Bank )
tramadol - pyrimethamine Pyrimethamine may decrease the effect of Tramadol by decreasing active metabolite production. (source: Drug Bank )
tramadol - quinidine Quinidine may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance. Quinidine may decrease the effect of Tramadol by decreasing active metabolite production. (source: Drug Bank )
tramadol - quinine Quinine may decrease the effect of Tramadol by decreasing active metabolite production. (source: Drug Bank )
tramadol - ranolazine Ranolazine may decrease the effect of Tramadol by decreasing active metabolite production. (source: Drug Bank )
tramadol - rasagiline Tramadol increases the risk of serotonin syndrome and seizure induction by the MAO inhibitor, Rasagiline. (source: Drug Bank )
tramadol - rifabutin Rifabutin may decrease the effect of Tramadol by increasing Tramadol metabolism and clearance. (source: Drug Bank )
tramadol - rifampin Rifampin may decrease the effect of Tramadol by increasing Tramadol metabolism and clearance. (source: Drug Bank )
tramadol - rifapentine Rifapentine may decrease the effect of Tramadol by increasing Tramadol metabolism and clearance. (source: Drug Bank )
tramadol - ritonavir Ritonavir may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance. Ritonavir may decrease the effect of Tramadol by decreasing active metabolite production. (source: Drug Bank )
tramadol - rizatriptan Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome. (source: Drug Bank )
tramadol - s-adenosylmethionine Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome. (source: Drug Bank )
tramadol - saquinavir Saquinavir may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance. (source: Drug Bank )
tramadol - selegiline Tramadol increases the risk of serotonin syndrome and seizure induction by the MAO inhibitor, Selegiline. (source: Drug Bank )
tramadol - sertraline Tramadol increases the risk of serotonin syndrome and seizures. Sertraline may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance. Sertraline may decrease the effect of Tramadol by decreasing active metabolite production. (source: Drug Bank )
tramadol - sibutramine Sibutramine may incrase the serotonergic effect of the Tramadol. Concomitant therapy should be avoided. (source: Drug Bank )
tramadol - sumatriptan Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome. (source: Drug Bank )
tramadol - telithromycin Telithromycin may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance. (source: Drug Bank )
tramadol - terbinafine Terbinafine may decrease the effect of Tramadol by decreasing active metabolite production. (source: Drug Bank )
tramadol - tetracycline Tetracycline may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance. (source: Drug Bank )
tramadol - thioridazine Thioridazine may decrease the effect of Tramadol by decreasing active metabolite production. (source: Drug Bank )
tramadol - ticlopidine Ticlopidine may decrease the effect of Tramadol by decreasing active metabolite production. (source: Drug Bank )
tramadol - tranylcypromine Tramadol increases the risk of serotonin syndrome and seizure induction by the MAO inhibitor, Tranylcypromine. Tranylcypromine may decrease the effect of Tramadol by decreasing active metabolite production. (source: Drug Bank )
tramadol - trazodone Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome. (source: Drug Bank )
tramadol - trimipramine Tramadol increases the risk of serotonin syndrome and seizures. (source: Drug Bank )
tramadol - venlafaxine Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome. (source: Drug Bank )
tramadol - verapamil Verapamil may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance. (source: Drug Bank )
tramadol - voriconazole Voriconzole may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance. (source: Drug Bank )
tramadol - zolmitriptan Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome. (source: Drug Bank )
tranylcypromine - tramadol Increased risk of serotonin syndrome. Use caution during concomitant therapy and monitor for symptoms of serotonin syndrome. (source: Drug Bank )
trazodone - tramadol Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome. (source: Drug Bank )
trazodone - tramadol Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome. (source: Drug Bank )
trimipramine - tramadol Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome. (source: Drug Bank )
triprolidine - tramadol The CNS depressants, Triprolidine and Tramadol, may increase adverse/toxic effects due to additivity. Monitor for increased CNS depressant effects during concomitant therapy. (source: Drug Bank )
triprolidine - tramadol The CNS depressants, Triprolidine and Tramadol, may increase adverse/toxic effects due to additivity. Monitor for increased CNS depressant effects during concomitant therapy. (source: Drug Bank )
venlafaxine - tramadol Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome. (source: Drug Bank )
voriconazole - tramadol Voriconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of tramadol by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of tramadol if voriconazole is initiated, discontinued or dose changed. (source: Drug Bank )
zolmitriptan - tramadol Use of two serotonin modulators, such as zolmitriptan and tramadol, increases the risk of serotonin syndrome. Consider alternate therapy or monitor for serotonin syndrome during concomitant therapy. (source: Drug Bank )

Curated Information ?

EvidenceDisease
No Dosing Guideline available DL No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Epidermal Necrolysis, Toxic
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Fractures, Bone
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Heroin Dependence
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
Nausea
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
neuropathic pain
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Opioid-Related Disorders
No Dosing Guideline available DL CA VA No VIP available No VIP available
Pain
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Pain, Postoperative
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
Respiratory Insufficiency
No Dosing Guideline available DL No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Stevens-Johnson Syndrome

Relationships from National Drug File - Reference Terminology (NDF-RT)

May Treat
Contraindicated With

Publications related to tramadol: 69

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Clinical and educational impact of pharmacogenomics testing: a case series from the INGENIOUS trial. Pharmacogenomics. 2017. Pierson Rebecca C, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Increased risk of hospitalization for ultrarapid metabolizers of cytochrome P450 2D6. Pharmacogenomics and personalized medicine. 2017. Takahashi Paul Y, et al. PubMed
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The role of cytochrome P450 pharmacogenomics in chronic non-cancer pain patients. Expert opinion on drug metabolism & toxicology. 2016. Tverdohleb Tatiana, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Cytochrome P-450 gene and drug interaction analysis in patients referred for pharmacogenetic testing. American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists. 2016. Hocum Brian Thomas, et al. PubMed
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Pharmacogenomically actionable medications in a safety net health care system. SAGE open medicine. 2016. Carpenter Janet S, et al. PubMed
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Development of Human Membrane Transporters: Drug Disposition and Pharmacogenetics. Clinical pharmacokinetics. 2015. Mooij Miriam G, et al. PubMed
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Effect of the CYP2D6 gene polymorphism on postoperative analgesia of tramadol in Han nationality nephrectomy patients. European journal of clinical pharmacology. 2015. Dong Hong, et al. PubMed
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Naltrexone vs Placebo for the Treatment of Alcohol Dependence: A Randomized Clinical Trial. JAMA psychiatry. 2015. Oslin David W, et al. PubMed
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Pharmacogenetics of opioid response. Clinical pharmacology and therapeutics. 2015. Somogyi A A, et al. PubMed
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A Case of Respiratory Depression in a Child With Ultrarapid CYP2D6 Metabolism After Tramadol. Pediatrics. 2015. Orliaguet Gilles, et al. PubMed
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OPRM1 genotype and naltrexone response in depressed alcohol-dependent patients. Pharmacogenetics and genomics. 2015. Foulds James A, et al. PubMed
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Methadone dose in heroin-dependent patients: role of clinical factors, comedications, genetic polymorphisms and enzyme activity. British journal of clinical pharmacology. 2014. Mouly S, et al. PubMed
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Association of OPRM1 A118G variant with risk of morphine-induced respiratory depression following spine fusion in adolescents. The pharmacogenomics journal. 2014. Chidambaran V, et al. PubMed
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Rescue morphine in mechanically ventilated newborns associated with combined OPRM1 and COMT genotype. Pharmacogenomics. 2014. Matic Maja, et al. PubMed
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PharmGKB summary: tramadol pathway. Pharmacogenetics and genomics. 2014. Gong Li, et al. PubMed
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PharmGKB summary: very important pharmacogene information for SLC22A1. Pharmacogenetics and genomics. 2014. Goswami Srijib, et al. PubMed
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A logistic equation to determine the validity of tramadol from related gene polymorphisms and psychological factors. Pharmacogenomics. 2014. Zhao Qin, et al. PubMed
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CYP2D6 and pharmacogenomics: where does future research need to focus? Part 1: technical aspects. Pharmacogenomics. 2014. Gaedigk Andrea, et al. PubMed
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Challenges in pharmacogenetics. European journal of clinical pharmacology. 2013. Cascorbi Ingolf, et al. PubMed
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Association of OPRM1 and COMT single-nucleotide polymorphisms with hospital length of stay and treatment of neonatal abstinence syndrome. JAMA : the journal of the American Medical Association. 2013. Wachman Elisha M, et al. PubMed
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Cytochrome P450-mediated drug metabolism in the brain. Journal of psychiatry & neuroscience : JPN. 2012. Miksys Sharon, et al. PubMed
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Mutations in monoamine oxidase (MAO) genes in mice lead to hypersensitivity to serotonin-enhancing drugs: implications for drug side effects in humans. The pharmacogenomics journal. 2012. Fox M A, et al. PubMed
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Human mu-opioid receptor gene A118G polymorphism predicts the efficacy of tramadol/acetaminophen combination tablets (ultracet) in oxaliplatin-induced painful neuropathy. Cancer. 2012. Liu Yu-Chang, et al. PubMed
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Impact of genetic polymorphisms in ABCB1, CYP2B6, OPRM1, ANKK1 and DRD2 genes on methadone therapy in Han Chinese patients. Pharmacogenomics. 2011. Hung Chin-Chuan, et al. PubMed
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Near-fatal tramadol cardiotoxicity in a CYP2D6 ultrarapid metabolizer. European journal of clinical pharmacology. 2011. Elkalioubie Ahmed, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA VIP No VIP available
Genetically Polymorphic OCT1: Another Piece in the Puzzle of the Variable Pharmacokinetics and Pharmacodynamics of the Opioidergic Drug Tramadol. Clinical pharmacology and therapeutics. 2011. Tzvetkov M V, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Uniform assessment and ranking of opioid μ receptor binding constants for selected opioid drugs. Regulatory toxicology and pharmacology : RTP. 2011. Volpe Donna A, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Pharmacogenetics: From Bench to Byte- An Update of Guidelines. Clinical pharmacology and therapeutics. 2011. Swen J J, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Lack of Association of OPRM1 and ABCB1 Single-Nucleotide Polymorphisms to Oxycodone Response in Postoperative Pain. Journal of clinical pharmacology. 2011. Zwisler Stine T, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Developmental pharmacology of tramadol during infancy: ontogeny, pharmacogenetics and elimination clearance. Paediatric anaesthesia. 2011. Allegaert Karel, et al. PubMed
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From evidence based medicine to mechanism based medicine. Reviewing the role of pharmacogenetics. International journal of clinical pharmacy. 2011. Wilffert Bob, et al. PubMed
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Absorption, distribution, metabolism and excretion pharmacogenomics of drugs of abuse. Pharmacogenomics. 2011. Meyer Markus R, et al. PubMed
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Study of the OPRM1 A118G genetic polymorphism associated with postoperative nausea and vomiting induced by fentanyl intravenous analgesia. Minerva anestesiologica. 2011. Zhang W, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Antidepressant-induced akathisia-related homicides associated with diminishing mutations in metabolizing genes of the CYP450 family. Pharmacogenomics and personalized medicine. 2011. Lucire Yolande, et al. PubMed
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Systematic review of pharmacoeconomic studies of pharmacogenomic tests. Pharmacogenomics. 2010. Beaulieu Mathieu, et al. PubMed
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Adverse events in analgesic treatment with tramadol associated with CYP2D6 extensive-metaboliser and OPRM1 high-expression variants. Annals of the rheumatic diseases. 2010. Kim Eunjin, et al. PubMed
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Personalized therapy in pain management: where do we stand?. Pharmacogenomics. 2010. Stamer Ulrike M, et al. PubMed
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Relationship of CYP2D6 genetic polymorphisms and the pharmacokinetics of tramadol in Chinese volunteers. Journal of clinical pharmacy and therapeutics. 2010. Li Q, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Association between OPRM1 gene polymorphisms and fentanyl sensitivity in patients undergoing painful cosmetic surgery. Pain. 2009. Fukuda Kenichi, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Warfarin interactions with substances listed in drug information compendia and in the FDA-approved label for warfarin sodium. Clinical pharmacology and therapeutics. 2009. Anthony M, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Mu-opioid receptor (A118G) single-nucleotide polymorphism affects alfentanil requirements for extracorporeal shock wave lithotripsy: a pharmacokinetic-pharmacodynamic study. British journal of anaesthesia. 2009. Ginosar Y, et al. PubMed
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Cytochrome P450 2D6. Pharmacogenetics and genomics. 2009. Owen Ryan P, et al. PubMed
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Utilization of pharmacogenomics and therapeutic drug monitoring for opioid pain management. Pharmacogenomics. 2009. Jannetto Paul J, et al. PubMed
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Cross-sectional analysis of the influence of currently known pharmacogenetic modulators on opioid therapy in outpatient pain centers. Pharmacogenetics and genomics. 2009. Lötsch Jörn, et al. PubMed
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Escitalopram is a weak inhibitor of the CYP2D6-catalyzed O-demethylation of (+)-tramadol but does not reduce the hypoalgesic effect in experimental pain. Clinical pharmacology and therapeutics. 2009. Noehr-Jensen L, et al. PubMed
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The hypoalgesic effect of oxycodone in human experimental pain models in relation to the CYP2D6 oxidation polymorphism. Basic & clinical pharmacology & toxicology. 2009. Zwisler Stine T, et al. PubMed
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Functional pharmacogenetics/genomics of human cytochromes P450 involved in drug biotransformation. Analytical and bioanalytical chemistry. 2008. Zanger Ulrich M, et al. PubMed
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Respiratory depression with tramadol in a patient with renal impairment and CYP2D6 gene duplication. Anesthesia and analgesia. 2008. Stamer Ulrike M, et al. PubMed
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Genetic variability of the mu-opioid receptor influences intrathecal fentanyl analgesia requirements in laboring women. Pain. 2008. Landau Ruth, et al. PubMed
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Pharmacogenetics of analgesics: toward the individualization of prescription. Pharmacogenomics. 2008. Rollason Victoria, et al. PubMed
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Association of ABCB1/MDR1 and OPRM1 gene polymorphisms with morphine pain relief. Clinical pharmacology and therapeutics. 2008. Campa D, et al. PubMed
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An evaluation of mu-opioid receptor (OPRM1) as a predictor of naltrexone response in the treatment of alcohol dependence: results from the Combined Pharmacotherapies and Behavioral Interventions for Alcohol Dependence (COMBINE) study. Archives of general psychiatry. 2008. Anton Raymond F, et al. PubMed
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Effects of the CYP2D6 gene duplication on the pharmacokinetics and pharmacodynamics of tramadol. Journal of clinical psychopharmacology. 2008. Kirchheiner Julia, et al. PubMed
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Stevens-Johnson syndrome and toxic epidermal necrolysis: assessment of medication risks with emphasis on recently marketed drugs. The EuroSCAR-study. The Journal of investigative dermatology. 2008. Mockenhaupt Maja, et al. PubMed
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Pharmacologic management of neuropathic pain: evidence-based recommendations. Pain. 2007. Dworkin Robert H, et al. PubMed
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Comparative metabolic capabilities and inhibitory profiles of CYP2D6.1, CYP2D6.10, and CYP2D6.17. Drug metabolism and disposition: the biological fate of chemicals. 2007. Shen Hongwu, et al. PubMed
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Concentrations of tramadol and O-desmethyltramadol enantiomers in different CYP2D6 genotypes. Clinical pharmacology and therapeutics. 2007. Stamer U M, et al. PubMed
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Exploring joint effects of genes and the clinical efficacy of morphine for cancer pain: OPRM1 and COMT gene. Pain. 2007. Reyes-Gibby Cielito C, et al. PubMed
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Effect of the CYP2D6*10 C188T polymorphism on postoperative tramadol analgesia in a Chinese population. European journal of clinical pharmacology. 2006. Wang GuoXiang, et al. PubMed
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Response to hydrocodone, codeine and oxycodone in a CYP2D6 poor metabolizer. Progress in neuro-psychopharmacology & biological psychiatry. 2006. Susce Margaret T, et al. PubMed
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The analgesic effect of tramadol after intravenous injection in healthy volunteers in relation to CYP2D6. Anesthesia and analgesia. 2006. Enggaard Thomas P, et al. PubMed
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CYP2D6 polymorphism, tramadol pharmacokinetics and pupillary response. European journal of clinical pharmacology. 2006. Slanar Ondrej, et al. PubMed
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Tramadol as a new probe for cytochrome P450 2D6 phenotyping: a population study. Clinical pharmacology and therapeutics. 2005. Pedersen Rasmus Steen, et al. PubMed
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A rapid and simple CYP2D6 genotyping assay--case study with the analgetic tramadol. Metabolism: clinical and experimental. 2003. Borlak Jürgen, et al. PubMed
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Impact of CYP2D6 genotype on postoperative tramadol analgesia. Pain. 2003. Stamer Ulrike M, et al. PubMed
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Post-mortem SNP analysis of CYP2D6 gene reveals correlation between genotype and opioid drug (tramadol) metabolite ratios in blood. Forensic science international. 2003. Levo Antti, et al. PubMed
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The hypoalgesic effect of tramadol in relation to CYP2D6. Clinical pharmacology and therapeutics. 1996. Poulsen L, et al. PubMed
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[Pharmacology of tramadol]. Drugs. 1997. Dayer P, et al. PubMed
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Polymorphic CYP2D6 mediates O-demethylation of the opioid analgesic tramadol. European journal of clinical pharmacology. 1997. Paar W D, et al. PubMed

LinkOuts

Web Resource:
Wikipedia
National Drug Code Directory:
0045-0659-60
DrugBank:
DB00193
KEGG Compound:
C07153
PubChem Compound:
33741
PubChem Substance:
175579
46506256
BindingDB:
50176262
ChemSpider:
31105
Therapeutic Targets Database:
DAP000140
FDA Drug Label at DailyMed:
c0938808-fe14-4b8d-98c4-d04dcc5c9642

Clinical Trials

These are trials that mention tramadol and are related to either pharmacogenetics or pharmacogenomics.

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Sources for PharmGKB drug information: DrugBank, PubChem.