Pharmacogenetic Analysis Enables Optimization of Pain Therapy: A Case Report of Ineffective Oxycodone Therapy
Abstract
1. Introduction
2. Materials and Methods
3. Case Presentation
4. Discussion and Pharmaceutical Assessment
4.1. Assessment of Oxycodone
4.2. Assessment of Fentanyl and Morphine
4.3. Assessment of Non-Opioid Analgesics
4.4. Pharmaceutical Recommendation and Outcome
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Substance | Schedule |
---|---|
Oxycodone/Naloxone SR a 20/10 mg | 1-0-1-0 |
Oxycodone oral Liq b 10 mg/mL | PRN c (max. 7 mg/day) |
Ibuprofen 600 mg | 1-1-1-0 |
Metamizol gtt d 0.5 mg/mL | 2-2-2-2 mL |
Venlafaxine ER e 150 mg | 1-0-0-0 |
Pantoprazole 40 mg | PRN c (max. 1 tablet/day) |
various laxatives | different |
Gene | Variant (Additionally Tested Variants in Gen Locus) | Genotype | Predicted Phenotype (Activity Score) |
---|---|---|---|
CYP2C9 | rs1057910 c.1075A > C (in *3) (rs1799853, rs9332131, rs7900194, rs28371685) | A/C | intermediate metabolizer (AS = 1, reduced function) |
CYP2C8 | (rs10509681, rs11572080, rs1934951) | WT a, *1 | n.d. d (n.d. d) |
CYP2C19 | (rs4244285, rs4986893, rs12248560, rs28399504) | WT a, *1 | normal metabolizer (n.d. d) |
CYP2D6 | rs3892097 c.506-1G > A (in *4) rs1065852 c.100C > T (in *4 and *10) (CNV c, rs35742686, rs5030655, rs5030867, rs5030865, rs5030656, rs201377835, rs28371706, rs59421388, rs28371725) | G/A C/T | intermediate metabolizer (AS = 1, reduced function) |
CYP3A5 | rs776746 c.219-237G > A (in *3) | A/G | intermediate metabolizer (n.d. d) |
UGT2B7 | rs7439366 c.802C > T (in *2) | C/T | n.d.d (substance specific) |
OPRM1 | rs1799971 c.118A > G | A/G | n.d. d (substance specific) |
COMT | rs4680 c.472G > A (rs165599, rs4646316, rs9332377) | A/G | n.d. d (substance specific) |
ABCB1 | rs2032583 c.2685 + 49T > C rs1045642 c.3435T > C rs2032582 c.2677G > A or c.2677G > T (rs1128503) | T/T C/T G/G | n.d. d (substance specific) |
Substance | Clinical Effect | Pharmaceutical Assessment | Pharmaceutical Recommendation |
---|---|---|---|
Oxycodone | insufficient analgesic efficacy | Metabolic shift to inactive noroxycodone due to decreased activity of CYP2D6, increased activity of CYP3A5 and a drug interaction with metamizole. Impaired drug response at the µ-opioid receptor. | Avoid opiates that are bioactivated by CYP2D6 or inactivated by CYP3A5. Switch to hydromorphone or tapentadol. |
Fentanyl | insufficient analgesic efficacy | Increased inactivation due to increased activity of CYP3A5 and a drug interaction with metamizole. Impaired drug response at the µ-opioid receptor. | |
Morphine | insufficient analgesic efficacy | Impaired drug response at the µ-opioid receptor. | |
Ibuprofen | gastrointestinal side effects | Decreased inactivation due to decreased activity of CYP2C9 and thus an increased risk of gastrointestinal side effects. | Avoid NSAIDs a that are inactivated by CYP2C9. Switch to paracetamol. Combine NSAIDs a with a PPI b. |
Venlafaxine | good antidepressant but insufficient analgesic efficacy | Reduced metabolism to its active metabolite due to decreased activity of CYP2D6. Limited penetration of the blood–brain barrier due to the ABCB1 variant. | Continue venlafaxine therapy. Pregabalin as additional therapy option. |
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Wiss, F.M.; Stäuble, C.K.; Meyer zu Schwabedissen, H.E.; Allemann, S.S.; Lampert, M.L. Pharmacogenetic Analysis Enables Optimization of Pain Therapy: A Case Report of Ineffective Oxycodone Therapy. J. Pers. Med. 2023, 13, 829. https://doi.org/10.3390/jpm13050829
Wiss FM, Stäuble CK, Meyer zu Schwabedissen HE, Allemann SS, Lampert ML. Pharmacogenetic Analysis Enables Optimization of Pain Therapy: A Case Report of Ineffective Oxycodone Therapy. Journal of Personalized Medicine. 2023; 13(5):829. https://doi.org/10.3390/jpm13050829
Chicago/Turabian StyleWiss, Florine M., Céline K. Stäuble, Henriette E. Meyer zu Schwabedissen, Samuel S. Allemann, and Markus L. Lampert. 2023. "Pharmacogenetic Analysis Enables Optimization of Pain Therapy: A Case Report of Ineffective Oxycodone Therapy" Journal of Personalized Medicine 13, no. 5: 829. https://doi.org/10.3390/jpm13050829
APA StyleWiss, F. M., Stäuble, C. K., Meyer zu Schwabedissen, H. E., Allemann, S. S., & Lampert, M. L. (2023). Pharmacogenetic Analysis Enables Optimization of Pain Therapy: A Case Report of Ineffective Oxycodone Therapy. Journal of Personalized Medicine, 13(5), 829. https://doi.org/10.3390/jpm13050829