Individualized Hydrocodone Therapy Based on Phenotype, Pharmacogenetics, and Pharmacokinetic Dosing

Linares, Oscar A.; Fudin, Jeffrey; Daly, Annemarie L.; Boston, Raymond C.

doi:10.1097/ajp.0000000000000214

Cited by 17 publications

(10 citation statements)

References 52 publications

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“…The model also showed that about 40% of a codeine dose was converted to morphine in EM subjects, and about 51% was converted to morphine in ultrarapid-metabolizers… Our study suggests that pharmacogenetics for personalized dosing might be most effectively advanced by studying the interplay between pharmacogenetics, population pharmacokinetics, and clinical pharmacokinetics." 197 Individualized Hydrocodone Therapy Based on Phenotype, Pharmacogenetics, and Pharmacokinetic Dosing http://www.ncbi.nlm.nih.gov/pubmed/?25621429 198 "Our results demonstrate that pharmacogenetics afford clinicians an opportunity to individualize [hydrocodone] HC dosing, while adding enhanced opportunity to account for its conversion to HM in the body." 198 Gene Tested: Cytochrome P450 3A4/5: (CYP3A4/5) There is a large amount of variability in psychotropic drug response and variations in CYP450 genes, including CYP3A4/5, may impact this variability.…”

Section: Impact Of Multiple Inhibitors or Substrates Of Cytochrome P4mentioning

confidence: 82%

“…197 Individualized Hydrocodone Therapy Based on Phenotype, Pharmacogenetics, and Pharmacokinetic Dosing http://www.ncbi.nlm.nih.gov/pubmed/?25621429 198 "Our results demonstrate that pharmacogenetics afford clinicians an opportunity to individualize [hydrocodone] HC dosing, while adding enhanced opportunity to account for its conversion to HM in the body." 198 Gene Tested: Cytochrome P450 3A4/5: (CYP3A4/5) There is a large amount of variability in psychotropic drug response and variations in CYP450 genes, including CYP3A4/5, may impact this variability. There are several articles which review the relevant clinical implications of altered CYP3A4/5 metabolism.…”

Section: Impact Of Multiple Inhibitors or Substrates Of Cytochrome P4mentioning

confidence: 82%

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Polymorphisms in Serotonergic Pathways Influence the Outcome of Antidepressant Therapy in Psychiatric Inpatients

Staeker

Leucht

Laika

et al. 2014

Genetic Testing and Molecular Biomarkers

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Serotonergic pathways are known to play an essential role in the effects generated by antidepressants. Polymorphisms in serotonin receptor and transporter genes have been identified as an important factor. To investigate which of these polymorphisms may be useful to predict clinical outcome, we assessed their effect in a naturalistic clinical study. We studied the influence of the 5-hydroxytryptamine transporter (5-HTT) variable number of tandem repeats (VNTR), 5-HTTLPR/rs25531 and a 5-HTR2A intron 2 SNP with regard to response and side effects in 273 psychiatric inpatients. Main clinical assessments included Clinical Global Impressions ratings, paranoid depression scale self-rating scale and Dosage Record, and Treatment Emergent Symptoms (DOTES) Scale. We found significant associations between 5-HTTLPR/rs25531 S/L(G) alleles and response and side effects in 100 patients with selective serotonin reuptake inhibitor (SSRI) treatment (p = 0.037, CGI-I ≤ 2: 0% vs. 19% and p = 0.0005, DOTES cluster c: 0.76 vs. 0.19). 5-HTT VNTR and 5-HTR2A intron 2 polymorphisms were associated significantly with adverse effects in patients with selective and nonselective SRI (5-HTT VNTR 12/12: n = 170, p = 0.0001, side effect rates: 51% vs. 19% and rs7997012 [A/A]: n = 50, p = 0.020, side effects rates: 43% vs. 11%). No impact of the polymorphisms on mirtazapine treatment was found. Our study confirms the influence of serotonergic polymorphisms at the receptor and transporter level on SSRI response and side effects, supporting previous reports based on various study designs. The effects were strong enough to be noticed clinically in this naturalistic setting. However, randomized controlled trials are warranted to provide unequivocal evidence of the clinical usefulness of pretherapeutic screening for these polymorphisms.

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Section: Impact Of Multiple Inhibitors or Substrates Of Cytochrome P4mentioning

confidence: 82%

Section: Impact Of Multiple Inhibitors or Substrates Of Cytochrome P4mentioning

confidence: 82%

Polymorphisms in Serotonergic Pathways Influence the Outcome of Antidepressant Therapy in Psychiatric Inpatients

Staeker

Leucht

Laika

et al. 2014

Genetic Testing and Molecular Biomarkers

View full text Add to dashboard Cite

show abstract

“…(14) Further, pharmacogenetics data suggest that opioids including hydrocodone, oxycodone, and codeine may be ineffective in up to 10% of the Caucasian population. (30,31,32) As a result, best practice recommendations note that opioid analgesics should be reserved for the minority of situations in which optimal doses of NSAIDs and/or acetaminophen/aspirin provide insufficient pain management. (14,29)…”

Section: Discussionmentioning

confidence: 99%

Dental opioid prescribing and multiple opioid prescriptions among dental patients

McCauley¹,

Hyer²,

Ramakrishnan³

et al. 2016

The Journal of the American Dental Association

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Background Despite increased attention to dentists’ role in curbing opioid misuse, abuse, and diversion, information regarding prescribing practices and the frequency of multiple concurrent opioid prescriptions among dental patients is limited. Methods Prescription drug monitoring program (PDMP) data for South Carolina representing dispensed medication for patients prescribed at least one opioid by a dentist over the most recently available two-year frame (2012–2013) was reviewed. Descriptive analyses examined: (1) types, frequency of dental opioid prescriptions; and, (2) frequency of existing multiple concurrent opioid prescriptions among dental patients. Results Nearly all dispensed dental opioid prescriptions (99.9%; n = 653,650) were for immediate release opioids and were initial fills (96.2%). Hydrocodone (76.1%) and oxycodone (12.2%) combination products were the most frequently dispensed opioids prescribed by dentists. Individuals under 21 years of age received 11.2% of dentist prescribed opioids dispensed. Patients with multiple concurrent opioid prescriptions were identified within 30-day (n=113,818), 90-day (n=166,124), and 180-day (n=205,576) timeframes. Conclusions Dentists prescribed a high volume of immediate release opioids dispensed in South Carolina. A notable minority of dental patients had incident(s) of multiple pre-existing opioid prescriptions, a factor implicated in patient misuse, abuse, overdose, and diversion Practical Implications Use of a PDMP prior to prescribing provides a record of controlled substances dispensed to a patient, and may inform prescribing, coordination of care, and addiction screening or referral. Patients should be provided information regarding misuse behaviors and their risks, as well as the importance of secure storage and disposal of leftover opioid medications.

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“…This patient's genotype predicts a CYP2D6 intermediate metabolizer phenotype which has been shown to occur iñ 13% of African Americans; thus, pharmacogenomic testing would have predicted substantially lower active metabolites of tramadol and hydrocodone and consequently, inefficacy (Swen et al, 2011;Crews et al, 2014;Linares et al, 2015). In addition, she was also taking fluoxetine to treat her depression, a common co-morbidity with chronic pain, which would have reduced further her endogenous CYP2D6 activity.…”

Section: Discussionmentioning

confidence: 98%

“…The patient's family history was significant, as her mother progressed to end-stage renal disease. Her CYP2D6 genotype was *5/*17, a gene deletion which is reported to occur in 2-11% of people and is consistent with intermediate metabolism making tramadol and hydrocodone less effective (Swen et al, 2011;Crews et al, 2014;Linares et al, 2015). A retrospective look at the urine drug screen noted the absence of any hydromorphone, the more active metabolite of hydrocodone, even though hydrocodone was detected (233 ng/ml).…”

Section: Case Presentationmentioning

confidence: 98%

Nephrotoxicity in a Patient With Inadequate Pain Control: Potential Role of Pharmacogenetic Testing for Cytochrome P450 2D6 and Apolipoprotein L1

2020

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A case is presented which demonstrates the perils of opioid inefficacy and how pharmacogenomic testing may have prevented nonsteroidal anti-inflammatory drug (NSAID)-induced nephrotoxicity and progression to chronic kidney disease (CKD). A 62 year-old female with back pain was treated with tramadol and hydrocodone; however, neither proved effective. Consequently, to control her pain, she resorted to cocaine, marijuana, and high dose nonsteroidal anti-inflammatory drugs (NSAIDs). She eventually developed CKD. To identify CKD contributors, she underwent genotyping for Apolipoprotein L1 (APOL1), a known risk factor of CKD, as well as relevant pharmacogenomic genes. Her APOL1 genotype was *G1(GM)/*G1(GM), placing her at increased risk of CKD progression. Her CYP2D6 genotype was *5/*17, consistent with intermediate metabolism, making opioid drugs reliant on CYP2D6 activation, such as tramadol and hydrocodone, relatively ineffective in this patient. Thus, this patient was at genetic risk for CKD and reduced opioid efficacy. We conclude that this genetic combination likely contributed to opioid inefficacy and the eventual progression to CKD.

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Individualized Hydrocodone Therapy Based on Phenotype, Pharmacogenetics, and Pharmacokinetic Dosing

Abstract: Our results demonstrate that pharmacogenetics afford clinicians an opportunity to individualize HC dosing, while adding enhanced opportunity to account for its conversion to HM in the body.

Cited by 17 publications

References 52 publications

Polymorphisms in Serotonergic Pathways Influence the Outcome of Antidepressant Therapy in Psychiatric Inpatients

Polymorphisms in Serotonergic Pathways Influence the Outcome of Antidepressant Therapy in Psychiatric Inpatients

Dental opioid prescribing and multiple opioid prescriptions among dental patients

Nephrotoxicity in a Patient With Inadequate Pain Control: Potential Role of Pharmacogenetic Testing for Cytochrome P450 2D6 and Apolipoprotein L1

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