Duloxetine/hydrocodone/paracetamol/metoprolol

Abstract

Drug-drug interaction induced phenoconversion: case report A 66-year-old woman exhibited phenoconversion following co-administration of duloxetine with hydrocodone/paracetamol and metoprolol tartrate for chronic pain, major depression disorder (MDD) or hypertension with heart failure. The woman presented with a medical history of obesity (class III), uncontrolled MDD, hypertension, heart failure, uncontrolled chronic pain (multifactorial nature), gout, hypothyroidism, atrial fibrillation, gastroesophageal reflux disease (GERD), type 2 diabetes mellitus, diarrhoea, nausea, insomnia and candidiasis. She had been receiving treatment with oral hydrocodone/ paracetamol [Hydrocodone/acetaminophen] 7.5/325mg four times a day as needed, oral duloxetine 30mg twice a day, oral metoprolol tartrate 100mg twice a day and various other concomitant medications. Her medication risk score (MRS) was 32. During enrollment in the program of All-inclusive Care for the Elderly (PACE), her chief complaints included poor multifactorial pain control and inappropriate control of depression. Initially, duloxetine was chosen to treat the depression. She received duloxetine for over 10 years, only minor improvement was observed in MDD. Of note, while receiving metoprolol tartrate, she had borderline bradycardia. Clinical pharmacist advised pharmacogenomics (PGx) test for optimization analgesic and antidepressant regimen. DNA sample was obtained by buccal swab and analysed, and clinical pharmacist was consulted for the interpretation of PGx results and multidrug interaction screening. Genotypic results revealed that she was a CYP2D6 intermediate metabolizer (IM) with a *1/*4 genotype. PGx test findings were integrated into the CDSS. Clinical pharmacist evaluated the PGx findings, CDSS-generated MRS, concomitant medications and patient-specific other factors. Her CYP2D6 IM status and drug-gene interactions (DGIs) might have affected metabolism of duloxetine, hydrocodone and metoprolol. Reduced CYP2D6 enzyme activity alters the clearance of metoprolol and duloxetine, which increases the risk of toxicity associated with these medications. Decreased CYP2D6 activity also decreases the conversion of hydrocodone to hydromorphone, which might have increased the risk of pharmacotherapy failure. It was thought that duloxetine might have competitively inhibited the metabolism of metoprolol and hydrocodone leading to druginduced phenoconversion to poor metabolizer for these two drugs [pharmacokinetic interaction; time to reactions onset not stated]. The drug-drug interaction of duloxetine lead to increased effect of metoprolol causing borderline bradycardia and decreased effect of hydrocodone led to poor control of pain. The clinical pharmacist recommended the woman to changed hydrocodone/ paracetamol to morphine, duloxetine to desvenlafaxine and metoprolol to carvedilol. These recommendations were accepted by her primary care physician. These therapy changes resulted in improvement in depression status, pain control and quality of life. It also increased her heart rate, and she reported improved movement, cognition and sleep pattern.