PACE Case: Driving Improved Health Outcomes by Mitigating Competitive Inhibition and Potential Adverse Events

Challenge

DH is a 67-year-old female PACE participant with a history of gastroesophageal reflux disease (GERD), hyperlipidemia, overactive bladder, hypertension, vitamin D deficiency, asthma, osteoarthritis, depression, and insomnia. During a recent visit to the PACE center, DH expressed feeling more depressed lately. Her MedWise Risk ScoreTM is 16 out of 50 (moderate risk), attributed to her anticholinergic burden, sedative burden and competitive inhibition interactions.

The participant’s medication regimen includes:

  • Pantoprazole 40mg once daily
  • Oxybutynin ER 10mg once daily
  • Amlodipine 10mg once daily
  • Cholecalciferol 1000 int units once daily
  • Docusate 100mg twice daily
  • Diclofenac 1% gel 2gm to right knee and both ankles 4 times daily as needed
  • Aspirin 81mg once daily
  • Sertraline 50mg once daily
  • Ferrous sulfate 325mg once daily
  • Atorvastatin 20mg once daily
  • Melatonin 3mg at bedtime
  • Albuterol sulfate HFA 2 puffs 4 times daily as needed

Solution

The CareKinesis clinical pharmacist performed a comprehensive medication safety review and provided to the PACE prescriber recommendations to optimize the participant’s current treatment regimen and reduce risk of potential adverse events. The pharmacist’s recommended interventions and prescriber approved regimen changes are as follows:

  • Oxybutynin is a highly anticholinergic medication associated with physical risks among older adults, including delirium, new onset dementia, and serious falls. Limiting exposure to this medication may help reduce the risk of these adverse events. The concentration of oxybutynin may be higher than expected when concomitantly administered with amlodipine due to competitive inhibition of CYP3A4. The increased risk of oxybutynin toxicity can result in anticholinergic effects, dizziness, and drowsiness. Since pharmacologic treatment was indicated for overactive bladder, mirabegron, an alternative medication without anticholinergic properties, was initiated, and oxybutynin was discontinued, eliminating the anticholinergic effects and mitigating the interaction.
  • Long-term proton pump inhibitor therapy has been associated with increased osteoporosis-related fracture risk along with electrolyte imbalances, B12 malabsorption, and clostridium difficile infection. Due to competitive inhibition of CYP2C19, the concentration of pantoprazole may be higher than expected when concomitantly administered with sertraline, resulting in an increased risk of pantoprazole toxicity. To reduce potential adverse event risk, famotidine 20mg was initiated for acid suppression, and pantoprazole was discontinued, mitigating the potential adverse event risk.
  • DH was tolerating sertraline, which was initiated two months prior. For optimal depression treatment, her sertraline dose was increased from 50mg to 100mg daily.

Outcome

Following implementation of the clinically appropriate medication changes, the participant’s MedWise Risk Score was reduced from 16 (moderate risk) to 7 (low risk).

The reduction is attributed to the following:

  • Mitigating competitive inhibition at CYP2C19 between pantoprazole and sertraline. Famotidine was initiated as a safer alternative for the treatment of GERD.
  • Mitigating competitive inhibition at CYP3A4 between oxybutynin and amlodipine, and discontinuing oxybutynin, a highly anticholinergic medication. Mirabegron was initiated as a safer alternative for the treatment of overactive bladder.

Further, increasing the participant’s sertraline dose has improved her depression and is helping her daily activity level.

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