PACE Case: Mitigating Medication-Related Fall and Fracture Risk

Challenge

MD is a 74-year-old female Programs of All-Inclusive Care for the Elderly (PACE) participant who recently experienced a fall with a lumbar compression fracture that resulted in hospitalization. MD has a past medical history of glaucoma, cerebrovascular accident (CVA), hypertension, hyperlipidemia, gastroesophageal reflux disease (GERD), depression, allergic rhinitis, constipation, hypomagnesemia, anemia of chronic kidney disease (CKD), and vitamin D deficiency. Her MedWise Risk Score™ is 19 out of 50 (moderate).

The participant’s medication regimen includes:

  • Brimonidine tartrate 0.1%, 1 drop in both eyes twice daily
  • Latanoprost 0.005%, 1 drop in each eye daily in evening
  • Aspirin 81mg, 1 tablet daily
  • Clopidogrel 75mg, 1 tablet daily
  • Amlodipine 10mg, 1 tablet daily at bedtime
  • Atorvastatin 80mg, 1 tablet daily at bedtime
  • Bisoprolol 10mg, 1 tablet daily
  • Ezetimibe 10mg, 1 tablet daily
  • Pantoprazole 20mg, 1 tablet daily
  • Sertraline 25mg, 1 tablet daily
  • Fluticasone nasal spray, 1 spray in each nostril daily
  • Senna/Docusate 8.6-50mg, 2 tablets at bedtime
  • Magnesium oxide 400mg, 1 tablet daily
  • Iron carbonyl/Ascorbic acid 65mg-125mg, 1 tablet daily
  • Cholecalciferol 2000 intl units, 2 tablets daily

Participant Assessment

Older adults who sustain a fracture may be at a high risk (approximately 2-fold increase) of sustaining a new fracture. Although this association cannot be explained by any one cause, the absolute risk of new fracture rises with increasing age and decreasing bone mineral density. Therefore, older adults who sustain a fracture at any skeletal site should be screened for osteoporosis.
The prodrug, clopidogrel, is bio-transformed into its active metabolite by the CYP2C19 enzyme. The formation of the active metabolite may be lower than expected when concomitantly administered with sertraline due to competitive inhibition of CYP2C19. As a result, will have an increased risk of therapeutic failure from clopidogrel, resulting in increased risk of cardiovascular events.

Recommendations

The following recommendations were provided by the CareKinesis clinical pharmacist and accepted by the PACE prescriber during a Falls Committee meeting:

  • In consideration of recent fall with fragility fracture, denosumab 60mg SC every six months was initiated. Since denosumab may cause or exacerbate hypocalcemia, and increased risk observed with renal dysfunction, calcium levels were to be obtained and if pre-existing hypocalcemia, will correct prior to therapy. NOTE: Bisphosphonate therapy is contraindicated since CrCl 30 mL/min.
  • Cholecalciferol 2000 intl units, 2 tablets (4000) daily was changed to calcium carbonate / cholecalciferol 600mg-800 intl units, 1 tablet twice daily. A follow-up 25OHD was obtained since it was previously 30.5 ng/mL. Studies have shown benefit with 25OHD at approximately 30 ng/mL, while > 50 ng/mL associated with increased fall risk.
  • Pantoprazole was discontinued, upon discharge from SNF. Long-term proton pump inhibitor (PPI) therapy has been associated with increased osteoporosis-related fracture risk since it decreases bone mineral density. B12 and Magnesium were within normal limits when last tested.
  • DAPT therapy was re-evaluated since therapy duration exceeded 12 months, and the ACC DAPT score indicated a low risk for clotting, therefore prolonged DAPT was not recommended. Clopidogrel was discontinued and aspirin 81mg daily is to continue to reduce the risk of bleeding. There was also CYP2C19 competitive inhibition interaction with sertraline, and being that clopidogrel is a pro-drug, it had potential therapeutic failure. If clopidogrel were to continue, the administration time of clopidogrel should be changed from the morning to bedtime to mitigate the interaction.

Conclusion

Following the clinically appropriate medication changes, the participant’s MedWise Risk Score™ decreased from 19 (moderate risk) to 8 (low risk). Medication-related fall, subsequent fracture and bleeding risk was mitigated.

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