An 89-year-old female PACE participant has a past medical history of rheumatoid arthritis (RA), urinary incontinence, peripheral edema, and gastroesophageal reflux disease (GERD). The participant also has limited mobility after falling and breaking her hip. Her daughter, who is also her primary caregiver, contacts the PACE prescriber to express concern over her mother’s current medication regimen, especially her pain management. She states that her mother’s pain mostly stems from RA and it is not relieved when given hydrocodone/acetaminophen. However, her mother does experience pain relief with the use of Voltaren® gel, which is not regularly administered. The caregiver denies a diagnosis of depression or anxiety, and states that mood medications are used to control “sundowning” behaviors and agitation later in the day/evening. She adds that her mother’s urinary incontinence is severe and still requires overactive bladder medication therapy. The participant’s MedWise Risk Score™ is 37 out of 50 (Very High).
The PACE prescriber requested that the CareKinesis clinical pharmacist conduct a Medication Safety Review, focusing primarily on pain management and deprescribing. The patient’s current medications include:
- Aspirin 325 mg, 1 tablet by mouth daily
- Fentanyl 50 mcg/hr Transdermal Patch, 1 patch topically every 72 hours
- Fluoxetine 20 mg, 1 capsule by mouth daily
- Furosemide 20 mg, 1 tablet by mouth daily
- Gabapentin 100 mg, 1 capsule by mouth daily
- Hydrocodone 5 mg-Acetaminophen 325 mg, 1 tablet by mouth 3 times a day and 1 tablet by mouth as needed
- Hydroxychloroquine 200 mg, 2 tablets by mouth daily
- Loperamide 2 mg, 1 tablet by mouth 3 times a day as needed
- Lorazepam 0.5 mg, 1/2 tablet (0.25 mg) by mouth twice daily
- Omeprazole 20 mg delayed-release, 1 capsule by mouth once daily
- Ondansetron 4 mg, 1 tablet by mouth every 8 hours as needed
- Docusate-Senna 8.6 mg-50 mg, 1 tablet by mouth twice daily
- Simvastatin 40 mg, 1 tablet by mouth daily
- Solifenacin 10 mg, 1 tablet by mouth daily
- Voltaren® 1% topical gel, apply to affected areas 4 times a day as needed
The clinical pharmacist recognized several medication-related problems. The participant’s MedWise Risk Score identified that the patient had a “very high” sedative burden, of which contributing medications were lorazepam, fentanyl, fluoxetine, gabapentin, hydrocodone, ondansetron, omeprazole, and solifenacin. Similarly, the patient had a “very high” anticholinergic burden, of which contributing medications were solifenacin, fentanyl, furosemide, and loperamide. Several medications increased the patient’s risk of QTc prolongation, including ondansetron, hydrocodone, fluoxetine, furosemide, hydroxychloroquine, loperamide, omeprazole, and solifenacin. Additionally, there were several potential multi-drug interactions identified using the Medication Risk Mitigation Matrix™.
Hydrocodone is metabolized by CYP2D6 to the active metabolite hydromorphone, which is responsible for the analgesic effects of hydrocodone. Fluoxetine is a strong affinity substrate of CYP2D6 and, when co-administered, may competitively inhibit the metabolism of hydrocodone, resulting in lower concentrations of the active metabolite; this may put the patient at risk of pharmacotherapy failure. In contrast, there may be higher concentrations of the parent drug, increasing the risk of adverse effects (i.e., over sedation, respiratory depression). Hydrocodone is also metabolized to inactive metabolites by CYP3A4. Omeprazole is a moderate affinity substrate of CYP3A4 and, when co-administered, may competitively inhibit the metabolism of hydrocodone. This may further increase the risk of adverse effects.
Additionally, the clinical pharmacist recognized that the patient’s pain regimen, consisting of gabapentin, fentanyl and hydrocodone, is not preferred for pain associated with RA. In addition to disease-modifying antirheumatic drugs (DMARD), the recommended adjunct, or first-line, therapy for pain management includes topical or systemic NSAIDs, or corticosteroids.1,2 The patient takes aspirin 325 mg daily for pain, however, this is not one of the recommended NSAIDs in RA and may increase risk of GI bleeding for the patient.
The clinical pharmacist also identified a potential prescribing cascade with furosemide and solifenacin. The patient was treated for an adverse effect of furosemide (e.g., urinary frequency) with an anticholinergic medication. Anticholinergics have been shown to cause or worsen symptoms of dementia, such as confusion and memory loss. The patient is being treated for symptoms of dementia with lorazepam and fluoxetine. The patient’s history of falling added additional concern due to the amount of fall risk-inducing drugs (FRIDs) onboard (e.g., opioids, fluoxetine, lorazepam, solifenacin, simvastatin). Due to the patient’s age, the risk associated with simvastatin (i.e., myopathy) may outweigh the benefit of primary prevention of ASCVD.
Clinical Pharmacist Recommendations:
After reviewing the medications and subjective information, the clinical pharmacist provided the following recommendations for prescriber and caregiver consideration:
- Consider a slow taper of fluoxetine (over 2-4 weeks) to trial a drug holiday. Of note, discontinuing fluoxetine may increase the effects of hydrocodone. While tapering fluoxetine, continue to monitor the patient closely and reduce the dose of hydrocodone, as needed. After discontinuing fluoxetine, if the patient’s sundowning is not well-controlled by lorazepam, another SSRI, like sertraline, may be considered to replace fluoxetine. Sertraline, which has fewer CYP450 interactions, may be considered as an alternative agent. Additionally, omeprazole should be changed to pantoprazole to decrease potential competitive inhibition with sertraline via CYP2C19.
- Consider changing the patient’s dose of topical diclofenac from as needed to scheduled dosing for added pain relief. The maximum daily dose of diclofenac gel is 8 or 16 g per joint per day for upper or lower extremities, respectively (total body daily max dose is 32 g/day). If additional pain medications are deemed necessary, consider starting a low dose of oral meloxicam and escalating as tolerated. Please note, continuing PPI therapy and reducing aspirin to 81 mg prior to starting an NSAID may reduce the risk of GI bleeds. Also, consider deprescribing other pain medications that may not be appropriate for RA pain, such as gabapentin, fentanyl and/or hydrocodone. Taper the medications slowly to avoid withdrawal reactions.
- Consider re-evaluating the risks (i.e., myopathy) and benefits of continued statin therapy. Prior to discontinuing simvastatin 40 mg, consider all patient specific factors including functional decline, co-morbidities, frailty, and life-expectancy, as these factors may limit the potential benefits of statin therapy. If statin therapy is warranted, consider switching to pravastatin 40 mg, to decrease the potential risks of competitive inhibition and lower the risk of myopathy. The dose can be increased to 80 mg, if necessary.
- Consider obtaining an EKG for this patient. She is at an increased risk of QT prolongation due to her female gender, age, and the concurrent use of several QT prolonging medications. If the current medications will be continued, please monitor for dizziness, palpitations, and irregular heart rhythm or syncope, as well as, potassium and magnesium levels.
- Given the potential for a prescribing cascade with furosemide and solifenacin, consider a gradual taper of the furosemide. Solifenacin carries high anticholinergic burden and can increase risk of cognitive and physical impairment. Decreasing the furosemide dose may allow for a decrease in the need for solifenacin. Eventually, it may be appropriate to consider a drug holiday to determine if solifenacin is needed.
With the changes in medications made by the prescriber based on the clinical pharmacist’s recommendations, the participant is on her way to a significant risk reduction. The prescriber accepted the recommendation to taper fluoxetine, hydrocodone, and furosemide, and agreed to discontinue simvastatin and reduce the participant’s aspirin dose from 325 mg to 81 mg. The participant appreciated the reduction in pill burden and the caregiver has reported significant improvement in urinary frequency. The caregiver reported feeling more confident with her mother’s medication regimen during discussions with the clinician. After recommendations are fully accepted and tapering is complete, the risk score will have decreased from 37 out of 50 to 27 out of 50. The pharmacist will continue to re-assess the patient’s medications and follow up with the PACE clinician to ensure proper monitoring and appropriate medication therapy changes.
- Singh JA, Saag KG, Bridges SL, et al. 2015 American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis. Arthritis Rheumatol. 2016;68(1): 1-26.
- Voltaren [package insert]. Parsippany, NJ: Novartis Consumer Health, Inc; 2009.
- AGS Beers Criteria® Update Expert Panel. American Geriatrics Society 2019 Updated AGS Beers Criteria® for Potentially Inappropriate Medication Use in Older Adults. J Am Geriatr Soc 2019;67(4): 674-694.