PACE Case: Med Interruptions = Relief? (digoxin)

A 90-year-old female participant who has been in and out of the hospital a few times within the past six months was enrolled to PACE services in May 2014, with the following diagnoses: abdominal mass, bladder cancer, and chronic kidney disease. The mass and the cancer were both recently successfully treated. Blood pressure noted to be 162/85.

Upon enrollment to PACE, her medication regimen included:

amlodipine besylate 2.5mg (Norvasc) – 1 tab daily for hypertension (since 4/2014)
atorvastatin calcium 20mg (Lipitor) – 1 tab daily for hyperlipidemia (since 4/2014)
pantoprazole solium 40mg (Protonix) – 1 tab daily before breakfast for GERD (since 5/2014)
metoprolol succinate ER 50mg (Toprol XL)– 1 tab BID for hypertension (since 11/2009)
digoxin 0.125mg – 1 tab daily for hypertension, arythmia (since 1/2014)

She was recently prescribed ferrous gluconate and had an iron infusion to restore her iron stores and increase hemoglobin productions.

During the PACE enrollment process, she reported that she becomes more healthy and vigorous at the hospital where her medications are ‘interrupted’. When she returns home and resumes her medication regimen, she becomes faint, lethargic, weak and nauseous and she occasionally vomits.

The CareKinesis Clinical Pharmacist was asked to perform a Comprehensive Medication Review (CMR) upon admission to assess whether her medications were causing these symptom patterns.

CMR & RECOMMENDATIONS:

Medication with Potential for Adverse Outcome – Digoxin:
We recommend to evaluate the “free” (unbound) digoxin level and kidney function (creatinine clearance), and then adjust the dose accordingly.

Digoxin is typically used in patients with atrial fibrillation (afib). When the heart gets out of sync, the turbulence can lead to a decreased outflow of blood and increase the risk of her “throwing clots” (increased risk of stroke, embolisms, etc.).

When circulating in the bloodstream, digoxin is very highly protein bound. This means that in a “normal” patient, about 98% of the circulating digoxin is stuck to the protein molecule albumin and is inactive. The 2% that is “free”(not protein bound) is active, and provides the pharmacologic effects and also associated with adverse effects.

This participant’s digoxin level is within the therapeutic range @ 0.97 ng/mL (normal for afib = 0.8-2.0 ng/mL).  However, over the last few months, her albumin levels have been subtherapeutic: 3.4, 2.3, 2.9, 3.2 gm/dL, respectively (normal = 3.4 – 5.0 gm/dL). With low albumin, there is less protein to which the digoxin can be bound. Therefore, the free fraction may increase from what may have been 2% to 3%, resulting in a 50% increase of the unbound digoxin level. While the serum digoxin level may be within therapeutic range, the “free” (unbound) level may be high (contributing to toxicity).

Only 16% of digoxin is eliminated from the body via liver metabolism. The remaining 84% is renally eliminated, “unchanged” (by the kidneys).  With her renal impairment, there is an increased risk of digoxin accumulating (normal elimination half-life is 36 to 48 hours, which is further prolonged) and causing adverse effects, including dizziness, nausea and vomiting.

Disease state that may be associated with Adverse Effects – Iron Deficiency Anemia:
Lack of hemoglobin will impair the body’s ability to move oxygen around to her vital organs. It can result in an increased heart & breathing rate, dizziness and fainting. The ferrous gluconate and infusion will be helpful if the problem is secondary to her ability to take in and absorb iron (diet) or if her deficiency is secondary to a bleeding episode. However, if her anemia is compounded by her body’s ability to produce red blood cells secondary to her chronic kidney disease, erythropoietin therapy may be indicated. Recommend to have a nephrology consult if have not already to assess chronic kidney disease.

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