NUR 6410 Module 1 Pharmacokinetics Case: Apixaban Dosing in an 83-Year-Old Woman Example

Two of Three Criteria: Pharmacokinetics, Aging and an Apixaban Order for an 83-Year-Old Woman Weighing 57 Kilograms

Student Name

Master of Science in Nursing, Thomas Edison State University

NUR-6410: Advanced Pharmacology

Mentor Name

Month Day, Year

Two of Three Criteria: Pharmacokinetics, Aging and an Apixaban Order for an 83-Year-Old Woman Weighing 57 Kilograms

Introduction

Mrs. V. is an invented patient: 83, a former seamstress, widowed, climbing one flight of stairs to her Trenton apartment each day. During her spring checkup the nurse practitioner felt an uneven pulse, and the tracing that followed showed atrial fibrillation. She has hypertension treated with amlodipine and had a minor stroke-like episode that resolved in a day three years ago. She weighs 57 kilograms and her serum creatinine is 1.1 milligrams per deciliter. Her stroke risk is high, and anticoagulation is indicated. The prescribing question is not whether to anticoagulate but how much of which drug to give a small, elderly woman whose body handles medicines differently from the trial populations that set standard doses.

Choosing the Drug

In the ARISTOTLE trial, Granger et al. (2011) assigned upward of eighteen thousand people with the arrhythmia to apixaban or to warfarin by chance. Yearly strokes and emboli ran at 1.27 percent with apixaban against 1.60 percent with warfarin, serious bleeds at 2.13 against 3.09 percent, and fewer people died. For Mrs. V., who lives alone and would struggle to reach a clinic for frequent INR checks, a drug with fewer interactions and no routine blood monitoring also fits her life. Apixaban is the choice; the harder work is the dose.

How Aging Changes Drug Handling

Mangoni and Jackson (2004) describe the changes that matter most in older adults. Absorption is usually little changed for oral tablets. Distribution shifts because lean body mass and total body water fall while body fat rises, so water-soluble drugs reach higher concentrations in a smaller person and fat-soluble drugs linger longer. Hepatic metabolism through the cytochrome P450 system declines modestly with reduced liver mass and blood flow. The most predictable change is renal: glomerular filtration falls with age, and because older adults have less muscle, their serum creatinine can look normal while their kidney function is well below that of a young adult.

That last point applies directly to Mrs. V. A creatinine of 1.1 sounds unremarkable. Her muscle mass, however, is small, so the creatinine her body makes each day is small, and a value of 1.1 represents reduced filtration.

Estimating Her Kidney Function

Cockcroft and Gault (1976) built a formula that turns three bedside numbers into an estimate of how fast the kidneys clear creatinine, and it trims the result for women. For Mrs. V. the calculation is (140 minus 83) multiplied by 57, divided by 72 multiplied by 1.1, and then multiplied by 0.85. That gives 3,249 divided by 79.2, or about 41 milliliters per minute, and about 35 milliliters per minute after the correction for sex. Her kidneys clear drugs at roughly a third of the rate of a healthy young adult.

Applying the Labeled Dose Rule

About a quarter of apixaban is cleared by the kidneys, with the rest handled by liver metabolism and intestinal excretion, so reduced clearance raises exposure without making the drug unusable. The label carries over the ARISTOTLE rule (Granger et al., 2011): the usual 5 milligrams twice a day drops to 2.5 milligrams twice a day once any two of three markers are present, namely an age of at least 80, a body that weighs no more than 60 kilograms, or a creatinine that has climbed to 1.5. Mrs. V. meets two, her age and her weight. Her creatinine does not meet the third, but two are enough.

This is a point where students often go wrong. The apixaban rule uses serum creatinine, not the calculated clearance, and the two can point in different directions. Mrs. V.'s clearance of about 35 milliliters per minute might tempt a prescriber to reduce the dose on clearance alone, and in another patient with normal age and weight that reduction would be off label and could leave her underprotected against stroke. In Mrs. V.'s case both routes reach the same answer, but the paper bases the order on the labeled criteria.

Pharmacodynamic Sensitivity

Pharmacokinetics describes what her body does to the drug; pharmacodynamics describes what the drug does to her. Mangoni and Jackson (2004) note that older adults are often more sensitive to anticoagulants at a given concentration, and their consequences of bleeding are worse. Fragile skin, a history of falls or a small subdural bleed after a minor head knock can turn a routine bleed into a fatal one. Mrs. V. reports no falls, but she climbs a flight of stairs each day. Her amlodipine has no meaningful interaction with apixaban, but if she were later given a strong inhibitor of both CYP3A4 and P-glycoprotein, such as ketoconazole, her apixaban levels would rise further.

The Order and Its Monitoring

Apixaban 2.5 milligrams by mouth twice daily, about 12 hours apart, continued long term. Before starting, a complete blood count and liver panel are checked. Kidney function and blood count are repeated at least yearly, and more often if she becomes dehydrated, starts a new drug or shows signs of decline, since her dose already sits at the low step and any further slide in kidney function would push her drug levels higher still. Her medication list is reviewed at every visit for new interacting drugs, including over-the-counter nonsteroidal anti-inflammatory drugs, which add bleeding risk.

Patient Education

Mrs. V. is taught that missing doses removes protection quickly because apixaban's effect wears off within a day, to take it with or without food at the same times each day, to call about tarry stools, pink urine or bruises she cannot explain, and to go straight to the emergency department after any fall where her head hits something. Ibuprofen and naproxen are off her list for arthritis flares, and she carries a wallet card naming apixaban for any dentist or emergency team. A pill organizer with morning and evening compartments helps her keep the twice-daily schedule.

Conclusion

The order for Mrs. V. came from pharmacokinetic reasoning applied to one person. Her age and small size lower drug clearance and raise exposure, her normal-looking creatinine hides reduced filtration and her age increases her sensitivity to bleeding. The labeled rule, which counts age, weight and serum creatinine, gives her 2.5 milligrams twice daily, and a monitoring and teaching plan follows from the same principles.

References

Cockcroft, D. W., & Gault, M. H. (1976). Prediction of creatinine clearance from serum creatinine. Nephron, 16(1), 31-41. https://doi.org/10.1159/000180580

Granger, C. B., Alexander, J. H., McMurray, J. J. V., Lopes, R. D., Hylek, E. M., Hanna, M., Al-Khalidi, H. R., Ansell, J., Atar, D., Avezum, A., Bahit, M. C., Diaz, R., Easton, J. D., Ezekowitz, J. A., Flaker, G., Garcia, D., Geraldes, M., Gersh, B. J., Golitsyn, S., ... Wallentin, L. (2011). Apixaban versus warfarin in patients with atrial fibrillation. New England Journal of Medicine, 365(11), 981-992. https://doi.org/10.1056/NEJMoa1107039

Mangoni, A. A., & Jackson, S. H. D. (2004). Age-related changes in pharmacokinetics and pharmacodynamics: Basic principles and practical applications. British Journal of Clinical Pharmacology, 57(1), 6-14. https://doi.org/10.1046/j.1365-2125.2003.02007.x