From the Guidelines
Apixaban and morphine are the medications that typically require dose adjustments in certain clinical situations, with apixaban needing adjustment for patients with renal impairment, low body weight (≤60 kg), or advanced age (≥80 years), and morphine dosing adjusted based on pain severity, patient response, renal function, and age.
Medication Adjustments
- Apixaban: the standard dose of 5 mg twice daily may need to be reduced to 2.5 mg twice daily in patients with renal impairment, low body weight (≤60 kg), or advanced age (≥80 years) 1.
- Morphine: dosing should be adjusted based on pain severity, patient response, renal function, and age, with careful titration to minimize respiratory depression risks 1.
No Adjustment Needed
- Norco (hydrocodone/acetaminophen): may need adjustment primarily due to the acetaminophen component in patients with liver disease, but standard dosing is typically appropriate otherwise.
- Losartan and metoprolol: generally don't require specific dose adjustments unless there are significant changes in blood pressure, heart rate, or kidney function. These adjustments are important because inappropriate dosing of anticoagulants like apixaban can lead to bleeding complications or reduced efficacy, while opioids like morphine require careful management to balance pain control with side effect risks 1.
From the FDA Drug Label
Apixaban is metabolized mainly via CYP3A4 with minor contributions from CYP1A2, 2C8, 2C9, 2C19, and 2J2. The effects of coadministered drugs on the pharmacokinetics of apixaban are summarized in Figure 2 In dedicated studies conducted in healthy subjects, famotidine, atenolol, prasugrel, and enoxaparin did not meaningfully alter the pharmacokinetics of apixaban In studies conducted in healthy subjects, apixaban did not meaningfully alter the pharmacokinetics of digoxin, naproxen, atenolol, prasugrel, or acetylsalicylic acid.
The medications that need to be adjusted are:
- Norco: Apixaban is metabolized by CYP3A4 and Norco (which contains oxycodone) is also a substrate of CYP3A4, so there may be an interaction.
- Losartan: No dose adjustment is necessary.
- Metoprolol: No dose adjustment is necessary.
- Morphine: No information is available in the provided drug labels to suggest a dose adjustment is necessary for morphine when coadministered with apixaban 2.
From the Research
Medication Adjustment
The following medications may need to be adjusted when taken with Apixaban:
- Norco: There is no direct evidence in the provided studies to suggest that Norco needs to be adjusted when taken with Apixaban.
- Losartan: There is no direct evidence in the provided studies to suggest that Losartan needs to be adjusted when taken with Apixaban.
- Metoprolol: There is no direct evidence in the provided studies to suggest that Metoprolol needs to be adjusted when taken with Apixaban.
- Morphine: There is no direct evidence in the provided studies to suggest that Morphine needs to be adjusted when taken with Apixaban.
Apixaban Dose Adjustment
Apixaban dose adjustment is based on age, weight, and serum creatinine in non-valvular atrial fibrillation (NVAF) 3. The criteria for dose adjustment include:
- Age ≥80 years
- Body weight ≤60 kg
- Serum creatinine ≥1.5 mg/dL However, some studies suggest that these criteria may need to be re-evaluated 3.
Interactions with Other Medications
There is limited information in the provided studies about the interactions between Apixaban and the listed medications. However, it is known that Apixaban can interact with other medications, such as warfarin, and that the risk of bleeding may be increased when Apixaban is taken with certain medications 4, 5.
Special Populations
Some populations, such as patients >75 years old, or those with cancer, low or high body weight, or poor renal function, may require special consideration when taking Apixaban 6.