E.T. is a 66-year-old obese female patient is to undergo a TKR at a local teaching hospital. The medical team plans to start E.T. on warfarin therapy for venous thromboembolism prophylaxis with an INR target range of 1.8 to 2.3 for a duration of 3 weeks. The first dose will be administered in the evening on the day of surgery.

• Her medical history includes epilepsy for the past 10 years, controlled with phenytoin; hypercholesterolemia for the past 15 years, for which she takes pravastatin; and HTN for the past 20 years, for which she takes lisinopril.
  She takes acetaminophen for headaches and has taken OTC medicines as needed, but doesn’t recall the names of the products.
• Her social history includes a 1-pack-year history of smoking. She does not drink alcohol.
• Her renal and hepatic functions are within normal range

 

The medical team plans to prescribe a combination analgesic (oxycodone/acetaminophen) for postop pain management. In a phone conversation with a friend E.T. expressed that she felt depressed. As a result, her friend brought he a bottle of St. John’s Wort. Please provide appropriate recommendations regarding E.T.’s therapy, including the use of St. John’s Wort.

 

For depression, St. John wort (SJW) is widely used as it can be found over the counter. However, SJW has multiple interactions with many commonly used drugs so, it is not wise to use the medication without consultation (1). Also, there are inconsistent evidence of the efficacy of SJW in managing depression. For this patient, I would advise to avoid St. John wort because of its interaction with phenytoin and Warfarin. SJW interacts with anticonvulsants such as phenytoin and leads to reduce blood of anticonvulsant, which puts the patient in increased risk of seizure (2). Furthermore, SJW induces cytochrome P (CYP) 1A2, 2C19, 2C9, and 3A4, which can result in unstable INR due to decreasing the serum warfarin level (1,3). For this patient, Warfarin is critical drug to prevent venous thromboembolism, so I would advise patient to avoid concurrent use of Warfarin and SJW. For depression, I would recommend the patient to consult a mental health care provider.

 

No interactions were found between oxycodone and acetaminophen, but adults should not take more than 3,000 to 4,000 mg of acetaminophen each day to prevent hepatotoxicity. Also, I would advise the patient to avoid nonprescription acetaminophen or other medication that contains acetaminophen to prevent toxicity. In addition, SJW can reduce serum oxycodone level, which makes the medication less effective in treating pain, hence another reason for patient to avoid SJW. Additionally, a concurrent use of oxycodone and SJW can cause side effects such as “watery eyes, excessive sweating, fever, chills, flushing, restlessness, irritability, anxiety, depression, pupil dilation, tremor, rapid heartbeat, body aches, and etc” (4). Therefore, overall the patient should not be on SJW and follow the oxycodone/acetaminophen regimen.

 

Q: Pravastatin, the medication E.T. was taking prior to admission is not available on the hospital’s formulary. You have prescribed the formulary preferred agent, rosuvastatin for postsurgery use, and you receive an electronic health record (EHR) drug interaction alert regarding the statin and warfarin. How would you manage the situation?

 

The concurrent use of Rosuvastatin and warfarin increase the risk of bleeding because both have a Grade C interaction and may result in an increase in International Normalised Ratio (INR) (6). The enhanced anticoagulation effects are not seen on patients, who were on warfarin and Atorvastatin. According to a journal from Association of Colleges of Pharmacy, “Atorvastatin does not appear to interact with warfarin and should be considered the preferred statin for patients receiving warfarin therapy” (5). Therefore, in order to prevent increase risk of bleeding in this post-surgical patient, I would first consider atorvastatin and Warfarin. Pravastatin is a low- moderate intensity statin and if the patient was on Pravastatin 40mg, then the patient can be prescribed equivalent dose of atorvastatin 10 mg daily (7). However, if the hospital does not have that formulary, then I would prescribe rosuvastatin, but INR would need to be monitor really closely (6). The benefits of rosuvastatin in this patient outweighs the risk, hence close monitoring of INR can allow concomitant administration of rosuvastatin and warfarin.

 

Sources

1. https://www-uptodate-com.york.ezproxy.cuny.edu/contents/clinical-use-of-st-johns-wort?search=St.%20John%E2%80%99s%20Wort&source=search_result&selectedTitle=1~150&usage_type=default&display_rank=1#H14
2. https://gpnotebook.com/simplepage.cfm?ID=-1617297334
3. Henderson, L., Yue, Q. Y., Bergquist, C., Gerden, B., & Arlett, P. (2002). St John’s wort (Hypericum perforatum): drug interactions and clinical outcomes. British journal of clinical pharmacology, 54(4), 349–356. https://doi.org/10.1046/j.1365-2125.2002.01683.x
4. https://www.drugs.com/drug-interactions/ibuprofen-oxycodone-with-st-john-s-wort-1311-0-2106-0.html
5. https://accpjournals.onlinelibrary.wiley.com/doi/abs/10.1592/phco.24.2.285.33137
6. https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(03)15396-2/fulltext
7. http://www.vhpharmsci.com/vhformulary/Tools/HMGCOA-equivalence.htm