Pharmacokinetic and Pharmacodynamic Interactions between Food or Herbal Products and Oral Anticoagulants: Evidence Review, Practical Recommendations, and Knowledge Gaps.

Interactions between food and oral anticoagulants (OACs), particularly vitamin K antagonists such as warfarin, are widely recognized and may also be clinically relevant for direct OACs. Pharmacokinetic and pharmacodynamic interactions with food or herbs can lead to anticoagulation potentiation, increased risk of bleeding, or reduced drug efficacy, all compromising patient safety. We conducted a systematic search for randomized controlled trials (RCTs) on PubMed for assessments of interactions between OACs and various ingestants. Since the RCT evidence was slim, we also reviewed prospective longitudinal studies, case series, and case reports to identify possible associations between foods and anticoagulation therapy. We referred to basic or translational studies that shared putative explanations for such interactions, but we failed to identify high-quality evidence in most cases. The limited evidence, small sample size of the studies, conflicting results, and possible heterogeneity in the contents of herbal products prevent a conclusive assessment of these interactions. Existing evidence suggests that (1) cranberry juice consumption (up to 240 mL/d and probably even more) with warfarin is safe; (2) use of green leafy vegetables with a high daily content (more than 250 µg) of vitamin K should be cautioned for patients receiving warfarin, because it may decrease warfarin efficacy. It is also advisable for patients to maintain highly constant intake of green leafy vegetables to ensure stable warfarin effectiveness; (3) ginger, even in small quantities (excluding commercial ginger-flavored beverages, which contain only negligible amounts of ginger), and mango (more than one fruit) can both potentiate warfarin effects; (4) patients taking OACs should avoid St. John's wort due to diminished anticoagulant effect; and (5) consumption of less than 240 mL of grapefruit juice daily is unlikely to interact with OACs. Future longitudinal observational cohort studies and RCTs with larger sample sizes are needed to study specific interactions between food or herbal products and OACs.

Defining heparin resistance: communication from the ISTH SSC Subcommittee of Perioperative and Critical Care Thrombosis and Hemostasis.

The term heparin resistance (HR) is used by clinicians without specific criteria. We performed a literature search and surveyed our SSC membership to better define the term when applied to medical and intensive care unit patients. The most common heparin dosing strategy reported in the literature (53%) and by survey respondents (80.4%) was the use of weight-based dosing. Heparin monitoring results were similar based on the proportion of publications and respondents that reported the use of anti-Xa and activated partial thromboplastin time. The most common literature definition of HR was >35 000 U/d, but no consensus was reported among survey respondents regarding weight-based and the total dose of heparin when determining resistance. Respondent consensus on treating HR included antithrombin supplementation, direct thrombin inhibitors, or administering more heparin as the strategies available for treating HR. A range of definitions for HR exist. Given the common use of heparin weight-based dosing, future publications employing the term HR should include weight-based definitions, monitoring assay, and target level used. Further work is needed to develop a consensus for defining HR.

Cardiovascular Drug Interactions With Nirmatrelvir/Ritonavir in Patients With COVID-19: JACC Review Topic of the Week.

Nirmatrelvir-ritonavir (NMVr) is used to treat symptomatic, nonhospitalized patients with coronavirus disease-2019 (COVID-19) who are at high risk of progression to severe disease. Patients with cardiovascular risk factors and cardiovascular disease are at a high risk of developing adverse events from COVID-19 and as a result have a higher likelihood of receiving NMVr. Ritonavir, the pharmaceutical enhancer used in NMVr, is an inhibitor of the enzymes of CYP450 pathway, particularly CYP3A4 and to a lesser degree CYP2D6, and affects the P-glycoprotein pump. Co-administration of NMVr with medications commonly used to manage cardiovascular conditions can potentially cause significant drug-drug interactions and may lead to severe adverse effects. It is crucial to be aware of such interactions and take appropriate measures to avoid them. In this review, we discuss potential drug-drug interactions between NMVr and commonly used cardiovascular medications based on their pharmacokinetics and pharmacodynamic properties.

Pregnancy in a patient with cancer and heart failure: challenges and complexities.

A 24-year-old African American female (L.R.) with a history of smoking and gestational diabetes was diagnosed with Hodgkin lymphoma. She received multiple chemotherapies, including six cycles of ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine), followed by radiation therapy to left inguinal areas for a total of 30.6 Gy in 17 fractions; she obtained complete remission. Two years later, L.R. had disease relapse in the mediastinum and received two cycles of ESHAP (etoposide, methylprednisolone, high-dose cytarabine, cisplatin) followed by etoposide and ifosfamide. She then received BEAM (carmustine, etoposide, cytarabine, and melphalan) as a conditioning regimen and underwent autologous bone marrow transplant. Her post-transplant course was complicated by cytomegalovirus antigenemia, aspergillus pneumonia, and congestive heart failure with left ventricular ejection fraction (LVEF) of 20%-25%. She was treated with an ACE inhibitor (lisinopril) and a beta-blocker (carvedilol) with improvement of her LVEF to 30%-35%. A follow-up chest x-ray showed an increase in the size of the anterior mediastinal adenopathy suspicious for relapse of lymphoma, and at the same time she was also found to be 5 weeks pregnant. Given her cardiomyopathy, significant obesity, poorly controlled diabetes, and cancer recurrence, L.R. was advised by her gynecologist that the pregnancy was very high risk and might not be viable. The oncologists advised her to terminate the pregnancy within the first trimester, as she needed salvage radiotherapy treatment to the mediastinum and chemotherapy treatments that might endanger the fetus. However, the patient decided to continue with the pregnancy. A multidisciplinary team-which included a cardiologist, oncologist, high-risk obstetrician, pharmacist, and nurse practitioner-was then involved to provide care during the pregnancy. A social worker was also solicited to help with home and financial issues because L.R. was a single mother with a 2-year-old son. L.R. was treated with carvedilol and furosemide, with monthly cardiology clinical follow-up during the first and second trimesters, then every 2 weeks starting with the 28th week, and weekly thereafter until delivery. Between visits, she notified the clinic for symptoms of heart failure exacerbation and was seen as necessary. The possible in utero effects of both medications were discussed with the patient. L.R. had a normal uncomplicated pregnancy and delivered a 6-pound, 10-ounce healthy boy at 39 weeks via vaginal delivery and was discharged home 2 days later. A week after delivery, L.R. presented to the cardiology clinic in good spirits and was excited to show pictures of her newborn baby. She had no cardiac complaints and the repeat echocardiogram showed an unchanged LVEF of 30%-35%.