The patient is currently taking cannabidiol
Interaction found with [dabigatran etexilate 75 mg oral capsule]
| CrCl Function (ml/Min) | ||||
| Kidney failure | Severely decreased | Moderately to severely decreased | Mildly to moderately decreased | Normal to high |
Consider discontinuation of CBD product or lower dose of dabigatran depending on patient adverse event profile. Additionally, patients with poor renal function are at higher risk of experiencing adverse effects. May also consider use of apixaban or rivaroxaban, as these DOACS seem to pose less of risk for interaction.
DOACS are substrates of P-glycoprotein (P-gp). Concomitant use with P-gp inhibitors can lead to severe advere events as have been reported in case controlled studies. CBD medications are potentially potent inhibitors of P-gp (see the evidence summary below). The risk of a serious adverse event might be reduced by minimizing additional risks or discontinuing the offending natural product.
The currently available DOACs are substrates of P-glycoprotein (P-gp). Product labels for these agents warn against the use of P-gp inhibitors due to decreased metabolism that leads to increased concentration and exposure, and ultimately, an increased risk of bleeding.1,2,3,4 In a group of 91,330 nonvalvular atrial fibrillation patients receiving DOACs (apixaban, edoxaban, rivaroxaban, and dabigatran), the major bleeding incidence rate differences per 1000 person-years of for a DOAC combined with amiodarone (P-gp inhibitor) vs DOAC alone was 13.94 (99% CI, 9.76-18.13). An additional analysis was done using the 12 concurrent medications categorized into two groups: a P-gp competitors group (digoxin, verapamil, diltiazem, amiodarone, and cyclosporine) and P-gp competitors and CYP3A4 inhibitors group (atorvastatin; fluconazole; ketoconazole, itraconazole, voriconazole, or posaconazole; erythromycin or clarithromycin; and dronedarone). In this analysis, the concurrent use of a DOAC with either group was associated with an increased risk of bleeding.5
In a separate case-control study, 89,284 patients with AF and venous thromboembolism were evaluated for increased risk of bleeding due to effects of P-gp/CYP3A inhibition or induction effect. For the P-gp inhibitors verapamil and amiodarone, verapamil was associated with a significant bleeding risk in univariate and multivariate analysis 1.61 (95% CI 1.06–2.50), 1.56 (1.02–2.39), respectively. Amiodarone bleeding risk in univariate and in multivariate analysis was 1.31 (1.04–1.64), 1.22 (0.98–1.54), respectively. The highest bleeding risks were associated with dabigatran‐verapamil, rivaroxaban‐verapamil, and rivaroxaban‐amiodarone with odds ratios of 2.29 (1.13–4.60), 2.18 (1.07–4.40), and 1.68 (1.14–2.49), respectively.6 Dabigatran (brand name: Pradaxa) additionally has warnings with potential severe renal impairment. According to the product labeling for dabigatran, concomitant use of P-gp inhibitors could possibly cause increased exposure of dabigatran compared to either factor alone.3
Few studies have been conducted evaluating P-gp inhibition effects of CBD containing substances; however, evidence supports CBD being a potent P-gp inhibitor. Zhu et. al. showed that CBD had similar P-gp inhibition effect as compared to verapamil on the accumulation of doxorubicin and rhodamine 123(Rh123), both known P-gp substrates. The intracellular accumulation of Rh123 was increased 1.4 to 2.2-fold in the presence of 10 and 30 uM CBD, respectively. The intracellular accumulation of doxorubicin was increased by 3.7 and 7.4-fold in the presence of 10 and 30 uM CBD, respectively.7
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