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Pradaxa
Classes
Direct Thrombin Inhibitors
Administration
NOTE: A MedGuide is available for dabigatran and is to be dispensed with every prescription and prescription refill.
Dabigatran is available in different dosage forms and not all dosage forms are approved for the same indications and age groups. In addition, there are differences between the dosage forms with respect to dosing due to differences in bioavailability. Do not substitute different dosage forms (for example, capsules) for oral pellets on a milligram-to-milligram basis and do not combine more than one dosage form to achieve the total dose.
Capsules
Administer without regard to food. May administer with food if gastrointestinal distress occurs.
Swallow capsules whole with a full glass of water. Do not open, break, crush, or chew prior to or during administration. Breaking, chewing, or emptying the contents of the capsule could result in increased systemic exposure of dabigatran, which may increase the risk for bleeding.
If a dose is missed, administer as soon as possible on the same day. However, skip the missed dose if it cannot be taken at least 6 hours before the next scheduled dose.
Storage: Due to the potential for product breakdown from moisture and loss of potency, capsules must be dispensed and stored in the manufacturer bottle with the original desiccant cap or blister package. Do not repackage or store capsules in any other container. If dispensed in the manufacturer bottle, the product must be used within 4 months of opening.
Oral pellets
Administer the prepared medication before meals to ensure that the patient takes the full dose.
Remove the prescribed number of dabigatran oral pellet packets from the aluminum bag; keep unused packets in the aluminum bag.
Do not open the packets until ready for use.
Tap the packet of oral pellets on a flat surface to ensure that the contents settle to the bottom.
Administer with only specific soft foods or apple juice.
Administration with soft foods: Mix oral pellets in a small cup with 10 mL of soft foods at room temperature, such as baby rice cereal (prepared with water), mashed carrots, applesauce, mashed banana, and stir well. Administer the soft food and oral pellet mixture.
Administration with apple juice: The oral pellets may be spooned directly into the patient's mouth and swallowed with apple juice or added to a cup with approximately 30 to 60 mL of apple juice for drinking. If any pellets remain in the cup after drinking, add a little more apple juice and administer; repeat process until no pellets remain in the cup.
Do not administer via syringes or feeding tubes or with milk, milk products, or soft foods containing milk products.
If the patient does not take all the mixed dabigatran oral pellets, do not give another dose at that time. Give the next scheduled dose about 12 hours later.
If a dose is missed, administer as soon as possible on the same day. However, skip the missed dose if it cannot be taken at least 6 hours before the next scheduled dose.
Storage: Administer immediately after mixing or within 30 minutes after mixing. If the dabigatran dose is not administered within 30 minutes of mixing, discard the dose and prepare a new dose. Use oral pellet packets within 6 months of opening the aluminum bag.
Adverse Reactions
GI bleeding / Delayed / 3.1-6.1
anaphylactoid reactions / Rapid / 0-1.0
anaphylactic shock / Rapid / 0-1.0
intracranial bleeding / Delayed / 0.1-0.3
spinal hematoma / Delayed / Incidence not known
pericardial effusion / Delayed / Incidence not known
esophageal ulceration / Delayed / Incidence not known
peptic ulcer / Delayed / Incidence not known
angioedema / Rapid / Incidence not known
thrombosis / Delayed / Incidence not known
myocardial infarction / Delayed / Incidence not known
stroke / Early / Incidence not known
agranulocytosis / Delayed / Incidence not known
bleeding / Early / 0-20.0
edema / Delayed / 0-1.0
thrombocytopenia / Delayed / 1.0-1.0
anemia / Delayed / 1.0-1.0
leukopenia / Delayed / 1.0-1.0
hypoalbuminemia / Delayed / 1.0-1.0
vaginal bleeding / Delayed / Incidence not known
esophagitis / Delayed / Incidence not known
gastritis / Delayed / Incidence not known
neutropenia / Delayed / Incidence not known
dyspepsia / Early / 1.0-9.0
vomiting / Early / 1.0-8.0
headache / Early / 1.5-8.0
pharyngitis / Delayed / 1.0-6.0
epistaxis / Delayed / 3.4-5.0
diarrhea / Early / 1.0-5.0
abdominal pain / Early / 1.0-5.0
nausea / Early / 3.4-5.0
fever / Early / 3.0-3.0
menorrhagia / Delayed / 2.8-2.8
pruritus / Rapid / 0-1.0
rash / Early / 0-1.0
urticaria / Rapid / 0-1.0
gastroesophageal reflux / Delayed / Incidence not known
alopecia / Delayed / Incidence not known
Boxed Warning
Avoid the abrupt discontinuation of dabigatran in the absence of adequate alternative anticoagulation. Discontinuing dabigatran puts patients at an increased risk of thrombotic events. If dabigatran must be discontinued for reasons other than pathological bleeding or completion of therapy, consider administering another anticoagulant, and reinitiate therapy with dabigatran as soon as medically appropriate.
Consider the benefits and risks before neuraxial intervention in patients anticoagulated or to be anticoagulated with dabigatran. Epidural or spinal hematomas that may result in long-term or permanent paralysis may occur in patients who are anticoagulated and are receiving neuraxial anesthesia or undergoing spinal puncture. To reduce the potential risk of bleeding, it is best to perform the placement or removal of an epidural catheter or lumbar puncture when the anticoagulant effect of dabigatran is low based on the pharmacokinetic profile of dabigatran. The exact timing to reach a sufficiently low anticoagulant effect in each patient is not known. Factors that can increase the risk of developing epidural or spinal hematomas in these patients include use of indwelling epidural catheters; concomitant use of other drugs that affect hemostasis, such as nonsteroidal anti-inflammatory drugs (NSAIDs), platelet inhibitors, other anticoagulants; history of spinal deformity or spinal surgery; and traumatic or repeated epidural or spinal puncture. If epidural anesthesia, lumbar puncture, or spinal anesthesia is employed, monitor patients frequently for signs and symptoms of neurological impairment (e.g., midline back pain, sensory and motor deficits (numbness, tingling, or weakness in lower limbs), bowel and/or bladder dysfunction). Instruct patients to immediately report if they experience any of the above signs or symptoms. If signs or symptoms of spinal hematoma are suspected, initiate urgent diagnosis and treatment including consideration for spinal cord decompression even though such treatment may not prevent or reverse neurological sequelae.
Common Brand Names
Pradaxa
Dea Class
Rx
Description
Oral direct thrombin inhibitor
Used in adults for reduction of risk of stroke and systemic embolism in patients with non-valvular atrial fibrillation, for treatment and reduction in risk of recurrence of DVT and PE, and for the prophylaxis of DVT and PE after hip replacement surgery; used in pediatric patients 3 months and older for VTE in patients who have been treated with a parenteral anticoagulant for at least 5 days and to reduce the risk of recurrence of VTE in patients who have been previously treated
No routine monitoring; anticoagulant effect can be reversed with idarucizumab (adults) when clinically indicated
Dosage And Indications
NOTE: Dabigatran is available in different dosage forms and not all dosage forms are approved for the same indications and age groups. In addition, there are differences between the dosage forms with respect to dosing due to differences in bioavailability. Do not substitute different dosage forms (for example, capsules) for oral pellets on a milligram-to-milligram basis and do not combine more than 1 dosage form to achieve the total dose.
Oral dosage (capsules) Adults
150 mg PO twice daily. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. Data from the RE-LY trial (n = 18,113) indicate dabigatran 150 mg PO twice daily was associated with lower rates of stroke and systemic embolism (2.2% vs. 3.4%; HR 0.65, CI 0.52 to 0.81; p less than 0.0001) compared to warfarin. For eligible patients, direct oral anticoagulants are preferred over warfarin therapy.
NOTE: Dabigatran is available in different dosage forms and not all dosage forms are approved for the same indications and age groups. In addition, there are differences between the dosage forms with respect to dosing due to differences in bioavailability. Do not substitute different dosage forms (for example, capsules) for oral pellets on a milligram-to-milligram basis and do not combine more than 1 dosage form to achieve the total dose.
For the treatment of DVT and PE in adults after 5 to 10 days of initial therapy with a parenteral anticoagulant. Oral dosage (capsules) Adults
150 mg PO twice daily for at least 3 months. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.
260 mg PO twice daily.
220 mg PO twice daily.
185 mg PO twice daily.
150 mg PO twice daily.
110 mg PO twice daily.
75 mg PO twice daily.
260 mg PO twice daily.
220 mg PO twice daily.
170 mg PO twice daily.
140 mg PO twice daily.
110 mg PO twice daily.
90 mg PO twice daily.
70 mg PO twice daily.
180 mg PO twice daily.
140 mg PO twice daily.
100 mg PO twice daily.
110 mg PO twice daily.
100 mg PO twice daily.
90 mg PO twice daily.
80 mg PO twice daily.
60 mg PO twice daily.
70 mg PO twice daily.
60 mg PO twice daily.
50 mg PO twice daily.
50 mg PO twice daily.
40 mg PO twice daily.
40 mg PO twice daily.
30 mg PO twice daily.
NOTE: Dabigatran is available in different dosage forms and not all dosage forms are approved for the same indications and age groups. In addition, there are differences between the dosage forms with respect to dosing due to differences in bioavailability. Do not substitute different dosage forms (for example, capsules) for oral pellets on a milligram-to-milligram basis and do not combine more than 1 dosage form to achieve the total dose.
For DVT prophylaxis and pulmonary embolism prophylaxis in persons undergoing hip replacement surgery or hip fracture surgery†. Oral dosage (capsules) Adults
110 mg PO as a single dose starting 1 to 4 hours after surgery, then 220 mg PO once daily. If dabigatran is not started on the day of surgery, initiate treatment with 220 mg PO once daily. The FDA-approved labeling recommends continuation of prophylaxis for 28 to 35 days after hip replacement surgery. Guidelines recommend continuation of prophylaxis for at least 10 to 14 days; up to 35 days is recommended. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. Dabigatran is recommended as an alternative to low molecular weight heparin in persons undergoing major orthopedic surgery. The concomitant use of an intermittent pneumatic compression device (IPCD) during the hospital stay is encouraged. For persons who decline or are uncooperative with injections or an IPCD, dabigatran is a preferred alternative for thromboprophylaxis.
75 or 110 mg PO as a single dose starting 1 to 4 hours after surgery, then 150 or 220 mg PO once daily. Continue prophylaxis for at least 10 to 14 days; up to 35 days is recommended. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. Data indicate that dabigatran 150 or 220 mg once daily was non-inferior to enoxaparin for reducing the risk of total venous thromboembolism and all-cause mortality after total knee replacement surgery. There was no significant difference in the frequency of major bleeding events between both dabigatran doses and enoxaparin. Dabigatran is recommended as an alternative to the preferred low molecular weight heparin as antithrombotic prophylaxis for persons undergoing major orthopedic surgery. The concomitant use of an intermittent pneumatic compression device (IPCD) during the hospital stay is also encouraged. For persons who decline or are uncooperative with injections or an IPCD, dabigatran is a preferred alternative for thromboprophylaxis.
150 mg PO twice daily. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.
260 mg PO twice daily.
220 mg PO twice daily.
185 mg PO twice daily.
150 mg PO twice daily.
110 mg PO twice daily.
75 mg PO twice daily.
260 mg PO twice daily.
220 mg PO twice daily.
170 mg PO twice daily.
140 mg PO twice daily.
110 mg PO twice daily.
90 mg PO twice daily.
70 mg PO twice daily.
180 mg PO twice daily.
140 mg PO twice daily.
100 mg PO twice daily.
110 mg PO twice daily.
100 mg PO twice daily.
90 mg PO twice daily.
80 mg PO twice daily.
60 mg PO twice daily.
70 mg PO twice daily.
60 mg PO twice daily.
50 mg PO twice daily.
50 mg PO twice daily.
40 mg PO twice daily.
40 mg PO twice daily.
30 mg PO twice daily.
Dosing Considerations
Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.
Renal ImpairmentAdults:
For reduction in risk of stroke and systemic embolism in non-valvular atrial fibrillation:
CrCl more than 30 mL/minute: No dosage adjustment needed.
CrCl 15 to 30 mL/minute: 75 mg PO twice daily.
CrCl less than 15 mL/minute: Dosing recommendations are not provided by the manufacturer.
With concomitant use of P-glycoprotein (P-gp) inhibitors:
CrCl 30 to 50 mL/minute: Dose reduction to 75 mg PO twice daily should be considered when coadministered with the P-gp inhibitors dronedarone or ketoconazole; dose adjustment is not necessary when coadministered with other P-gp inhibitors.
CrCl less than 30 mL/minute: Avoid coadministration.
For treatment or reduction in risk of recurrence of DVT and PE and prophylaxis of DVT and PE after hip replacement surgery:
CrCl more than 30 mL/minute: No dosage adjustment needed.
CrCl 30 mL/minute or less: Dosing recommendations are not provided by the manufacturer.
With concomitant use of P-glycoprotein (P-gp) inhibitors:
CrCl less than 50 mL/minute: Avoid coadministration.
Pediatric patients:
eGFR 50 mL/minute/1.73 m2 or more: No dosage adjustment needed.
eGFR less than 50 mL/minute/1.73 m2: Avoid use; dabigatran has not been studied in pediatric patients with renal impairment and dosing recommendations cannot be provided for these patients.
Hemodialysis
Dabigatran is removed by dialysis; dosing recommendations are not provided by the manufacturer.
Drug Interactions
Abciximab: (Moderate) The use of abciximab within 7 days of use an oral anticoagulant is contraindicated unless the patient's prothrombin time is less than or equal to 1.2 times the control value. Because abciximab inhibits platelet aggregation, additive effects may be seen when abciximab is given in combination with other agents that affect hemostasis such as other platelet inhibitors (e.g., aspirin, ASA, clopidogrel, dipyridamole, ticlopidine), thrombolytic agents (e.g., alteplase, reteplase, streptokinase), and anticoagulants (e.g., heparin, warfarin). However, in clinical trials with abciximab, aspirin and heparin were administered concomitantly. The bleeding risk is significantly increased with concurrent abciximab and thrombolytic therapy; the risks of combination therapy should be weighed against the potential benefits. The GUSTO V study evaluated reduced-dose reteplase in combination with full dose abciximab, in comparison to full dose reteplase alone in patients with acute myocardial infarction (MI); all patients received concurrent aspirin and heparin therapy. The combination regimen was associated with a two-fold increase in moderate to severe non-intracranial bleeding complications, including spontaneous GI bleeding. In addition, large doses of salicylates (>= 3 to 4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. Although NSAIDs lacks platelet inhibitory effects, an increased risk for GI bleeding is possible when NSAIDs are administered during abciximab therapy.
Abrocitinib: (Moderate) Monitor for an increase in dabigatran-related adverse reactions if coadministration with abrocitinib is necessary in patients with creatinine clearance (CrCl) greater than 50 mL/minute. Avoid coadministration in patients with CrCl less than 50 mL/minute when dabigatran is administered for treatment or reduction in risk of recurrence of deep venous thrombosis (DVT) or pulmonary embolism (PE) or prophylaxis of DVT or PE following hip replacement surgery. Avoid coadministration in patients with CrCl less than 30 mL/minute in patients with non-valvular atrial fibrillation. Serum concentrations of dabigatran are expected to be higher in patients with renal impairment compared to patients with normal renal function. Dabigatran is a P-gp substrate and abrocitinib is a P-gp inhibitor.
Acetaminophen; Aspirin, ASA; Caffeine: (Major) Educate patients about the signs of increased bleeding and the need to report these signs to a healthcare provider immediately if coadministration of dabigatran and aspirin or another salicylate is necessary. Dabigatran can cause significant and, sometimes, fatal bleeding. This risk may be increased by concurrent use of chronic salicylate therapy.
Acetaminophen; Aspirin: (Major) Educate patients about the signs of increased bleeding and the need to report these signs to a healthcare provider immediately if coadministration of dabigatran and aspirin or another salicylate is necessary. Dabigatran can cause significant and, sometimes, fatal bleeding. This risk may be increased by concurrent use of chronic salicylate therapy.
Acetaminophen; Aspirin; Diphenhydramine: (Major) Educate patients about the signs of increased bleeding and the need to report these signs to a healthcare provider immediately if coadministration of dabigatran and aspirin or another salicylate is necessary. Dabigatran can cause significant and, sometimes, fatal bleeding. This risk may be increased by concurrent use of chronic salicylate therapy.
Acetaminophen; Ibuprofen: (Major) Educate patients about the signs of increased bleeding and the need to report these signs to a healthcare provider immediately if coadministration of dabigatran and a nonsteroidal antiinflammatory drug (NSAID) is necessary. Dabigatran can cause significant and, sometimes, fatal bleeding. This risk may be increased by concurrent use of chronic NSAID therapy.
Adagrasib: (Moderate) Monitor for an increase in dabigatran-related adverse reactions if coadministration with adagrasib is necessary in patients with creatinine clearance (CrCl) greater than 50 mL/minute. Avoid coadministration in patients with CrCl less than 50 mL/minute when dabigatran is administered for treatment or reduction in risk of recurrence of deep venous thrombosis (DVT) or pulmonary embolism (PE) or prophylaxis of DVT or PE following hip replacement surgery. Avoid coadministration in patients with CrCl less than 30 mL/minute in patients with non-valvular atrial fibrillation. Serum concentrations of dabigatran are expected to be higher in patients with renal impairment compared to patients with normal renal function. Dabigatran is a P-gp substrate and adagrasib is a P-gp inhibitor.
Ado-Trastuzumab emtansine: (Moderate) Use caution if coadministration of anticoagulants with ado-trastuzumab emtansine is necessary due to reports of severe and sometimes fatal hemorrhage, including intracranial bleeding, with ado-trastuzumab emtansine therapy. Consider additional monitoring when concomitant use is medically necessary. While some patients who experienced bleeding during ado-trastuzumab therapy were also receiving anticoagulation therapy, others had no known additional risk factors.
Alteplase: (Major) Based on the pharmacology of dabigatran, other oral anticoagulants and thrombolytic agents could cause additive risk of bleeding when given concurrently with dabigatran.
Altretamine: (Moderate) Due to the thrombocytopenic effects of altretamine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants.
Aminosalicylate sodium, Aminosalicylic acid: (Major) Educate patients about the signs of increased bleeding and the need to report these signs to a healthcare provider immediately if coadministration of dabigatran and aspirin or another salicylate is necessary. Dabigatran can cause significant and, sometimes, fatal bleeding. This risk may be increased by concurrent use of chronic salicylate therapy.
Amiodarone: (Moderate) Increased serum concentrations of dabigatran are possible when dabigatran, a P-glycoprotein (P-gp) substrate, is coadministered with amiodarone, a P-gp inhibitor. Patients should be monitored for increased adverse effects of dabigatran. When dabigatran is administered for treatment or reduction in risk of recurrence of deep venous thrombosis (DVT) or pulmonary embolism (PE) or prophylaxis of DVT or PE following hip replacement surgery, avoid coadministration with P-gp inhibitors like amiodarone in patients with CrCl less than 50 mL/minute. When dabigatran is used in patients with non-valvular atrial fibrillation and severe renal impairment (CrCl less than 30 mL/minute), avoid coadministration with amiodarone, as serum concentrations of dabigatran are expected to be higher than when administered to patients with normal renal function. Coadministration of dabigatran and a single oral dose of 600 mg amiodarone resulted in an increase in dabigatran AUC and Cmax by 58% and 50%, respectively. In addition, coadministration resulted in a 65% increase in renal clearance of dabigatran. Due to the long half-life of amiodarone, the increase in renal clearance may persist after discontinuation of amiodarone. Data from the RE-LY trial indicate no significant changes in dabigatran trough concentrations were seen in patients who received concomitant therapy with amiodarone. In clinical studies, dabigatran was found to have no effect on the pharmacokinetics of amiodarone. P-gp inhibition and renal impairment are the major independent factors that result in increased exposure to dabigatran.
Amlodipine; Celecoxib: (Major) Educate patients about the signs of increased bleeding and the need to report these signs to a healthcare provider immediately if coadministration of dabigatran and a nonsteroidal antiinflammatory drug (NSAID) is necessary. Dabigatran can cause significant and, sometimes, fatal bleeding. This risk may be increased by concurrent use of chronic NSAID therapy.
Amoxicillin; Clarithromycin; Omeprazole: (Moderate) Increased serum concentrations of dabigatran are possible when dabigatran, a P-glycoprotein (P-gp) substrate, is coadministered with clarithromycin, a P-gp inhibitor. Although the coadministration of dabigatran and clarithromycin has no effect on the pharmacokinetics of dabigatran or clarithromycin in healthy subjects, patients should be monitored for increased adverse effects of dabigatran. When dabigatran is administered for treatment or reduction in risk of recurrence of deep venous thrombosis (DVT) or pulmonary embolism (PE) or prophylaxis of DVT or PE following hip replacement surgery, avoid coadministration with P-gp inhibitors like clarithromycin in patients with CrCl less than 50 mL/minute. When dabigatran is used in patients with non-valvular atrial fibrillation and severe renal impairment (CrCl less than 30 mL/minute), avoid coadministration with clarithromycin, as serum concentrations of dabigatran are expected to be higher than when administered to patients with normal renal function. P-gp inhibition and renal impairment are the major independent factors that result in increased exposure to dabigatran.
Anagrelide: (Moderate) Although anagrelide inhibits platelet aggregation at high doses, there is a potential additive risk for bleeding if anagrelide is given in combination with other agents that effect hemostasis such as other anticoagulants. In addition, large doses of salicylates (>= 3 to 4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. An in vivo interaction study in humans demonstrated that a single 1 mg dose of anagrelide administered concomitantly with a single dose of aspirin 900 mg was well tolerated; there was no effect on bleeding time, PT, or PTT. However, aspirin alone produced a marked inhibition of platelet aggregation ex vivo; anagrelide enhanced the platelet inhibition effects of aspirin slightly. In addition, a phase II trial, aspirin (81 mg or 325 mg) was randomly assigned to patients with atrial fibrillation receiving dabigatran (150 mg twice daily). Data obtained from logistic regression analysis suggest that the concomitant administration of aspirin and dabigatran may increase the risk of bleeding from 12% to 18% (81 mg aspirin) or 24% (325 mg aspirin). Monitor patients closely for signs of bleeding if dabigatran or anagrelide is given concomitantly with aspirin.
Antithrombin III: (Major) Avoid use of dabigatran with antithrombin III due to the increased bleeding risk. Monitor patients closely and promptly evaluate any signs or symptoms of bleeding if dabigatran and other anticoagulants are used concomitantly. Coadministration of dabigatran and other anticoagulants may increase the risk of bleeding. Long-term concomitant treatment with dabigatran and other anticoagulants is not recommended; short-term use may be necessary for patients transitioning to or from dabigatran.
Apalutamide: (Major) Coadministration of dabigatran with apalutamide should generally be avoided due to the risk of deceased dabigatran exposure which may reduce efficacy. Dabigatran is a P-glycoprotein (P-gp) substrate and apalutamide is a weak P-gp inducer.
Apixaban: (Major) Avoid concomitant use of apixaban and dabigatran due to the increased risk for bleeding. Short-term overlaps in anticoagulation therapy may be necessary for patients transitioning from one anticoagulant to another. Monitor patients closely and promptly evaluate any signs or symptoms of bleeding if the use of multiple anticoagulants is necessary.
Argatroban: (Major) Avoid use of dabigatran with argatroban due to the increased bleeding risk. Monitor patients closely and promptly evaluate any signs or symptoms of bleeding if dabigatran and other anticoagulants are used concomitantly. Coadministration of dabigatran and other anticoagulants may increase the risk of bleeding. Long-term concomitant treatment with dabigatran and other anticoagulants is not recommended; short-term use may be necessary for patients transitioning to or from dabigatran.
Aspirin, ASA: (Major) Educate patients about the signs of increased bleeding and the need to report these signs to a healthcare provider immediately if coadministration of dabigatran and aspirin or another salicylate is necessary. Dabigatran can cause significant and, sometimes, fatal bleeding. This risk may be increased by concurrent use of chronic salicylate therapy.
Aspirin, ASA; Butalbital; Caffeine: (Major) Educate patients about the signs of increased bleeding and the need to report these signs to a healthcare provider immediately if coadministration of dabigatran and aspirin or another salicylate is necessary. Dabigatran can cause significant and, sometimes, fatal bleeding. This risk may be increased by concurrent use of chronic salicylate therapy.
Aspirin, ASA; Caffeine: (Major) Educate patients about the signs of increased bleeding and the need to report these signs to a healthcare provider immediately if coadministration of dabigatran and aspirin or another salicylate is necessary. Dabigatran can cause significant and, sometimes, fatal bleeding. This risk may be increased by concurrent use of chronic salicylate therapy.
Aspirin, ASA; Caffeine; Orphenadrine: (Major) Educate patients about the signs of increased bleeding and the need to report these signs to a healthcare provider immediately if coadministration of dabigatran and aspirin or another salicylate is necessary. Dabigatran can cause significant and, sometimes, fatal bleeding. This risk may be increased by concurrent use of chronic salicylate therapy.
Aspirin, ASA; Carisoprodol: (Major) Educate patients about the signs of increased bleeding and the need to report these signs to a healthcare provider immediately if coadministration of dabigatran and aspirin or another salicylate is necessary. Dabigatran can cause significant and, sometimes, fatal bleeding. This risk may be increased by concurrent use of chronic salicylate therapy.
Aspirin, ASA; Carisoprodol; Codeine: (Major) Educate patients about the signs of increased bleeding and the need to report these signs to a healthcare provider immediately if coadministration of dabigatran and aspirin or another salicylate is necessary. Dabigatran can cause significant and, sometimes, fatal bleeding. This risk may be increased by concurrent use of chronic salicylate therapy.
Aspirin, ASA; Citric Acid; Sodium Bicarbonate: (Major) Educate patients about the signs of increased bleeding and the need to report these signs to a healthcare provider immediately if coadministration of dabigatran and aspirin or another salicylate is necessary. Dabigatran can cause significant and, sometimes, fatal bleeding. This risk may be increased by concurrent use of chronic salicylate therapy.
Aspirin, ASA; Dipyridamole: (Major) Educate patients about the signs of increased bleeding and the need to report these signs to a healthcare provider immediately if coadministration of dabigatran and aspirin or another salicylate is necessary. Dabigatran can cause significant and, sometimes, fatal bleeding. This risk may be increased by concurrent use of chronic salicylate therapy. (Moderate) Because dipyridamole is a platelet inhibitor, there is a potential additive risk for bleeding if dipyridamole is given in combination with other agents that affect hemostasis.
Aspirin, ASA; Omeprazole: (Major) Educate patients about the signs of increased bleeding and the need to report these signs to a healthcare provider immediately if coadministration of dabigatran and aspirin or another salicylate is necessary. Dabigatran can cause significant and, sometimes, fatal bleeding. This risk may be increased by concurrent use of chronic salicylate therapy.
Aspirin, ASA; Oxycodone: (Major) Educate patients about the signs of increased bleeding and the need to report these signs to a healthcare provider immediately if coadministration of dabigatran and aspirin or another salicylate is necessary. Dabigatran can cause significant and, sometimes, fatal bleeding. This risk may be increased by concurrent use of chronic salicylate therapy.
Atazanavir; Cobicistat: (Moderate) Monitor for an increase in dabigatran-related adverse reactions if coadministration with cobicistat is necessary in patients with creatinine clearance (CrCl) greater than 50 mL/minute. Avoid coadministration in patients with CrCl less than 50 mL/minute when dabigatran is administered for treatment or reduction in risk of recurrence of deep venous thrombosis (DVT) or pulmonary embolism (PE) or prophylaxis of DVT or PE following hip replacement surgery. Avoid coadministration in patients with CrCl less than 30 mL/minute in patients with non-valvular atrial fibrillation. Serum concentrations of dabigatran are expected to be higher in patients with renal impairment compared to patients with normal renal function. Dabigatran is a P-gp substrate and cobicistat is a P-gp inhibitor.
Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Major) Educate patients about the signs of increased bleeding and the need to report these signs to a healthcare provider immediately if coadministration of dabigatran and aspirin or another salicylate is necessary. Dabigatran can cause significant and, sometimes, fatal bleeding. This risk may be increased by concurrent use of chronic salicylate therapy.
Berotralstat: (Moderate) Monitor for an increase in dabigatran-related adverse reactions if coadministration with berotralstat is necessary in patients with CrCl greater than 50 mL/minute. Avoid coadministration in patients with CrCl less than 50 mL/minute when dabigatran is administered for treatment or reduction in risk of recurrence of deep venous thrombosis (DVT) or pulmonary embolism (PE) or prophylaxis of DVT or PE following hip replacement surgery. Avoid coadministration in patients with CrCl less than 30 mL/minute in patients with non-valvular atrial fibrillation. Serum concentrations of dabigatran are expected to be higher in patients with renal impairment compared to patients with normal renal function. Dabigatran is a P-gp substrate and berotralstat is a P-gp inhibitor.
Betrixaban: (Major) Avoid use of betrixaban with dabigatran due to the increased bleeding risk. Monitor patients closely and promptly evaluate any signs or symptoms of bleeding if betrixaban and other anticoagulants are used concomitantly. Coadministration of betrixaban and other anticoagulants may increase the risk of bleeding. Long-term concomitant treatment with betrixaban and other anticoagulants is not recommended; short-term use may be necessary for patients transitioning to or from betrixaban.
Bismuth Subsalicylate: (Major) Educate patients about the signs of increased bleeding and the need to report these signs to a healthcare provider immediately if coadministration of dabigatran and aspirin or another salicylate is necessary. Dabigatran can cause significant and, sometimes, fatal bleeding. This risk may be increased by concurrent use of chronic salicylate therapy.
Bismuth Subsalicylate; Metronidazole; Tetracycline: (Major) Educate patients about the signs of increased bleeding and the need to report these signs to a healthcare provider immediately if coadministration of dabigatran and aspirin or another salicylate is necessary. Dabigatran can cause significant and, sometimes, fatal bleeding. This risk may be increased by concurrent use of chronic salicylate therapy.
Bivalirudin: (Major) Avoid use of dabigatran with bivalirudin due to the increased bleeding risk. Monitor patients closely and promptly evaluate any signs or symptoms of bleeding if dabigatran and other anticoagulants are used concomitantly. Coadministration of dabigatran and other anticoagulants may increase the risk of bleeding. Long-term concomitant treatment with dabigatran and other anticoagulants is not recommended; short-term use may be necessary for patients transitioning to or from dabigatran.
Brigatinib: (Moderate) Monitor for an increase in dabigatran-related adverse reactions, including bleeding, if coadministration with brigatinib is necessary; the risk may be higher in patients with renal impairment. Dabigatran is a P-glycoprotein (P-gp) substrate. P-gp inhibition and renal impairment are the major independent factors that result in increased exposure to dabigatran. Brigatinib is a P-gp inhibitor in vitro and may have the potential to increase concentrations of P-gp substrates. Coadministration of dabigatran and a single oral dose of another P-gp inhibitor increased the dabigatran AUC and Cmax by 58% and 50%, respectively; there was additionally a 65% increase in renal clearance of dabigatran.
Bupivacaine; Meloxicam: (Major) Educate patients about the signs of increased bleeding and the need to report these signs to a healthcare provider immediately if coadministration of dabigatran and a nonsteroidal antiinflammatory drug (NSAID) is necessary. Dabigatran can cause significant and, sometimes, fatal bleeding. This risk may be increased by concurrent use of chronic NSAID therapy.
Butalbital; Aspirin; Caffeine; Codeine: (Major) Educate patients about the signs of increased bleeding and the need to report these signs to a healthcare provider immediately if coadministration of dabigatran and aspirin or another salicylate is necessary. Dabigatran can cause significant and, sometimes, fatal bleeding. This risk may be increased by concurrent use of chronic salicylate therapy.
Cabozantinib: (Moderate) Monitor for an increase in dabigatran-related adverse reactions if coadministration with cabozantinib is necessary in patients with CrCL greater than 50 mL/minute. Avoid coadministration in patients with CrCL less than 50 mL/minute when dabigatran is administered for treatment or reduction in risk of recurrence of deep venous thrombosis (DVT) or pulmonary embolism (PE) or prophylaxis of DVT or PE following hip replacement surgery. Avoid coadministration in patients with CrCL less than 30 mL/minute in patients with non-valvular atrial fibrillation. Serum concentrations of dabigatran are expected to be higher in patients with renal impairment compared to patients with normal renal function. Cabozantinib is a P-glycoprotein (P-gp) inhibitor and has the potential to increase plasma concentrations of P-gp substrates such as dabigatran; however, the clinical relevance of this finding is unknown.
Cannabidiol: (Moderate) Monitor for an increase in dabigatran-related adverse reactions if coadministration with cannabidiol is necessary in patients with creatinine clearance (CrCl) greater than 50 mL/minute. Avoid coadministration in patients with CrCl less than 50 mL/minute when dabigatran is administered for treatment or reduction in risk of recurrence of deep venous thrombosis (DVT) or pulmonary embolism (PE) or prophylaxis of DVT or PE following hip replacement surgery. Avoid coadministration in patients with CrCl less than 30 mL/minute and non-valvular atrial fibrillation. Serum concentrations of dabigatran are expected to be higher in patients with renal impairment compared to patients with normal renal function. Dabigatran is a P-gp substrate and cannabidiol is a P-gp inhibitor.
Caplacizumab: (Major) Avoid concomitant use of caplacizumab and anticoagulants when possible. Assess and monitor closely for bleeding if use together is necessary. Interrupt use of caplacizumab if clinically significant bleeding occurs.
Capmatinib: (Moderate) Monitor for an increase in dabigatran-related adverse reactions if coadministration with capmatinib is necessary in patients with CrCL greater than 50 mL/minute. Avoid coadministration in patients with CrCL less than 50 mL/minute when dabigatran is administered for treatment or reduction in risk of recurrence of deep venous thrombosis (DVT) or pulmonary embolism (PE) or prophylaxis of DVT or PE following hip replacement surgery. Avoid coadministration in patients with CrCL less than 30 mL/minute in patients with non-valvular atrial fibrillation. Serum concentrations of dabigatran are expected to be higher in patients with renal impairment compared to patients with normal renal function. Dabigatran is a P-glycoprotein substrate and capmatinib is a P-gp inhibitor.
Carbamazepine: (Major) Avoid the concomitant administration of dabigatran and drugs that are strong inducers of P-gp, such as carbamazepine. Concomitant administration of dabigatran and carbamazepine results in decreased plasma concentrations of dabigatran that may be insufficient to achieve the intended therapeutic effect.
Carvedilol: (Moderate) Increased serum concentrations of dabigatran are possible when dabigatran, a P-glycoprotein (P-gp) substrate, is coadministered with carvedilol, a P-gp inhibitor. Patients should be monitored for increased adverse effects of dabigatran. When dabigatran is administered for treatment or reduction in risk of recurrence of deep venous thrombosis (DVT) or pulmonary embolism (PE) or prophylaxis of DVT or PE following hip replacement surgery, avoid coadministration with P-gp inhibitors like carvedilol in patients with CrCl less than 50 mL/minute. When dabigatran is used in patients with non-valvular atrial fibrillation and severe renal impairment (CrCl less than 30 mL/minute), avoid coadministration with carvedilol, as serum concentrations of dabigatran are expected to be higher than when administered to patients with normal renal function. P-gp inhibition and renal impairment are the major independent factors that result in increased exposure to dabigatran.
Celecoxib: (Major) Educate patients about the signs of increased bleeding and the need to report these signs to a healthcare provider immediately if coadministration of dabigatran and a nonsteroidal antiinflammatory drug (NSAID) is necessary. Dabigatran can cause significant and, sometimes, fatal bleeding. This risk may be increased by concurrent use of chronic NSAID therapy.
Celecoxib; Tramadol: (Major) Educate patients about the signs of increased bleeding and the need to report these signs to a healthcare provider immediately if coadministration of dabigatran and a nonsteroidal antiinflammatory drug (NSAID) is necessary. Dabigatran can cause significant and, sometimes, fatal bleeding. This risk may be increased by concurrent use of chronic NSAID therapy.
Chlorambucil: (Moderate) Due to the thrombocytopenic effects of chlorambucil, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants.
Chloroquine: (Moderate) Use caution if chloroquine is coadministered with dabigatran due to the potential for increased dabigatran exposure which may increase the risk of bleeding. Dabigatran is a P-gp substrate; limited data suggests that chloroquine is a P-gp inhibitor.
Chlorpheniramine; Ibuprofen; Pseudoephedrine: (Major) Educate patients about the signs of increased bleeding and the need to report these signs to a healthcare provider immediately if coadministration of dabigatran and a nonsteroidal antiinflammatory drug (NSAID) is necessary. Dabigatran can cause significant and, sometimes, fatal bleeding. This risk may be increased by concurrent use of chronic NSAID therapy.
Choline Salicylate; Magnesium Salicylate: (Major) Educate patients about the signs of increased bleeding and the need to report these signs to a healthcare provider immediately if coadministration of dabigatran and aspirin or another salicylate is necessary. Dabigatran can cause significant and, sometimes, fatal bleeding. This risk may be increased by concurrent use of chronic salicylate therapy.
Cilostazol: (Moderate) The safety of cilostazol has not been established with concomitant administration of anticoagulants. Because cilostazol is a platelet aggregation inhibitor, concomitant administration with similar acting drugs could theoretically result in an increased risk of bleeding due to additive pharmacodynamic effects, and combinations of these agents should be approached with caution. Patients on anticoagulants should be monitored for changes in response to anticoagulation therapy if cilostazol is administered concurrently.
Citalopram: (Moderate) Advise patients of the increased bleeding risk associated with the concomitant use of selective serotonin reuptake inhibitors (SSRIs) and anticoagulants like dabigatran. Case reports and epidemiological studies have demonstrated an association between use of drugs that interfere with serotonin reuptake and gastrointestinal bleeding.
Clarithromycin: (Moderate) Increased serum concentrations of dabigatran are possible when dabigatran, a P-glycoprotein (P-gp) substrate, is coadministered with clarithromycin, a P-gp inhibitor. Although the coadministration of dabigatran and clarithromycin has no effect on the pharmacokinetics of dabigatran or clarithromycin in healthy subjects, patients should be monitored for increased adverse effects of dabigatran. When dabigatran is administered for treatment or reduction in risk of recurrence of deep venous thrombosis (DVT) or pulmonary embolism (PE) or prophylaxis of DVT or PE following hip replacement surgery, avoid coadministration with P-gp inhibitors like clarithromycin in patients with CrCl less than 50 mL/minute. When dabigatran is used in patients with non-valvular atrial fibrillation and severe renal impairment (CrCl less than 30 mL/minute), avoid coadministration with clarithromycin, as serum concentrations of dabigatran are expected to be higher than when administered to patients with normal renal function. P-gp inhibition and renal impairment are the major independent factors that result in increased exposure to dabigatran.
Clofarabine: (Moderate) Due to the thrombocytopenic effects of clofarabine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants.
Clopidogrel: (Moderate) Coadministration of dabigatran and clopidogrel (300 mg or 600 mg loading dose) resulted in an increase in dabigatran AUC and Cmax of 30% and 40%, respectively; however capillary bleeding times were not further prolonged compared to clopidogrel monotherapy. In addition, coagulation measures for dabigatran's effect (aPTT, ECT, and TT) were unchanged, and inhibition of platelet aggregation (IPA), a measure of clopidogrel's effect, was unchanged. However, the manufacturer notes that the concomitant use of dabitatran and platelet inhibiting agents may increase the risk of bleeding. Monitor patients closely for signs of bleeding if dabigatran is given concomitantly with any platelet inhibiting agents.
Cobicistat: (Moderate) Monitor for an increase in dabigatran-related adverse reactions if coadministration with cobicistat is necessary in patients with creatinine clearance (CrCl) greater than 50 mL/minute. Avoid coadministration in patients with CrCl less than 50 mL/minute when dabigatran is administered for treatment or reduction in risk of recurrence of deep venous thrombosis (DVT) or pulmonary embolism (PE) or prophylaxis of DVT or PE following hip replacement surgery. Avoid coadministration in patients with CrCl less than 30 mL/minute in patients with non-valvular atrial fibrillation. Serum concentrations of dabigatran are expected to be higher in patients with renal impairment compared to patients with normal renal function. Dabigatran is a P-gp substrate and cobicistat is a P-gp inhibitor.
Collagenase: (Moderate) Cautious use of injectable collagenase by patients taking anticoagulants is advised. The efficacy and safety of administering injectable collagenase to a patient taking an anticoagulant within 7 days before the injection are unknown. Receipt of injectable collagenase may cause an ecchymosis or bleeding at the injection site.
Conivaptan: (Moderate) Increased serum concentrations of dabigatran are possible when dabigatran, a P-glycoprotein (P-gp) substrate, is coadministered with conivaptan, a P-gp inhibitor. Patients should be monitored for increased adverse effects of dabigatran. When dabigatran is administered for treatment or reduction in risk of recurrence of deep venous thrombosis (DVT) or pulmonary embolism (PE) or prophylaxis of DVT or PE following hip replacement surgery, avoid coadministration with P-gp inhibitors like conivaptan in patients with CrCl less than 50 mL/minute. When dabigatran is used in patients with non-valvular atrial fibrillation and severe renal impairment (CrCl less than 30 mL/minute), avoid coadministration with conivaptan, as serum concentrations of dabigatran are expected to be higher than when administered to patients with normal renal function. P-gp inhibition and renal impairment are the major independent factors that result in increased exposure to dabigatran.
Cyclosporine: (Major) Avoid concomitant use of dabigatran and cyclosporine. Increased serum concentrations of dabigatran and an increased risk of bleeding are possible when dabigatran, a P-glycoprotein (P-gp) substrate, is coadministered with cyclosporine, a P-gp inhibitor. P-gp inhibition is a major independent factor that results in increased exposure to dabigatran.
Cytarabine, ARA-C: (Moderate) Due to the thrombocytopenic effects of pyrimidine analogs, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants.
Daclatasvir: (Moderate) Increased serum concentrations of dabigatran are possible when dabigatran, a P-glycoprotein (P-gp) substrate, is coadministered with daclatasvir, a P-gp inhibitor. Patients should be monitored for increased adverse effects of dabigatran. When dabigatran is administered for treatment or reduction in risk of recurrence of deep venous thrombosis (DVT) or pulmonary embolism (PE) or prophylaxis of DVT or PE following hip replacement surgery, avoid coadministration with P-gp inhibitors like daclatasvir in patients with CrCl less than 50 mL/minute. When dabigatran is used in patients with non-valvular atrial fibrillation and severe renal impairment (CrCl less than 30 mL/minute), avoid coadministration with daclatasvir, as serum concentrations of dabigatran are expected to be higher than when administered to patients with normal renal function. P-gp inhibition and renal impairment are the major independent factors that result in increased exposure to dabigatran.
Dalteparin: (Major) Avoid use of dabigatran with dalteparin due to the increased bleeding risk. Monitor patients closely and promptly evaluate any signs or symptoms of bleeding if dabigatran and other anticoagulants are used concomitantly. Coadministration of dabigatran and other anticoagulants may increase the risk of bleeding. Long-term concomitant treatment with dabigatran and other anticoagulants is not recommended; short-term use may be necessary for patients transitioning to or from dabigatran.
Danazol: (Major) Danazol can decrease hepatic synthesis of procoagulant factors, increasing the possibility of bleeding when used concurrently with anticoagulants.
Darunavir; Cobicistat: (Moderate) Monitor for an increase in dabigatran-related adverse reactions if coadministration with cobicistat is necessary in patients with creatinine clearance (CrCl) greater than 50 mL/minute. Avoid coadministration in patients with CrCl less than 50 mL/minute when dabigatran is administered for treatment or reduction in risk of recurrence of deep venous thrombosis (DVT) or pulmonary embolism (PE) or prophylaxis of DVT or PE following hip replacement surgery. Avoid coadministration in patients with CrCl less than 30 mL/minute in patients with non-valvular atrial fibrillation. Serum concentrations of dabigatran are expected to be higher in patients with renal impairment compared to patients with normal renal function. Dabigatran is a P-gp substrate and cobicistat is a P-gp inhibitor.
Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Moderate) Monitor for an increase in dabigatran-related adverse reactions if coadministration with cobicistat is necessary in patients with creatinine clearance (CrCl) greater than 50 mL/minute. Avoid coadministration in patients with CrCl less than 50 mL/minute when dabigatran is administered for treatment or reduction in risk of recurrence of deep venous thrombosis (DVT) or pulmonary embolism (PE) or prophylaxis of DVT or PE following hip replacement surgery. Avoid coadministration in patients with CrCl less than 30 mL/minute in patients with non-valvular atrial fibrillation. Serum concentrations of dabigatran are expected to be higher in patients with renal impairment compared to patients with normal renal function. Dabigatran is a P-gp substrate and cobicistat is a P-gp inhibitor.
Dasatinib: (Moderate) Monitor for evidence of bleeding if coadministration of dasatinib and anticoagulants is necessary. Dasatinib can cause serious and fatal bleeding. Concomitant anticoagulants may increase the risk of hemorrhage.
Deferasirox: (Moderate) Because gastric ulceration and GI bleeding have been reported in patients taking deferasirox, use caution when coadministering with other drugs known to increase the risk of peptic ulcers or gastric hemorrhage including anticoagulants.
Defibrotide: (Contraindicated) Coadministration of defibrotide with antithrombotic agents like anticoagulants is contraindicated. The pharmacodynamic activity and risk of hemorrhage with antithrombotic agents are increased if coadministered with defibrotide. If therapy with defibrotide is necessary, discontinue systemic antithrombotic agents (not including use for routine maintenance or reopening of central venous catheters) prior to initiation of defibrotide therapy. Consider delaying the onset of defibrotide treatment until the effects of the antithrombotic agent have abated.
Desirudin: (Major) Any agent which may enhance the risk of hemorrhage should generally be discontinued before initiating desirudin therapy. These agents include anticoagulants. If coadministration cannot be avoided, close clinical and laboratory monitoring should be conducted. If a patient is switched from oral anticoagulants to desirudin therapy or from desirudin to oral anticoagulants, the anticoagulant activity should continue to be closely monitored with appropriate methods. That activity should be taken into account in the evaluation of the overall coagulation status of the patient during the switch.
Dextran: (Moderate) Because of the potential effects of certain dextran formulations on bleeding time, use with caution in patients on anticoagulants concurrently.
Dextromethorphan; Quinidine: (Moderate) Increased serum concentrations of dabigatran are possible when dabigatran, a P-glycoprotein (P-gp) substrate, is coadministered with quinidine, a P-gp inhibitor. Patients should be monitored for increased adverse effects of dabigatran. When dabigatran is administered for treatment or reduction in risk of recurrence of deep venous thrombosis (DVT) or pulmonary embolism (PE) or prophylaxis of DVT or PE following hip replacement surgery, avoid coadministration with P-gp inhibitors like quinidine in patients with CrCl less than 50 mL/minute. When dabigatran is used in patients with non-valvular atrial fibrillation and severe renal impairment (CrCl less than 30 mL/minute), avoid coadministration with quinidine, as serum concentrations of dabigatran are expected to be higher than when administered to patients with normal renal function. Coadministration of quinidine 200 mg every 2 hours up to a total dose of 1000 mg and dabigatran administered over 3 consecutive days, the last evening dose on Day 3 with or without quinidine pre-dosing, resulted in an increase in dabigatran AUC and Cmax of 53% and 56%, respectively. P-gp inhibition and renal impairment are the major independent factors that result in increased exposure to dabigatran.
Diclofenac: (Major) Educate patients about the signs of increased bleeding and the need to report these signs to a healthcare provider immediately if coadministration of dabigatran and a nonsteroidal antiinflammatory drug (NSAID) is necessary. Dabigatran can cause significant and, sometimes, fatal bleeding. This risk may be increased by concurrent use of chronic NSAID therapy.
Diclofenac; Misoprostol: (Major) Educate patients about the signs of increased bleeding and the need to report these signs to a healthcare provider immediately if coadministration of dabigatran and a nonsteroidal antiinflammatory drug (NSAID) is necessary. Dabigatran can cause significant and, sometimes, fatal bleeding. This risk may be increased by concurrent use of chronic NSAID therapy.
Diflunisal: (Major) Educate patients about the signs of increased bleeding and the need to report these signs to a healthcare provider immediately if coadministration of dabigatran and a nonsteroidal antiinflammatory drug (NSAID) is necessary. Dabigatran can cause significant and, sometimes, fatal bleeding. This risk may be increased by concurrent use of chronic NSAID therapy.
Diphenhydramine; Ibuprofen: (Major) Educate patients about the signs of increased bleeding and the need to report these signs to a healthcare provider immediately if coadministration of dabigatran and a nonsteroidal antiinflammatory drug (NSAID) is necessary. Dabigatran can cause significant and, sometimes, fatal bleeding. This risk may be increased by concurrent use of chronic NSAID therapy.
Diphenhydramine; Naproxen: (Major) Educate patients about the signs of increased bleeding and the need to report these signs to a healthcare provider immediately if coadministration of dabigatran and a nonsteroidal antiinflammatory drug (NSAID) is necessary. Dabigatran can cause significant and, sometimes, fatal bleeding. This risk may be increased by concurrent use of chronic NSAID therapy.
Dipyridamole: (Moderate) Because dipyridamole is a platelet inhibitor, there is a potential additive risk for bleeding if dipyridamole is given in combination with other agents that affect hemostasis.
Dronedarone: (Major) Increased serum concentrations of dabigatran are possible when dabigatran, a P-glycoprotein (P-gp) substrate, is coadministered with dronedarone, a P-gp inhibitor. Patients should be monitored for increased adverse effects of dabigatran. When dabigatran is administered for treatment or reduction in risk of recurrence of deep venous thrombosis (DVT) or pulmonary embolism (PE) or prophylaxis of DVT or PE following hip replacement surgery, avoid coadministration with P-gp inhibitors like dronedarone in patients with CrCl less than 50 mL/minute. When used in patients with non-valvular atrial fibrillation, avoid the coadministration of dabigatran and dronedarone in patients with severe renal impairment (CrCl less than 30 mL/minute), and reduce the dabigatran dose to 75 mg twice daily when dronedarone and dabigatran are coadministered in patients with moderate renal impairment (CrCl 30 to 50 mL/min). Simultaneous administration of dabigatran and dronedarone (administered once or twice daily) increases exposure to dabigatran by 70 to 140% compared to dabigatran alone. The increase in exposure is only 30 to 60% higher compared to dabigatran alone when dronedarone is administered 2 hours after dabigatran. P-gp inhibition and renal impairment are the major independent factors that result in increased exposure to dabigatran.
Edoxaban: (Major) Avoid concurrent use of edoxaban with dabigatran due to the increased bleeding risk. Monitor patients closely and promptly evaluate any signs or symptoms of bleeding if edoxaban and other anticoagulants are used concomitantly. Coadministration of edoxaban and other anticoagulants may increase the risk of bleeding. Long-term concomitant treatment with edoxaban and other anticoagulants is not recommended; short-term use may be necessary for patients transitioning to or from edoxaban.
Elacestrant: (Moderate) Monitor for an increase in dabigatran-related adverse reactions if coadministration with elacestrant is necessary in patients with creatinine clearance (CrCl) greater than 50 mL/minute. Avoid coadministration in patients with CrCl less than 50 mL/minute when dabigatran is administered for treatment or reduction in risk of recurrence of deep venous thrombosis (DVT) or pulmonary embolism (PE) or prophylaxis of DVT or PE following hip replacement surgery. Avoid coadministration in patients with CrCl less than 30 mL/minute in patients with non-valvular atrial fibrillation. Serum concentrations of dabigatran are expected to be higher in patients with renal impairment compared to patients with normal renal function. Dabigatran is a P-gp substrate and elacestrant is a P-gp inhibitor.
Elagolix: (Moderate) Increased serum concentrations of dabigatran are possible when dabigatran, a P-glycoprotein (P-gp) substrate, is coadministered with elagolix, a P-gp inhibitor. Although coadministration may have no effect on the pharmacokinetics of dabigatran in healthy subjects, patients should be monitored for increased adverse effects of dabigatran. When dabigatran is administered for treatment or reduction in risk of recurrence of deep venous thrombosis (DVT) or pulmonary embolism (PE) or prophylaxis of DVT or PE following hip replacement surgery, avoid coadministration with P-gp inhibitors like elagolix in patients with CrCl less than 50 mL/minute. When dabigatran is used in patients with non-valvular atrial fibrillation and severe renal impairment (CrCl less than 30 mL/minute), avoid coadministration with elagolix, as serum concentrations of dabigatran are expected to be higher than when administered to patients with normal renal function. P-gp inhibition and renal impairment are the major independent factors that result in increased exposure to dabigatran.
Elagolix; Estradiol; Norethindrone acetate: (Moderate) Increased serum concentrations of dabigatran are possible when dabigatran, a P-glycoprotein (P-gp) substrate, is coadministered with elagolix, a P-gp inhibitor. Although coadministration may have no effect on the pharmacokinetics of dabigatran in healthy subjects, patients should be monitored for increased adverse effects of dabigatran. When dabigatran is administered for treatment or reduction in risk of recurrence of deep venous thrombosis (DVT) or pulmonary embolism (PE) or prophylaxis of DVT or PE following hip replacement surgery, avoid coadministration with P-gp inhibitors like elagolix in patients with CrCl less than 50 mL/minute. When dabigatran is used in patients with non-valvular atrial fibrillation and severe renal impairment (CrCl less than 30 mL/minute), avoid coadministration with elagolix, as serum concentrations of dabigatran are expected to be higher than when administered to patients with normal renal function. P-gp inhibition and renal impairment are the major independent factors that result in increased exposure to dabigatran.
Elexacaftor; tezacaftor; ivacaftor: (Moderate) Monitor for an increase in dabigatran-related adverse reactions if coadministration with ivacaftor is necessary in patients with creatinine clearance (CrCl) greater than 50 mL/min. Avoid coadministration in patients with CrCl less than 50 mL/min when dabigatran is administered for treatment or reduction in risk of recurrence of deep venous thrombosis (DVT) or pulmonary embolism (PE) or prophylaxis of DVT or PE following hip replacement surgery. Avoid coadministration in patients with CrCl less than 30 mL/min in patients with non-valvular atrial fibrillation. Serum concentrations of dabigatran are expected to be higher in patients with renal impairment compared to patients with normal renal function. Dabigatran is a P-glycoprotein substrate and ivacaftor is a P-gp inhibitor.
Eliglustat: (Major) Increased serum concentrations of dabigatran are possible when dabigatran, a P-glycoprotein (P-gp) substrate, is coadministered with eliglustat, a P-gp inhibitor. Patients should be monitored for increased adverse effects of dabigatran. When dabigatran is administered for treatment or reduction in risk of recurrence of deep venous thrombosis (DVT) or pulmonary embolism (PE) or prophylaxis of DVT or PE following hip replacement surgery, avoid coadministration with P-gp inhibitors like eliglustat in patients with CrCl less than 50 mL/minute. When dabigatran is used in patients with non-valvular atrial fibrillation and severe renal impairment (CrCl less than 30 mL/minute), avoid coadministration with eliglustat, as serum concentrations of dabigatran are expected to be higher than when administered to patients with normal renal function. P-gp inhibition and renal impairment are the major independent factors that result in increased exposure to dabigatran.
Eltrombopag: (Moderate) Use caution when discontinuing eltrombopag in patients receiving anticoagulants (e.g., warfarin, enoxaparin, dabigatran, rivaroxaban). The risk of bleeding and recurrent thrombocytopenia is increased in patients receiving these drugs when eltrombopag is discontinued.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Moderate) Monitor for an increase in dabigatran-related adverse reactions if coadministration with cobicistat is necessary in patients with creatinine clearance (CrCl) greater than 50 mL/minute. Avoid coadministration in patients with CrCl less than 50 mL/minute when dabigatran is administered for treatment or reduction in risk of recurrence of deep venous thrombosis (DVT) or pulmonary embolism (PE) or prophylaxis of DVT or PE following hip replacement surgery. Avoid coadministration in patients with CrCl less than 30 mL/minute in patients with non-valvular atrial fibrillation. Serum concentrations of dabigatran are expected to be higher in patients with renal impairment compared to patients with normal renal function. Dabigatran is a P-gp substrate and cobicistat is a P-gp inhibitor.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Monitor for an increase in dabigatran-related adverse reactions if coadministration with cobicistat is necessary in patients with creatinine clearance (CrCl) greater than 50 mL/minute. Avoid coadministration in patients with CrCl less than 50 mL/minute when dabigatran is administered for treatment or reduction in risk of recurrence of deep venous thrombosis (DVT) or pulmonary embolism (PE) or prophylaxis of DVT or PE following hip replacement surgery. Avoid coadministration in patients with CrCl less than 30 mL/minute in patients with non-valvular atrial fibrillation. Serum concentrations of dabigatran are expected to be higher in patients with renal impairment compared to patients with normal renal function. Dabigatran is a P-gp substrate and cobicistat is a P-gp inhibitor.
Enasidenib: (Moderate) Monitor for an increase in dabigatran-related adverse reactions if coadministration with enasidenib is necessary in patients with creatinine clearance (CrCl) greater than 50 mL/minute. Avoid coadministration in patients with CrCl less than 50 mL/minute when dabigatran is administered for treatment or reduction in risk of recurrence of deep venous thrombosis (DVT) or pulmonary embolism (PE) or prophylaxis of DVT or PE following hip replacement surgery. Avoid coadministration in patients with CrCl less than 30 mL/minute in patients with non-valvular atrial fibrillation. Serum concentrations of dabigatran are expected to be higher in patients with renal impairment compared to patients with normal renal function. Dabigatran is a P-glycoprotein substrate and enasidenib is a P-gp inhibitor.
Enoxaparin: (Major) Avoid use of dabigatran with enoxaparin due to the increased bleeding risk. Monitor patients closely and promptly evaluate any signs or symptoms of bleeding if dabigatran and other anticoagulants are used concomitantly. Coadministration of dabigatran and other anticoagulants may increase the risk of bleeding. Long-term concomitant treatment with dabigatran and other anticoagulants is not recommended; short-term use may be necessary for patients transitioning to or from dabigatran.
Epoprostenol: (Moderate) When used concurrently with anticoagulants, epoprostenol may increase the risk of bleeding.
Eptifibatide: (Moderate) Concomitant use of eptifibatide and other agents that may affect hemostasis, such as anticoagulants, may be associated with an increased risk of bleeding.
Erythromycin: (Moderate) Increased serum concentrations of dabigatran are possible when dabigatran, a P-glycoprotein (P-gp) substrate, is coadministered with erythromycin, a P-gp inhibitor. Patients should be monitored for increased adverse effects of dabigatran. When dabigatran is administered for treatment or reduction in risk of recurrence of deep venous thrombosis (DVT) or pulmonary embolism (PE), or prophylaxis of DVT or PE following hip replacement surgery, avoid coadministration with P-gp inhibitors like erythromycin in patients with CrCl less than 50 mL/minute. When dabigatran is used in patients with non-valvular atrial fibrillation and severe renal impairment (CrCl less than 30 mL/minute), avoid coadministration with erythromycin, as serum concentrations of dabigatran are expected to be higher than when administered to patients with normal renal function. P-gp inhibition and renal impairment are the major independent factors that result in increased exposure to dabigatran.
Escitalopram: (Moderate) Advise patients of the increased bleeding risk associated with the concomitant use of selective serotonin reuptake inhibitors (SSRIs) and anticoagulants like dabigatran. Case reports and epidemiological studies have demonstrated an association between use of drugs that interfere with serotonin reuptake and gastrointestinal bleeding.
Esterified Estrogens; Methyltestosterone: (Moderate) Methyltestosterone can increase the effects of anticoagulants through reduction of procoagulant factor. Patients receiving oral anticoagulant therapy should be closely monitored, especially when methyltestosterone treatment is initiated or discontinued.
Etodolac: (Major) Educate patients about the signs of increased bleeding and the need to report these signs to a healthcare provider immediately if coadministration of dabigatran and a nonsteroidal antiinflammatory drug (NSAID) is necessary. Dabigatran can cause significant and, sometimes, fatal bleeding. This risk may be increased by concurrent use of chronic NSAID therapy.
Etravirine: (Moderate) Monitor for an increase in dabigatran-related adverse reactions if coadministration with etravirine is necessary in patients with creatinine clearance (CrCl) greater than 50 mL/min. Avoid coadministration in patients with CrCl less than 50 mL/min when dabigatran is administered for treatment or reduction in risk of recurrence of deep venous thrombosis (DVT) or pulmonary embolism (PE) or prophylaxis of DVT or PE following hip replacement surgery. Avoid coadministration in patients with CrCl less than 30 mL/min in patients with non-valvular atrial fibrillation. Serum concentrations of dabigatran are expected to be higher in patients with renal impairment compared to patients with normal renal function. Dabigatran is a P-glycoprotein substrate and etravirine is a P-gp inhibitor.
Ezetimibe; Simvastatin: (Moderate) Consider a statin other than lovastatin or simvastatin if HMG-CoA reductase inhibition is necessary for a patient receiving dabigatran. Increased serum concentrations of dabigatran are possible when coadministered with lovastatin. If use together is medically necessary, patients should be monitored for increased adverse effects of dabigatran and an increased risk for bleeding. A mechanism for this interaction may be the inhibition of P-gp by simvastatin; dabigatran is a P-gp substrate. In one clinical trial, patients receiving dabigatran with lovastatin or simvastatin experienced a higher risk of major hemorrhage relative to the use of other statins that are not P-gp inhibitors. P-gp inhibition and renal impairment are the major independent factors that result in increased exposure to dabigatran.
Fenoprofen: (Major) Educate patients about the signs of increased bleeding and the need to report these signs to a healthcare provider immediately if coadministration of dabigatran and a nonsteroidal antiinflammatory drug (NSAID) is necessary. Dabigatran can cause significant and, sometimes, fatal bleeding. This risk may be increased by concurrent use of chronic NSAID therapy.
Fish Oil, Omega-3 Fatty Acids (Dietary Supplements): (Moderate) Drug interactions with fish oil, omega-3 fatty acids (Dietary Supplements) or fish oil, omega-3 fatty acids (FDA-approved) are unclear at this time. However, because fish oil, omega-3 fatty acids inhibit platelet aggregation, caution is advised when fish oils are used concurrently with anticoagulants, platelet inhibitors, or thrombolytic agents. Theoretically, the risk of bleeding may be increased, but some studies that combined these agents did not produce clinically significant bleeding events. In one placebo-controlled, randomized, double-blinded, parallel study, patients receiving stable, chronic warfarin therapy were administered various doses of fish oil supplements to determine the effect on INR determinations. Patients were randomized to receive a 4-week treatment period of either placebo or 3 or 6 grams of fish oil daily. Patients were followed on a twice-weekly basis for INR determinations and adverse reactions. There was no statistically significant difference in INRs between the placebo or treatment period within each group. There was also no difference in INRs found between groups. One episode of ecchymosis was reported, but no major bleeding episodes occurred. The authors concluded that fish oil supplementation in doses of 3-6 grams per day does not have a statistically significant effect on the INR of patients receiving chronic warfarin therapy. However, an increase in INR from 2.8 to 4.3 in a patient stable on warfarin therapy has been reported when increasing the dose of fish oil, omega-3 fatty acids from 1 gram/day to 2 grams/day. The INR decreased once the patient decreased her dose of fish oil to 1 gram/day. This implies that a dose-related effect of fish oil on warfarin may be possible. Patients receiving warfarin that initiate concomitant fish oil therapy should have their INR monitored more closely and the dose of warfarin adjusted accordingly.
Fluoxetine: (Moderate) Advise patients of the increased bleeding risk associated with the concomitant use of selective serotonin reuptake inhibitors (SSRIs) and anticoagulants like dabigatran. Case reports and epidemiological studies have demonstrated an association between use of drugs that interfere with serotonin reuptake and gastrointestinal bleeding.
Flurbiprofen: (Major) Educate patients about the signs of increased bleeding and the need to report these signs to a healthcare provider immediately if coadministration of dabigatran and a nonsteroidal antiinflammatory drug (NSAID) is necessary. Dabigatran can cause significant and, sometimes, fatal bleeding. This risk may be increased by concurrent use of chronic NSAID therapy.
Fluvoxamine: (Moderate) Advise patients of the increased bleeding risk associated with the concomitant use of selective serotonin reuptake inhibitors (SSRIs) and anticoagulants like dabigatran. Case reports and epidemiological studies have demonstrated an association between use of drugs that interfere with serotonin reuptake and gastrointestinal bleeding.
Fondaparinux: (Major) Avoid use of dabigatran with fondaparinux due to the increased bleeding risk. Monitor patients closely and promptly evaluate any signs or symptoms of bleeding if dabigatran and other anticoagulants are used concomitantly. Coadministration of dabigatran and other anticoagulants may increase the risk of bleeding. Long-term concomitant treatment with dabigatran and other anticoagulants is not recommended; short-term use may be necessary for patients transitioning to or from dabigatran.
Fosamprenavir: (Major) In general, avoid coadministration of dabigatran with P-glycoprotein (P-gp) inducers, such as fosamprenavir. Concomitant administration of dabigatran and rifampin, another P-gp inducer, resulted in a significant decrease in dabigatran AUC and Cmax.
Fosphenytoin: (Major) Coadministration of dabigatran with fosphenytoin should generally be avoided due to the risk of deceased dabigatran exposure which may reduce its efficacy. Dabigatran is a P-glycoprotein (P-gp) substrate and fosphenytoin is a P-gp inducer.
Fostamatinib: (Moderate) Avoid the coadministration of dabigatran and fostamatinib in patients with severe renal impairment (CrCl less than 30 mL/minute). When dabigatran is administered for treatment or reduction in risk of recurrence of deep venous thrombosis (DVT) or pulmonary embolism (PE) or prophylaxis of DVT or PE following hip replacement surgery, avoid coadministration with P-gp inhibitors like fostamatinib in patients with CrCl less than 50 mL/minute. Coadministration may result in increased dabigatran serum concentrations, increasing the risk of dabigatran adverse effects. Dabigatran is a substrate of P-glycoprotein (P-gp) and fostamatinib is a P-gp inhibitor. P-gp inhibition and renal impairment are the major independent factors that result in increased exposure to dabigatran.
Futibatinib: (Moderate) Monitor for an increase in dabigatran-related adverse reactions if coadministration with futibatinib is necessary in patients with creatinine clearance (CrCl) greater than 50 mL/minute. Avoid coadministration in patients with CrCl less than 50 mL/minute when dabigatran is administered for treatment or reduction in risk of recurrence of deep venous thrombosis (DVT) or pulmonary embolism (PE) or prophylaxis of DVT or PE following hip replacement surgery. Avoid coadministration in patients with CrCl less than 30 mL/minute in patients with non-valvular atrial fibrillation. Serum concentrations of dabigatran are expected to be higher in patients with renal impairment compared to patients with normal renal function. Dabigatran is a P-gp substrate and futibatinib is a P-gp inhibitor.
Garlic, Allium sativum: (Moderate) Garlic produces clinically significant antiplatelet effects so additive risk of bleeding may occur if anticoagulants are given in combination. Avoid concurrent use of herbs which interact with anticoagulants when possible. If garlic dietary supplements are taken, monitor the INR or other appropriate parameters to attain clinical and anticoag
Gilteritinib: (Moderate) Monitor for an increase in dabigatran-related adverse reactions if coadministration with gilteritinib is necessary in patients with creatinine clearance (CrCl) greater than 50 mL/minute. Avoid coadministration in patients with CrCl less than 50 mL/minute when dabigatran is administered for treatment or reduction in risk of recurrence of deep venous thrombosis (DVT) or pulmonary embolism (PE) or prophylaxis of DVT or PE following hip replacement surgery. Avoid coadministration in patients with CrCl less than 30 mL/minute in patients with non-valvular atrial fibrillation. Serum concentrations of dabigatran are expected to be higher in patients with renal impairment compared to patients with normal renal function. Dabigatran is a P-gp substrate and gilteritinib is a P-gp inhibitor.
Ginger, Zingiber officinale: (Moderate) Additive bleeding may occur if anticoagulants are given in combination with ginger, zingiber officinale. Ginger inhibits thromboxane synthetase (platelet aggregation inducer) and is a prostacyclin agonist. Patients taking ginger and an anticoagulant should be monitored closely for bleeding.
Ginkgo, Ginkgo biloba: (Moderate) Monitor for signs or symptoms of bleeding with coadministration of ginkgo biloba and Direct Oral Anticoagulants (DOACs) as an increased bleeding risk may occur. Although data are mixed, ginkgo biloba is reported to inhibit platelet aggregation and several case reports describe bleeding complications with ginkgo biloba, with or without concomitant drug therapy.
Glecaprevir; Pibrentasvir: (Moderate) Increased serum concentrations of dabigatran are possible when dabigatran, a P-glycoprotein (P-gp) substrate, is coadministered with glecaprevir, a P-gp inhibitor. Patients should be monitored for increased adverse effects of dabigatran. When dabigatran is administered for treatment or reduction in risk of recurrence of deep venous thrombosis (DVT) or pulmonary embolism (PE) or prophylaxis of DVT or PE following hip replacement surgery, avoid coadministration with P-gp inhibitors like glecaprevir in patients with CrCl less than 50 mL/minute. When dabigatran is used in patients with non-valvular atrial fibrillation and severe renal impairment (CrCl less than 30 mL/minute), avoid coadministration with glecaprevir, as serum concentrations of dabigatran are expected to be higher than when administered to patients with normal renal function. In drug interaction studies, coadministration of dabigatran with glecaprevir; pibrentasvir resulted in over a 2-fold increase in the AUC of dabigatran. (Moderate) Increased serum concentrations of dabigatran are possible when dabigatran, a P-glycoprotein (P-gp) substrate, is coadministered with pibrentasvir, a P-gp inhibitor. Patients should be monitored for increased adverse effects of dabigatran. When dabigatran is administered for treatment or reduction in risk of recurrence of deep venous thrombosis (DVT) or pulmonary embolism (PE) or prophylaxis of DVT or PE following hip replacement surgery, avoid coadministration with P-gp inhibitors like pibrentasvir in patients with CrCl less than 50 mL/minute. When dabigatran is used in patients with non-valvular atrial fibrillation and severe renal impairment (CrCl less than 30 mL/minute), avoid coadministration with pibrentasvir, as serum concentrations of dabigatran are expected to be higher than when administered to patients with normal renal function. In drug interaction studies, coadministration of dabigatran with glecaprevir; pibrentasvir resulted in over a 2-fold increase in the AUC of dabigatran.
Grapefruit juice: (Moderate) Increased serum concentrations of dabigatran are possible when dabigatran, a P-glycoprotein (P-gp) substrate, is coadministered with grapefruit juice, a P-gp inhibitor. Patients should be monitored for increased adverse effects of dabigatran. When dabigatran is administered for treatment or reduction in risk of recurrence of deep venous thrombosis (DVT) or pulmonary embolism (PE), avoid coadministration with P-gp inhibitors like grapefruit juice in patients with CrCl < 50 ml/min. When dabigatran is used in patients with non-valvular atrial fibrillation and severe renal impairment (CrCl < 30 ml/min), avoid coadministration with grapefruit juice, as serum concentrations of dabigatran are expected to be higher than when administered to patients with normal renal function. P-gp inhibition and renal impairment are the major independent factors that result in increased exposure to dabigatran.
Green Tea: (Moderate) Green tea has demonstrated antiplatelet and fibrinolytic actions in animals. It is possible that the use of green tea may increase the risk of bleeding if co-administered with anticoagulants (e.g., enoxaparin, heparin, warfarin, and others), thrombolytic agents, or platelet inhibitors (e.g., aspirin, clopidogrel, cilostazol and others). Caution and careful monitoring of clinical and/or laboratory parameters are warranted if green tea is coadministered with any of these agents. Exogenous administration or occult sources of vitamin K may decrease or reverse the activity of warfarin; stability of the diet can be an important factor in maintaining anticoagulation goals. Occult sources of vitamin K include green tea and green tea dietary supplements. Published data are limited in regard to this interaction. A patient with previous INRs of 3.2 and 3.79 on a dose of 7.5mg daily of warfarin (goal INR 2.5 to 3.5) had an INR of 1.37. One month later, the patient's INR was 1.14. The patient admitted that he had started consuming 0.51 gallon of green tea daily approximately one week prior to the INR of 1.37. The patient denied noncompliance and other changes in diet, medications, or health. The patient discontinued green tea and one week later his INR was 2.55. While the amount of vitamin K in a single cup of brewed green tea may not be high (0.03 mcg/100 g), the actual amount may vary from cup to cup depending on the amount of tea leaves used, the length of time the tea bags are allowed to brew, and the volume of tea consumed. Additionally, if a patient drinks multiple cups of tea per day, the amount of vitamin K could reach significance. It is recommended that patients on warfarin maintain a stable intake of green tea.
Hemin: (Major) Because hemin has exhibited transient, mild anticoagulant effects during clinical studies, concurrent use of anticoagulants should be avoided. The extent and duration of the hypocoagulable state induced by hemin has not been established.
Heparin: (Major) Avoid use of dabigatran with heparin due to the increased bleeding risk. Monitor patients closely and promptly evaluate any signs or symptoms of bleeding if dabigatran and other anticoagulants are used concomitantly. Coadministration of dabigatran and other anticoagulants may increase the risk of bleeding. Long-term concomitant treatment with dabigatran and other anticoagulants is not recommended; short-term use may be necessary for patients transitioning to or from dabigatran.
Hydrocodone; Ibuprofen: (Major) Educate patients about the signs of increased bleeding and the need to report these signs to a healthcare provider immediately if coadministration of dabigatran and a nonsteroidal antiinflammatory drug (NSAID) is necessary. Dabigatran can cause significant and, sometimes, fatal bleeding. This risk may be increased by concurrent use of chronic NSAID therapy.
Hydroxychloroquine: (Moderate) Use caution if hydroxychloroquine is coadministered with dabigatran due to the potential for increased dabigatran exposure which may increase the risk of bleeding. Dabigatran is a P-gp substrate; limited data suggests that hydroxychloroquine is a P-gp inhibitor.
Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate; Sodium Biphosphate: (Major) Educate patients about the signs of increased bleeding and the need to report these signs to a healthcare provider immediately if coadministration of dabigatran and aspirin or another salicylate is necessary. Dabigatran can cause significant and, sometimes, fatal bleeding. This risk may be increased by concurrent use of chronic salicylate therapy.
Ibritumomab Tiuxetan: (Major) During and after therapy, avoid the concomitant use of Yttrium (Y)-90 ibrutumomab tiuxetan with drugs that interfere with coagulation such as anticoagulants; the risk of bleeding may be increased. If coadministration with anticoagulants is necessary, monitor platelet counts more frequently for evidence of thrombocytopenia.
Ibrutinib: (Moderate) The concomitant use of ibrutinib and anticoagulant agents such as dabigatran may increase the risk of bleeding; monitor patients for signs of bleeding. Severe bleeding events have occurred with ibrutinib therapy including intracranial hemorrhage, GI bleeding, hematuria, and post procedural hemorrhage; some events were fatal. The mechanism for bleeding with ibrutinib therapy is not well understood.
Ibuprofen: (Major) Educate patients about the signs of increased bleeding and the need to report these signs to a healthcare provider immediately if coadministration of dabigatran and a nonsteroidal antiinflammatory drug (NSAID) is necessary. Dabigatran can cause significant and, sometimes, fatal bleeding. This risk may be increased by concurrent use of chronic NSAID therapy.
Ibuprofen; Famotidine: (Major) Educate patients about the signs of increased bleeding and the need to report these signs to a healthcare provider immediately if coadministration of dabigatran and a nonsteroidal antiinflammatory drug (NSAID) is necessary. Dabigatran can cause significant and, sometimes, fatal bleeding. This risk may be increased by concurrent use of chronic NSAID therapy.
Ibuprofen; Oxycodone: (Major) Educate patients about the signs of increased bleeding and the need to report these signs to a healthcare provider immediately if coadministration of dabigatran and a nonsteroidal antiinflammatory drug (NSAID) is necessary. Dabigatran can cause significant and, sometimes, fatal bleeding. This risk may be increased by concurrent use of chronic NSAID therapy.
Ibuprofen; Pseudoephedrine: (Major) Educate patients about the signs of increased bleeding and the need to report these signs to a healthcare provider immediately if coadministration of dabigatran and a nonsteroidal antiinflammatory drug (NSAID) is necessary. Dabigatran can cause significant and, sometimes, fatal bleeding. This risk may be increased by concurrent use of chronic NSAID therapy.
Icosapent ethyl: (Moderate) Icosapent ethyl is an ethyl ester of the omega-3 fatty acid eicosapentaenoic acid (EPA). Because omega-3 fatty acids inhibit platelet aggregation, caution is advised when icosapent ethyl is used concurrently with anticoagulants, platelet inhibitors, or thrombolytic agents. Theoretically, the risk of bleeding may be increased, but some studies that combined these agents did not produce clinically significant bleeding events. In one placebo-controlled, randomized, double-blinded, parallel study, patients receiving stable, chronic warfarin therapy were administered various doses of fish oil supplements to determine the effect on INR determinations. Patients were randomized to receive a 4-week treatment period of either placebo or 3 or 6 grams of fish oil daily. Patients were followed on a twice-weekly basis for INR determinations and adverse reactions. There was no statistically significant difference in INRs between the placebo or treatment period within each group. There was also no difference in INRs found between groups. One episode of ecchymosis was reported, but no major bleeding episodes occurred. The authors concluded that fish oil supplementation in doses of 36 grams per day does not have a statistically significant effect on the INR of patients receiving chronic warfarin therapy. However, an increase in INR from 2.8 to 4.3 in a patient stable on warfarin therapy has been reported when increasing the dose of fish oil, omega-3 fatty acids from 1 gram/day to 2 grams/day. The INR decreased once the patient decreased her dose of fish oil to 1 gram/day. This implies that a dose-related effect of fish oil on warfarin may be possible. Patients receiving warfarin that initiate concomitant icosapent ethyl therapy should have their INR monitored more closely and the dose of warfarin adjusted accordingly.
Iloprost: (Moderate) When used concurrently with anticoagulants, inhaled iloprost may increase the risk of bleeding.
Indomethacin: (Major) Educate patients about the signs of increased bleeding and the need to report these signs to a healthcare provider immediately if coadministration of dabigatran and a nonsteroidal antiinflammatory drug (NSAID) is necessary. Dabigatran can cause significant and, sometimes, fatal bleeding. This risk may be increased by concurrent use of chronic NSAID therapy.
Inotersen: (Moderate) Use caution with concomitant use of inotersen and anticoagulants due to the potential risk of bleeding from thrombocytopenia. Consider discontinuation of anticoagulants in a patient taking inotersen with a platelet count of less than 50,000 per microliter.
Intravenous Lipid Emulsions: (Moderate) Drug interactions with fish oil, omega-3 fatty acids (Dietary Supplements) or fish oil, omega-3 fatty acids (FDA-approved) are unclear at this time. However, because fish oil, omega-3 fatty acids inhibit platelet aggregation, caution is advised when fish oils are used concurrently with anticoagulants, platelet inhibitors, or thrombolytic agents. Theoretically, the risk of bleeding may be increased, but some studies that combined these agents did not produce clinically significant bleeding events. In one placebo-controlled, randomized, double-blinded, parallel study, patients receiving stable, chronic warfarin therapy were administered various doses of fish oil supplements to determine the effect on INR determinations. Patients were randomized to receive a 4-week treatment period of either placebo or 3 or 6 grams of fish oil daily. Patients were followed on a twice-weekly basis for INR determinations and adverse reactions. There was no statistically significant difference in INRs between the placebo or treatment period within each group. There was also no difference in INRs found between groups. One episode of ecchymosis was reported, but no major bleeding episodes occurred. The authors concluded that fish oil supplementation in doses of 3-6 grams per day does not have a statistically significant effect on the INR of patients receiving chronic warfarin therapy. However, an increase in INR from 2.8 to 4.3 in a patient stable on warfarin therapy has been reported when increasing the dose of fish oil, omega-3 fatty acids from 1 gram/day to 2 grams/day. The INR decreased once the patient decreased her dose of fish oil to 1 gram/day. This implies that a dose-related effect of fish oil on warfarin may be possible. Patients receiving warfarin that initiate concomitant fish oil therapy should have their INR monitored more closely and the dose of warfarin adjusted accordingly.
Isavuconazonium: (Moderate) Increased serum concentrations of dabigatran are possible when dabigatran, a P-glycoprotein (P-gp) substrate, is coadministered with isavuconazonium, a mild P-gp inhibitor. Patients should be monitored for increased adverse effects of dabigatran. When dabigatran is administered for treatment or reduction in risk of recurrence of deep venous thrombosis (DVT) or pulmonary embolism (PE) or prophylaxis of DVT or PE following hip replacement surgery, avoid coadministration with P-gp inhibitors like isavuconazonium in patients with CrCl less than 50 mL/minute. When dabigatran is used in patients with non-valvular atrial fibrillation and severe renal impairment (CrCl less than 30 mL/minute), avoid coadministration with isavuconazonium, as serum concentrations of dabigatran are expected to be higher than when administered to patients with normal renal function. P-gp inhibition and renal impairment are the major independent factors that result in increased exposure to dabigatran.
Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Major) In general, avoid coadministration of dabigatran with P-gp inducers, such as rifampin. Concomitant administration of 600 mg rifampin for 7 days followed by a single dose of dabigatran decreased dabigatran AUC and Cmax by 66% and 67%, respectively. Dabigatran exposure returned to normal 7 days after cessation of rifampin therapy.
Isoniazid, INH; Rifampin: (Major) In general, avoid coadministration of dabigatran with P-gp inducers, such as rifampin. Concomitant administration of 600 mg rifampin for 7 days followed by a single dose of dabigatran decreased dabigatran AUC and Cmax by 66% and 67%, respectively. Dabigatran exposure returned to normal 7 days after cessation of rifampin therapy.
Istradefylline: (Moderate) Increased serum concentrations of dabigatran are possible when dabigatran, a P-glycoprotein (P-gp) substrate, is coadministered with istradefylline, a P-gp inhibitor. Although the coadministration of dabigatran and istradefylline may have no effect on the pharmacokinetics of dabigatran or istradefylline in healthy subjects, patients should be monitored for increased adverse effects of dabigatran. When dabigatran is administered for treatment or reduction in risk of recurrence of deep venous thrombosis (DVT) or pulmonary embolism (PE) or prophylaxis of DVT or PE following hip replacement surgery, avoid coadministration with P-gp inhibitors like istradefylline in patients with CrCl less than 50 mL/minute. When dabigatran is used in patients with non-valvular atrial fibrillation and severe renal impairment (CrCl less than 30 mL/minute), avoid coadministration with istradefylline, as serum concentrations of dabigatran are expected to be higher than when administered to patients with normal renal function. P-gp inhibition and renal impairment are the major independent factors that result in increased exposure to dabigatran.
Itraconazole: (Moderate) Increased serum concentrations of dabigatran are possible when dabigatran, a P-glycoprotein (P-gp) substrate, is coadministered with itraconazole, a P-gp inhibitor. Patients should be monitored for increased adverse effects of dabigatran. When dabigatran is administered for treatment or reduction in risk of recurrence of deep venous thrombosis (DVT) or pulmonary embolism (PE) or prophylaxis of DVT or PE following hip replacement surgery, avoid coadministration with P-gp inhibitors like itraconazole in patients with CrCl less than 50 mL/minute. When dabigatran is used in patients with non-valvular atrial fibrillation and severe renal impairment (CrCl less than 30 mL/minute), avoid coadministration with itraconazole, as serum concentrations of dabigatran are expected to be higher than when administered to patients with normal renal function. P-gp inhibition and renal impairment are the major independent factors that result in increased exposure to dabigatran.
Ivacaftor: (Moderate) Monitor for an increase in dabigatran-related adverse reactions if coadministration with ivacaftor is necessary in patients with creatinine clearance (CrCl) greater than 50 mL/min. Avoid coadministration in patients with CrCl less than 50 mL/min when dabigatran is administered for treatment or reduction in risk of recurrence of deep venous thrombosis (DVT) or pulmonary embolism (PE) or prophylaxis of DVT or PE following hip replacement surgery. Avoid coadministration in patients with CrCl less than 30 mL/min in patients with non-valvular atrial fibrillation. Serum concentrations of dabigatran are expected to be higher in patients with renal impairment compared to patients with normal renal function. Dabigatran is a P-glycoprotein substrate and ivacaftor is a P-gp inhibitor.
Ketoconazole: (Moderate) Avoid if possible; monitor for dabigatran side effects if use with ketoconazole is necessary. For specific dosage recommendations based on the indication for which dabigatran has been prescribed and the patient's renal function, it is best to consult the product label. P-gp inhibition and impaired renal function are the major independent factors that result in increased exposure to dabigatran. Concomitant use of P-gp inhibitors in patients with renal impairment is expected to produce increased exposure of dabigatran compared to that seen with either factor alone. Dabigatran is a P-gp substrate and ketoconazole is a P-gp inhibitor. Coadministration with multiple daily doses of 400 mg ketoconazole increased dabigatran AUC by 153%.
Ketoprofen: (Major) Educate patients about the signs of increased bleeding and the need to report these signs to a healthcare provider immediately if coadministration of dabigatran and a nonsteroidal antiinflammatory drug (NSAID) is necessary. Dabigatran can cause significant and, sometimes, fatal bleeding. This risk may be increased by concurrent use of chronic NSAID therapy.
Ketorolac: (Major) Educate patients about the signs of increased bleeding and the need to report these signs to a healthcare provider immediately if coadministration of dabigatran and a nonsteroidal antiinflammatory drug (NSAID) is necessary. Dabigatran can cause significant and, sometimes, fatal bleeding. This risk may be increased by concurrent use of chronic NSAID therapy.
Lansoprazole; Amoxicillin; Clarithromycin: (Moderate) Increased serum concentrations of dabigatran are possible when dabigatran, a P-glycoprotein (P-gp) substrate, is coadministered with clarithromycin, a P-gp inhibitor. Although the coadministration of dabigatran and clarithromycin has no effect on the pharmacokinetics of dabigatran or clarithromycin in healthy subjects, patients should be monitored for increased adverse effects of dabigatran. When dabigatran is administered for treatment or reduction in risk of recurrence of deep venous thrombosis (DVT) or pulmonary embolism (PE) or prophylaxis of DVT or PE following hip replacement surgery, avoid coadministration with P-gp inhibitors like clarithromycin in patients with CrCl less than 50 mL/minute. When dabigatran is used in patients with non-valvular atrial fibrillation and severe renal impairment (CrCl less than 30 mL/minute), avoid coadministration with clarithromycin, as serum concentrations of dabigatran are expected to be higher than when administered to patients with normal renal function. P-gp inhibition and renal impairment are the major independent factors that result in increased exposure to dabigatran.
Lapatinib: (Moderate) Monitor patients for increased dabigatran-related adverse reactions if coadministration with lapatinib is necessary. Avoid coadministration of lapatinib in patients with CrCL less than 50 mL/minute when dabigatran is administered for treatment or reduction in risk of recurrence of deep venous thrombosis (DVT) or pulmonary embolism (PE) or prophylaxis of DVT or PE following hip replacement surgery. Avoid coadministration with lapatinib when dabigatran is used in patients with non-valvular atrial fibrillation and severe renal impairment (CrCL less than 30 mL/minute), as serum concentrations of dabigatran are expected to be higher than when administered to patients with normal renal function. Dabigatran is a P-glycoprotein (P-gp) substrate and lapatinib is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased the dabigatran AUC and Cmax by 58% and 50%, respectively. P-gp inhibition and renal impairment are the major independent factors that result in increased exposure to dabigatran.
Lasmiditan: (Moderate) Monitor for an increase in dabigatran-related adverse reactions if coadministration with lasmiditan is necessary in patients with creatinine clearance (CrCl) greater than 50 mL/minute. Avoid coadministration in patients with CrCl less than 50 mL/minute when dabigatran is administered for treatment or reduction in risk of recurrence of deep venous thrombosis (DVT) or pulmonary embolism (PE) or prophylaxis of DVT or PE following hip replacement surgery. Avoid coadministration in patients with CrCl less than 30 mL/minute in patients with non-valvular atrial fibrillation. Serum concentrations of dabigatran are expected to be higher in patients with renal impairment compared to patients with normal renal function. Dabigatran is a P-gp substrate and lasmiditan is a P-gp inhibitor.
Ledipasvir; Sofosbuvir: (Moderate) Increased serum concentrations of dabigatran are possible when dabigatran, a P-glycoprotein (P-gp) substrate, is coadministered with ledipasvir; sofosbuvir. Ledipasvir is a P-gp inhibitor. Patients should be monitored for increased adverse effects of dabigatran. When dabigatran is administered for treatment or reduction in risk of recurrence of deep venous thrombosis (DVT) or pulmonary embolism (PE) or prophylaxis of DVT or PE following hip replacement surgery, avoid coadministration with P-gp inhibitors like ledipasvir; sofosbuvir in patients with CrCl less than 50 mL/minute. When dabigatran is used in patients with non-valvular atrial fibrillation and severe renal impairment (CrCl less than 30 mL/minute), avoid coadministration with ledipasvir; sofosbuvir, as serum concentrations of dabigatran are expected to be higher than when administered to patients with normal renal function. P-gp inhibition and renal impairment are the major independent factors that result in increased exposure to dabigatran.
Lenacapavir: (Moderate) Monitor for an increase in dabigatran-related adverse reactions if coadministration with lenacapavir is necessary in patients with creatinine clearance (CrCl) greater than 50 mL/minute. Avoid coadministration in patients with CrCl less than 50 mL/minute when dabigatran is administered for treatment or reduction in risk of recurrence of deep venous thrombosis (DVT) or pulmonary embolism (PE) or prophylaxis of DVT or PE following hip replacement surgery. Avoid coadministration in patients with CrCl less than 30 mL/minute in patients with non-valvular atrial fibrillation. Serum concentrations of dabigatran are expected to be higher in patients with renal impairment compared to patients with normal renal function. Dabigatran is a P-gp substrate and lenacapavir is a P-gp inhibitor.
Levoketoconazole: (Moderate) Avoid if possible; monitor for dabigatran side effects if use with ketoconazole is necessary. For specific dosage recommendations based on the indication for which dabigatran has been prescribed and the patient's renal function, it is best to consult the product label. P-gp inhibition and impaired renal function are the major independent factors that result in increased exposure to dabigatran. Concomitant use of P-gp inhibitors in patients with renal impairment is expected to produce increased exposure of dabigatran compared to that seen with either factor alone. Dabigatran is a P-gp substrate and ketoconazole is a P-gp inhibitor. Coadministration with multiple daily doses of 400 mg ketoconazole increased dabigatran AUC by 153%.
Lomitapide: (Moderate) Concomitant use of lomitapide and dabigatran may result in increased serum concentrations of dabigatran. According to the manufacturer of lomitapide, dose reduction of dabigatran should be considered during concurrent use. Lomitapide is an inhibitor of P-glycoprotein (P-gp) and dabigatran is a P-gp substrate.
Lomustine, CCNU: (Moderate) Due to the bone marrow suppressive and thrombocytopenic effects of lomustine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants.
Lonafarnib: (Moderate) Monitor for an increase in dabigatran-related adverse reactions if coadministration with lonafarnib is necessary in patients with CrCl greater than 50 mL/minute. Avoid coadministration in patients with CrCl less than 50 mL/minute when dabigatran is administered for treatment or reduction in risk of recurrence of deep venous thrombosis (DVT) or pulmonary embolism (PE) or prophylaxis of DVT or PE following hip replacement surgery. Avoid coadministration in patients with CrCl less than 30 mL/minute in patients with non-valvular atrial fibrillation. Serum concentrations of dabigatran are expected to be higher in patients with renal impairment compared to patients with normal renal function. Dabigatran is a P-glycoprotein substrate and lonafarnib is a P-gp inhibitor.
Lopinavir; Ritonavir: (Moderate) Monitor for an increase in dabigatran-related adverse reactions if coadministration with ritonavir is necessary in patients with creatinine clearance (CrCl) greater than 50 mL/minute. Avoid coadministration in patients with CrCl less than 50 mL/minute when dabigatran is administered for treatment or reduction in risk of recurrence of deep venous thrombosis (DVT) or pulmonary embolism (PE) or prophylaxis of DVT or PE following hip replacement surgery. Avoid coadministration in patients with CrCl less than 30 mL/minute in patients with non-valvular atrial fibrillation. Serum concentrations of dabigatran are expected to be higher in patients with renal impairment compared to patients with normal renal function. Dabigatran is a P-gp substrate and ritonavir is a P-gp inhibitor.
Lorlatinib: (Major) Coadministration of dabigatran with lorlatinib should generally be avoided due to the risk of deceased dabigatran exposure which may reduce its efficacy. Dabigatran is a P-glycoprotein (P-gp) substrate and lorlatinib is a P-gp inducer.
Lovastatin: (Moderate) Consider a statin other than lovastatin or simvastatin if HMG-CoA reductase inhibition is necessary for a patient receiving dabigatran. Increased serum concentrations of dabigatran are possible when coadministered with lovastatin. If use together is medically necessary, patients should be monitored for increased adverse effects of dabigatran and an increased risk for bleeding. A mechanism for this interaction may be the inhibition of P-gp by lovastatin; dabigatran is a P-gp substrate. In one clinical trial, patients receiving dabigatran with lovastatin or simvastatin experienced a higher risk of major hemorrhage relative to the use of other statins that are not P-gp inhibitors. P-gp inhibition and renal impairment are the major independent factors that result in increased exposure to dabigatran.
Lumacaftor; Ivacaftor: (Major) Concomitant use of dabigatran and lumacaftor; ivacaftor may alter dabigatran exposure; avoid coadministration if possible. Dabigatran is a substrate of the drug transporter P-glycoprotein (P-gp). In vitro data suggest that lumacaftor; ivacaftor has the potential to both induce and inhibit P-gp. The net effect of lumacaftor; ivacaftor on P-gp transport is not clear, but substrate exposure may be affected. FDA-approved labeling for dabigatran recommends, in general, to avoid coadministration with P-gp inducers. Concomitant administration of dabigatran and rifampin, another P-gp inducer, resulted in a significant decrease in dabigatran AUC and Cmax. Labeling also recommends to avoid coadministration with P-gp inhibitors in patients with a CrCl less than 50 mL/minute when used for treatment or reduction in risk of deep vein thrombosis (DVT) or pulmonary embolism or prophylaxis of DVT or PE following hip replacement surgery and in patients with non-valvular atrial fibrillation and severe renal impairment (CrCl less than 30 mL/minute), as serum concentrations of dabigatran are expected to be higher than when administered to patients with normal renal function.
Lumacaftor; Ivacaftor: (Moderate) Monitor for an increase in dabigatran-related adverse reactions if coadministration with ivacaftor is necessary in patients with creatinine clearance (CrCl) greater than 50 mL/min. Avoid coadministration in patients with CrCl less than 50 mL/min when dabigatran is administered for treatment or reduction in risk of recurrence of deep venous thrombosis (DVT) or pulmonary embolism (PE) or prophylaxis of DVT or PE following hip replacement surgery. Avoid coadministration in patients with CrCl less than 30 mL/min in patients with non-valvular atrial fibrillation. Serum concentrations of dabigatran are expected to be higher in patients with renal impairment compared to patients with normal renal function. Dabigatran is a P-glycoprotein substrate and ivacaftor is a P-gp inhibitor.
Magnesium Salicylate: (Major) Educate patients about the signs of increased bleeding and the need to report these signs to a healthcare provider immediately if coadministration of dabigatran and aspirin or another salicylate is necessary. Dabigatran can cause significant and, sometimes, fatal bleeding. This risk may be increased by concurrent use of chronic salicylate therapy.
Maribavir: (Moderate) Monitor for an increase in dabigatran-related adverse reactions if coadministration with maribavir is necessary in patients with creatinine clearance (CrCl) greater than 50 mL/minute. Avoid coadministration in patients with CrCl less than 50 mL/minute when dabigatran is administered for treatment or reduction in risk of recurrence of deep venous thrombosis (DVT) or pulmonary embolism (PE) or prophylaxis of DVT or PE following hip replacement surgery. Avoid coadministration in patients with CrCl less than 30 mL/minute in patients with non-valvular atrial fibrillation. Serum concentrations of dabigatran are expected to be higher in patients with renal impairment compared to patients with normal renal function. Dabigatran is a P-gp substrate and maribavir is a P-gp inhibitor.
Meclofenamate Sodium: (Major) Educate patients about the signs of increased bleeding and the need to report these signs to a healthcare provider immediately if coadministration of dabigatran and a nonsteroidal antiinflammatory drug (NSAID) is necessary. Dabigatran can cause significant and, sometimes, fatal bleeding. This risk may be increased by concurrent use of chronic NSAID therapy.
Mefenamic Acid: (Major) Educate patients about the signs of increased bleeding and the need to report these signs to a healthcare provider immediately if coadministration of dabigatran and a nonsteroidal antiinflammatory drug (NSAID) is necessary. Dabigatran can cause significant and, sometimes, fatal bleeding. This risk may be increased by concurrent use of chronic NSAID therapy.
Mefloquine: (Moderate) Increased serum concentrations of dabigatran are possible when dabigatran, a P-glycoprotein (P-gp) substrate, is coadministered with mefloquine, a P-gp inhibitor. Patients should be monitored for increased adverse effects of dabigatran. When dabigatran is administered for treatment or reduction in risk of recurrence of deep venous thrombosis (DVT) or pulmonary embolism (PE), or prophylaxis of DVT or PE following hip replacement surgery, avoid coadministration with P-gp inhibitors like mefloquine in patients with CrCl less than 50 mL/minute. When dabigatran is used in patients with non-valvular atrial fibrillation and severe renal impairment (CrCl less than 30 mL/minute), avoid coadministration with mefloquine, as serum concentrations of dabigatran are expected to be higher than when administered to patients with normal renal function. P-gp inhibition and renal impairment are the major independent factors that result in increased exposure to dabigatran.
Meloxicam: (Major) Educate patients about the signs of increased bleeding and the need to report these signs to a healthcare provider immediately if coadministration of dabigatran and a nonsteroidal antiinflammatory drug (NSAID) is necessary. Dabigatran can cause significant and, sometimes, fatal bleeding. This risk may be increased by concurrent use of chronic NSAID therapy.
Methenamine; Sodium Salicylate: (Major) Educate patients about the signs of increased bleeding and the need to report these signs to a healthcare provider immediately if coadministration of dabigatran and aspirin or another salicylate is necessary. Dabigatran can cause significant and, sometimes, fatal bleeding. This risk may be increased by concurrent use of chronic salicylate therapy.
Methotrexate: (Major) Avoid concomitant use of methotrexate and direct oral anticoagulants due to the risk of severe methotrexate-related adverse reactions. If concomitant use is unavoidable, closely monitor for adverse reactions. Methotrexate is approximately 50% protein bound; direct oral anticoagulants are highly protein-bound. Coadministration may displace methotrexate from its protein binding sites, increasing methotrexate plasma concentrations.
Methoxsalen: (Minor) Agents, such as anticoagulants, that decrease clotting could decrease the efficacy of photosensitizing agents used in photodynamic therapy.
Methylsulfonylmethane, MSM: (Moderate) Increased effects from concomitant anticoagulant drugs such as increased bruising or blood in the stool have been reported in patients taking methylsulfonylmethane, MSM. Although these effects have not been confirmed in published medical literature or during clinical studies, clinicians should consider using methylsulfonylmethane, MSM with caution in patients who are taking anticoagulants such as warfarin until data confirming the safety of MSM in patients taking these drugs are available. During one of the available, published clinical trials in patients with osteoarthritis, those patients with bleeding disorders or using anticoagulants or antiplatelets were excluded from enrollment. Patients who choose to consume methylsulfonylmethane, MSM while receiving warfarin should be observed for increased bleeding.
Methyltestosterone: (Moderate) Methyltestosterone can increase the effects of anticoagulants through reduction of procoagulant factor. Patients receiving oral anticoagulant therapy should be closely monitored, especially when methyltestosterone treatment is initiated or discontinued.
Mifepristone: (Major) When mifepristone is used for the termination of pregnancy, concurrent use of anticoagulants is contraindicated due to the increased risk of serious bleeding. It is not clear if mifepristone exhibits a pharmacokinetic interaction with dabigatran. Use together with caution when mifepristone is given chronically for other conditions, such as Cushing's syndrome. Increased serum concentrations of dabigatran might be possible as mifepristone may be an inhibitor of P-gp. Patients should be monitored for bleeding and increased adverse effects of dabigatran. P-gp inhibition and renal impairment are the major independent factors that result in increased exposure to dabigatran. Different recommendations may apply to the use of mifepristone with dabigatran when the patient is also renally impaired. Due to the slow eilimination of mifepristone, any interaction that does occur may be prolonged.
Miltefosine: (Moderate) Caution is advised when administering miltefosine with anticoagulants, as use of these drugs together may increase risk for bleeding. Miltefosine, when administered for the treatment of visceral leishmaniasis, has been associated with thrombocytopenia; monitor platelet counts in patients receiving treatment for this indication. In addition, monitor closely for increased bleeding if use in combination with an anticoagulant.
Mitapivat: (Moderate) Monitor for an increase in dabigatran-related adverse reactions if coadministration with mitapivat is necessary in patients with creatinine clearance (CrCl) greater than 50 mL/minute. Avoid coadministration in patients with CrCl less than 50 mL/minute when dabigatran is administered for treatment or reduction in risk of recurrence of deep venous thrombosis (DVT) or pulmonary embolism (PE) or prophylaxis of DVT or PE following hip replacement surgery. Avoid coadministration in patients with CrCl less than 30 mL/minute in patients with non-valvular atrial fibrillation. Serum concentrations of dabigatran are expected to be higher in patients with renal impairment compared to patients with normal renal function. Dabigatran is a P-gp substrate and mitapivat is a P-gp inhibitor.
Mycophenolate: (Moderate) Mycophenolate may causes thrombocytopenia and increase the risk for bleeding. Agents which may lead to an increased incidence of bleeding in patients with thrombocytopenia include anticoagulants.
Nabumetone: (Major) Educate patients about the signs of increased bleeding and the need to report these signs to a healthcare provider immediately if coadministration of dabigatran and a nonsteroidal antiinflammatory drug (NSAID) is necessary. Dabigatran can cause significant and, sometimes, fatal bleeding. This risk may be increased by concurrent use of chronic NSAID therapy.
Naproxen: (Major) Educate patients about the signs of increased bleeding and the need to report these signs to a healthcare provider immediately if coadministration of dabigatran and a nonsteroidal antiinflammatory drug (NSAID) is necessary. Dabigatran can cause significant and, sometimes, fatal bleeding. This risk may be increased by concurrent use of chronic NSAID therapy.
Naproxen; Esomeprazole: (Major) Educate patients about the signs of increased bleeding and the need to report these signs to a healthcare provider immediately if coadministration of dabigatran and a nonsteroidal antiinflammatory drug (NSAID) is necessary. Dabigatran can cause significant and, sometimes, fatal bleeding. This risk may be increased by concurrent use of chronic NSAID therapy.
Naproxen; Pseudoephedrine: (Major) Educate patients about the signs of increased bleeding and the need to report these signs to a healthcare provider immediately if coadministration of dabigatran and a nonsteroidal antiinflammatory drug (NSAID) is necessary. Dabigatran can cause significant and, sometimes, fatal bleeding. This risk may be increased by concurrent use of chronic NSAID therapy.
Nelarabine: (Moderate) Due to the thrombocytopenic effects of nelarabine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants.
Nelfinavir: (Moderate) Increased serum concentrations of dabigatran are possible when dabigatran, a P-glycoprotein (P-gp) substrate, is coadministered with nelfinavir, a P-gp inhibitor. Patients should be monitored for increased adverse effects of dabigatran. When dabigatran is administered for treatment or reduction in risk of recurrence of deep venous thrombosis (DVT) or pulmonary embolism (PE), or prophylaxis of DVT or PE following hip replacement surgery, avoid coadministration with P-gp inhibitors like nelfinavir in patients with CrCl less than 50 mL/minute. When dabigatran is used in patients with non-valvular atrial fibrillation and severe renal impairment (CrCl less than 30 mL/minute), avoid coadministration with nelfinavir, as serum concentrations of dabigatran are expected to be higher than when administered to patients with normal renal function. P-gp inhibition and renal impairment are the major independent factors that result in increased exposure to dabigatran.
Neratinib: (Moderate) Monitor for an increase in dabigatran-related adverse reactions if coadministration with neratinib is necessary in patients with creatinine clearance (CrCl) greater than 50 mL/minute. Avoid coadministration in patients with CrCl less than 50 mL/minute when dabigatran is administered for treatment or reduction in risk of recurrence of deep venous thrombosis (DVT) or pulmonary embolism (PE) or prophylaxis of DVT or PE following hip replacement surgery. Avoid coadministration in patients with CrCl less than 30 mL/minute in patients with non-valvular atrial fibrillation. Serum concentrations of dabigatran are expected to be higher in patients with renal impairment compared to patients with normal renal function. Dabigatran is a P-glycoprotein (P-gp) substrate and neratinib is a P-gp inhibitor.
Niacin; Simvastatin: (Moderate) Consider a statin other than lovastatin or simvastatin if HMG-CoA reductase inhibition is necessary for a patient receiving dabigatran. Increased serum concentrations of dabigatran are possible when coadministered with lovastatin. If use together is medically necessary, patients should be monitored for increased adverse effects of dabigatran and an increased risk for bleeding. A mechanism for this interaction may be the inhibition of P-gp by simvastatin; dabigatran is a P-gp substrate. In one clinical trial, patients receiving dabigatran with lovastatin or simvastatin experienced a higher risk of major hemorrhage relative to the use of other statins that are not P-gp inhibitors. P-gp inhibition and renal impairment are the major independent factors that result in increased exposure to dabigatran.
Nintedanib: (Moderate) Nintedanib is a VEGFR inhibitor and may increase the risk of bleeding. Monitor patients who are taking anticoagulants closely and adjust anticoagulation therapy as necessary. Use nintedanib in patients with known risk of bleeding only if the anticipated benefit outweighs the potential risk.
Nirmatrelvir; Ritonavir: (Major) Depending on the patients renal function and dabigatran indication, concomitant use with ritonavir-boosted nirmatrelvir should either be avoided, or the dose of dabigatran should be reduced. Coadministration increases dabigatran exposure and maximum plasma concentration resulting in increased bleeding risk. Dabigatran is a P-glycoprotein (P-gp) substrate and nirmatrelvir is a P-gp inhibitor. (Moderate) Monitor for an increase in dabigatran-related adverse reactions if coadministration with ritonavir is necessary in patients with creatinine clearance (CrCl) greater than 50 mL/minute. Avoid coadministration in patients with CrCl less than 50 mL/minute when dabigatran is administered for treatment or reduction in risk of recurrence of deep venous thrombosis (DVT) or pulmonary embolism (PE) or prophylaxis of DVT or PE following hip replacement surgery. Avoid coadministration in patients with CrCl less than 30 mL/minute in patients with non-valvular atrial fibrillation. Serum concentrations of dabigatran are expected to be higher in patients with renal impairment compared to patients with normal renal function. Dabigatran is a P-gp substrate and ritonavir is a P-gp inhibitor.
Nonsteroidal antiinflammatory drugs: (Major) Educate patients about the signs of increased bleeding and the need to report these signs to a healthcare provider immediately if coadministration of dabigatran and a nonsteroidal antiinflammatory drug (NSAID) is necessary. Dabigatran can cause significant and, sometimes, fatal bleeding. This risk may be increased by concurrent use of chronic NSAID therapy.
Obinutuzumab: (Moderate) Fatal hemorrhagic events have been reported in patients treated with obinutuzumab; all events occured during cycle 1. Monitor all patients for thrombocytopenia and bleeding, and consider withholding concomitant medications which may increase bleeding risk (i.e., anticoagulants, platelet inhibitors), especially during the first cycle.
Olanzapine; Fluoxetine: (Moderate) Advise patients of the increased bleeding risk associated with the concomitant use of selective serotonin reuptake inhibitors (SSRIs) and anticoagulants like dabigatran. Case reports and epidemiological studies have demonstrated an association between use of drugs that interfere with serotonin reuptake and gastrointestinal bleeding.
Omacetaxine: (Major) Avoid the concomitant use of omacetaxine and anticoagulants when the platelet count is less than 50,000 cells/microliter due to an increased risk of bleeding.
Omidubicel: (Moderate) Because of the potential effects of certain dextran formulations on bleeding time, use with caution in patients on anticoagulants concurrently.
Orlistat: (Moderate) Patients on chronic stable doses of anticoagulants, like dabigatran, should be monitored closely for changes in coagulation parameters when orlistat is prescribed. Reports of decreased prothrombin, increased INR, and unbalanced anticoagulant treatment resulting in change of hemostatic parameters have been reported in patients treated concomitantly with orlistat and anticoagulants.
Osimertinib: (Moderate) Monitor for an increase in dabigatran-related adverse reactions if coadministration with osimertinib is necessary. When dabigatran is administered for treatment or reduction in risk of recurrence of deep venous thrombosis (DVT) or pulmonary embolism (PE) or prophylaxis of DVT or PE following hip replacement surgery, avoid coadministration with osimertinib in patients with CrCL less than 50 mL/minute. When dabigatran is used in patients with non-valvular atrial fibrillation and severe renal impairment (CrCL less than 30 mL/minute), avoid coadministration with osimertinib, as serum concentrations of dabigatran are expected to be higher than when administered to patients with normal renal function. Increased serum concentrations of dabigatran are possible when dabigatran, a P-glycoprotein (P-gp) substrate, is coadministered with osimertinib, a P-gp inhibitor; P-gp inhibition and renal impairment are the major independent factors that result in increased exposure to dabigatran. Coadministration of dabigatran and a single oral dose of another P-gp inhibitor increased the dabigatran AUC and Cmax by 58% and 50%, respectively; there was additionally a 65% increase in renal clearance of dabigatran.
Oxaliplatin: (Major) Increase the frequency of monitoring in patients who are receiving concomitant therapy with oxaliplatin and dabigatran. Prolonged PT/INR occasionally associated with hemorrhage have been reported in patients who received oxaliplatin in combination with fluorouracil/leucovorin while on anticoagulants.
Oxandrolone: (Moderate) An increased effect of anticoagulants may occur with oxandrolone; the anticoagulant dosage may need adjustment downward with oxandrolone initiation or adjustment upward with oxandrolone discontinuation to maintain the desired clinical effect. Oxandrolone suppresses clotting factors II, V, VII, and X, which results in an increased prothrombin time. An increase in plasminogen-activator activity, and serum concentrations of plasminogen, protein C, and antithrombin III have occurred with several 17-alpha-alkylated androgens. For example, concurrent use of oxandrolone and warfarin may result in unexpectedly large increases in the INR or prothrombin time (PT). A multidose study of oxandrolone (5 or 10 mg PO twice daily) in 15 healthy individuals concurrently treated with warfarin resulted in significant increases in warfarin half-life and AUC; a 5.5-fold decrease in the mean warfarin dosage from 6.13 mg/day to 1.13 mg/day (approximately 80 to 85% dose reduction) was necessary to maintain a target INR of 1.5. According to the manufacturer, if oxandrolone therapy is initiated in a patient already receiving warfarin, the dose of warfarin may need to be decreased significantly to reduce the potential for excessive INR elevations and associated risk of serious bleeding events. The patient should be closely monitored with frequent evaluation of the INR and clinical parameter, and the dosage of warfarin should be adjusted as necessary until a stable target INR is achieved. Careful monitoring of the INR and necessary adjustment of the warfarin dosage are also recommended when the androgen therapy is changed or discontinued.
Oxaprozin: (Major) Educate patients about the signs of increased bleeding and the need to report these signs to a healthcare provider immediately if coadministration of dabigatran and a nonsteroidal antiinflammatory drug (NSAID) is necessary. Dabigatran can cause significant and, sometimes, fatal bleeding. This risk may be increased by concurrent use of chronic NSAID therapy.
Pacritinib: (Moderate) Monitor for an increase in dabigatran-related adverse reactions if coadministration with pacritinib is necessary in patients with creatinine clearance (CrCl) greater than 50 mL/minute. Avoid coadministration in patients with CrCl less than 50 mL/minute when dabigatran is administered for treatment or reduction in risk of recurrence of deep venous thrombosis (DVT) or pulmonary embolism (PE) or prophylaxis of DVT or PE following hip replacement surgery. Avoid coadministration in patients with CrCl less than 30 mL/minute in patients with non-valvular atrial fibrillation. Serum concentrations of dabigatran are expected to be higher in patients with renal impairment compared to patients with normal renal function. Dabigatran is a P-gp substrate and pacritinib is a P-gp inhibitor.
Paroxetine: (Moderate) Advise patients of the increased bleeding risk associated with the concomitant use of selective serotonin reuptake inhibitors (SSRIs) and anticoagulants like dabigatran. Case reports and epidemiological studies have demonstrated an association between use of drugs that interfere with serotonin reuptake and gastrointestinal bleeding.
Pentosan: (Major) Pentosan is a weak anticoagulant. Pentosan has 1/15 the anticoagulant activity of heparin. An additive risk of bleeding may be seen in patients receiving other anticoagulants (e.g., dabigatran) in combination with pentosan.
Phenobarbital: (Major) In general, avoid coadministration of dabigatran with P-glycoprotein (P-gp) inducers, such as phenobarbital. Concomitant administration of dabigatran and rifampin, another P-gp inducer, resulted in a significant decrease in dabigatran AUC and Cmax.
Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Major) In general, avoid coadministration of dabigatran with P-glycoprotein (P-gp) inducers, such as phenobarbital. Concomitant administration of dabigatran and rifampin, another P-gp inducer, resulted in a significant decrease in dabigatran AUC and Cmax.
Phenytoin: (Major) Coadministration of dabigatran with phenytoin should generally be avoided due to the risk of deceased dabigatran exposure which may reduce its efficacy. Dabigatran is a P-glycoprotein (P-gp) substrate and phenytoin is a P-gp inducer.
Piperacillin; Tazobactam: (Moderate) Some penicillins (e.g., piperacillin) can inhibit platelet aggregation, which may increase the risk of bleeding with any anticoagulants. Clinically important bleeding of this type, however, is relatively rare. The concomitant use of warfarin with many classes of antibiotics, including penicillins, may result in an increased INR thereby potentiating the risk for bleeding. Inhibition of vitamin K synthesis due to alterations in the intestinal flora may be a mechanism; however, concurrent infection is also a potential risk factor for elevated INR. Monitor patients for signs and symptoms of bleeding. Additionally, increased monitoring of the INR, especially during initiation and upon discontinuation of the antibiotic, may be necessary in patients receiving warfarin.
Pirfenidone: (Moderate) Increased serum concentrations of dabigatran are possible when dabigatran, a P-glycoprotein (P-gp) substrate, is coadministered with pirfenidone, a weak P-gp inhibitor. Patients should be monitored for increased adverse effects of dabigatran. When dabigatran is administered for treatment or reduction in risk of recurrence of deep venous thrombosis (DVT) or pulmonary embolism (PE) or prophylaxis of DVT or PE following hip replacement surgery, avoid coadministration with P-gp inhibitors like pirfenidone in patients with CrCl less than 50 mL/minute. When dabigatran is used in patients with non-valvular atrial fibrillation and severe renal impairment (CrCl less than 30 mL/minute), avoid coadministration with pirfenidone, as serum concentrations of dabigatran are expected to be higher than when administered to patients with normal renal function. P-gp inhibition and renal impairment are the major independent factors that result in increased exposure to dabigatran.
Piroxicam: (Major) Educate patients about the signs of increased bleeding and the need to report these signs to a healthcare provider immediately if coadministration of dabigatran and a nonsteroidal antiinflammatory drug (NSAID) is necessary. Dabigatran can cause significant and, sometimes, fatal bleeding. This risk may be increased by concurrent use of chronic NSAID therapy.
Pirtobrutinib: (Moderate) Monitor for an increase in dabigatran-related adverse reactions if coadministration with pirtobrutinib is necessary in patients with creatinine clearance (CrCl) greater than 50 mL/minute. Avoid coadministration in patients with CrCl less than 50 mL/minute when dabigatran is administered for treatment or reduction in risk of recurrence of deep venous thrombosis (DVT) or pulmonary embolism (PE) or prophylaxis of DVT or PE following hip replacement surgery. Avoid coadministration in patients with CrCl less than 30 mL/minute in patients with non-valvular atrial fibrillation. Serum concentrations of dabigatran are expected to be higher in patients with renal impairment compared to patients with normal renal function. Dabigatran is a P-gp substrate and pirtobrutinib is a P-gp inhibitor.
Posaconazole: (Moderate) Increased serum concentrations of dabigatran are possible when dabigatran, a P-glycoprotein (P-gp) substrate, is coadministered with posaconazole, a P-gp inhibitor. Patients should be monitored for increased adverse effects of dabigatran. When dabigatran is administered for treatment or reduction in risk of recurrence of deep venous thrombosis (DVT) or pulmonary embolism (PE) or prophylaxis of DVT or PE following hip replacement surgery, avoid coadministration with P-gp inhibitors like posaconazole in patients with CrCl less than 50 mL/minute. When dabigatran is used in patients with non-valvular atrial fibrillation and severe renal impairment (CrCl less than 30 mL/minute), avoid coadministration with posaconazole, as serum concentrations of dabigatran are expected to be higher than when administered to patients with normal renal function. P-gp inhibition and renal impairment are the major independent factors that result in increased exposure to dabigatran.
Prasterone, Dehydroepiandrosterone, DHEA (Dietary Supplements): (Major) Prasterone (DHEA) is contraindicated for use in patients with active deep vein thrombosis, pulmonary embolism or history of these conditions. Prasterone is also contraindicated in patients with active arterial thromboembolic disease (for example, stroke and myocardial infarction), or a history of these conditions. Thus, patients receiving anticoagulation due to a history of these conditions are not candidates for prasterone treatment. DHEA is converted to androgens and estrogens within the human body and thus may affect hemostasis via androgenic or estrogenic effects. Estrogens increase the production of clotting factors VII, VIII, IX, and X. Androgens, such as testosterone, increase the synthesis of several anticoagulant and fibrinolytic proteins. Because of the potential effects on coagulation, patients receiving prasterone or DHEA concurrently with preventative anticoagulants (e.g., warfarin or heparin) or other platelet inhibitors, including aspirin, ASA should be monitored for side effects or the need for dosage adjustments.
Prasterone, Dehydroepiandrosterone, DHEA (FDA-approved): (Major) Prasterone (DHEA) is contraindicated for use in patients with active deep vein thrombosis, pulmonary embolism or history of these conditions. Prasterone is also contraindicated in patients with active arterial thromboembolic disease (for example, stroke and myocardial infarction), or a history of these conditions. Thus, patients receiving anticoagulation due to a history of these conditions are not candidates for prasterone treatment. DHEA is converted to androgens and estrogens within the human body and thus may affect hemostasis via androgenic or estrogenic effects. Estrogens increase the production of clotting factors VII, VIII, IX, and X. Androgens, such as testosterone, increase the synthesis of several anticoagulant and fibrinolytic proteins. Because of the potential effects on coagulation, patients receiving prasterone or DHEA concurrently with preventative anticoagulants (e.g., warfarin or heparin) or other platelet inhibitors, including aspirin, ASA should be monitored for side effects or the need for dosage adjustments.
Prasugrel: (Moderate) Concomitant use of prasugrel and other agents that may affect hemostasis, such as anticoagulants, may be associated with an increased risk of bleeding.
Pretomanid: (Moderate) Monitor for an increase in dabigatran-related adverse reactions if coadministration with pretomanid is necessary in patients with creatinine clearance (CrCl) greater than 50 mL/minute. Avoid coadministration in patients with CrCl less than 50 mL/minute when dabigatran is administered for treatment or reduction in risk of recurrence of deep venous thrombosis (DVT) or pulmonary embolism (PE) or prophylaxis of DVT or PE following hip replacement surgery. Avoid coadministration in patients with CrCl less than 30 mL/minute in patients with non-valvular atrial fibrillation. Serum concentrations of dabigatran are expected to be higher in patients with renal impairment compared to patients with normal renal function. Dabigatran is a P-gp substrate and pretomanid is a P-gp inhibitor.
Primidone: (Major) In general, avoid coadministration of dabigatran with primidone because of P-gp induction by phenobarbital, an active metabolite of primidone. Concomitant administration of dabigatran and rifampin, another P-gp inducer, resulted in a significant decrease in dabigatran AUC and Cmax.
Propafenone: (Moderate) Increased serum concentrations of dabigatran are possible when dabigatran, a P-glycoprotein (P-gp) substrate, is coadministered with propafenone, a P-gp inhibitor. Patients should be monitored for increased adverse effects of dabigatran. When dabigatran is administered for treatment or reduction in risk of recurrence of deep venous thrombosis (DVT) or pulmonary embolism (PE) or prophylaxis of DVT or PE following hip replacement surgery, avoid coadministration with P-gp inhibitors like propafenone in patients with CrCl less than 50 mL/minute. When dabigatran is used in patients with non-valvular atrial fibrillation and severe renal impairment (CrCl less than 30 mL/minute), avoid coadministration with propafenone, as serum concentrations of dabigatran are expected to be higher than when administered to patients with normal renal function. P-gp inhibition and renal impairment are the major independent factors that result in increased exp osure to dabigatran.
Quinidine: (Moderate) Increased serum concentrations of dabigatran are possible when dabigatran, a P-glycoprotein (P-gp) substrate, is coadministered with quinidine, a P-gp inhibitor. Patients should be monitored for increased adverse effects of dabigatran. When dabigatran is administered for treatment or reduction in risk of recurrence of deep venous thrombosis (DVT) or pulmonary embolism (PE) or prophylaxis of DVT or PE following hip replacement surgery, avoid coadministration with P-gp inhibitors like quinidine in patients with CrCl less than 50 mL/minute. When dabigatran is used in patients with non-valvular atrial fibrillation and severe renal impairment (CrCl less than 30 mL/minute), avoid coadministration with quinidine, as serum concentrations of dabigatran are expected to be higher than when administered to patients with normal renal function. Coadministration of quinidine 200 mg every 2 hours up to a total dose of 1000 mg and dabigatran administered over 3 consecutive days, the last evening dose on Day 3 with or without quinidine pre-dosing, resulted in an increase in dabigatran AUC and Cmax of 53% and 56%, respectively. P-gp inhibition and renal impairment are the major independent factors that result in increased exposure to dabigatran.
Ranolazine: (Moderate) Increased serum concentrations of dabigatran are possible when dabigatran, a P-glycoprotein (P-gp) substrate, is coadministered with ranolazine, a P-gp inhibitor. Patients should be monitored for increased adverse effects of dabigatran. When dabigatran is administered for treatment or reduction in risk of recurrence of deep venous thrombosis (DVT) or pulmonary embolism (PE) or prophylaxis of DVT or PE following hip replacement surgery, avoid coadministration with P-gp inhibitors like ranolazine in patients with CrCl less than 50 mL/minute. When dabigatran is used in patients with non-valvular atrial fibrillation and severe renal impairment (CrCl less than 30 mL/minute), avoid coadministration with ranolazine, as serum concentrations of dabigatran are expected to be higher than when administered to patients with normal renal function. P-gp inhibition and renal impairment are the major independent factors that result in increased exposure to dabigatran.
Reteplase, r-PA: (Major) Based on the pharmacology of dabigatran, other oral anticoagulants and thrombolytic agents could cause additive risk of bleeding when given concurrently with dabigatran.
Rifampin: (Major) In general, avoid coadministration of dabigatran with P-gp inducers, such as rifampin. Concomitant administration of 600 mg rifampin for 7 days followed by a single dose of dabigatran decreased dabigatran AUC and Cmax by 66% and 67%, respectively. Dabigatran exposure returned to normal 7 days after cessation of rifampin therapy.
Ritonavir: (Moderate) Monitor for an increase in dabigatran-related adverse reactions if coadministration with ritonavir is necessary in patients with creatinine clearance (CrCl) greater than 50 mL/minute. Avoid coadministration in patients with CrCl less than 50 mL/minute when dabigatran is administered for treatment or reduction in risk of recurrence of deep venous thrombosis (DVT) or pulmonary embolism (PE) or prophylaxis of DVT or PE following hip replacement surgery. Avoid coadministration in patients with CrCl less than 30 mL/minute in patients with non-valvular atrial fibrillation. Serum concentrations of dabigatran are expected to be higher in patients with renal impairment compared to patients with normal renal function. Dabigatran is a P-gp substrate and ritonavir is a P-gp inhibitor.
Rivaroxaban: (Major) Avoid use of dabigatran with rivaroxaban due to the increased bleeding risk. Monitor patients closely and promptly evaluate any signs or symptoms of bleeding if dabigatran and other anticoagulants are used concomitantly. Coadministration of dabigatran and other anticoagulants may increase the risk of bleeding. Long-term concomitant treatment with dabigatran and other anticoagulants is not recommended; short-term use may be necessary for patients transitioning to or from dabigatran.
Rolapitant: (Moderate) Increased serum concentrations of dabigatran are possible when dabigatran, a P-glycoprotein (P-gp) substrate, is coadministered with rolapitant, a P-gp inhibitor. Patients should be monitored for increased adverse effects of dabigatran. When dabigatran is administered for treatment or reduction in risk of recurrence of deep venous thrombosis (DVT) or pulmonary embolism (PE) or prophylaxis of DVT or PE following hip replacement surgery, avoid coadministration with P-gp inhibitors like rolapitant in patients with CrCl less than 50 mL/minute. When dabigatran is used in patients with non-valvular atrial fibrillation and severe renal impairment (CrCl less than 30 mL/minute), avoid coadministration with rolapitant, as serum concentrations of dabigatran are expected to be higher than when administered to patients with normal renal function. P-gp inhibition and renal impairment are the major independent factors that result in increased exposure to dabigatran.
Salicylates: (Major) Educate patients about the signs of increased bleeding and the need to report these signs to a healthcare provider immediately if coadministration of dabigatran and aspirin or another salicylate is necessary. Dabigatran can cause significant and, sometimes, fatal bleeding. This risk may be increased by concurrent use of chronic salicylate therapy.
Salsalate: (Major) Educate patients about the signs of increased bleeding and the need to report these signs to a healthcare provider immediately if coadministration of dabigatran and aspirin or another salicylate is necessary. Dabigatran can cause significant and, sometimes, fatal bleeding. This risk may be increased by concurrent use of chronic salicylate therapy.
Saquinavir: (Moderate) Increased serum concentrations of dabigatran are possible when dabigatran, a P-glycoprotein (P-gp) substrate, is coadministered with saquinavir, a P-gp inhibitor. Patients should be monitored for increased adverse effects of dabigatran. When dabigatran is administered for treatment or reduction in risk of recurrence of deep venous thrombosis (DVT) or pulmonary embolism (PE) or prophylaxis of DVT or PE following hip replacement surgery, avoid coadministration with P-gp inhibitors like saquinavir in patients with CrCl less than 50 mL/minute. When dabigatran is used in patients with non-valvular atrial fibrillation and severe renal impairment (CrCl less than 30 mL/minute), avoid coadministration with saquinavir, as serum concentrations of dabigatran are expected to be higher than when administered to patients with normal renal function. P-gp inhibition and renal impairment are the major independent factors that result in increased exposure to dabigatran.
Selective serotonin reuptake inhibitors: (Moderate) Advise patients of the increased bleeding risk associated with the concomitant use of selective serotonin reuptake inhibitors (SSRIs) and anticoagulants like dabigatran. Case reports and epidemiological studies have demonstrated an association between use of drugs that interfere with serotonin reuptake and gastrointestinal bleeding.
Selpercatinib: (Moderate) Monitor for an increase in dabigatran-related adverse reactions if coadministration with selpercatinib is necessary in patients with creatinine clearance (CrCl) greater than 50 mL/minute. Avoid coadministration in patients with CrCl less than 50 mL/minute when dabigatran is administered for treatment or reduction in risk of recurrence of deep venous thrombosis (DVT) or pulmonary embolism (PE) or prophylaxis of DVT or PE following hip replacement surgery. Avoid coadministration in patients with CrCl less than 30 mL/minute in patients with non-valvular atrial fibrillation. Serum concentrations of dabigatran are expected to be higher in patients with renal impairment compared to patients with normal renal function. Dabigatran is a P-gp substrate and selpercatinib is a P-gp inhibitor.
Serotonin norepinephrine reuptake inhibitors: (Moderate) Advise patients of the increased bleeding risk associated with the concomitant use of serotonin norepinephrine reuptake inhibitors (SNRIs) and anticoagulants like dabigatran. Case reports and epidemiological studies have demonstrated an association between use of drugs that interfere with serotonin reuptake and gastrointestinal bleeding.
Sertraline: (Moderate) Advise patients of the increased bleeding risk associated with the concomitant use of selective serotonin reuptake inhibitors (SSRIs) and anticoagulants like dabigatran. Case reports and epidemiological studies have demonstrated an association between use of drugs that interfere with serotonin reuptake and gastrointestinal bleeding.
Simvastatin: (Moderate) Consider a statin other than lovastatin or simvastatin if HMG-CoA reductase inhibition is necessary for a patient receiving dabigatran. Increased serum concentrations of dabigatran are possible when coadministered with lovastatin. If use together is medically necessary, patients should be monitored for increased adverse effects of dabigatran and an increased risk for bleeding. A mechanism for this interaction may be the inhibition of P-gp by simvastatin; dabigatran is a P-gp substrate. In one clinical trial, patients receiving dabigatran with lovastatin or simvastatin experienced a higher risk of major hemorrhage relative to the use of other statins that are not P-gp inhibitors. P-gp inhibition and renal impairment are the major independent factors that result in increased exposure to dabigatran.
Sodium Iodide: (Moderate) Anticoagulants may alter sodium iodide I-131 pharmacokinetics and dynamics for up to 1 week after administrations.
Sodium Phenylbutyrate; Taurursodiol: (Moderate) Monitor for an increase in dabigatran-related adverse reactions if coadministration with taurursodiol is necessary in patients with creatinine clearance (CrCl) greater than 50 mL/minute. Avoid coadministration in patients with CrCl less than 50 mL/minute when dabigatran is administered for treatment or reduction in risk of recurrence of deep venous thrombosis (DVT) or pulmonary embolism (PE) or prophylaxis of DVT or PE following hip replacement surgery. Avoid coadministration in patients with CrCl less than 30 mL/minute in patients with non-valvular atrial fibrillation. Serum concentrations of dabigatran are expected to be higher in patients with renal impairment compared to patients with normal renal function. Dabigatran is a P-gp substrate and taurursodiol is a P-gp inhibitor.
Sodium Zirconium Cyclosilicate: (Moderate) Administer dabigatran 2 hours before or 2 hours after sodium zirconium cyclosilicate. Simultaneous coadministration may decrease the absorption of dabigatran due to the effects of sodium zirconium cyclosilicate on gastric pH. Coadministration of sodium zirconium cyclosilicate decreased the systemic exposure of dabigatran by approximately 30%.
Sofosbuvir; Velpatasvir; Voxilaprevir: (Moderate) Increased dabigatran serum concentrations may occur when dabigatran is coadministered with voxilaprevir. Monitor dabigatran serum concentrations and adjust dabigatran dose as necessary. Dabigatran is a P-glycoprotein (P-gp) substrate and voxilaprevir inhibits P-gp.
Sorafenib: (Moderate) Monitor for an increase in dabigatran-related adverse reactions if coadministration with sorafenib is necessary in patients with creatinine clearance (CrCl) greater than 50 mL/min. Avoid coadministration in patients with CrCl less than 50 mL/min when dabigatran is administered for treatment or reduction in risk of recurrence of deep venous thrombosis (DVT) or pulmonary embolism (PE) or prophylaxis of DVT or PE following hip replacement surgery. Avoid coadministration in patients with CrCl less than 30 mL/min in patients with non-valvular atrial fibrillation. Serum concentrations of dabigatran are expected to be higher in patients with renal impairment compared to patients with normal renal function. Dabigatran is a P-glycoprotein substrate and sorafenib is a P-gp inhibitor.
Sotorasib: (Moderate) Monitor for an increase in dabigatran-related adverse reactions if coadministration with sotorasib is necessary in patients with creatinine clearance (CrCl) greater than 50 mL/min. Avoid coadministration in patients with CrCl less than 50 mL/min when dabigatran is administered for treatment or reduction in risk of recurrence of deep venous thrombosis (DVT) or pulmonary embolism (PE) or prophylaxis of DVT or PE following hip replacement surgery. Avoid coadministration in patients with CrCl less than 30 mL/min in patients with non-valvular atrial fibrillation. Serum concentrations of dabigatran are expected to be higher in patients with renal impairment compared to patients with normal renal function. Dabigatran is a P-glycoprotein substrate and sotorasib is a P-gp inhibitor.
Sparsentan: (Moderate) Monitor for an increase in dabigatran-related adverse reactions if coadministration with sparsentan is necessary in patients with creatinine clearance (CrCl) greater than 50 mL/minute. Avoid coadministration in patients with CrCl less than 50 mL/minute when dabigatran is administered for treatment or reduction in risk of recurrence of deep venous thrombosis (DVT) or pulmonary embolism (PE) or prophylaxis of DVT or PE following hip replacement surgery. Avoid coadministration in patients with CrCl less than 30 mL/minute in patients with non-valvular atrial fibrillation. Serum concentrations of dabigatran are expected to be higher in patients with renal impairment compared to patients with normal renal function. Dabigatran is a P-gp substrate and sparsentan is a P-gp inhibitor.
St. John's Wort, Hypericum perforatum: (Major) In general, avoid coadministration of dabigatran with P-gp inducers, such as St. John's Wort, Hypericum perforatum. Concomitant administration of dabigatran and rifampin, another P-gp inducer, resulted in a significant decrease in dabigatran AUC and Cmax.
Sulindac: (Major) Educate patients about the signs of increased bleeding and the need to report these signs to a healthcare provider immediately if coadministration of dabigatran and a nonsteroidal antiinflammatory drug (NSAID) is necessary. Dabigatran can cause significant and, sometimes, fatal bleeding. This risk may be increased by concurrent use of chronic NSAID therapy.
Sumatriptan; Naproxen: (Major) Educate patients about the signs of increased bleeding and the need to report these signs to a healthcare provider immediately if coadministration of dabigatran and a nonsteroidal antiinflammatory drug (NSAID) is necessary. Dabigatran can cause significant and, sometimes, fatal bleeding. This risk may be increased by concurrent use of chronic NSAID therapy.
Telavancin: (Moderate) Telavancin has no effect on coagulation or platelet aggregation; however, caution is advised when administering telavancin concurrently with anticoagulants as telavancin may interfere with laboratory tests used in monitoring these medications. The coagulation tests affected by telavancin include prothrombin time (PT), international normalized ratio (INR), activated partial thromboplastin time (aPTT), activated clotting time, and coagulation based factor Xa tests. When measured shortly after completion of a telavancin infusion, the results of these tests are increased; however, the effects of telavancin on these tests dissipate over time as plasma concentrations of telavancin decrease. Therefore, when administering telavancin in conjunction with anticoagulants ensure that blood samples for these coagulation tests are collected as close as possible to the patient's next telavancin dose.
Temsirolimus: (Moderate) Monitor for an increase in dabigatran-related adverse reactions if coadministration with temsirolimus is necessary in patients with CrCL greater than 50 mL/minute. Avoid coadministration in patients with CrCL less than 50 mL/minute when dabigatran is administered for treatment or reduction in risk of recurrence of deep venous thrombosis (DVT) or pulmonary embolism (PE) or prophylaxis of DVT or PE following hip replacement surgery. Avoid coadministration in patients with CrCL less than 30 mL/minute in patients with non-valvular atrial fibrillation. Dabigatran is a P-glycoprotein (P-gp) substrate and temsirolimus is a P-gp inhibitor. Concomitant use is likely to lead to increased concentrations of dabigatran; serum concentrations of dabigatran are expected to be higher in patients with renal impairment compared to patients with normal renal function.
Tenecteplase: (Major) Based on the pharmacology of dabigatran, other oral anticoagulants and thrombolytic agents could cause additive risk of bleeding when given concurrently with dabigatran.
Tepotinib: (Moderate) Monitor for an increase in dabigatran-related adverse reactions if coadministration with tepotinib is necessary in patients with creatinine clearance (CrCl) greater than 50 mL/min. Avoid coadministration in patients with CrCl less than 50 mL/min when dabigatran is administered for treatment or reduction in risk of recurrence of deep venous thrombosis (DVT) or pulmonary embolism (PE) or prophylaxis of DVT or PE following hip replacement surgery. Avoid coadministration in patients with CrCl less than 30 mL/min in patients with non-valvular atrial fibrillation. Serum concentrations of dabigatran are expected to be higher in patients with renal impairment compared to patients with normal renal function. Dabigatran is a P-glycoprotein substrate and tepotinib is a P-gp inhibitor. Concomitant use has been observed to increase dabigatran peak and overall exposure by 40% and 50%, respectively.
Tezacaftor; Ivacaftor: (Moderate) Monitor for an increase in dabigatran-related adverse reactions if coadministration with ivacaftor is necessary in patients with creatinine clearance (CrCl) greater than 50 mL/min. Avoid coadministration in patients with CrCl less than 50 mL/min when dabigatran is administered for treatment or reduction in risk of recurrence of deep venous thrombosis (DVT) or pulmonary embolism (PE) or prophylaxis of DVT or PE following hip replacement surgery. Avoid coadministration in patients with CrCl less than 30 mL/min in patients with non-valvular atrial fibrillation. Serum concentrations of dabigatran are expected to be higher in patients with renal impairment compared to patients with normal renal function. Dabigatran is a P-glycoprotein substrate and ivacaftor is a P-gp inhibitor.
Thrombolytic Agents: (Major) Based on the pharmacology of dabigatran, other oral anticoagulants and thrombolytic agents could cause additive risk of bleeding when given concurrently with dabigatran.
Ticagrelor: (Moderate) Increased serum concentrations of dabigatran are possible when dabigatran, a P-glycoprotein (P-gp) substrate, is coadministered with ticagrelor, a mild P-gp inhibitor. Patients should be monitored for increased adverse effects of dabigatran. When dabigatran is administered for treatment or reduction in risk of recurrence of deep venous thrombosis (DVT) or pulmonary embolism (PE) or prophylaxis of DVT or PE following hip replacement surgery, avoid coadministration with P-gp inhibitors like ticagrelor in patients with CrCl less than 50 mL/minute. When dabigatran is used in patients with non-valvular atrial fibrillation and severe renal impairment (CrCl less than 30 mL/minute), avoid coadministration with ticagrelor, as serum concentrations of dabigatran are expected to be higher than when administered to patients with normal renal function. Coadministration of ticagrelor modestly increases plasma concentrations of dabigatran; the magnitude of increase dependent on the dose and timing of ticagrelor administration. Concurrent use of dabigatran 110 mg PO twice daily and ticagrelor 90 mg PO twice daily increased the dabigatran AUC and Cmax by 26% and 29%, respectively. When coadministered with a loading dose of ticagrelor 180 mg PO, the AUC and Cmax of dabigatran increased by 49% and 65%, respectively; but when ticagrelor 180 mg was given 2 hours after dabigatran, the AUC and Cmax of dabigatran increased by only 27% and 24%, respectively. P-gp inhibition and renal impairment are the major independent factors that result in increased exposure to dabigatran.
Ticlopidine: (Moderate) Because ticlopidine inhibits platelet aggregation, a potential additive risk for bleeding exists if ticlopidine is given in combination with other agents that affect hemostasis such as anticoagulants. Per the manufacturer of ticlopidine, if a patient is switched from an anticoagulant or a thrombolytic agent to ticlopidine, the former drug should be discontinued prior to the administration of ticlopidine.
Tipranavir: (Major) In general, avoid coadministration of dabigatran with P-gp inducers, such as tipranavir, a mild inducer. Concomitant administration of dabigatran and rifampin, another P-gp inducer, resulted in a significant decrease in dabigatran AUC and Cmax.
Tirofiban: (Moderate) Concomitant use of tirofiban and other agents that affect hemostasis, such as anticoagulants, may be associated with an increased risk of bleeding.
Tolmetin: (Major) Educate patients about the signs of increased bleeding and the need to report these signs to a healthcare provider immediately if coadministration of dabigatran and a nonsteroidal antiinflammatory drug (NSAID) is necessary. Dabigatran can cause significant and, sometimes, fatal bleeding. This risk may be increased by concurrent use of chronic NSAID therapy.
Trandolapril; Verapamil: (Moderate) Increased serum concentrations of dabigatran are possible when dabigatran, a P-glycoprotein (P-gp) substrate, is coadministered with verapamil, a P-gp inhibitor. Patients should be monitored for increased adverse effects of dabigatran while taking products containing verapamil including trandolapril; verapamil. When dabigatran is administered for treatment or reduction in risk of recurrence of deep venous thrombosis (DVT) or pulmonary embolism (PE) or prophylaxis of DVT or PE following hip replacement surgery, avoid coadministration with P-gp inhibitors like verapamil in patients with CrCl less than 50 mL/minute. When dabigatran is used in patients with non-valvular atrial fibrillation and severe renal impairment (CrCl less than 30 mL/minute), avoid coadministration with verapamil, as serum concentrations of dabigatran are expected to be higher than when administered to patients with normal renal function. Concomitant administration of verapamil and dabigatran results in an increased Cmax and AUC of dabigatran; the extent depends on the formulation of verapamil and timing of administration. The greatest increase in exposure of dabigatran occurs when verapamil is present in the gut when dabigatran is taken. In a pharmacokinetic study, immediate-release verapamil given 1 hour prior to dabigatran administration produced the greatest increase in exposure. If verapamil is administered 2 hours after dabigatran administration, the increase in AUC is negligible. Data from the RE-LY trial indicate no significant changes in dabigatran trough concentrations were seen in patients who received concomitant therapy with verapamil. P-gp inhibition and renal impairment are the major independent factors that result in increased exposure to dabigatran.
Trazodone: (Moderate) Patients should be instructed to monitor for signs and symptoms of bleeding while taking trazodone concurrently with anticoagulants and to promptly report any bleeding events to the practitioner. Serotonergic agents may increase the risk of bleeding when combined with anticoagulants via inhibition of serotonin uptake by platelets; however, the absolute risk is not known. It would be prudent for clinicians to monitor the INR and patient's clinical status closely if trazodone is added to or removed from the regimen of a patient stabilized on anticoagulant therapy.
Treprostinil: (Moderate) When used concurrently with anticoagulants, treprostinil may increase the risk of bleeding.
Tucatinib: (Moderate) Monitor for an increase in dabigatran-related adverse reactions if coadministration with tucatinib is necessary in patients with CrCL greater than 50 mL/minute. Avoid coadministration in patients with CrCL less than 50 mL/minute when dabigatran is administered for treatment or reduction in risk of recurrence of deep venous thrombosis (DVT) or pulmonary embolism (PE) or prophylaxis of DVT or PE following hip replacement surgery. Avoid coadministration in patients with CrCL less than 30 mL/minute in patients with non-valvular atrial fibrillation. Serum concentrations of dabigatran are expected to be higher in patients with renal impairment compared to patients with normal renal function. Dabigatran is a P-glycoprotein substrate and tucatinib is a P-gp inhibitor.
Valdecoxib: (Major) Educate patients about the signs of increased bleeding and the need to report these signs to a healthcare provider immediately if coadministration of dabigatran and a nonsteroidal antiinflammatory drug (NSAID) is necessary. Dabigatran can cause significant and, sometimes, fatal bleeding. This risk may be increased by concurrent use of chronic NSAID therapy.
Vemurafenib: (Moderate) Increased serum concentrations of dabigatran are possible when dabigatran, a P-glycoprotein (P-gp) substrate, is coadministered with vemurafenib, a mild P-gp inhibitor. Patients should be monitored for increased adverse effects of dabigatran. When dabigatran is administered for treatment or reduction in risk of recurrence of deep venous thrombosis (DVT) or pulmonary embolism (PE) or prophylaxis of DVT or PE following hip replacement surgery, avoid coadministration with P-gp inhibitors like vemurafenib in patients with CrCl less than 50 mL/minute. When dabigatran is used in patients with non-valvular atrial fibrillation and severe renal impairment (CrCl less than 30 mL/minute), avoid coadministration with vemurafenib, as serum concentrations of dabigatran are expected to be higher than when administered to patients with normal renal function. P-gp inhibition and renal impairment are the major independent factors that result in increased exposure to dabigatran.
Verapamil: (Moderate) Increased serum concentrations of dabigatran are possible when dabigatran, a P-glycoprotein (P-gp) substrate, is coadministered with verapamil, a P-gp inhibitor. Patients should be monitored for increased adverse effects of dabigatran while taking products containing verapamil including trandolapril; verapamil. When dabigatran is administered for treatment or reduction in risk of recurrence of deep venous thrombosis (DVT) or pulmonary embolism (PE) or prophylaxis of DVT or PE following hip replacement surgery, avoid coadministration with P-gp inhibitors like verapamil in patients with CrCl less than 50 mL/minute. When dabigatran is used in patients with non-valvular atrial fibrillation and severe renal impairment (CrCl less than 30 mL/minute), avoid coadministration with verapamil, as serum concentrations of dabigatran are expected to be higher than when administered to patients with normal renal function. Concomitant administration of verapamil and dabigatran results in an increased Cmax and AUC of dabigatran; the extent depends on the formulation of verapamil and timing of administration. The greatest increase in exposure of dabigatran occurs when verapamil is present in the gut when dabigatran is taken. In a pharmacokinetic study, immediate-release verapamil given 1 hour prior to dabigatran administration produced the greatest increase in exposure. If verapamil is administered 2 hours after dabigatran administration, the increase in AUC is negligible. Data from the RE-LY trial indicate no significant changes in dabigatran trough concentrations were seen in patients who received concomitant therapy with verapamil. P-gp inhibition and renal impairment are the major independent factors that result in increased exposure to dabigatran.
Verteporfin: (Moderate) Use caution if coadministration of verteporfin with anticoagulants is necessary due to the risk of decreased verteporfin efficacy. Verteporfin is a light-activated drug. Once activated, local damage to neovascular endothelium results in a release of procoagulant and vasoactive factors resulting in platelet aggregation, fibrin clot formation, and vasoconstriction. Concomitant use of drugs that decrease clotting could decrease the efficacy of verteporfin therapy.
Vilazodone: (Moderate) Patients should be instructed to monitor for signs and symptoms of bleeding while taking vilazodone concurrently with anticoagulants and to promptly report any bleeding events to the practitioner. Serotonergic agents may increase the risk of bleeding when combined with anticoagulants via inhibition of serotonin uptake by platelets; however, the absolute risk is not known. In addition, both vilazodone and warfarin are highly protein bound, which may result in displacement of warfarin from protein binding sites and an increased anticoagulant effect. It would be prudent for clinicians to monitor the INR and clinical status of the patient closely if vilazodone is added to or removed from the regimen of a patient stabilized on warfarin.
Voclosporin: (Moderate) Monitor for an increase in dabigatran-related adverse reactions if coadministration with voclosporin is necessary in patients with creatinine clearance (CrCl) greater than 50 mL/min. Avoid coadministration in patients with CrCl less than 50 mL/min when dabigatran is administered for treatment or reduction in risk of recurrence of deep venous thrombosis (DVT) or pulmonary embolism (PE) or prophylaxis of DVT or PE following hip replacement surgery. Avoid coadministration in patients with CrCl less than 30 mL/min in patients with non-valvular atrial fibrillation. Serum concentrations of dabigatran are expected to be higher in patients with renal impairment compared to patients with normal renal function. Dabigatran is a P-glycoprotein substrate and voclosporin is a P-gp inhibitor.
Vonoprazan; Amoxicillin; Clarithromycin: (Moderate) Increased serum concentrations of dabigatran are possible when dabigatran, a P-glycoprotein (P-gp) substrate, is coadministered with clarithromycin, a P-gp inhibitor. Although the coadministration of dabigatran and clarithromycin has no effect on the pharmacokinetics of dabigatran or clarithromycin in healthy subjects, patients should be monitored for increased adverse effects of dabigatran. When dabigatran is administered for treatment or reduction in risk of recurrence of deep venous thrombosis (DVT) or pulmonary embolism (PE) or prophylaxis of DVT or PE following hip replacement surgery, avoid coadministration with P-gp inhibitors like clarithromycin in patients with CrCl less than 50 mL/minute. When dabigatran is used in patients with non-valvular atrial fibrillation and severe renal impairment (CrCl less than 30 mL/minute), avoid coadministration with clarithromycin, as serum concentrations of dabigatran are expected to be higher than when administered to patients with normal renal function. P-gp inhibition and renal impairment are the major independent factors that result in increased exposure to dabigatran.
Vorapaxar: (Major) Avoid concomitant use of vorapaxar and warfarin or other anticoagulants. Because vorapaxar inhibits platelet aggregation, a potential additive risk for bleeding exists if vorapaxar is given in combination with other agents that affect hemostasis such as anticoagulants. In a phase II trial, aspirin (81 mg or 325 mg) was randomly assigned to patients with atrial fibrillation receiving dabigatran (150 mg twice daily). Data obtained from logistic regression analysis suggest that the concomitant administration of aspirin and dabigatran may increase the risk of bleeding from 12% to 18% (81 mg aspirin) or 24% (325 mg aspirin). Monitor patients closely for signs of bleeding if dabigatran is given concomitantly with other platelet inhibitors.
Vortioxetine: (Moderate) Platelet aggregation may be impaired by vortioxetine due to platelet serotonin depletion, possibly increasing the risk of a bleeding complication (e.g., gastrointestinal bleeding, ecchymoses, epistaxis, hematomas, petechiae, hemorrhage) in patients receiving anticoagulants. Bleeding events related to drugs that inhibit serotonin reuptake have ranged from ecchymosis to life-threatening hemorrhages. Patients should be instructed to monitor for signs and symptoms of bleeding while taking vortioxetine concurrently with anticoagulants and to promptly report any bleeding events to the practitioner. Co-administration of vortioxetine and warfarin has not been shown to significantly affect the pharmacokinetics of either agent.
Warfarin: (Major) Avoid use of dabigatran with warfarin due to the increased bleeding risk. Monitor patients closely and promptly evaluate any signs or symptoms of bleeding if dabigatran and other anticoagulants are used concomitantly. Coadministration of dabigatran and other anticoagulants may increase the risk of bleeding. Long-term concomitant treatment with dabigatran and other anticoagulants is not recommended; short-term use may be necessary for patients transitioning to or from dabigatran.
Zonisamide: (Moderate) Increased serum concentrations of dabigatran are possible when dabigatran, a P-glycoprotein (P-gp) substrate, is coadministered with zonisamide, a mild P-gp inhibitor. Patients should be monitored for increased adverse effects of dabigatran. When dabigatran is administered for treatment or reduction in risk of recurrence of deep venous thrombosis (DVT) or pulmonary embolism (PE) or prophylaxis of DVT or PE following hip replacement surgery, avoid coadministration with P-gp inhibitors like zonisamide in patients with CrCl less than 50 mL/minute. When dabigatran is used in patients with non-valvular atrial fibrillation and severe renal impairment (CrCl less than 30 mL/minute), avoid coadministration with zonisamide, as serum concentrations of dabigatran are expected to be higher than when administered to patients with normal renal function. P-gp inhibition and renal impairment are the major independent factors that result in increased exposure to dabigatran.
How Supplied
Dabigatran etexilate/Pradaxa Oral Cap: 75mg, 110mg, 150mg
Pradaxa Oral Pellet: 20mg, 30mg, 40mg, 50mg, 110mg, 150mg
Maximum Dosage
300 mg/day PO for capsules; safety and efficacy of oral pellets have not been established.
Geriatric300 mg/day PO for capsules; safety and efficacy of oral pellets have not been established.
AdolescentsCapsules
weighing 81 kg or more: 520 mg/day PO.
weighing 61 to 80 kg: 440 mg/day PO.
weighing 41 to 60 kg: 370 mg/day PO.
weighing 26 to 40 kg: 300 mg/day PO.
Oral pellets
Safety and efficacy have not been established.
Capsules
8 to 12 years:
weighing 61 to 80 kg: 440 mg/day PO.
weighing 41 to 60 kg: 370 mg/day PO.
weighing 26 to 40 kg: 300 mg/day PO.
weighing 16 to 25 kg: 220 mg/day PO.
weighing 11 to 15 kg: 150 mg/day PO.
1 to 7 years: Safety and efficacy have not been established.
Oral pellets
12 years: Safety and efficacy have not been established.
1 to 11 years:
weighing 41 kg or more: 520 mg/day PO.
weighing 26 to 40 kg: 440 mg/day PO.
weighing 21 to 25 kg:
2 to 11 years: 440 mg/day PO.
18 to 23 months: 360 mg/day PO.
weighing 16 to 20 kg:
2 to 11 years: 340 mg/day PO.
12 to 23 months: 280 mg/day PO.
weighing 13 to 15 kg: 280 mg/day PO.
weighing 11 to 12 kg:
18 months to 11 years: 220 mg/day PO.
12 to 17 months: 200 mg/day PO.
weighing 9 to 10 kg: 180 mg/day PO.
weighing 7 to 8 kg: 140 mg/day PO.
weighing 5 to 6 kg: 100 mg/day PO.
Capsules
Safety and efficacy have not been established.
Oral pellets
3 to 11 months:
weighing 13 to 15 kg:
11 months: 280 mg/day PO.
10 months: 200 mg/day PO.
weighing 11 to 12 kg: 200 mg/day PO.
weighing 9 to 10 kg:
11 months: 180 mg/day PO.
6 to 10 months: 160 mg/day PO.
5 months: 120 mg/day PO.
weighing 7 to 8 kg:
9 to 11 months: 140 mg/day PO.
4 to 8 months: 120 mg/day PO.
3 months: 100 mg/day PO.
weighing 5 to 6 kg:
5 to 11 months: 100 mg/day PO.
3 to 4 months: 80 mg/day PO.
weighing 4 kg: 80 mg/day PO.
weighing 3 kg: 60 mg/day PO.
1 to 2 months: Safety and efficacy have not been established.
Safety and efficacy have not been established.
Mechanism Of Action
Dabigatran and its active metabolites are competitive, direct thrombin inhibitors that inhibit both free and clot-bound thrombin. Dabigatran prevents thrombin-induced platelet aggregation and the development of a thrombus by preventing the thrombin-mediated conversion of fibrinogen into fibrin during the coagulation cascade.
Pharmacokinetics
Dabigatran etexilate mesylate is administered orally. It is absorbed as the dabigatran etexilate ester, which is then hydrolyzed forming dabigatran, the active moiety. Dabigatran is approximately 35% bound to plasma proteins with a volume of distribution of 50 to 70 L. Pharmacokinetics are proportional to dose. After oral absorption, dabigatran is metabolized by esterases to 4 active acyl glucuronides that have pharmacological activity similar to dabigatran; each acyl glucuronide accounts for less than 10% of total dabigatran in the plasma. It is eliminated primarily in the urine. The half-life is 12 to 17 hours in healthy adult subjects.
Dabigatran prolongs the activated partial thromboplastin time (aPTT), ecarin clotting time (ECT), and thrombin time (TT) at recommended therapeutic doses. The median peak aPTT is approximately 2 times control after an oral dose of 150 mg and is 1.5 times control 12 hours after the last dose, with less than 10% of patients exceeding 2 times control. In patients receiving the 150 mg dose in the RE-LY trial, the median trough aPTT was 52 (40 to 76) seconds and the median trough ECT was 63 (44 to 103) seconds. The INR may or may not be elevated in patients receiving dabigatran and is relatively insensitive to the activity of dabigatran.
Affected cytochrome P450 isoenzymes and drug transporter: P-gp
Dabigatran is a substrate of the efflux transporter P-glycoprotein (P-gp) and plasma concentrations may be affected by P-gp inhibitors and inducers. Dabigatran is not an inhibitor, inducer, or substrate of CYP450 enzymes.
Capsules: The absolute bioavailability after oral administration is 3% to 7%. The maximum plasma concentration (Cmax) occurs 1 hour after administration in the fasted state. Administration of dabigatran after a high-fat meal delays the time to Cmax by 2 hours but has no effect on the bioavailability of dabigatran. Oral bioavailability increases by 75% when the pellets are taken without the capsule shell.
Oral pellets: Dabigatran oral pellets show 37% higher relative bioavailability in healthy adults compared to dabigatran capsules. In addition, the relative bioavailability between the 2 dosage forms is age dependent. The relative bioavailability observed in adult patients cannot be translated to pediatric patients. The capsule and oral pellet formulations are not interchangeable.
After intravenous administration, 80% of the dabigatran dose is eliminated renally.
Pregnancy And Lactation
Breast-feeding is not recommended during treatment with dabigatran. There are no data on the presence of dabigatran in human milk, the effects on the breast-fed child, or on milk production. If pharmacotherapy is necessary in the nursing mother, previous American Academy of Pediatrics (AAP) recommendations considered warfarin as usually compatible with breast-feeding. Low-molecular weight heparins and heparin have relatively high molecular weights ; therefore, these drugs are not expected to be excreted into human milk to a clinically significant degree.