Generic Name: Dabigatran Etexilate Mesylate
Class: Direct Thrombin Inhibitors
Chemical Name: N - [[2 - [[[4 - (Aminoiminomethyl)phenyl]amino]methyl] - 1 - methyl - 1H - benzimidazol - 5 - yl]carbonyl] - N - 2 - pyridinyl - β - alanine
Molecular Formula: C₂₅H₂₅N₇O₃C₃₄H₄₁N₇O₅C₃₄H₄₁N₇O₅•CH₄O₃S
CAS Number: 211914-51-1

Introduction

Anticoagulant; a synthetic reversible direct thrombin inhibitor.^{1 2 10 13}

Uses for Pradaxa

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

Embolism Associated with Atrial Fibrillation

Reduction in risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation.^{1 2 3 5 18 20 21 30 32}

The American College of Chest Physicians (ACCP), the American College of Cardiology, AHA, and other experts currently recommend antithrombotic therapy in all patients with persistent, permanent, or paroxysmal atrial fibrillation, unless such therapy is contraindicated.^{19 20 21 39 990 999 1007}

Choice of antithrombotic therapy is based on patient's level of risk for stroke.^{999 1007} In general, oral anticoagulant therapy is recommended in patients with high (and possibly also moderate) risk for stroke, while aspirin is recommended in low-risk patients and those with contraindications to oral anticoagulant therapy.^{999 1007} Patients considered to be at increased risk of stroke generally include those with a history of stroke or TIA, or those with ≥2 of the following risk factors: advanced age (e.g., ≥75 years of age), history of hypertension, diabetes mellitus, or recent exacerbation of CHF.^{999 1007}

Slideshow: Can Prescription Drugs Lead to Weight Gain?

ACCP and other experts suggest the use of dabigatran as an alternative to warfarin in selected patients with atrial fibrillation at increased risk of stroke.^{18 19 20 41 1007}

When selecting an appropriate anticoagulant, consider patient's risks of stroke and bleeding, compliance, availability of facilities to monitor INR, patient preference, cost, and degree of current INR control in patients already taking warfarin.^{8 18 19 21 999 1007}

Cardioversion of Atrial Fibrillation/Flutter

Has been used for prevention of stroke and systemic embolism in patients undergoing pharmacologic or electric cardioversion for atrial fibrillation/flutter†.¹⁰⁰⁷

Although warfarin is traditionally used, dabigatran is recommended by ACCP as an acceptable choice of anticoagulant for precardioversion anticoagulation in patients with atrial fibrillation lasting >48 hours or of unknown duration; prolonged precardioversion anticoagulation generally is not required in patients with atrial fibrillation of short duration (e.g., ≤48 hours).¹⁰⁰⁷

Thromboprophylaxis in Orthopedic Surgery

Has been used for prevention of thromboembolism in patients undergoing major orthopedic surgery (total hip-replacement or total knee-replacement surgery)†.¹⁰⁰³

ACCP considers dabigatran an acceptable option for pharmacologic thromboprophylaxis in patients undergoing total hip- or knee-replacement surgery; however, a low molecular weight heparin (LMWH) generally is preferred.¹⁰⁰³ Dabigatran may be a reasonable choice when an LMWH is not available or cannot be used.¹⁰⁰³

When selecting an appropriate thromboprophylaxis regimen, consider factors such as relative efficacy, bleeding risk, logistics, and compliance.¹⁰⁰³

Treatment of Acute Venous Thromboembolism

Has been used for treatment and secondary prevention of acute venous thromboembolism†.¹⁰⁰⁵

Recommended by ACCP as an acceptable option for long-term anticoagulation in patients with proximal DVT and/or PE after initial treatment with a parenteral anticoagulant; however, pending additional data, ACCP suggests use of warfarin or LMWH over dabigatran in such patients.¹⁰⁰⁵

Cerebral Embolism

Has been used for secondary prevention of cardioembolic stroke in patients with TIAs† or ischemic stroke† and concurrent atrial fibrillation.¹⁰⁰⁹ ACCP suggests use of dabigatran (150 mg twice daily) over warfarin in such patients.¹⁰⁰⁹

Antiplatelet agents generally preferred over oral anticoagulation for secondary prevention of noncardioembolic stroke in patients with a history of ischemic stroke or TIA.¹⁰⁰⁹

Pradaxa Dosage and Administration

General

• Routine laboratory coagulation monitoring not required.^{1 10 41}

Administration

Oral Administration

Administer orally twice daily without regard to meals.¹

Do not remove capsules from bottle or blister package until time of use.³⁶ (See Stability.)

Swallow capsules whole; do not chew, break, or empty the contents of the capsule.¹

Administer a missed dose as soon as it is remembered on same day; however, do not administer missed dose if it cannot be taken ≥6 hours before next scheduled dose.¹

Dosage

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

Available as dabigatran etexilate mesylate; dosage expressed in terms of the prodrug, dabigatran etexilate.¹

Adults

Embolism Associated with Atrial Fibrillation

Oral

Patients with Cl_cr >30 mL/minute: 150 mg twice daily.¹

Transferring from Warfarin

Discontinue warfarin and begin dabigatran when INR is <2.¹

Transferring to Warfarin

Initiate warfarin before discontinuing dabigatran.¹

For Cl_cr >50 mL/minute, begin warfarin 3 days before discontinuing dabigatran.¹

For Cl_cr 31–50 mL/minute, begin warfarin 2 days before discontinuing dabigatran.¹

For Cl_cr 15–30 mL/minute, begin warfarin 1 day before discontinuing dabigatran.¹

For Cl_cr <15 mL/minute, recommendations not available.¹

Dabigatran may affect INR; INR for monitoring warfarin is more reliable ≥2 days after dabigatran discontinuance.¹

Transferring from Parenteral Anticoagulants

Initiate dabigatran within 2 hours prior to what would have been the time of the next scheduled intermittent parenteral anticoagulant dose.¹

Initiate dabigatran at the time of discontinuance of the continuously administered parenteral anticoagulant.¹

Transferring to Parenteral Anticoagulants

Initiate parenteral anticoagulants after discontinuing dabigatran.¹

For Cl_cr ≥30 mL/minute, begin parenteral anticoagulant 12 hours after the last dose of dabigatran.¹

For Cl_cr <30 mL/minute, begin parenteral anticoagulant 24 hours after the last dose of dabigatran.¹

Managing Anticoagulation in Patients Requiring Invasive Procedures

When possible, withhold dabigatran prior to invasive or surgical procedures.¹ (See Risks of Interruption of Therapy under Cautions.) When surgery cannot be delayed, weigh increased risk of bleeding against urgency of intervention.¹ Bleeding risk best assessed using ecarin clotting time (ECT); aPTT may be used if ECT is unavailable.¹

For Cl_cr ≥50 mL/minute, withhold dabigatran beginning 1–2 days prior to procedure.¹

For Cl_cr <50 mL/minute, withhold dabigatran beginning 3–5 days prior to procedure.¹

Consider withholding drug for longer periods in patients who may require complete hemostasis (e.g., prior to major surgery, spinal puncture, placement of spinal or epidural catheter or port).¹

Prescribing Limits

Adults

Embolism Associated with Atrial Fibrillation

Oral

Maximum 150 mg twice daily.¹

Special Populations

Renal Impairment

Embolism Associated with Atrial Fibrillation

Oral

In patients with Cl_cr 15–30 mL/minute, reduce dosage to 75 mg twice daily.¹

In patients with Cl_cr 30–50 mL/minute and receiving concomitant therapy with dronedarone or systemic ketoconazole, consider dosage reduction to 75 mg twice daily.¹ (See Drugs Affecting P-glycoprotein Transport under Interactions.)

In patients with Cl_cr <15 mL/minute or receiving hemodialysis, manufacturer states that dosage recommendations not available.¹

Hepatic Impairment

No specific dosage recommendations at this time.¹

Geriatric Patients

No specific dosage recommendations at this time.¹

Cautions for Pradaxa

Contraindications

• Active pathologic bleeding.¹

• History of serious hypersensitivity reaction to dabigatran (e.g., anaphylaxis, anaphylactic shock).¹

Warnings/Precautions

Bleeding

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

Dabigatran increases the risk of hemorrhage and may cause serious, sometimes fatal bleeding.¹ In the Randomized Evaluation of Long-term Anticoagulation Therapy (RE-LY) study, life-threatening bleeding occurred at a rate of 1.5% per year with dabigatran etexilate 150 mg twice daily versus 1.8% per year with adjusted-dose (INR 2–3) warfarin.¹

Risk factors for hemorrhage include concomitant use of other drugs that generally increase bleeding risk (e.g., antiplatelet agents, heparin, thrombolytic therapy, chronic use of NSAIAs) and labor and delivery.¹ Overdosage also may lead to hemorrhagic complications.¹

FDA and the manufacturer are currently analyzing postmarketing reports of serious, sometimes fatal bleeding events to determine if the rate of serious bleeding is higher than expected based on the RE-LY study.⁴² At this time, FDA believes that the drug's benefits in patients with nonvalvular atrial fibrillation continue to outweigh its risks when used appropriately.⁴² Patients should continue to take the drug as prescribed unless otherwise instructed by a clinician.⁴² (See Risks of Interruption of Therapy under Cautions.)

Promptly evaluate manifestations of blood loss (e.g., decrease in hemoglobin/hematocrit, hypotension) in patients receiving dabigatran.¹ Discontinue dabigatran in patients with active pathologic bleeding and institute appropriate therapy. ¹

There is no specific reversal agent for dabigatran.^{1 10} May consider use of ECT or aPTT to assess degree of anticoagulation, if necessary.¹ Dabigatran can be dialyzed (approximately 60% of the drug is removed over a 2- to 3-hour session; however, limited experience with use of this method to treat bleeding).^{1 10} Limited data suggest that procoagulant reversal agents such as anti-inhibitor coagulant complex (also known as activated prothrombin complex concentrate), factor VIIa (recombinant), or coagulation factor concentrates II, IX, or X, may be considered for reversal of anticoagulation, but clinical usefulness not established.¹ Protamine sulfate and vitamin K not expected to affect anticoagulant activity of dabigatran.¹ Consider use of platelet concentrates in case of thrombocytopenia or if long-acting antiplatelet drugs have been used.¹

Risks of Interruption of Therapy

Increased risk of stroke when anticoagulants, including dabigatran, are interrupted for active bleeding, elective surgery, or invasive procedures; minimize such interruptions.¹ Following unavoidable interruption in therapy, restart dabigatran as soon as clinically possible.¹ (See Managing Anticoagulation in Patients Requiring Invasive Procedures under Dosage and Administration.)

Drugs Affecting P-glycoprotein Transport

Inducers of P-glycoprotein transport (e.g., rifampin) reduce exposure to dabigatran; avoid concurrent use.¹

Inhibitors of P-glycoprotein transport (specifically dronedarone and systemic ketoconazole) may increase systemic exposure to dabigatran in patients with moderate renal impairment (Cl_cr 30–50 mL/minute); dosage reduction necessary.¹ Avoid concomitant use of P-glycoprotein inhibitors in patients with severe renal impairment (Cl_cr 15–30 mL/minute).¹ (See Drugs Affecting P-glycoprotein Transport under Interactions.)

Sensitivity Reactions

Hypersensitivity Reactions

Anaphylactic reactions, anaphylactic shock, allergic edema, urticaria, rash, and pruritus reported.¹

Specific Populations

Pregnancy

Category C.¹ ACCP recommends that dabigatran be avoided in pregnant women because of a lack of data and experience.¹⁰¹²

Safety and efficacy during labor and delivery not established; consider risks of bleeding and of stroke with dabigatran use in this setting.¹

Lactation

Not known whether dabigatran is distributed into milk.¹ Manufacturer states to use caution.¹ ACCP recommends the use of alternative anticoagulants during breastfeeding.¹⁰¹²

Pediatric Use

Safety and efficacy not established.¹

Geriatric Use

In a large clinical trial in patients with atrial fibrillation, 82% were ≥65 years of age, and 40% were ≥75 years of age.¹ Risk of bleeding increases with age.^{1 28}

Renal Impairment

Increased exposure and anticoagulant effects in patients with renal impairment.¹ Assess renal function prior to initiation of therapy and periodically thereafter as clinically indicated.¹ Dosage adjustments may be necessary depending on degree of renal impairment.¹ (See Renal Impairment under Dosage and Administration.)

Common Adverse Effects

Hemorrhage and gastritis-like symptoms (i.e., GERD, esophagitis, erosive gastritis, gastric hemorrhage, hemorrhagic gastritis, hemorrhagic erosive gastritis, GI ulcer).^{1 3}

Interactions for Pradaxa

Does not inhibit or induce, and is not a substrate for, CYP isoenzymes.^{1 13}

Substrate for the P-glycoprotein transport system.^{1 41}

Drugs Affecting or Metabolized by Hepatic Microsomal Enzymes

Pharmacokinetic interactions with drugs metabolized by CYP isoenzymes unlikely.^{1 2 6 13}

Drugs Affecting P-glycoprotein Transport

P-glycoprotein inducers: Potential pharmacokinetic interaction (reduced dabigatran exposure); avoid concomitant use.¹

P-glycoprotein inhibitors: Potential pharmacokinetic interaction (increased dabigatran exposure).¹ Concomitant use of these drugs in patients with moderate renal impairment (Cl_cr 30–50 mL/minute) expected to further increase exposure; consider dosage reduction in these situations.¹ Concomitant use of certain other P-glycoprotein inhibitors does not necessitate dosage adjustments (see Specific Drugs under Interactions); do not extrapolate such findings to all P-glycoprotein inhibitors.¹

Drugs Affecting Hemostasis

Potentially increased risk of bleeding when used concomitantly with other agents that increase bleeding risk.¹ Monitor for and promptly evaluate manifestations of bleeding (e.g., decrease in hemoglobin/hematocrit, hypotension).¹ (See Bleeding under Cautions.)

Specific Drugs

Drug	Interaction	Comments
Amiodarone	Increased dabigatran concentrations and AUC; increased renal clearance of dabigatran1 No meaningful alteration of amiodarone pharmacokinetics1	Dosage adjustment not necessary1 Increased renal clearance of dabigatran may persist after amiodarone discontinuance due to long amiodarone half-life1
Anticoagulants, other	Increased risk of bleeding1	Monitor for bleeding manifestations1
Aspirin	Increased risk of bleeding1 6 Potential increased risk of bleeding with chronic NSAIA use1	Monitor for bleeding manifestations1 Large clinical trial in patients with atrial fibrillation demonstrated a 2-fold increase in major bleeding events/year with concomitant aspirin and dabigatran; similar to observed increased risk with concurrent aspirin and warfarin6
Atorvastatin	Pharmacokinetic interaction unlikely1 9
Clarithromycin	Pharmacokinetic interaction unlikely1	Dosage adjustments not necessary1
Clopidogrel	Increased risk of bleeding1 6 Potentially increased dabigatran concentrations and AUC1	Monitor for bleeding manifestations1 Large clinical trial in patients with atrial fibrillation demonstrated a 2-fold increase in major bleeding events/year with concomitant clopidogrel and dabigatran; similar to observed increased risk with concurrent clopidogrel and warfarin6
Diclofenac	Pharmacokinetic interaction unlikely1 Potentially increased risk of bleeding with chronic NSAIA use1	Monitor for bleeding manifestations1
Digoxin	Pharmacokinetic interaction unlikely1
Dronedarone	Increased systemic exposure to dabigatran by 1.7- to 2-fold1	Consider dosage reduction to 75 mg twice daily in patients with Clcr 30–50 mL/minute1
Enoxaparin	Increased risk of bleeding1 No alteration in dabigatran systemic exposure or pharmacodynamic assessments (i.e., aPTT, ECT, thrombin time [TT]) when dabigatran started 24 hours after last dose of enoxaparin1	Monitor for bleeding manifestations1
Heparin	Increased risk of bleeding1	Monitor for bleeding manifestations1
Ketoconazole	Increased dabigatran concentrations and AUC1	Consider dosage reduction to 75 mg twice daily in patients with Clcr 30–50 mL/minute1
NSAIAs	Increased risk of bleeding with chronic NSAIA use1	Monitor for bleeding manifestations1
Pantoprazole	Decreased dabigatran concentrations and AUC1 6 34 Pharmacokinetics of pantoprazole not affected1 34	Interaction not considered clinically important1 6 7
Quinidine	Increased dabigatran concentrations and AUC1	Dosage adjustment not necessary1
Ranitidine	Pharmacokinetic interaction unlikely1
Rifampin	Potentially decreased dabigatran concentrations and AUC1	Avoid concurrent use1
Thrombolytic agents	Increased risk of bleeding1	Monitor for bleeding manifestations1
Verapamil	Potentially increased dabigatran concentrations and AUC1	Dosage adjustment not necessary1 Interaction dependent on verapamil formulation and timing of administration; verapamil immediate release given 1 hour prior to dabigatran increased dabigatran AUC 2.4-fold, while verapamil given 2 hours after dabigatran had negligible effects1
Warfarin	Increased risk of bleeding1	INR for monitoring warfarin more accurate ≥2 days after discontinuing dabigatran1 (see Transferring to Warfarin and see Transferring from Warfarin, under Dosage and Administration)

Pradaxa Pharmacokinetics

Dabigatran etexilate is absorbed after oral administration of dabigatran etexilate mesylate and hydrolyzed to the active moiety, dabigatran, by esterases in plasma and the liver.^{1 13 7} Dabigatran undergoes conjugation to acyl glucuronides that have similar pharmacologic activity to dabigatran and account for approximately 20% of the total plasma dabigatran concentration.^{1 11 12 13} The pharmacokinetics of dabigatran are generally described in terms of total plasma dabigatran concentrations, which includes the major acyl glucuronide metabolites.^{1 11} Dabigatran exhibits linear, dose-dependent pharmacokinetics.¹

Absorption

Bioavailability

Absolute bioavailability of dabigatran following oral administration of dabigatran etexilate approximately 3–7%.¹

Steady-state expected within 3 days when given 3 times daily.¹²

Onset

Peak plasma concentration attained approximately 1–2 hours following oral administration.^{1 11 13} Maximal effects on coagulation assays expected within 2 hours of administration; such effects correlate with peak plasma concentrations.^{1 11 13}

Duration

Effects on anticoagulation assays decline by approximately 50% at 12 hours after administration.¹¹

Food

High-fat meal delays time to peak plasma concentration by 2 hours but does not affect bioavailability.¹

Special Populations

When dabigatran was administered 1–3 hours after completing hip arthroplasty, time to peak plasma concentrations was delayed to 6 hours but returned to normal day after surgery.^{2 12} There was no effect on AUC.^{2 12}

In patients with mild, moderate, or severe renal impairment, AUC estimated to be increased 1.5-, 3.2-, or 6.3-fold respectively; peak plasma concentrations increased 1.1-, 1.7-, or 2.1-fold, respectively.^{1 14}

Distribution

Extent

Not known whether dabigatran distributes into milk.¹

Plasma Protein Binding

Approximately 35%.^{1 13}

Elimination

Metabolism

Dabigatran etexilate is a prodrug of dabigatran;² rapidly absorbed following oral administration and hydrolyzed in the plasma to dabigatran, the active moiety.^{1 11}

Elimination Route

Bioavailable dabigatran excreted principally (80%) in urine as unchanged drug.^{1 13} Approximately 86% of total dose is eliminated in the feces.¹

Half-life

12–17 hours.^{1 11}

Special Populations

In patients with mild, moderate, or severe renal impairment, plasma half-life averages 15, 18, or 28 hours, respectively.¹

In patients with moderate hepatic impairment (Child-Pugh class B), large interpatient variability apparent, but no consistent change in exposure or pharmacodynamic response.^{1 15 41}

Stability

Storage

Oral

Capsules

25°C (may be exposed to 15–30°C).¹ Store in original package (i.e., bottles or blister pack) to protect from moisture.¹

Advise patients about special storage and handling requirements.³⁶ Dispense only in original bottle with desiccant cap to minimize product breakdown from moisture.³⁶ While manufacturer currently advises use of capsules in bottle within 30 days after first opening bottle,¹ FDA states that data under review indicate potency is maintained for 60 days after first opening bottle.³⁶ (See Advice to Patients.)

Once bottle is opened, manufacturer recommends that drug be used within 30 days.¹ Keep bottle tightly closed.¹

Keep out of reach of children.¹

Actions

• Selective, competitive, reversible direct thrombin inhibitor.^{2 12} Prevents thrombus formation by binding free and clot-bound thrombin, thereby inhibiting the conversion of fibrinogen to fibrin.^{1 2 12} Also inhibits thrombin-mediated platelet aggregation.^{1 2 12}

• Administered and absorbed as dabigatran etexilate mesylate, an inactive ester prodrug; hydrolyzed by esterases in plasma and liver to dabigatran, the principal active moiety.^{1 7 11 13} Dabigatran metabolized to several acyl glucuronides with similar activity as dabigatran.^{1 11}

• Prolongs TT and ECT linearly over the range of therapeutic plasma concentrations.^{1 10 11} Prolongs aPTT in a curvilinear manner.^{1 10 11} INR may be elevated, but is not a reliable assessment of dabigatran activity.^{1 10 11} ECT is the preferred method for measuring anticoagulant activity of dabigatran; median trough (12 hours post-dose) value of 63 seconds with dabigatran etexilate 150 mg twice daily.^{1 10} May also use aPTT qualitatively, with a ratio >1 indicating presence of drug in plasma; average peak or trough values of 2 or 1.5 times control, respectively, with dabigatran etexilate 150 mg twice daily.^{1 10 12 39}

Advice to Patients

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

• Risk of bleeding.¹ Patients should seek emergency medical care if they experience manifestations of serious bleeding (e.g., unusual bruising, including bruises with unknown cause or that enlarge; pink or brown urine; red or black, tarry stool; coughing up blood; vomiting blood; vomitus with the appearance of coffee grounds).¹

• Patients should consult healthcare provider for other manifestations of bleeding (e.g., pain, swelling, or discomfort in a joint, headaches, dizziness, weakness, recurrent nose bleeds, unusual bleeding from the gums, prolonged bleeding from a cut, heavier than normal menstrual or vaginal bleeding).¹

• Risk of adverse GI reactions.¹ Patients should consult healthcare provider if they experience dyspepsia, burning, nausea, abdominal pain/discomfort, epigastric discomfort, or indigestion.¹

• Patients should inform healthcare provider that they are taking dabigatran before scheduling any invasive or dental procedure.¹

• Importance of swallowing capsules whole, without breaking, chewing, or otherwise emptying the contents of the capsule.¹ Do not sprinkle contents of capsules on food or into a beverage.¹

• Importance of taking dabigatran exactly as prescribed.¹ Do not stop taking dabigatran without discussing with prescriber.¹

• Instruct patients to take missed dose as soon as remembered but only if it can be taken at least 6 hours prior to next scheduled dose.¹

• Importance of seeking emergency care or immediately calling poison control center in the event of overdosage.¹

• Importance of informing patient of special storage and handling requirements for drug.^{1 36} Store only in original container, not in pill boxes or organizers.^{1 36} Protect from moisture.¹ Remove only one capsule from container right before use, then close bottle tightly.^{1 36} When more than one bottle is dispensed, only open one bottle at a time.¹ Do not open or puncture blister on blister package until time of use.³⁶ Per manufacturer, use capsules within 4 months after the bottle is first opened.¹ (See Stability.)

• Importance of providing patient a copy of manufacturer’s patient information.¹

• Importance of women informing their clinician if they are or plan to become pregnant or plan to breast-feed.¹

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as any concomitant illnesses (e.g., cardiovascular disease).¹

• Importance of informing patients of other important precautionary information.¹ (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Dabigatran etexilate mesylate

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Oral	Capsules	75 mg (of dabigatran etexilate)	Pradaxa	Boehringer Ingelheim
		150 mg (of dabigatran etexilate)	Pradaxa	Boehringer Ingelheim

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 02/2013. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Pradaxa 150MG Capsules (BOEHRINGER INGELHEIM): 60/$245.99 or 180/$706.93

Pradaxa 75MG Capsules (BOEHRINGER INGELHEIM): 30/$123.99 or 90/$353.98