Dabigatran Etexilate

WARNING: (A) PREMATURE DISCONTINUATION OF DABIGATRAN ETEXILATE CAPSULES INCREASES THE RISK OF THROMBOTIC EVENTS, and (B) SPINAL/EPIDURAL HEMATOMA

BOXED WARNING SECTION

(A) PREMATURE DISCONTINUATION OF DABIGATRAN ETEXILATE CAPSULES INCREASES THE RISK OF THROMBOTIC EVENTS Premature discontinuation of any oral anticoagulant, including Dabigatran Etexilate Capsules, increases the risk of thrombotic events. If anticoagulation with Dabigatran Etexilate Capsules is discontinued for a reason other than pathological bleeding or completion of a course of therapy, consider coverage with another anticoagulant [see Dosage and Administration ( 2.6 , 2.7 , 2.8 ) and Warnings and Precautions ( 5.1 )]. (B) SPINAL/EPIDURAL HEMATOMA Epidural or spinal hematomas may occur in patients treated with Dabigatran Etexilate Capsules who are receiving neuraxial anesthesia or undergoing spinal puncture. These hematomas may result in long-term or permanent paralysis. Consider these risks when scheduling patients for spinal procedures. 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 non-steroidal anti-inflammatory drugs (NSAIDs), platelet inhibitors, other anticoagulants a history of traumatic or repeated epidural or spinal punctures a history of spinal deformity or spinal surgery optimal timing between the administration of Dabigatran Etexilate Capsules and neuraxial procedures is not known [see Warnings and Precautions ( 5.3 )]. Monitor patients frequently for signs and symptoms of neurological impairment. If neurological compromise is noted, urgent treatment is necessary [see Warnings and Precautions ( 5.3 )]. Consider the benefits and risks before neuraxial intervention in patients anticoagulated or to be anticoagulated [see Warnings and Precautions ( 5.3 )].

1 INDICATIONS AND USAGE

INDICATIONS & USAGE SECTION

2 DOSAGE AND ADMINISTRATION

DOSAGE & ADMINISTRATION SECTION

3 DOSAGE FORMS AND STRENGTHS

DOSAGE FORMS & STRENGTHS SECTION

150 mg capsules with a white to pale yellow pellets filled in HPMC capsule size “0EL” light navy blue opaque cap and light cream opaque body imprinted with “150” on body and “DAB” on cap in black ink. 110 mg capsules with a white to pale yellow pellets filled in HPMC capsule size "0" light blue opaque body and light blue opaque cap imprinted with "110" on body and "Dab" on cap in black ink. 75 mg capsules with a white to pale yellow pellets filled in HPMC capsule size “1” light cream opaque cap and light cream opaque body imprinted with “DAB” on cap and “75” on body in black ink.

4 CONTRAINDICATIONS

CONTRAINDICATIONS SECTION

Dabigatran Etexilate Capsules is contraindicated in patients with: • Active pathological bleeding [see Warnings and Precautions ( 5.2 ) and Adverse Reactions ( 6.1 )] • History of a serious hypersensitivity reaction to dabigatran, dabigatran etexilate, or to one of the excipients of the product (e.g., anaphylactic reaction or anaphylactic shock) [see Adverse Reactions ( 6.1 )] • Mechanical prosthetic heart valve [see Warnings and Precautions ( 5.4 )]

5 WARNINGS AND PRECAUTIONS

WARNINGS AND PRECAUTIONS SECTION

6 ADVERSE REACTIONS

ADVERSE REACTIONS SECTION

The following clinically significant adverse reactions are described elsewhere in the labeling: Increased Risk of Thrombotic Events after Premature Discontinuation [see Warnings and Precautions (5.1)] Risk of Bleeding [see Warnings and Precautions (5.2)] Spinal/Epidural Anesthesia or Puncture [see Warnings and Precautions (5.3)] Thromboembolic and Bleeding Events in Patients with Prosthetic Heart Valves [see Warnings and Precautions (5.4)] Increased Risk of Thrombosis in Patients with Triple-Positive Antiphospholipid Syndrome [see Warnings and Precautions (5.6)] The most serious adverse reactions reported with Dabigatran Etexilate Capsules were related to bleeding [see Warnings and Precautions (5.2)] .

7 DRUG INTERACTIONS

DRUG INTERACTIONS SECTION

8 USE IN SPECIFIC POPULATIONS

USE IN SPECIFIC POPULATIONS SECTION

10 OVERDOSAGE

OVERDOSAGE SECTION

Accidental overdose may lead to hemorrhagic complications. In the event of hemorrhagic complications, initiate appropriate clinical support, discontinue treatment with Dabigatran Etexilate Capsules, and investigate the source of bleeding. A specific reversal agent (idarucizumab) is available for adult patients. Dabigatran is primarily eliminated by the kidneys with a low plasma protein binding of approximately 35%. Hemodialysis can remove dabigatran; however, data supporting this approach are limited. Using a high-flux dialyzer, blood flow rate of 200 mL/min, and dialysate flow rate of 700 mL/min, approximately 49% of total dabigatran can be cleared from plasma over 4 hours. At the same dialysate flow rate, approximately 57% can be cleared using a dialyzer blood flow rate of 300 mL/min, with no appreciable increase in clearance observed at higher blood flow rates. Upon cessation of hemodialysis, a redistribution effect of approximately 7% to 15% is seen. The effect of dialysis on dabigatran’s plasma concentration would be expected to vary based on patient specific characteristics. Measurement of aPTT or ECT may help guide therapy [see Warnings and Precautions (5.2) and Clinical Pharmacology (12.2)].

11 DESCRIPTION

DESCRIPTION SECTION

The chemical name for dabigatran etexilate mesylate, a direct thrombin inhibitor, is β-Alanine, N-[[2-[[[4-[[[(hexyloxy)carbonyl]amino]iminomethyl]phenyl]amino]methyl]-1-methyl-1H-benzimidazol-5-yl]carbonyl]-N-2-pyridinyl-,ethyl ester, methanesulfonate. The empirical formula is C 34 H 41 N 7 O 5 ⋅ CH 4 O 3 S and the molecular weight is 723.86 (mesylate salt), 627.75 (free base). The structural formula is: Dabigatran etexilate mesylate is a white to pale yellow powder. A saturated solution in pure water has a solubility of 1.8 mg/mL. It is freely soluble in methanol, slightly soluble in ethanol, and sparingly soluble in isopropanol. Dabigatran Etexilate Capsules are supplied in 75 mg, 110 mg, and 150 mg strengths for oral administration. Each capsule contains dabigatran etexilate mesylate as the active ingredient: 150 mg dabigatran etexilate (equivalent to 172.95 mg dabigatran etexilate mesylate), 110 mg dabigatran etexilate (equivalent to 126.83 mg dabigatran etexilate mesylate), or 75 mg dabigatran etexilate (equivalent to 86.48 mg dabigatran etexilate mesylate) along with the following inactive ingredients: Butylated hydroxy toluene, citric acid monohydrate crystal, hydroxy propyl cellulose, hypromellose, hypromellose phthalate, macrogol, methacrylic acid copolymer, microcrystalline cellulose, polyethylene glycol 600, polyvinyl alcohol, povidone (k-value-25), sodium bicarbonate, talc, tartaric acid and titanium dioxide. The capsule shell is composed of hypromellose, titanium dioxide, FD&C red #40 & FD&C blue #1 (150 mg and 110 mg), FD&C yellow #6 (75 mg and 150 mg). The imprinting ink contains shellac, propylene glycol, strong ammonia solution, black iron oxide & potassium hydroxide.

12 CLINICAL PHARMACOLOGY

CLINICAL PHARMACOLOGY SECTION

13 NONCLINICAL TOXICOLOGY

NONCLINICAL TOXICOLOGY SECTION

14 CLINICAL STUDIES

CLINICAL STUDIES SECTION

16 HOW SUPPLIED/STORAGE AND HANDLING

HOW SUPPLIED SECTION

Dabigatran Etexilate Capsules 75 mg capsules have a light cream opaque cap and light cream opaque body imprinted with “DAB” on cap and “75” on body in black ink. The capsules are supplied in the packages listed: • NDC 67877-474-60 Unit of use bottle of 60 capsules Dabigatran Etexilate Capsules 110 mg capsules have a light blue opaque body and light blue opaque cap imprinted with "110" on body and "Dab" on cap in black ink. The capsules are supplied in the packages listed: • NDC 67877-624-60 Unit of use bottle of 60 capsules • NDC 67877-624-31 Blister package containing 60 (10 x 6) Unit-dose Capsules Dabigatran Etexilate Capsules 150 mg capsules have a light navy blue opaque cap and light cream opaque body imprinted with “150” on body and “DAB” on cap in black ink. The capsules are supplied in the packages listed: • NDC 67877-475-60 Unit of use bottle of 60 capsules Bottles Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature]. Once opened, the product must be used within 4 months. Keep the bottle tightly closed. Store in the original package to protect from moisture. Blisters Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature]. Store in the original package to protect from moisture. Keep out of the reach of children.

17 PATIENT COUNSELING INFORMATION

INFORMATION FOR PATIENTS SECTION

Advise the patient or caregiver to read the FDA-approved patient labeling (Medication Guide). Instructions for Patients Tell patients to take Dabigatran Etexilate Capsules exactly as prescribed. Remind patients not to discontinue Dabigatran Etexilate Capsules without talking to the healthcare provider who prescribed it. Keep Dabigatran Etexilate Capsules in the original bottle to protect from moisture. Do not put Dabigatran Etexilate Capsules in pill boxes or pill organizers. When more than one bottle is dispensed to the patient, instruct them to open only one bottle at a time. Instruct patient to remove only one capsule from the opened bottle at the time of use. The bottle should be immediately and tightly closed. Advise patients not to chew or break the capsules before swallowing them and not to open the capsules and take the pellets alone. Advise patients that the capsule should be taken with a full glass of water. [see Boxed Warning, Dosage and Administration (2.5)] Bleeding Inform patients that they may bleed more easily, may bleed longer, and should call their healthcare provider for any signs or symptoms of bleeding [see Warnings and Precautions (5.2)]. Instruct patients to seek emergency care right away if they have any of the following, which may be a sign or symptom of serious bleeding: Unusual bruising (bruises that appear without known cause or that get bigger) Pink or brown urine Red or black, tarry stools Coughing up blood Vomiting blood, or vomit that looks like coffee grounds Instruct patients to call their healthcare provider or to get prompt medical attention if they experience any signs or symptoms of bleeding: Pain, swelling or discomfort in a joint Headaches, dizziness, or weakness Reoccurring nose bleeds Unusual bleeding from gums Bleeding from a cut that takes a long time to stop Menstrual bleeding or vaginal bleeding that is heavier than normal If patients have had neuraxial anesthesia or spinal puncture, and particularly, if they are taking concomitant NSAIDs or platelet inhibitors, advise patients to watch for signs and symptoms of spinal or epidural hematoma, such as back pain, tingling, numbness (especially in the lower limbs), muscle weakness, and stool or urine incontinence. If any of these symptoms occur, advise the patient to contact his or her physician immediately [see Boxed Warning] . Gastrointestinal Adverse Reactions Instruct patients to call their healthcare provider if they experience any signs or symptoms of dyspepsia or gastritis: Dyspepsia (upset stomach), burning, or nausea Abdominal pain or discomfort Epigastric discomfort, GERD (gastric indigestion) [see Adverse Reactions (6.1)] Invasive or Surgical Procedures Instruct patients to inform their healthcare provider that they are taking Dabigatran Etexilate Capsules before any invasive procedure (including dental procedures) is scheduled [see Dosage and Administration (2.8)] . Concomitant Medications Ask patients to list all prescription medications, over-the-counter medications, or dietary supplements they are taking or plan to take so their healthcare provider knows about other treatments that may affect bleeding risk (e.g., aspirin or NSAIDs) or dabigatran exposure (e.g., dronedarone or systemic ketoconazole) [see Warnings and Precautions (5.2, 5.5)] . Prosthetic Heart Valves Instruct patients to inform their healthcare provider if they will have or have had surgery to place a prosthetic heart valve [see Warnings and Precautions (5.4)] . Allergic Reactions Advise adult patients and caregivers that some adults taking Dabigatran Etexilate Capsules have developed symptoms of an allergic reaction. Advise adult patients or caregivers to inform their healthcare provider if they develop symptoms of an allergic reaction, such as hives, rash, or itching. Advise adult patients or caregivers to seek emergency medical attention if they develop chest pain or tightness, swelling of the face or tongue, trouble breathing or wheezing, or feeling dizzy or faint. Pregnancy Advise patients to inform their healthcare provider immediately if they become pregnant or intend to become pregnant during treatment with Dabigatran Etexilate Capsules [see Use in Specific Populations (8.1)]. Lactation Advise patients not to breastfeed if they are taking Dabigatran Etexilate Capsules [see Use in Specific Populations (8.2)]. Pediatric use information is approved for Boehringer Ingelheim Pharmaceuticals, Inc.’s Pradaxa (dabigatran etexilate) capsules. However, due to Boehringer Ingelheim Pharmaceuticals, Inc.’s marketing exclusivity rights, this drug product is not labeled with that information. Manufactured by: Alkem Laboratories Ltd., INDIA. Distributed by: Ascend Laboratories, LLC Parsippany, NJ 07054 Revised: July 2024

MEDICATION GUIDE

SPL UNCLASSIFIED SECTION

Dabigatran Etexilate Capsules (DA-bi-GAT-ran e-TEX-i-late) This Medication Guide is for Dabigatran Etexilate Capsules. Read this Medication Guide before you start taking Dabigatran Etexilate Capsules and each time you get a refill. There may be new information. This Medication Guide does not take the place of talking with your healthcare provider about your medical condition or your treatment. What is the most important information I should know about Dabigatran Etexilate Capsules? People with atrial fibrillation (a type of irregular heartbeat) are at an increased risk of forming a blood clot in the heart, which can travel to the brain, causing a stroke, or to other parts of the body. Dabigatran Etexilate Capsules lowers your chance of having a stroke by helping to prevent clots from forming. If you stop taking Dabigatran Etexilate Capsules, you may have increased risk of forming a clot in your blood. Do not stop taking Dabigatran Etexilate Capsules without talking to the healthcare provider who prescribes it for you. Stopping Dabigatran Etexilate Capsules increases your risk of having a stroke. Dabigatran Etexilate Capsules may need to be stopped, if possible, before surgery or a medical or dental procedure. Ask the healthcare provider who prescribed Dabigatran Etexilate Capsules for you when you should stop taking it. Your healthcare provider will tell you when you may start taking Dabigatran Etexilate Capsules again after your surgery or procedure. If you have to stop taking Dabigatran Etexilate Capsules, your healthcare provider may prescribe another medicine to help prevent a blood clot from forming. Dabigatran Etexilate Capsules can cause bleeding which can be serious, and sometimes lead to death. This is because Dabigatran Etexilate Capsules is a blood thinner medicine that lowers the chance of blood clots forming in your body. You may have a higher risk of bleeding if you take Dabigatran Etexilate Capsules and : are over 75 years old have kidney problems have stomach or intestine bleeding that is recent or keeps coming back, or you have a stomach ulcer take other medicines that increase your risk of bleeding, including: aspirin or aspirin-containing products long-term (chronic) use of non-steroidal anti-inflammatory drugs (NSAIDs) a medicine that contains warfarin sodium a medicine that contains heparin a medicine that contains clopidogrel bisulfate a medicine that contains prasugrel have certain kidney problems and also take a medicine that contains dronedarone or ketoconazole tablets. Tell your healthcare provider if you take any of these medicines. Ask your healthcare provider or pharmacist if you are not sure if your medicine is one listed above. Dabigatran Etexilate Capsules can increase your risk of bleeding because it lessens the ability of your blood to clot. During treatment with Dabigatran Etexilate Capsules: o you may bruise more easily o it may take longer for any bleeding to stop Call your healthcare provider or get medical help right away if you have any of these signs or symptoms of bleeding: o unexpected bleeding or bleeding that lasts a long time, such as: unusual bleeding from the gums nose bleeds that happen often menstrual bleeding or vaginal bleeding that is heavier than normal o bleeding that is severe or you cannot control o pink or brown urine o red or black stools (looks like tar) o bruises that happen without a known cause or get larger o cough up blood or blood clots o vomit blood or your vomit looks like “coffee grounds” o unexpected pain, swelling, or joint pain o headaches, feeling dizzy or weak Take Dabigatran Etexilate Capsules exactly as prescribed. Do not stop taking Dabigatran Etexilate Capsules without first talking to the healthcare provider who prescribes it for you. Stopping Dabigatran Etexilate Capsules may increase your risk of a stroke. Spinal or epidural blood clots (hematoma). People who take a blood thinner medicine (anticoagulant) like Dabigatran Etexilate Capsules, and have medicine injected into their spinal and epidural area, or have a spinal puncture have a risk of forming a blood clot that can cause long-term or permanent loss of the ability to move (paralysis). Your risk of developing a spinal or epidural blood clot is higher if: o a thin tube called an epidural catheter is placed in your back to give you certain medicine o you take NSAIDs or a medicine to prevent blood from clotting o you have a history of difficult or repeated epidural or spinal punctures o you have a history of problems with your spine or have had surgery on your spine If you take Dabigatran Etexilate Capsules and receive spinal anesthesia or have a spinal puncture, your healthcare provider should watch you closely for symptoms of spinal or epidural blood clots. Tell your healthcare provider right away if you have back pain, tingling, numbness, muscle weakness (especially in your legs and feet), loss of control of the bowels or bladder (incontinence). See “What are the possible side effects of Dabigatran Etexilate Capsules?” for more information about side effects. What is Dabigatran Etexilate Capsules? Dabigatran Etexilate Capsules is a prescription medicine that is used to: in adults: reduce the risk of stroke and blood clots in adults who have a medical condition called atrial fibrillation that is not caused by a heart valve problem. With atrial fibrillation, part of the heart does not beat the way it should. This can lead to blood clots forming and increase your risk of a stroke. treat blood clots in the veins of your legs (deep vein thrombosis) and lungs (pulmonary embolism) after you have been treated with an injectable medicine to treat your blood clots for 5 to 10 days. reduce your risk of blood clots from happening again in the veins of your legs (deep vein thrombosis) and lungs (pulmonary embolism) after you have received treatment for blood clots. help prevent blood clots in your legs (venous thrombosis) and lungs (pulmonary embolism) after you have just had hip replacement surgery. It is not known if Dabigatran Etexilate Capsules are safe and effective in children with atrial fibrillation not caused by a heart valve problem, or in children who have undergone hip replacement surgery. Do not take Dabigatran Etexilate Capsules if you: currently have certain types of abnormal bleeding. Talk to your healthcare provider before taking Dabigatran Etexilate Capsules if you currently have unusual bleeding. have had a serious allergic reaction to any of the ingredients in Dabigatran Etexilate Capsules. See the end of this Medication Guide for a complete list of ingredients in Dabigatran Etexilate Capsules. Ask your healthcare provider Ask your healthcare provider if you are not sure. have ever had or plan to have a valve in your heart replaced with a mechanical (artificial) prosthetic heart valve Before taking Dabigatran Etexilate Capsules, tell your healthcare provider about all of your medical conditions, including if you: have kidney problems have ever had bleeding problems have ever had stomach ulcers have antiphospholipid syndrome (APS) are pregnant or plan to become pregnant. It is not known if Dabigatran Etexilate Capsules will harm your unborn baby. Tell your healthcare provider right away if you become pregnant during treatment with Dabigatran Etexilate Capsules. Females who are able to become pregnant: Talk with your healthcare provider about pregnancy planning during treatment with Dabigatran Etexilate Capsules. Talk with your healthcare provider about your risk for severe uterine bleeding if you are treated with blood thinner medicines, including Dabigatran Etexilate Capsules. are breastfeeding or plan to breastfeed. It is not known if Dabigatran passes into your breast milk. You should not breastfeed during treatment with Dabigatran Etexilate Capsules. Talk to your healthcare provider about the best way to feed your baby during treatment with Dabigatran Etexilate Capsules. Tell all of your healthcare pr...

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL

NDC 67877-474-60 Dabigatran Etexilate capsules 75 mg Rx Only 60 Capsules. NDC 67877-624-60 Dabigatran Etexilate capsules 110 mg Rx Only 60 Capsules. NDC 67877-475-60 Dabigatran Etexilate capsules 150 mg Rx Only 60 Capsules. NDC 67877-624-31 Dabigatran Etexilate capsules 110 mg Rx Only 60 Capsules (Carton Label)