How is pradaxa supplied

Increased risk of serious bleeding. Suspend treatment before invasive therapy or surgery, including dental procedures see full labeling ; restart promptly. Bioprosthetic heart valve or triple-positive antiphospholipid syndrome: not recommended. Monitor renal function prior to initiation, then periodically as clinically indicated; discontinue if acute renal failure develops and consider alternate therapy.

Avoid lapses in therapy. Severe renal impairment. Females of reproductive potential. Tell your healthcare provider about all your medical conditions, including if you have kidney problems, bleeding problems, stomach ulcers, or have antiphospholipid syndrome APS.

Tell your healthcare provider if you are pregnant or plan to become pregnant. Tell your healthcare provider if you are a female who is able to become pregnant. Talk with your healthcare provider about your risk for severe bleeding from the uterus if you are treated with blood thinner medicines, including PRADAXA.

Tell your healthcare provider if you are breastfeeding or plan to breastfeed. It is important to tell your healthcare provider about all medicines prescription and over-the-counter , vitamins, and supplements you take.

The half-life of dabigatran in healthy subjects is 12 to 17 hours. After oral administration, dabigatran etexilate is converted to dabigatran. The cleavage of the dabigatran etexilate by esterase-catalyzed hydrolysis to the active principal dabigatran is the predominant metabolic reaction.

Dabigatran is not a substrate, inhibitor, or inducer of CYP enzymes. Dabigatran is subject to conjugation forming pharmacologically active acyl glucuronides. Renal Impairment. An open, parallel-group single-center study compared dabigatran pharmacokinetics in healthy subjects and patients with mild to moderate renal impairment receiving a single dose of PRADAXA mg.

Based on pharmacokinetic modeling, estimated exposure to dabigatran increases with the severity of renal function impairment Table 3. Similar findings were observed in the RE-LY trial. Hepatic Impairment. Administration of PRADAXA in patients with moderate hepatic impairment Child-Pugh B showed a large inter-subject variability, but no evidence of a consistent change in exposure or pharmacodynamics.

Drug Interactions. By Day 7 after cessation of rifampin treatment, dabigatran exposure was close to normal [see Warnings and Precautions 5. In studies with the P-gp inhibitors ketoconazole, amiodarone, verapamil, and quinidine, the time to peak, terminal half-life, and mean residence time of dabigatran were not affected.

Any observed changes in C max and AUC are described below. Dronedarone : Exposure to dabigatran is higher when it is administered with dronedarone than when it is administered alone 1. Verapamil : When dabigatran etexilate was coadministered with oral verapamil, the C max and AUC of dabigatran were increased. The extent of increase depends on the formulation of verapamil and timing of administration. If verapamil is present in the gut when dabigatran is taken, it will increase exposure to dabigatran with the greatest increase observed when a single dose of immediate-release verapamil is given one hour prior to dabigatran AUC increased by a factor of 2.

If verapamil is given 2 hours after dabigatran, the increase in AUC is negligible. In the population pharmacokinetics study from RE-LY, no important changes in dabigatran trough levels were observed in patients who received verapamil.

In the population pharmacokinetics study from RE-LY, no important changes in dabigatran trough levels were observed in patients who received amiodarone. Quinidine : Quinidine was given as mg dose every 2 hours up to a total dose of mg. Dabigatran etexilate was given over 3 consecutive days, the last evening dose on Day 3 with or without quinidine pre-dosing. Clarithromycin: Coadministered clarithromycin had no impact on the exposure to dabigatran.

The concomitant administration of dabigatran etexilate and clopidogrel resulted in no further prolongation of capillary bleeding times compared to clopidogrel monotherapy.

Diclofenac, Ranitidine, and Digoxin: None of these drugs alters exposure to dabigatran. In RE-LY, dabigatran plasma samples were also collected. The concomitant use of proton pump inhibitors, H2 antagonists, and digoxin did not appreciably change the trough concentration of dabigatran. Impact of Dabigatran on Other Drugs.

In clinical studies exploring CYP3A4, CYP2C9, P-gp and other pathways, dabigatran did not meaningfully alter the pharmacokinetics of amiodarone, atorvastatin, clarithromycin, diclofenac, clopidogrel, digoxin, pantoprazole, or ranitidine. Dabigatran was not carcinogenic when administered by oral gavage to mice and rats for up to 2 years.

Dabigatran was not mutagenic in in vitro tests, including bacterial reversion tests, mouse lymphoma assay and chromosomal aberration assay in human lymphocytes, and the in vivo micronucleus assay in rats. The clinical evidence for the efficacy of PRADAXA was derived from RE-LY Randomized Evaluation of Long-term Anticoagulant Therapy , a multi-center, multi-national, randomized parallel group trial comparing two blinded doses of PRADAXA mg twice daily and mg twice daily with open-label warfarin dosed to target INR of 2 to 3 in patients with non-valvular, persistent, paroxysmal, or permanent atrial fibrillation and one or more of the following additional risk factors:.

The primary objective of this study was to determine if PRADAXA was non-inferior to warfarin in reducing the occurrence of the composite endpoint, stroke ischemic and hemorrhagic and systemic embolism. Statistical superiority was also analyzed. A total of 18, patients were randomized and followed for a median of 2 years.

Thirty-two percent of the population had never been exposed to a VKA. The contributions of the components of the composite endpoint, including stroke by subtype, are shown in Table 5. The treatment effect was primarily a reduction in stroke. Centers were ranked post hoc by the percentage of time that warfarin-treated patients were in therapeutic range INR 2 to 3.

The color of the imprinting is black. The capsules are supplied in the packages listed:. Once opened, the product must be used within 30 days. In the studies The study was designed as an open-label, randomized, parallel-group, non-inferiority study.

Patients enrolled were randomized according to a scheme to either an age-appropriate formulation capsules, oral pellets, or oral solution of PRADAXA doses adjusted for age and weight after at least 5 days and no longer than 21 days of treatment with a parenteral anticoagulant, or to SOC comprised of low molecular weight heparins LMWH or vitamin K antagonists VKA or fondaparinux.

Inability to achieve target, after one up-titration, resulted in premature termination of study drug in 12 patients 6. The median treatment duration during the treatment period was 85 days. The efficacy of PRADAXA was established based on a composite endpoint of patients with complete thrombus resolution, freedom from recurrent venous thromboembolic event, and freedom from mortality related to venous thromboembolic event composite primary endpoint.

Of the randomized patients, 81 patients Subgroup analyses showed that there were no outliers in the treatment effect for the subgroups by age, sex, region, and presence of certain risk factors central venous line, congenital heart disease, malignant disease. Patients who required further anticoagulation due to the presence of a clinical risk factor after completing the initial treatment for confirmed VTE for at least 3 months or after completing the DIVERSITY study were included in the study.

Eligible patients received age- and weight adjusted doses of an age-appropriate formulation capsules or oral pellets of PRADAXA until the clinical risk factor resolved, or up to a maximum of 12 months. The primary endpoints of the study included the recurrence of VTE, major and minor bleeding events, and mortality overall and related to thrombotic or thromboembolic events at 6 and 12 months. The overall probability of being free from recurrence of VTE during the on-treatment period was 0.

The probability of being free from bleeding events during the on-treatment period was 0. No on-treatment deaths occurred. The color of the imprinting is black. The capsules are supplied in the packages listed:. Once opened, the product must be used within 4 months. Keep the bottle tightly closed. Store in the original package to protect from moisture. 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.

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:.

Instruct patients to call their healthcare provider or to get prompt medical attention if they experience any signs or symptoms of bleeding:. 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 ]. Instruct patients to call their healthcare provider if they experience any signs or symptoms of dyspepsia or gastritis:. Instruct patients to inform their healthcare provider that they are taking PRADAXA before any invasive procedure including dental procedures is scheduled [see Dosage and Administration 2. 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.

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. Advise adult patients or caregivers to inform their healthcare provider if they or their child develop symptoms of an allergic reaction, such as hives, rash, or itching. Advise adult patients or caregivers to seek emergency medical attention if they or their child develop chest pain or tightness, swelling of the face or tongue, trouble breathing or wheezing, or feeling dizzy or faint.

Distributed by: Boehringer Ingelheim Pharmaceuticals, Inc. Pradaxa capsules are NOT substitutable on a mg-to-mg basis with other dabigatran etexilate dosage forms.

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Approval: 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 PRADAXA and neuraxial procedures is not known [see Warnings and Precautions 5.

Table 1 Weight-Based PRADAXA Capsules Dosing for Pediatric Patients Aged 8 to Less Than 18 Years Actual Weight kg Dose mg Number of Capsules Needed 11 kg to less than 16 kg 75 mg twice daily one 75 mg capsule twice daily 16 kg to less than 26 kg mg twice daily one mg capsule twice daily 26 kg to less than 41 kg mg twice daily one mg capsule twice daily or two 75 mg capsules twice daily 41 kg to less than 61 kg mg twice daily one mg capsule plus one 75 mg capsule twice daily 61 kg to less than 81 kg mg twice daily two mg capsule twice daily 81 kg or greater mg twice daily one mg capsule plus one mg capsule twice daily or one mg capsule plus two 75 mg capsules twice daily.

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. Major bleeding events within each subcategory were counted once per patient, but patients may have contributed events to multiple subcategories. In case of recurrent events of the same category, the first event was considered.

Major Bleeding c 3. Patients can have more than one site of bleeding. Hypersensitivity Reactions In the 4 pivotal studies, drug hypersensitivity including urticaria, rash, and pruritus , allergic edema, anaphylactic reaction, and anaphylactic shock were reported in 0. Hypersensitivity Reactions In the two studies, drug hypersensitivity such as urticaria, rash, and pruritus was reported in 0.

Clinical Myocardial Infarction Events In the two studies, clinical myocardial infarction was reported in 2 0. Labor or delivery All patients receiving anticoagulants, including pregnant women, are at risk for bleeding. The structural formula is: Dabigatran etexilate mesylate is a yellow-white to yellow powder. Pediatrics As in adults, there is a correlation between plasma dabigatran concentrations and the degree of its anticoagulant effect in pediatric patients with venous thromboembolism.

Cardiac Electrophysiology No prolongation of the QTc interval was observed with dabigatran etexilate at doses up to mg. Elimination Dabigatran is eliminated primarily in the urine.

Metabolism After oral administration, dabigatran etexilate is converted to dabigatran. Renal Impairment An open, parallel-group, single-center study compared dabigatran pharmacokinetics in healthy adult subjects and adult patients with mild to moderate renal impairment receiving a single dose of PRADAXA Capsules mg.

Dosing recommendations in subjects with severe renal impairment are based on pharmacokinetic modeling [see Dosage and Administration 2. Drug Interactions A summary of the effect of coadministered drugs on dabigatran exposure in healthy adult subjects is shown in Figures 3. In the orthopedic hip surgery patients, limited clinical data with P-gp inhibitors is available. Impact of Dabigatran on Other Drugs In clinical studies exploring CYP3A4, CYP2C9, P-gp and other pathways, dabigatran did not meaningfully alter the pharmacokinetics of amiodarone, atorvastatin, clarithromycin, diclofenac, clopidogrel, digoxin, pantoprazole, or ranitidine.

For patients with multiple events each event is counted independently. Primary Composite Endpoint b 26 1. Primary Composite Endpoint b 3 0. 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. 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. 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.

Invasive or Surgical Procedures Instruct patients to inform their healthcare provider that they are taking PRADAXA before any invasive procedure including dental procedures is scheduled [see Dosage and Administration 2. 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.

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. This Medication Guide has been approved by the U. Food and Drug Administration.

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.

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.