Carvedilol

PD-Rx Pharmaceuticals, Inc.
PD-Rx Pharmaceuticals, Inc.

HIGHLIGHTS OF PRESCRIBING INFORMATION These highlights do not include all the information needed to use carvedilol safely and effectively. See full prescribing information for carvedilol tablets, USP. Carvedilol Tablets, USP Initial U.S. Approval: 1995 RECENT MAJOR CHANGES(5.9)(5.14)INDICATIONS AND USAGECarvedilol is an alpha/beta-adrenergic blocking agent indicated for the treatment of:  Left ventricular dysfunction following myocardial infarction in clinically stable patients (1.2) Hypertension (1.3) DOSAGE AND ADMINISTRATION Take with food. Individualize dosage and monitor during up-titration. (2) Left ventricular dysfunction following myocardial infarction: Start at 6.25 mg twice daily and increase to 12.5 mg then  25 mg twice daily after intervals of 3 to 10 days. A lower starting dose or slower titration may be used. (2.2) Hypertension: Start at 6.25 mg twice daily and increase if needed for blood pressure control to 12.5 mg then 25 mg twice daily over intervals of 1 to 2 weeks. (2.3) DOSAGE FORMS AND STRENGTHSTablets: 3.125 mg, 6.25 mg, 12.5 mg, or 25 mg (3) CONTRAINDICATIONS Bronchial asthma or related bronchospastic conditions (4) Second- or third-degree AV block (4) Sick sinus syndrome (4) Severe bradycardia (unless permanent pacemaker in place) (4) Patients in cardiogenic shock or decompensated heart failure requiring the use of IV inotropic therapy. (4) Severe hepatic impairment (2.4, 4) History of serious hypersensitivity reaction (e.g., Stevens-Johnson syndrome, anaphylactic reaction, angioedema) to any component of this medication or other medications containing carvedilol. (4) WARNINGS AND PRECAUTIONS Acute exacerbation of coronary artery disease upon cessation of therapy: Do not abruptly discontinue. (5.1) Bradycardia, hypotension, worsening heart failure/fluid retention may occur. Reduce the dose as needed. (5.2, 5.3, 5.4) Non-allergic bronchospasm (e.g., chronic bronchitis and emphysema): Avoid β-blockers. (4) However, if deemed necessary, use with caution and at lowest effective dose. (5.5) Diabetes: Monitor glucose as β-blockers may mask symptoms of hypoglycemia or worsen hyperglycemia. (5.6) Side EffectsMost common adverse events (6.1): Left ventricular dysfunction following myocardial infarction (≥10%): Dizziness, fatigue, hypotension, diarrhea, hyperglycemia, asthenia, bradycardia, weight increase Hypertension (≥5%): Dizziness To report SUSPECTED ADVERSE REACTIONS, contact Aurobindo Pharma USA, Inc. at 1-866-850-2876 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.DRUG INTERACTIONS CYP P450 2D6 enzyme inhibitors may increase and rifampin may decrease carvedilol levels. (7.1, 7.5) Hypotensive agents (e.g., reserpine, MAO inhibitors, clonidine) may increase the risk of hypotension and/or severe bradycardia. (7.2) Cyclosporine or digoxin levels may increase. (7.3, 7.4) Both digitalis glycosides and β-blockers slow atrioventricular conduction and decrease heart rate. Concomitant use can increase the risk of bradycardia. (7.4) Amiodarone may increase carvedilol levels resulting in further slowing of the heart rate or cardiac conduction. (7.6) Verapamil- or diltiazem-type calcium channel blockers may affect ECG and/or blood pressure. (7.7) Insulin and oral hypoglycemics action may be enhanced. (7.8)

FULL PRESCRIBING INFORMATION: CONTENTS*

• 1 CARVEDILOL INDICATIONS AND USAGE
  • 1.2 Left Ventricular Dysfunction Following Myocardial Infarction
  • 1.3 Hypertension
• 2 CARVEDILOL DOSAGE AND ADMINISTRATION
  • 2.2 Left Ventricular Dysfunction Following Myocardial Infarction
  • 2.3 Hypertension
  • 2.4 Hepatic Impairment
• 3 DOSAGE FORMS AND STRENGTHS
• 4 CARVEDILOL CONTRAINDICATIONS
• 5 WARNINGS AND PRECAUTIONS
  • 5.1 Cessation of Therapy
  • 5.2 Bradycardia
  • 5.3 Hypotension
  • 5.4 Heart Failure/Fluid Retention
  • 5.5 Non-allergic Bronchospasm
  • 5.6 Glycemic Control in Type 2 Diabetes
  • 5.7 Peripheral Vascular Disease
  • 5.8 Deterioration of Renal Function
  • 5.9 Major Surgery
  • 5.10 Thyrotoxicosis
  • 5.11 Pheochromocytoma
  • 5.12 Prinzmetal’s Variant Angina
  • 5.13 Risk of Anaphylactic Reaction
  • 5.14 Intraoperative Floppy Iris Syndrome
• 6 CARVEDILOL ADVERSE REACTIONS
  • 6.1 Clinical Studies Experience
  • 6.2 Laboratory Abnormalities
  • 6.3 Postmarketing Experience
• 7 DRUG INTERACTIONS
  • 7.1 CYP2D6 Inhibitors and Poor Metabolizers
  • 7.2 Hypotensive Agents
  • 7.3 Cyclosporine
  • 7.4 Digitalis Glycosides
  • 7.5 Inducers/Inhibitors of Hepatic Metabolism
  • 7.6 Amiodarone
  • 7.7 Calcium Channel Blockers
  • 7.8 Insulin or Oral Hypoglycemics
  • 7.9 Anesthesia
• 8 USE IN SPECIFIC POPULATIONS
  • 8.1 Pregnancy
  • 8.3 Nursing Mothers
  • 8.4 Pediatric Use
  • 8.5 Geriatric Use
• 10 OVERDOSAGE
• 11 CARVEDILOL DESCRIPTION
• 12 CLINICAL PHARMACOLOGY
  • 12.1 Mechanism of Action
  • 12.2 Pharmacodynamics
  • 12.3 Pharmacokinetics
  • 12.4 Specific Populations
  • 12.5 Drug-Drug Interactions
• 13 NONCLINICAL TOXICOLOGY
  • 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
• 14 CLINICAL STUDIES
  • 14.2 Left Ventricular Dysfunction Following Myocardial Infarction
  • 14.3 Hypertension
  • 14.4 Hypertension With Type 2 Diabetes Mellitus
• 16 HOW SUPPLIED/STORAGE AND HANDLING
• 17 PATIENT COUNSELING INFORMATION
  • 17.1 Patient Advice
• 17.2 FDA-Approved Patient Labeling
• PACKAGE LABEL-PRINCIPAL DISPLAY PANEL - 6.25 mg (1000 Tablet Bottle)

FULL PRESCRIBING INFORMATION

1 INDICATIONS AND USAGE

1.2 Left Ventricular Dysfunction Following Myocardial Infarction

1.3 Hypertension

2 DOSAGE AND ADMINISTRATION

2.2 Left Ventricular Dysfunction Following Myocardial Infarction

2.3 Hypertension

2.4 Hepatic Impairment

3 DOSAGE FORMS AND STRENGTHS

4 CONTRAINDICATIONS

• Bronchial asthma or related bronchospastic conditions. Deaths from status asthmaticus have been reported following single doses of carvedilol tablets.
• Second- or third-degree AV block
• Sick sinus syndrome
• Severe bradycardia (unless a permanent pacemaker is in place)
• Patients with cardiogenic shock or who have decompensated heart failure requiring the use of intravenous inotropic therapy. Such patients should first be weaned from intravenous therapy before initiating carvedilol tablets.
• Patients with severe hepatic impairment
• Patients with a history of a serious hypersensitivity reaction (e.g., Stevens-Johnson syndrome, anaphylactic reaction, angioedema) to any component of this medication or other medications containing carvedilol.

5 WARNINGS AND PRECAUTIONS

5.1 Cessation of Therapy

5.2 Bradycardia

5.3 Hypotension

5.4 Heart Failure/Fluid Retention

5.5 Non-allergic Bronchospasm

5.6 Glycemic Control in Type 2 Diabetes

5.7 Peripheral Vascular Disease

5.8 Deterioration of Renal Function

5.9 Major Surgery

5.10 Thyrotoxicosis

5.11 Pheochromocytoma

5.12 Prinzmetal’s Variant Angina

5.13 Risk of Anaphylactic Reaction

5.14 Intraoperative Floppy Iris Syndrome

6 ADVERSE REACTIONS

6.1 Clinical Studies Experience

6.2 Laboratory Abnormalities

6.3 Postmarketing Experience

7 DRUG INTERACTIONS

7.1 CYP2D6 Inhibitors and Poor Metabolizers

7.2 Hypotensive Agents

7.3 Cyclosporine

7.4 Digitalis Glycosides

7.5 Inducers/Inhibitors of Hepatic Metabolism

7.6 Amiodarone

7.7 Calcium Channel Blockers

7.8 Insulin or Oral Hypoglycemics

7.9 Anesthesia

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

8.3 Nursing Mothers

8.4 Pediatric Use

8.5 Geriatric Use

10 OVERDOSAGE

11 DESCRIPTION

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

12.2 Pharmacodynamics

12.3 Pharmacokinetics

12.4 Specific Populations

12.5 Drug-Drug Interactions

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

14 CLINICAL STUDIES

14.2 Left Ventricular Dysfunction Following Myocardial Infarction

14.3 Hypertension

14.4 Hypertension With Type 2 Diabetes Mellitus

In a double-blind study (GEMINI), carvedilol, added to an ACE inhibitor or angiotensin receptor blocker, was evaluated in a population with mild-to-moderate hypertension and well-controlled type 2 diabetes mellitus. The mean HbA1c at baseline was 7.2%. Carvedilol was titrated to a mean dose of 17.5 mg twice daily and maintained for 5 months. Carvedilol had no adverse effect on glycemic control, based on HbA1c measurements (mean change from baseline of 0.02%, 95% CI -0.06 to 0.1, p = NS) [see Warnings and Precautions (5.6)].

16 HOW SUPPLIED/STORAGE AND HANDLING

17 PATIENT COUNSELING INFORMATION

17.1 Patient Advice

• Patients should take carvedilol with food.
• Patients should not interrupt or discontinue using carvedilol without a physician’s advice.
• Patients should consult their physician if they experience signs or symptoms of worsening heart failure such as weight gain or increasing shortness of breath.
• Patients may experience a drop in blood pressure when standing, resulting in dizziness and, rarely, fainting. Patients should sit or lie down when these symptoms of lowered blood pressure occur.
• If experiencing dizziness or fatigue, patients should avoid driving or hazardous tasks.
• Patients should consult a physician if they experience dizziness or faintness, in case the dosage should be adjusted.
• Diabetic patients should report any changes in blood sugar levels to their physician.
• Contact lens wearers may experience decreased lacrimation.

17.2 FDA-Approved Patient Labeling

• To treat patients who had a heart attack that worsened how well the heart pumps
• To treat patients with high blood pressure (hypertension)

• Have severe heart failure and are hospitalized in the intensive care unit or require certain intravenous medications that help support circulation (inotropic medications)
• Are prone to asthma or other breathing problems
• Have a slow heartbeat or a heart that skips a beat (irregular heartbeat)
• Have liver problems
• Are allergic to any of the ingredients in carvedilol tablets. The active ingredient is carvedilol. See the end of this leaflet for a list of all the ingredients in carvedilol tablets.

• Have asthma or other lung problems (such as bronchitis or emphysema)
• Have problems with blood flow in your feet and legs (peripheral vascular disease) carvedilol tablets can make some of your symptoms worse.
• Have diabetes
• Have thyroid problems
• Have a condition called pheochromocytoma
• Have had severe allergic reactions
• Are pregnant or trying to become pregnant. It is not known if carvedilol tablets are safe for your unborn baby. You and your doctor should talk about the best way to control your high blood pressure during pregnancy.
• Are breastfeeding. It is not known if carvedilol passes into your breast milk. You should not breastfeed while using carvedilol tablets.
• Are scheduled for surgery and will be given anesthetic agents
• Are scheduled for cataract surgery and have taken or are currently taking carvedilol tablets.
• Are taking prescription or non-prescription medicines, vitamins, and herbal supplements. Carvedilol tablets and certain other medicines can affect each other and cause serious side effects. Carvedilol tablets may affect the way other medicines work. Also, other medicines may affect how well carvedilol tablets work.

• Take carvedilol tablets exactly as prescribed. Your doctor will tell you how many tablets to take and how often. In order to minimize possible side effects, your doctor might begin with a low dose and then slowly increase the dose.
• Do not stop taking carvedilol tablets and do not change the amount of carvedilol tablets you take without talking to your doctor.
• Tell your doctor if you gain weight or have trouble breathing while taking carvedilol tablets.
• Take carvedilol tablets with food.
• If you miss a dose of carvedilol tablets, take your dose as soon as you remember, unless it is time to take your next dose. Take your next dose at the usual time. Do not take 2 doses at the same time.
• If you take too much carvedilol, call your doctor or poison control center right away.

• Low blood pressure (which may cause dizziness or fainting when you stand up). If these happen, sit or lie down right away and tell your doctor.
• Tiredness. If you feel tired or dizzy you should not drive, use machinery, or do anything that needs you to be alert.
• Slow heartbeat.
• Changes in your blood sugar. If you have diabetes, tell your doctor if you have any changes in your blood sugar levels.
• Carvedilol tablets may hide some of the symptoms of low blood sugar, especially a fast heartbeat.
• Carvedilol tablets may mask the symptoms of hyperthyroidism (overactive thyroid).
• Worsening of severe allergic reactions.
• Rare but serious allergic reactions (including hives or swelling of the face, lips, tongue, and/or throat that may cause difficulty in breathing or swallowing) have happened in patients who were on carvedilol tablets. These reactions can be life-threatening.

• Store carvedilol tablets at 20 to 25°C (68 to 77°F). Keep the tablets dry.
• Safely, throw away carvedilol tablets that are out of date or no longer needed.
• Keep carvedilol tablets and all medicines out of the reach of children.

PACKAGE LABEL-PRINCIPAL DISPLAY PANEL - 6.25 mg (1000 Tablet Bottle)

Carvedilol Tablets, USP
6.25 mg
Pharmacist: Dispense the accompanying
Patient Information Leaflet to each patient.
Rx only           1000 Tablets

Carvedilol Carvedilol TABLET, FILM COATED Product Information Product Type Human prescription drug label Item Code (Source) NDC:43063-127(NDC:13107-143) Route of Administration ORAL DEA Schedule Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength Carvedilol CARVEDILOL 6.25 mg Inactive Ingredients Ingredient Name Strength lactose monohydrate SILICON DIOXIDE CROSPOVIDONE POVIDONE K30 SUCROSE MAGNESIUM STEARATE polyethylene glycol 400 polysorbate 80 titanium dioxide Hypromellose 2910 (5 Mpa.s) Product Characteristics Color Size Imprint Code Shape WHITE (White to Off-white) 8 mm E;02 OVAL Packaging # Item Code Package Description Marketing Start Date Marketing End Date 1 NDC:43063-127-93 180 in 1 BOTTLE, PLASTIC Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date ANDA ANDA078332 2009-03-23