Coreg SIDE EFFECTS Congestive Heart Failure Coreg has been evaluated for safety in congestive heart failure in more than 1,900 patients worldwide of whom 1,300 participated in U.S.clinical trials. Approximately 54% of the total treated population received Coreg for at least 6 months and 20% received Coreg for at least 12 months. The adverse experience profile of Coreg in congestive heart failure patients was consistent with the pharmacology of the drug and the health status of the patients. In U.S.clinical trials comparing Coreg in daily doses up to 100 mg (n=765) to placebo (n=437), 5.4% of Coreg patients discontinued for adverse experiences vs. 8.0% of placebo patients. Table 1 shows adverse events in U.S.placebo-controlled clinical trials of congestive heart failure patients that occurred with an incidence of greater than 2% regardless of causality and were more frequent in drug-treated patients than placebo-treated patients. Median study medication exposure was 6.33 months for both Coreg (carvedilol) and placebo patients. Table 1 Adverse Events in U. S. Placebo-Controlled Congestive Heart Failure Trials Incidence >2%, Regardless of Causality; Withdrawal Rates due to Adverse Events,   Adverse REACTIONS Withdrawals   Coreg (n=765) Placebo (n= 437) Coreg (n=765) Placebo (n=437)   % occurrence % occurrence % withdrawals % withdrawals  Autonomic Nervous System Sweating inceased 2.8 2.1      Body as a Whole Fatigue 23.9 22.4 5.7 0.7 Chest pain 14.4 14.2 0.1   Pain 8.6 7.6   0.2 Injury 5.9 5.5     Drug levels increased 5.1 3.7   0.2 Edema generalized 5.1 2.5     Edema dependent 3.7 1.8     Fever 3.1 2.3     Edema legs 22 0.2 0.1 0.2  Cardiovascular Bradycardia 8.8 8.8 0.8 — Hypotension 0.5 3.4 0.4 0.2 Syncope 3.4 2.5 0.3 0.2 Hypertension; 2.9 2.5 0.1 — AV block 29 0.5 —   Angina pectoris aggravated 2.0 1.1 — —  Central Nervous System Dizziness 32.4 19.2 0.4 — Headache 8.1 7.1 0.3   Paresthesia 2.0 1.8 0.1 —  Gastrointestinal Diarrhea 11.8 5.9 0.3 — Nausea 8.5 4.8 — — Abdominal pain 7.2 7.1 0.3 — Vomiting 6.3 4.3 0.1 —  Hemotologic Thrombocytopenia 2.0 0.5 0.1 —  Metabolic Hyperglycemia 12.2 7.8 0.1 — Weight increase 8.7 6.8 0.1 0.5 Gout 6.3 6.2 — — BUN increased 0.0 4.6 0.3 0.2 NPN increased 5.0 4.0 0.3 0.2 Hypercholesterolemia 4.1 2.5 — — Dehydration 2.1 1.6 — — Hypervolemia 2.0 0.9 — —  Musculoskeletal >Back pain 6.9 6.6 — — Arthralgia 6.4 4.8 0.1 0.2 Myalgia 3.4 2.7 — —  Resistance Mechanism Upper respiratory tract infection 18.3 17.6 — — Infection 2.2 0.9 — —  Respiratory Sinusitis 5.4 4.3 — — Bronchitis 5.4 3.4 — 0.2 Pharyngitis 3.1 2.7 — —  Urinary/Renal Urinary tract infection 3.1 2.7   — Hematuria 2.9 2.1 — —  Vision  Vision abnormal 5.0 1.8 0.1 — Incidence >2%, Regardless of Causality; Withdrawal Rates due to Adverse Events In addition to the events in Table 1, asthenia, cardiac failure, flatulence, anorexia, dyspepsia, palpitation, extrasystoles, hyperkalemia, arthritis, angina pectoris, insomnia, depression, anemia, viral infection, dyspnea, coughing, respiratory disorder, rhinitis, rash, and leg cramps were also reported; but rates were equal to, or more common in, placebo-treated patients. The following adverse events were reported more frequently with Coreg in U.S.placebo-controlled trials in patients with congestive heart failure: Incidence >1% to <2% Body as a Whole: Peripheral edema, allergy, sudden death, malaise, hypovolemia. Cardiovascular: Fluid overload, postural hypotension. Central and Peripheral Nervous System: Hypesthesia, vertigo. Gastrointestinal: Melena, periodontitis. Liver and Biliary System: SGPT increased, SGOT increased. Metabolic and Nutritional: Hyperuricemia, hypoglycemia, hyponatremia, increased alkaline phosphatase, glycosuria. Platelet, Bleeding and Clotting: Prothrombin decreased, purpura. Psychiatric: Somnolence. Reproductive, male: Impotence. Urinary System: Abnormal renal function, albuminuria. POSTMARKETING EXPERIENCE The following adverse reaction has been reported in post-marketing experience: reports of aplastic anemia have been rare and received only when carvedilol was administered concomitantly with other medications associated with the event. Hypertension Coreg (carvedilol) has been evaluated for safety in hypertension in more than 2,193 patients in U.S.clinical trials and in 2,976 patients in international clinical trials. Approximately 36% of the total treated population received Coreg for at least 6 months. In general, Coreg was well tolerated at doses up to 50 mg daily. Most adverse events reported during Coreg therapy were of mild to moderate severity. In U.S.controlled clinical trials directly comparing Coreg monotherapy in doses up to 50 mg (n=1,142) to placebo(n=462), 4.9% of Coreg patients discontinued for adverse events vs. 5.2% of placebo patients. Although there was no overall difference in discontinuation rates, discontinuations were more common in the carvedilol group for postural hypotension (1% vs.0). The overall incidence of adverse events in U.S. placebo-controlled trials was found to increase with increasing dose of Coreg. For individual adverse events this could only be distinguished for dizziness, which increased in frequency from 2% to 5% as total daily dose increased from 6.25 mg to 50 mg. Table 2 shows adverse events in U.S. placebo-controlled clinical trials for hypertension that occurred with an incidence of greater than 1 % regardless of causality, and that were more frequent in drug-treated patients than placebo-treated patients. Table 2 Adverse Events in U.S.Placebo-Controlled Hypertension Trials Incidence >1%, Regardless of Causality; Withdrawal Rates due to Adverse Events   Adverse REACTIONS Withdrawals   Coreg (n=1,142) Placebo (n=462) Coreg (n=1,142) Placebo (n=462)   % occurrence % occurrence % withdrawals % withdrawals  Body as a Whole Fatigue 4.3 3.9 0.3 5.2 Injury 2.9 2.5 1.1 —  Cardiovascular Bradycardia 21 0.2 0.4 — Postural hypertension 1.8   0.1 — Dependent edema 1.7 1.5 5.1 0.4 Peripheral edema 1.4 0.4 0.2 —  Central Nervous System Dizziness 5.2 5.4 0.4 1.3 Insomnia 1.6 0.6 — 0.2 Somnolence 1.8 1.5 — —  Gastrointestinal Abdominal pain 1.4 1.3 0.1 — Diarrhea 2.2 1.3 0.1 —   Hematological Thrombocytopenia 1.1 5.2 — —  Metabolic Hypertriglyceridemia 1.2 0. 2 — —  Musculoskeletal Back pain 2.3 1.5 0.1 —  Resistance Mechanism Upper respiratory tract infection 1.8 1.3 — —  Respiratory Rhinitis 2.1 1.9   — Pharyngitis 1.5 0.6     Dyspnea 1.4 0.9 5.4 1.2  Urinary/Renal Urinary tract infection 1.8 0.6 — — In addition to the events in Table 2, chest pain, dyspesia, headache, nausea, pain, sinusitis and upper respiratory tract infection were also reported, but rates were at least as great in placebo-treated patients. The following adverse events were reported as possibly or probably related in worldwide open or controlled trials with Coreg (carvedilol), in patients with hypertension or congestive heart failure. Incidence > 0.1% to £1% Cardiovascular: Peripheral ischemia, tachycardia. Central and Peripheral Nervous System: Hypokinesia. Gastrointestinal: Bilirubinemia, increased hepatic enzymes (0.2% of hypertension patients and 0.4% of congestive heart failure patients were discontinued from therapy because of increases in hepatic enzymes; see WARNINGS, Hepatic Injury). General: Substernal chest pain, edertia. Psychiatric: Nervousness, sleep disorder, aggravated depression, impaired concentration, abnormal thinking, paranoia, emotional lability. Respiratory System: Asthma (see CONTRAINDICATIONS). Reproductive: Male; decreased libido. Skin and Appendages: Prucitua, rash erythematous, rash maculopapular, rash psoriaform, photosensitivity reaction. Special Senses: Tinnitus. Urinary System: Micturition frequency. Autonomic Nervous System: Dry mouth, sweating increased. Metabolic and Nutritional: Hypokalemia, diabetes mellitus hypertriglyceridemia. Hemetologic: Anemia, leukopenia. The following events were reported in 30.1% of patients and are potentially important: complete AV block, bundle branch block, myocardial ischemia, cerebrovascular disorder, convulsions, migraine, neuralgia, paresia, anaphylactoid reaction, alopecia, exfoliative dermatitis, amnesia, GI hemorrhage, bronchospasm, pulmonary edema, decreased hearing, respiratory alkalosia, increased BUN, decreased HDL, pancytopenia and atypical lymphocytes. Other adverse events occurred sporadically in single patients and can not be distinguished from concurrent disease states or medications. Coreg therapy has not been associated with clinically significant changes in routine laboratory tests in hypertensive patients. No clinically relevant changes were noted in serum potassium, tasting serum glucose, total triglycerides, total cholesterol, HDL cholesterol, uricacid, blood urea nitrogen or creatinine. DRUG INTERACTIONS (Also see CLINICAL PHARMACOLOGY, Pharmacokinetic Drug-Drug Interactions.) Inhibitors of CYP2D6: poor metabolizers of debrisoquin: Interactions of carvedilol with strong inhibitors of CYP2D6 leuch as quinidine, fluoxetine, paroxetine, and propafen-one) have not been studied, but these drugs would be expected to increse blood levels of the R(+) enantiomer of carvedilol (see CLINICAL PHARMACOLOGY). Retrospective analysis of side effects in clinical trials showed that poor 2D6 metabolizers had a higher rate of dizziness during up-titration, presumably resulting from vasodilating effects of the higher concentrations of the b-blocking R(+) enantiomer Catecholamine-depleting agents: Patients taking both agents with b-blocking properties and a drug that can deplete catecholamines (e.g., reserpine and monoamine oxidase inhibitors) should be observed closely for signs of hypotension and/or severe bradycardia. Clonidine: Concomitant administration of clonidine With agents with b-blocking properties may potentiate blood-pressure-end heart-rate-lowering effects. When concomitant treatment with agents with b-blocking properties end clonidine is to be terminated, the b-blocking agent should be discontinued first. Clonidine therapy can then be discontinued several days later by gradually decreasing the dosage. Digoxin: Digoxin concentrations are increased by about 15% when digoxin and carvedilol are administered concomitantly. Both digoxin and Coreg AV conduction. Therefore, increased monitoring of digoxin is recommended when initiating, adjusting or discontinuing Coreg. Inducers and inhibitors of hepatic metabolism: Rifampin reduced plasma concentrations of carvedilol by about 70%. Cimetidine increased AUC by about 30% but caused no change in Cmax. Calcium channel blockers: Isolated cases of conduction disturbance (rarely with hemodynamic compromise) have been observed when Coreg is co-administered with diltiazem. As with other agents with b-blocking properties, if Coreg (carvedilol) is to be administered orally with calcium channel blockers of the verapamil or diltiazemtype, it is recommended that ECG and blood pressure be monitored. Insulin or oral hypoglycemics: Agents with b-blocking properties may enhance the blood-sugar-reducing effect of insulin and oral hypoglycemics. Therefore, inpatients taking insulin or oral hypoglycemics, regular monitoring of blood glucose is recommended. Buy Coreg Now   Buy Coreg Now