Coreg: Uses, Taking, Side Effects, Warnings

Chronically administered β-blocking therapy should not be routinely withdrawn prior to major surgery; however, the impaired ability of the heart to respond to reflex adrenergic stimuli may augment the risks of general anesthesia and surgical procedures. COREG should not be given to patients with severe hepatic synthroid afib impairment see CONTRAINDICATIONS. Our Coreg Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication. HCTZ (hydrochlorothiazide) used to treat high blood pressure (hypertension) and edema.

Four U.S. multicenter, double‑blind, placebo‑controlled trials enrolled 1,094 subjects (696 randomized to carvedilol) with NYHA class II‑III heart failure and ejection fraction less than or equal to 0.35. The vast majority were on digitalis, diuretics, and an ACE inhibitor at trial entry. An Australia‑New Zealand double‑blind, placebo‑controlled trial enrolled 415 subjects (half randomized to carvedilol) with less severe heart failure. All protocols excluded subjects expected to undergo cardiac transplantation during the 7.5 to 15 months of double‑blind follow‑up.

Adverse Reactions/Side Effects

Plasma concentrations achieved are proportional to the oral dose administered. When administered with food, the rate of absorption is slowed, as evidenced by a delay in the time to reach peak plasma levels, with no significant difference in extent of bioavailability. Taking COREG with food should minimize the risk of orthostatic hypotension. COREG significantly reduced systemic blood pressure, pulmonary artery pressure, right atrial pressure, systemic vascular resistance, and heart rate, while stroke volume index was increased. Therefore, increased monitoring of digoxin is recommended when initiating, adjusting, or discontinuing COREG see CLINICAL PHARMACOLOGY. Modest increases in mean trough cyclosporine concentrations were observed following initiation of carvedilol treatment in 21 renal transplant subjects suffering from chronic vascular rejection.

1 CYP2D6 Inhibitors and Poor Metabolizers

Based on mean AUC data, approximately 40% to 50% higher plasma concentrations of carvedilol were observed in subjects with hypertension and moderate to severe renal impairment compared with a control group of subjects with hypertension and normal renal function. Changes in mean peak plasma levels were less pronounced, approximately 12% to 26% higher in subjects with impaired renal function. Due to the α1-receptor blocking activity of carvedilol, blood pressure is lowered more in the standing than in the supine position, and symptoms of postural hypotension (1.8%), including rare instances of syncope, can occur.

This information does not take the place of talking with your doctor about your medical condition or your treatment. Consistent with its high degree of plasma protein-binding, carvedilol does not appear to be cleared significantly by hemodialysis. Carvedilol was negative when tested in a battery of genotoxicity assays, including the Ames and the CHO/HGPRT assays for mutagenicity and the in vitro hamster micronucleus and in vivo human lymphocyte cell tests for clastogenicity. Β-adrenergic blockade may mask clinical signs of hyperthyroidism, such as tachycardia.

• A lower starting dose may be used (3.125 mg twice daily) and/or the rate of up-titration may be slowed if clinically indicated (e.g., due to low blood pressure or heart rate, or fluid retention).
• Treatment of the index infarction included aspirin (85%), IV or oral β‑blockers (37%), nitrates (73%), heparin (64%), thrombolytics (40%), and acute angioplasty (12%).
• DOSAGE MUST BE INDIVIDUALIZED AND CLOSELY MONITORED BY A PHYSICIAN DURING UP-TITRATION.
• If you stop taking COREG suddenly, you could have chest pain and/or a heart attack.

Other analyses not prospectively planned included the sum of deaths and total cardiovascular hospitalizations. In situations where the primary end points of a trial do not show a significant benefit of treatment, assignment of significance values to the other results is complex, and such values need to be interpreted cautiously. Carvedilol was studied in 5 multicenter, placebo‑controlled trials, and in 1 active- controlled trial (COMET trial) involving subjects with mild-to-moderate heart failure. A total of 6,975 subjects with mild-to-severe heart failure were evaluated in placebo- controlled trials of carvedilol.

As with other β-blockers, if COREG is administered with calcium channel blockers of the verapamil or diltiazem type, it is recommended that ECG and blood pressure be monitored. Rifampin reduced plasma concentrations of carvedilol by about 70% see CLINICAL PHARMACOLOGY. Cimetidine increased AUC by about 30% but caused no change in C see CLINICAL PHARMACOLOGY.

Coreg Interactions

Therefore, caution should be taken in the administration of carvedilol to patients suspected of having pheochromocytoma. Concomitant administration with a diuretic can be expected to produce additive effects and exaggerate the orthostatic component of carvedilol action. Other drugs may interact with carvedilol, including prescription and over-the-counter medicines, vitamins, and herbal products.

Following oral administration, when postural hypotension has occurred, it has been transient and is uncommon when COREG is administered with food at the recommended starting dose and titration increments are closely followed see Dosage and Administration (2). Two placebo‑controlled trials compared the acute hemodynamic effects of COREG with baseline measurements in 59 and 49 subjects with NYHA class II‑IV heart failure receiving diuretics, ACE inhibitors, and digitalis. There were significant reductions in systemic blood pressure, pulmonary artery pressure, pulmonary capillary wedge pressure, and heart rate. Initial effects on cardiac output, stroke volume index, and systemic vascular resistance were small and variable. In clinical trials of subjects with heart failure, subjects with bronchospastic disease were enrolled if they did not require oral or inhaled medication to treat their bronchospastic disease. In such patients, it is recommended that carvedilol be used with caution.

In 2-year studies conducted in rats given carvedilol at doses up to 75 mg per kg per day (12 times the MRHD as mg per m²) or in mice given up to 200 mg per kg per day (16 times the MRHD as mg per m²), carvedilol had no carcinogenic effect. Β-blockers can precipitate or aggravate symptoms of arterial insufficiency in patients with peripheral vascular disease. Starting with a low dose, administration with food, and gradual up-titration should decrease the likelihood of syncope or excessive hypotension see DOSAGE AND ADMINISTRATION . Therefore, in patients taking insulin or oral hypoglycemics, regular monitoring of blood glucose is recommended see WARNINGS AND PRECAUTIONS. Conduction disturbance (rarely with hemodynamic compromise) has been observed when COREG is coadministered with diltiazem.