Coreg Carvedilol: Side Effects, Uses, Dosage, Interactions, Warnings

In clinical trials of primarily mild‑to‑moderate heart failure, hypotension and postural hypotension occurred in 9.7% and syncope in 3.4% of subjects receiving COREG compared with 3.6% and 2.5% of placebo subjects, respectively. The risk for these events was highest during the first 30 days of dosing, corresponding to the up‑titration period and was a cause for discontinuation of therapy in 0.7% of subjects receiving COREG, compared with 0.4% of placebo subjects. In a long‑term, placebo‑controlled trial in severe heart failure (COPERNICUS), hypotension and postural hypotension occurred in 15.1% and syncope in 2.9% of heart failure subjects receiving COREG compared with 8.7% and 2.3% of placebo subjects, respectively. These events were a cause for discontinuation of therapy in 1.1% of subjects receiving COREG, compared with 0.8% of placebo subjects.

Therefore, this medication may be used if the potential benefits to the mother outweigh the potential risks to the unborn child. If peripheral vasodilation dominates, it may be necessary to administer adrenaline or noradrenaline with continuous monitoring of circulatory conditions. For therapy- resistant bradycardia, pacemaker therapy should be performed. For bronchospasm, β- sympathomimetics (as aerosol or IV) or aminophylline IV should be given. In the event of seizures, slow IV injection of diazepam or clonazepam is recommended. Carvedilol (12.5 mg twice daily) did not have an effect on the steady-state prothrombin time ratios and did not alter the pharmacokinetics of R(+)- and S(-)-warfarin following concomitant administration with warfarin in 9 healthy volunteers.

Drug-Drug Interactions

• It is recommended that blood glucose be monitored when carvedilol dosing is initiated, adjusted, or discontinued.
• Modest increases in mean trough cyclosporine concentrations were observed following initiation of carvedilol treatment in 21 renal transplant subjects suffering from chronic vascular rejection.
• Demethylation and hydroxylation at the phenol ring produce 3 active metabolites with β-receptor blocking activity.
• 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.

Respiratory problems, bronchospasms, vomiting, lapses of consciousness, and generalized seizures may also occur. There are no data on the presence of carvedilol in human milk, the effects on the breastfed infant, or the effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for COREG and any potential adverse effects on the breastfed infant from COREG or from the underlying maternal condition. Hypertension in pregnancy increases the maternal risk for pre-eclampsia, gestational diabetes, premature delivery, and delivery complications (e.g., need for cesarean section and post-partum hemorrhage). Hypertension increases the fetal risk for intrauterine growth restriction and intrauterine death. Pregnant women with hypertension should be carefully monitored and managed accordingly.

Drug Interactions

A total of 6,975 subjects with mild-to-severe heart failure were evaluated in placebocontrolled trials of carvedilol. COREG is rapidly and extensively absorbed following oral administration, with absolute bioavailability of approximately 25% to 35% due to a significant degree of first-pass metabolism. Following oral administration, the apparent mean terminal elimination half-life of carvedilol generally ranges from 7 to 10 hours.

• 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.
• COREG should be taken with food to slow the rate of absorption and reduce the incidence of orthostatic effects.
• Carvedilol was studied in 5 multicenter, placebo-controlled trials, and in 1 activecontrolled trial (COMET trial) involving subjects with mild-to-moderate heart failure.
• COREG is indicated for the management of essential hypertension see Clinical Studies.
• In animal studies, pregnant animals were given this medication and had some babies born with problems.
• Cimetidine increased AUC by about 30% but caused no change in Cmax see Clinical Pharmacology (12.5).

1 Clinical Studies Experience

Occasionally it is necessary to lower the carvedilol dose or temporarily discontinue it. Such episodes do not preclude subsequent successful titration of, or a favorable response to, carvedilol. In a placebo-controlled trial of subjects with severe heart failure, worsening heart failure during the first 3 months was reported to a similar degree with carvedilol and with placebo. When treatment was maintained beyond 3 months, worsening heart failure was reported less frequently in subjects treated with carvedilol than with placebo. Worsening heart failure observed during long-term therapy is more likely to be related to the patients’ underlying disease than to treatment with carvedilol. In clinical trials, COREG caused bradycardia in about 2% of hypertensive subjects, 9% of subjects with heart failure, and 6.5% of subjects with myocardial infarction and left ventricular dysfunction.

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Add your drug list to My Med List to view medical information in a simple, easy-to-read, personalized format. Automatically receive FDA alerts, drug interaction warnings, plus data on food, allergy & condition interactions. Do not drive a car, use machinery, or do anything that needs you to be alert if you have these symptoms. Consistent with its high degree of plasma protein‑binding, carvedilol does not appear to be cleared significantly by hemodialysis. COREG is indicated for the management of essential hypertension see Clinical Studies (14.3, 14.4).

Do not drive a car or operate machinery until you know how Coreg affects you. 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. In a pharmacokinetic trial synthroid ototoxicity conducted in 8 healthy male subjects, rifampin (600 mg daily for 12 days) decreased the AUC and Cmax of carvedilol by about 70% see Drug Interactions (7.5). In a pharmacokinetic trial conducted in 10 healthy male subjects, cimetidine (1,000 mg per day) increased the steady-state AUC of carvedilol by 30% with no change in Cmax see Drug Interactions (7.5). Β-blockers may enhance the blood-sugar-reducing effect of insulin and oral hypoglycemics.

In the case of Coreg, there are no specific foods that you must exclude from your diet when receiving this medication. COREG is a white, oval, film-coated tablet containing 3.125 mg, 6.25 mg, 12.5 mg, or 25 mg of carvedilol. Inactive ingredients consist of colloidal silicon dioxide, crospovidone, hypromellose, lactose, magnesium stearate, polyethylene glycol, polysorbate 80, povidone, sucrose, and titanium dioxide. None of the multicenter trials had NYHA classification as a primary end point, but all such trials had it as a secondary end point. There was at least a trend toward improvement in NYHA class in a l trials.

Following concomitant administration of carvedilol (25 mg once daily) and digoxin (0.25 mg once daily) for 14 days, steady-state AUC and trough concentrations of digoxin were increased by 14% and 16%, respectively, in 12 subjects with hypertension see DRUG INTERACTIONS. Carvedilol is subject to the effects of genetic polymorphism with poor metabolizers of debrisoquin (a marker for cytochrome P450 2D6) exhibiting 2- to 3-fold higher plasma concentrations of R(+)-carvedilol compared with extensive metabolizers. In contrast, plasma levels of S(-)-carvedilol are increased only about 20% to 25% in poor metabolizers, indicating this enantiomer is metabolized to a lesser extent by cytochrome P450 2D6 than R(+)-carvedilol.