GlaxoSmithKline and Flamel Technologies' Coreg CR

Coreg CR (carvedilol phosphate) hashas received approval from the FDA.The extended-release capsules areindicated for the treatment of 3 cardiovascularconditions in adults: hypertension,left ventricular (LV) dysfunctionafter myocardial infarction (MI), andheart failure.¹

Although immediate-release carvedilolalready is marketed for the sameindications as Coreg CR, its twice-dailyadministration may be inconvenient forsome patients. Coreg CR is promoted toimprove patient adherence and to offera simplified treatment regimen throughits once-daily dosing. Coreg CR's once-dailyadministration is due to Flamel'sunique Micropump technology.¹

Carvedilol exerts its cardiovasculareffects through nonselective ?-adrenoreceptorblocking activity and a₁-adrenergic blocking activity.²

Clinical Trials

The Carvedilol or Metoprolol EuropeanTrial study evaluated more than3000 patients with heart failure, comparingthe use of carvedilol with theuse of metoprolol. The carvedilol groupwas found to live 1.4 years longer thanthe metoprolol group.

The Carvedilol Post-Infarct SurvivalControl in Left Ventricular Dysfunctiontrial studied carvedilol against placeboin 1959 patients with a recent MI andan LV ejection fraction of =40%. Mortalitywas found to be reduced by 23%in the carvedilol group.

The use of carvedilol in hypertensionwith concomitant diabetes wasevaluated in a trial called Comparing theGlycemic Effects of Carvedilol andMetoprolol in High Blood PressurePatients with Diabetes. The double-blindtrial studied carvedilol in additionto an angiotensin-converting enzymeinhibitor or an angiotensin receptorblocker in well-controlled type 2 diabeticpatients with mild-to-moderatehypertension. The study found thatcarvedilol lowered blood pressurewithout affecting blood glucose levels,lipids, or weight gain.^1,2

Safety

Coreg CR is contraindicated in patientswith a history of hypersensitivity tocarvedilol or its components, bronchialasthma or related conditions, second-orthird-degree atrioventricular block, sicksinus syndrome, severe bradycardiawithout a pacemaker, or cardiogenicshock, or in decompensated patientsusing intravenous inotropic treatment.

Patients with severe hepatic impairmentalso should not use Coreg CR.Patients with coronary artery diseasewho are using Coreg CR shouldbe warned against sudden discontinuationof treatment, which may result ina severe angina exacerbation, MI, orventricular arrhythmia. Discontinuationof Coreg CR, if appropriate, should occurover 1 to 2 weeks and under thesupervision of a health care provider.

Coreg CR should be used cautiouslyin patients with peripheral vascular disease,diabetes, hyperthyroidism, or nonallergicbronchospasm or in patients undergoinganesthesia or major surgery.²

Dose

The dose of Coreg CR is highly individualizedand often requires carefultitration for the treatment of heart failure,LV dysfunction following MI, orhypertension.

Patients already using immediate-releasecarvedilol may be converted toCoreg CR based on the following scale:

?3.125 mg 2?/day (6.25 mg total)converts to 10 mg 1?/day Coreg CR

?6.25 mg 2?/day (12.5 mg total) convertsto 20 mg 1?/day Coreg CR

?12.5 mg 2?/day (25 mg total) convertsto 40 mg 1?/day Coreg CR

?25 mg 2?/day (50 mg total) convertsto 80 mg 1?/day Coreg CR²

Patient Education

Coreg CR always should be takenwith food and never within 2 hours ofalcohol.

Pharmacists should advise patientsusing the medication to contact theirdoctor if signs of worsening heart failureoccur, such as weight gain or shortnessof breath. Patients should usecaution on standing, because dizzinessor fainting may occur. If these conditionsoccur and they are bothersome,they should be reported to a physician.

As a class,?-blockers may masksigns of hypoglycemia and may potentiatethe hypoglycemic effect of insulin.Any changes in blood glucose levelsshould be reported to a physician.

Side effects of Coreg CR may includeshortness of breath, decreased heartrate, weight gain, fatigue, hypotension,dizziness, or fainting.^1,2 Patients usingcontact lenses may notice decreasedlacrimation. Patients, however, nevershould discontinue Coreg CR treatmentwithout a physician's advice.

Dr. Holmberg is a pharmacist withPhoenix Children's Hospital, Phoenix,Ariz.

References

1. FDA approves new, once-a-day Coreg CR for the treatment of three keycardiovascular conditions. Available at: http://us.gsk.com/news/archive.htm. AccessedJanuary 2007.2. Coreg CR Complete Prescribing Information. Available at:http://us.gsk.com/products/assets/us_coregcr.pdf. Accessed January 2007.