Rockville, MD - The US Food and Drug Administration (FDA) has approved safety labeling revisions describing the use of carvedilol (Coreg, GlaxoSmithKline) tablets in diabetic patients and the risk for potentially fatal hyperthyroidism-related thyrotoxicosis and/or arrhythmia in patients receiving treatment with amiodarone (Cordarone, Wyeth) tablets or intravenous infusion.

On August 28, 2006, the FDA approved safety labeling changes for the use of carvedilol in diabetic patients.

In general, -adrenergic blockers can mask some manifestations of hypoglycemia, particularly tachycardia; nonselective -blockers such as carvedilol can also potentiate insulin-induced hypoglycemia and delay recovery of serum glucose levels. The FDA advises that patients subject to spontaneous hypoglycemia and diabetics receiving insulin/oral hypoglycemic drugs be warned of these possibilities.

According to previously existing statements in the drug's labeling, which have not changed under the current revisions, in diabetic patients with congestive heart failure, carvedilol therapy is linked to a risk of worsening hyperglycemia, which responds to increased hypoglycemic therapy. Monitoring of blood glucose levels is therefore advised on initiation, adjustment, or discontinuation of carvedilol therapy in diabetic patients.

The FDA notes that no studies have been conducted to determine the effects of carvedilol on glycemic control in diabetic patients with heart failure. However, a trial of carvedilol added to an angiotensin-converting-enzyme (ACE) inhibitor or angiotensin-receptor blocker (ARB) in patients with mild to moderate hypertension and well-controlled type 2 diabetes (the GEMINI study) showed that the drug had no adverse effects on glycemic control, as evaluated by changes from baseline HbA1_c at five months (0.02%; 95% CI -0.06 to 0.10; p>0.05).

On August 28, 2006, the FDA approved safety labeling revisions for amiodarone HCl to warn of the risk for potentially fatal hyperthyroidism-related thyrotoxicosis and/or arrhythmia associated with its use.

Amiodarone inhibits peripheral conversion of thyroxine (T4) to triiodothyronine (T3) and may cause increased T4 levels, decreased T3 levels, and increased levels of inactive reverse T3 (rT3) in clinically euthyroid patients; it is also a potential source of large amounts of inorganic iodine. Because of iodine release or perhaps for other reasons, amiodarone can cause either hypothyroidism or hyperthyroidism.

Thyroid function should be monitored before treatment and periodically thereafter, particularly in elderly patients and in those with a history of thyroid nodules, goiter, or other thyroid dysfunction. Because of the slow elimination of amiodarone and its metabolites, high plasma iodide levels, altered thyroid function, and abnormal thyroid-function tests can persist for several weeks or months after discontinuation of therapy.

Although hyperthyroidism occurs in approximately 2% of amiodarone-treated patients, its incidence is increased among those with prior inadequate dietary iodine intake. Amiodarone-induced hyperthyroidism can lead to thyrotoxicosis and/or arrhythmia breakthrough or aggravation, all of which can be fatal. The FDA advises that hyperthyroidism be considered if any new signs of arrhythmia appear during treatment.

The condition is best identified by relevant signs and symptoms, which are usually accompanied by abnormal increases in serum T3 radioimmunoassay, further elevations of serum T4, and subnormal serum thyroid-stimulating-hormone (TSH) levels. In equivocal cases, a flat TSH response to thyrotropin-releasing hormone may be used as a confirmatory test. Because of the risk for arrhythmia breakthroughs, aggressive medical treatment is indicated, and amiodarone dosing should be reduced or discontinued if possible. The FDA notes that the action of antithyroid agents may be delayed due to substantial amounts of preformed hormones stored in the gland.

Surgical management may be an option in patients who fail to respond to aggressive treatment of amiodarone-induced thyrotoxicosis or who are unable to discontinue use of the drug. The FDA notes that because experience with thyroidectomy for this indication is limited and could induce thyroid storm, careful surgical and anesthetic planning is warranted.