FDA Safety Changes: Aristospan, Videx/Videx EC, Coreg/Coreg ER

Yael Waknine

July 22, 2009

This activity is part of an ongoing CME/CE initiative to provide information on labeling changes reported by the FDA. Activities of this nature will be posted on Medscape on a weekly basis.

July 22, 2009 — The US Food and Drug Administration (FDA) has approved safety labeling revisions to warn against use of high-dose triamcinolone hexacetonide injection in the setting of traumatic brain injury, drug interactions with didanosine, and the rare risk for hypersensitivity reactions to carvedilol therapy.

High-Dose Corticosteroids Linked to Mortality Risk in Patients With Traumatic Brain Injury

On June 3, the FDA approved safety labeling revisions for triamcinolone hexacetonide injectable suspension (Aristospan; Sandoz, Inc) to warn against use of high corticosteroid doses in the treatment of traumatic brain injury.

The warning was based on data from a multicenter randomized, placebo-controlled study of the intravenous corticosteroid methylprednisolone hemisuccinate, showing an increase in early (at 2 weeks) and late (at 6 months) mortality rates in patients with cranial trauma who had no other clear indications for anti-inflammatory corticosteroid therapy.

Intralesional administration of triamcinolone hexacetonide is indicated for alopecia areata; discoid lupus erythematosus; keloids; localized hypertrophic, infiltrated, inflammatory lesions of granuloma annulare, lichen planus, lichen simplex chronicus (neurodermatitis), and psoriatic plaques; and necrobiosis lipoidica diabeticorum. The product may also be useful in cystic tumors of an aponeurosis or tendon (ganglia).

Didanosine Oral Solution and Delayed-Release Capsules (Videx, Videx EC) Linked to Drug Interactions

On June 10, the FDA approved revisions to the safety labeling for didanosine oral solution and delayed-release capsules (Videx and Videx EC; Bristol-Myers Squibb Co) to warn of drug interactions.

Coadministration of allopurinol is contraindicated because of increases in didanosine exposure that raise the risk for toxicity, the agency advised.

Coadministration of didanosine and ribavirin is likewise contraindicated because of increased exposure to the active didanosine metabolite dideoxyadenosine 5'-triphosphate. According to the FDA, fatal hepatic failure, peripheral neuropathy, pancreatitis, and symptomatic hyperlactatemia/lactic acidosis have been reported in patients receiving this drug combination.

The FDA also warned that concomitant use of methadone and didanosine oral solution is linked to a significant decrease in didanosine levels and therapeutic efficacy. If coadministration of methadone is necessary, didanosine delayed-release capsules should be used to mitigate this effect, and patients should be closely monitored for adequate clinical response in HIV RNA viral load.

Didanosine is a nucleoside reverse transcriptase inhibitor for use in combination with other antiretroviral agents for the treatment of HIV-1 infection.

Carvedilol Tablets and Controlled-Release Tablets (Coreg, Coreg CR) Linked to Rare Hypersensitivity Reactions

On June 23, the FDA approved revisions to the safety labeling for carvedilol tablets and carvedilol phosphate extended-release tablets (Coreg and Coreg CR; GlaxoSmithKline) to warn of the risk for hypersensitivity reactions.

The FDA has received rare reports of hypersensitivity reactions (eg, anaphylactic reaction, angioedema, and urticaria) in patients receiving carvedilol therapy, including those switching from the immediate-release to the extended-release formulation.

Use of carvedilol is contraindicated in patients with a history of serious hypersensitivity reactions (eg, Stevens-Johnson syndrome, anaphylactic reaction, or angioedema) to carvedilol or carvedilol-containing products.

The FDA notes that patients receiving beta-blocker therapy with a history of severe anaphylactic reaction to a variety of allergens may be more reactive to repeated challenge, whether accidental, diagnostic, or therapeutic. Such patients may be unresponsive to the usual doses of epinephrine used to treat allergic reactions.

Carvedilol is an alpha/beta-adrenergic blocking agent indicated for the treatment of mild to severe chronic heart failure, left ventricular dysfunction after a myocardial infarction in clinically stable patients, and hypertension.

Aristospan Prescribing Information

Videx Prescribing Information

Videx EC Prescribing Information

Coreg Prescribing Information

Coreg CR Prescribing Information


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