FDA Safety Changes: Ultram ER, Reyataz, Duragesic

July 9, 2008 — The US Food and Drug Administration (FDA) has approved safety labeling revisions to advise of drug interactions that can increase the risk for serotonin syndrome in patients receiving tramadol HCl, drug interactions between atazanavir sulfate and various agents in the statin drug class, drug interactions with fentanyl, and adverse events associated with improper use of fentanyl patches.

Tramadol HCl (Ultram ER) Drug Interactions Increase Risk for Serotonin Syndrome

On February 20, the FDA approved safety labeling revisions for tramadol HCl extended-release tablets (Ultram ER; Biovail Laboratories, Inc) to warn of the risk for potentially life-threatening serotonin syndrome associated with all tramadol products.

The risk for serotonin syndrome may be increased with concomitant use of serotonergic drugs, such as selective serotonin reuptake inhibitors (eg, escitalopram), serotonin-norepinephrine reuptake inhibitors, tricyclic antidepressants, monoamine oxidase inhibitors (MAOIs, including the reversible nonselective MAOI linezolid), and triptans; drugs that impair serotonin metabolism (including MAOIs); and those that reduce tramadol metabolic clearance, such as cytochrome P 450 isoenzyme 2D6 inhibitors (eg, quinidine, fluoxetine, paroxetine, and amitryptyline) and cytochrome P 450 isoenzyme 3A4 inhibitors (eg, ketoconazole and erythromycin).

Because these drug interactions may lead to the development of serotonin syndrome at recommended tramadol doses, coadministration of drugs that affect the serotonergic neurotransmitter system should be approached with caution. If combination therapy is clinically warranted, the patient should be carefully monitored, particularly during initiation of therapy and dose increases.

Symptoms of serotonin syndrome may include mental status changes (eg, agitation, hallucinations, and coma), autonomic instability (eg, tachycardia, labile blood pressure, and hyperthermia), neuromuscular aberrations (eg, hyperreflexia and incoordination), and gastrointestinal tract symptoms (eg, nausea, vomiting, and diarrhea).

Tramadol is a centrally acting synthetic analgesic. In its extended-release formulation, tramadol is indicated for the management of moderate to moderately severe chronic pain in adults who require around-the-clock treatment of their pain for an extended period.

Source:

1. FDA Safety Changes: Ultram ER, Reyataz, Duragesic