New Warnings About Ultram

Tramadol HCl (Ultram) is a centrally acting synthetic analgesic that was approved by the FDA in March 1995 for the management of moderate to moderately severe pain.

April 1996, tramadol's manufacturer sent "Dear Doctor" letters to physicians and other health care professionals alerting them to new safety information for tramadol, including its potential association with abuse, seizures, and anaphy-lactoid reactions.

At that time, the FDA had received 83 domestic reports of seizures or convulsions in patients receiving tramadol.The information in the "Dear Doctor" letters was also published in leading medical and pharmacy association journals.

The incidence of seizures with tramadol use is estimated to be less than 1%. Postmarketing experience suggests that the risk of convulsions may be increased with doses above the recommended dosing range; however, events also have occurred after a single dose and within the recommended dosing range.

Postmarketing data also suggest that most patients who experienced seizures while taking tramadol had a predisposing risk factor for seizures.

These included concomitant administration of tricyclic antidepressants, selective serotonin reuptake inhibitors (SSRI's), monoamine oxidase inhibitors (MAOI's), neuroleptics (e.g., phenothiazines), and other drugs known to reduce the seizure threshold.

Patients with a history of seizures or who are at risk for seizure (eg, due to head trauma or metabolic disorders) may also be predisposed to seizures with tramadol use. Of the 83 spontaneous reports of seizure to the FDA, a medical history or information on drug use was available in 68% and 65% of cases, respectively. Of these, at least one of the risk factors described above was identified in 58% of cases.

Tramadol's product labeling has been revised to include new warnings on the potential for abuse, seizures, and anaphylactoid reactions. The dosing recommendations, however, have remained unchanged.

For most patients the recommendation is 50 to 100 mg every 4 to 6 hours up to a maximum of 400 mg/day. In patients with a creatinine clearance rate below 30 ml/min, the dosing interval should be increased to every 12 hours and the daily dose should not exceed 200 ma.

Patients with cirrhosis should receive 50 mg every 12 hours, and patients older than 75 years of age should not receive more than 300 mg/day.