Tramadol hydrochloride was administered to 550 patients during the double-blind or open-label extension periods in U.S. studies of chronic nonmalignant pain. Of these patients, 375 were 65 years old or older. TABLE 2 reports the cumulative incidence rate of adverse reactions by 7, 30 and 90 days for the most frequent reactions (5% or more by 7 days).

The most frequently reported events were in the central nervous system and gastrointestinal system. Although the reactions listed in the table are felt to be probably related to tramadol administration, the reported rates also include some events that may have been due to underlying disease or concomitant medication.

The overall incidence rates of adverse experiences in these trials were similar for tramadol and the active control groups, acetaminophen 300 mg with codeine phosphate 30 mg, and aspirin 325 mg with codeine phosphate 30 mg. (TABLE 2)

Incidence 1% To Less Than 5%, Possibly Casually Related: The following lists adverse reactions that occurred with an incidence of 1% to less than 5% in clinical trials, and for which the possibility of a casual relationship with tramadol exists.

Body as a Whole: Malaise.
Cardiovascular: Vasodilation.
Central Nervous System: Anxiety, Confusion, Coordination disturbance, Euphoria, Nervousness, Sleep disorder.
Gastrointestinal: Abdominal pain, Anorexia, Flatulence.
Musculoskeletal: Hypertonia.
Skin: Rash.
Special Senses: Visual disturbance.
Urogenital: Urinary retention, Urinary frequency, Menopausal symptoms.

Other Adverse Experiences, Causal Relationship Unknown: A variety of other adverse events were reported infrequently in patients taking tramadol during clinical trials and/or reported in post-marketing experience. A causal relationship between tramadol and these events has not been determined. However, the most significant events are listed below as alerting information to the physician.