Tramadol (Tramal®) is a centrally acting analgesic which has been available in Australia for four years. Although chemically unrelated to the opiates, it stimulates opioid receptors and inhibits noradrenaline and serotonin uptake.

The Australian Adverse Drug Reactions Committee (ADRAC) has received 354 reports associated with tramadol. The most common reactions include nausea, vomiting, sweating, dizziness, rash, tremor and headache. The more serious adverse reactions reported are:

For the cases of convulsions, the median time to onset was 2 (range 1-19) days. Tramadol was the only suspected drug in 11 cases, but in 14 other cases the patient was taking additional drugs which may lower the seizure threshold, including propofol, bupropion, hydrocortisone, morphine, and tricyclic antidepressants. One patient had a history of epilepsy, and was also taking carbamazepine and phenytoin.

Tramadol may cause serotonin syndrome, particularly when it is used at high doses or in combination with other agents increasing serotonin levels (1). In 16 of the 20 cases, the patient was taking potentially interacting medicines including moclobemide, SSRIs, tricyclic antidepressants, sibutramine and St John's wort. Increases in hepatic enzymes were reported in 10 cases. One patient developed hepatic failure and died. All times to onset were short (range 1-19 days; median 9 days).

Tramadol may interact with warfarin to decrease prothrombin activity, although the mechanism is unknown (2). ADRAC has received five reports of this interaction. Monitoring should be considered when tramadol is started in patients taking warfarin. Although tramadol acts on opioid receptors, dependence and abuse appear to be rare (3). ADRAC has, however, received 11 reports of withdrawal symptoms with tramadol.

The use of tramadol has increased rapidly, with dispensings of oral formulations rising from 23 000 in 2000 to 580 000 in 2001 and over 1 100 000 in 2002. Prescribers should be alert to the more serious adverse reactions, especially those of a neuropsychiatric nature (4).

References

1. ADRAC. Tramadol and serotonin syndrome. Australian Adverse Drug Reactions Bulletin, 21: 14 (2001).

2. Sabbe, J.R., Sims, P.J., Sims, M.H. Tramadol-warfarin interaction. Pharmacotherapy, 18: 871-873 (1998).

3. FDA Committee. FDC ('Pink Sheets') Prescription Pharmaceuticals and Biotechnology, 60(18): 4-5 (1998).

4. ADRAC. Tramadol - Four years' experience. Australian Adverse Drug Reactions Bulletin, 22(1): 2 (2003).