Withdrawn drugs

All of the following drugs were withdrawn or had their licence removed because of

cardiovascular adverse effects at therapeutic doses EXCEPT which one?

a) Cisapride

b) Aprotinin

c) Droperidol

d) Co-proxamol

e) Rofecoxib

Answer: d

Explanation

Cisapride was withdrawn in 2000. This prokinetic agent was found to prolong the QT

interval and had been associated with 125 reported fatalities worldwide. The risks

were thought to outweigh the benefits. Aprotinin was withdrawn from the formulary

in 2008. A 2006 study by Mangano et al. demonstrated a doubling in the incidence of

serious renal damage. Congestive heart failure increased by 50% and strokes by 180%.

This was followed up by the BART study, which was halted following demonstration

of significantly increased mortality in the aprotonin-treated group. Droperidol is a

dopamine receptor antagonist that also prolongs the QT interval. It was withdrawn in

the UK in 2001 and has remained so up to the time of going to press. It is, however,

currently being relaunched throughout Europe. Co-proxamol is a combination of

paracetamol and dextropropoxyphene. It causes respiratory depression and cardiac

arrhythmias in overdose. It has some undesirable non-cardiovascular adverse effects at

therapeutic doses, such as dizziness and dependence, and some undesirable drug

interactions, such as with carbamazepine. Rofecoxib was removed from the formulary

in one of the most expensive drug withdrawals ever. Worldwide turnover of rofecoxib

in the year prior to withdrawal had exceeded $2 billion. The VIGOR study and the

APPROVE study demonstrated an increase in stroke and myocardial infarction in

patients on rofecoxib.

References

Mangano DT, Tudor IC, Dietzel C. The risk associated with aprotinin in cardiac

surgery. N Engl J Med 2006; 354(4): 353–65.

BART Investigators. A comparison of aprotinin and lysine analogues in high-risk

cardiac surgery. N Engl J Med 2008; 358(22): 2319–31. Online at http://content.nejm.

org/cgi/content/full/358/22/2319 (Accessed 30 October 2009)