Side-effects

Common side-effects reported from studies of tipranavir (Aptivus) include diarrhoea, nausea, tiredness, headache, vomiting and stomach cramps. Participants on the highest dose tested of 2000mg three times a day reported vertigo, mood alterations, slowed thinking and movement, and lack of concentration, which resolved when the drug was stopped .

In BI 1182, high rates of gastrointestinal side-effects were reported: 59% of patients experienced diarrhoea and 31% reported nausea. Around 20% experienced substantial blood triglyceride elevations. In the RESIST trials, serious (grade 3 or 4) liver toxicity was observed in 10% of tipranavir-treated patients, and developed more quickly than in patients taking other protease inhibitors. Similar effects were seen for fat and cholesterol elevations.

The United States Food and Drug Administration has called for more studies into these effects in order to guide use of the drug, and it has warned that liver function testing should be performed at initiation of tipranavir therapy and monitored throughout treatment. One small study has suggested that a dose adjustment is not necessary in patients with mild or moderate liver impairment, but more research is needed.¹ However, tipranavir should be used with caution in patients with elevated liver enzymes or hepatitis B or C.

Boehringer Ingelheim has also warned of the risk of rash developing in patients taking tipranavir, particularly in those with a sulphonamide allergy. This risk of rash developing may be increased by the oral contraceptive ethinylestradiol.

The relatively high rates of side-effects seen in patients in the RESIST trials may be due to the 200mg dose of ritonavir required for dosing, at least in part. This drawback may well restrict tipranavir’s use to highly treatment-experienced patients until side-effects can be reduced.

In July 2006, Boehringer Ingelheim issued a warning that 14 cases of bleeding within the skull had been seen among a total of 6840 patients taking the drug. The bleeding occurred a median of 525 days after starting the drug. Eight of the patients died. Since all of the patients had other risk factors for this bleeding, including surgery, injury or other conditions or medications that can cause bleeding, the company advises that patients with these risk factors should take ritonavir-boosted tipranavir with caution.