Caution needed with nelfinavir and some lipid-lowering drugs

Protease inhibitors can increase levels of lipids, including cholesterol and triglycerides, in the blood, increasing the risk of heart disease. To help reduce the risk of this complication, doctors often encourage their patients to exercise regularly, stop smoking and make changes to their diet. If these changes do not help, doctors then prescribe lipid-lowering drugs, commonly called statins.

Because statins and PIs are often processed by the same enzymes in the gut and liver, these two groups of drugs can interact. Specifically, PIs have the potential to raise or lower levels of statins in the blood, and vice versa. This interaction can increase the risk of new side effects or make pre-existing side effects worse. It is also possible that the effectiveness of PIs can be reduced because of drug interaction(s). To find out about possible drug interactions between PIs and statins, researchers in the US conducted small, short studies on 32 healthy, HIV negative subjects (16 female, 16 male) who were given one of the following statins for one month: atorvastatin (Lipitor) – 10 mg/day; simvastatin (Zocor) – 20 mg/day

After taking one of these drugs for two weeks, subjects also received nelfinavir 1,250 mg twice daily for 14 days. All drugs were taken with food.

Results – statins

The researchers found that there were indeed interactions between nelfinavir and the statins. In the case of atorvastatin, the amount of this drug that was absorbed nearly doubled when it was taken with nelfinavir. When simvastatin was taken with nelfinavir, levels of this statin in the blood were six times greater than when it was not taken with nelfinavir. Levels of these drugs in the blood did not differ between females and males.

Results – nelfinavir

Nelfinavir levels in the blood were not affected by the use of either statin. According to the researchers, the most commonly reported side effect of nelfinavir was diarrhoea – 53% of subjects reported this problem.

What to do

Statins can cause a range of side effects including fatigue and, more seriously, a form of muscle damage called rhabdomyolysis. To reduce the risk of developing this painful complication, the manufacturer of nelfinavir suggests that simvastatin not be used by people who are taking nelfinavir. They also suggest that if atorvastatin is prescribed for nelfinavir-users, it should be used with caution, starting at the lowest dose of 10 mg/day.

Comment

These data on nelfinavir and statins was previously presented at the 40th ICAAC, Toronto, September 2000, (presentation 425). It should be remembered that interactions with statins is a feature of the whole class of currently marketed protease inhibitors and caution should be observed with all PI’s coadministered with statins.

Further information and data are available from the excellent HIV drug interactions website provided by the Liverpool HIV Pharmacology Group.

Hsyu P-H, Schultz-Smith MD, Lillibridge JH, et al. Pharmacokinetic interactions between nelfinavir and 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors atorvastatin and simvastatin. Antimicrobial Agents and Chemotherapy 2001; 45(12): 3445-3450.

Source: CATIE – Canadian AIDS Treatment Information Exchange. For more information visit CATIE’s Information Network at