Protease inhibitors (PIs) are often used as part of combination therapy for people with HIV/AIDS (PHAs). Examples of protease inhibitors include the following:

• amprenavir (Agenerase)
• indinavir (Crixivan)
• lopinavir (Kaletra)
• nelfinavir (Viracept)
• ritonavir (Norvir)
• saquinavir (Fortovase)

One of the side effects associated with this group of drugs is that they can increase levels of fatty substances in the blood, known as lipids, including cholesterol and triglycerides. Increased levels of these lipids raise 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 U.S. 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 Lipitor, the amount of this drug that was absorbed nearly doubled when it was taken with nelfinavir. When Zocor 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 diarrhea -- 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 Zocor not be used by people who are taking nelfinavir. They also suggest that if Lipitor is prescribed for nelfinavir-users, it should be used with caution, starting at the lowest dose -- 10 mg/day.

References

1. Penzak S, Chuck SK, Stajich GV. Safety and efficacy of HMG-CoA reductase inhibitors for treatment of hyperlipidemia in patients with HIV infection. Pharmacotherapy 2000, 20:1066-1071.

2. 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.