Invirase – brand name

saquinavir – generic name

Invirase belongs to a class of HIV drugs called protease inhibitors (PIs).

The PIs block protease, a protein that HIV needs to make more copies of itself. Blocking this protein may slow down HIV disease.

The Food and Drug Administration (FDA) has approved Invirase for use in combination with other anti-HIV drugs for the treatment of HIV infection in adults and adolescents over 16 years old.

Invirase comes in:

• 200 mg and 500 mg hard-gel capsules

Invirase should be taken with low “boosting” doses of Norvir/ritonavir. The recommended dose is:

• Two 500 mg Invirase capsules plus one 100mg Norvir capsule twice a day (There are other possible combinations of Invirase and Norvir – check with your doctor).  If you are having trouble taking Norvir, your doctor may discuss combining Invirase with other PIs, such as Reyataz/atazanavir or Kaletra (lopinavir/ritonavir).

Invirase should be taken with meals or up to two hours after a meal. Taking Invirase with food increases the amount of drug in the bloodstream, making it more effective against HIV.

Invirase must be used in combination with other HIV medications to treat HIV.

Tell your doctor if you have liver or kidney problems, diabetes, or hemophilia.

As with all HIV drugs, it is important to take Invirase as prescribed by your doctor. Missing or skipping doses can cause your blood levels of the drug to fall too low and your virus can become resistant to the drugs. This may cause the drugs to stop working.

Invirase, combined with Norvir, may be used for people who are taking anti-HIV drugs for the first time.  However, in most cases, this is not the preferred initial therapy. If you have not previously received any treatment for your HIV, talk to your doctor about which initial treatment is best for you.

Invirase, combined with Norvir, may be used for people who are switching from other drugs that no longer work, but Invirase + Norvir may not work as well if HIV is resistant to certain other PIs.

Your doctor can run a resistance test to help determine whether Invirase is likely to work for you.

If your virus develops resistance to Invirase, the drug may stop working or may not work as well for you. You also may not get as much benefit from the other PIs.

Sometimes taking more than one medication can cause drug interactions. Taking certain drugs (including some anti-fungals, TB drugs, other HIV drugs, drugs to treat erectile dysfunction such as Viagra™, Levitra™, or Cialis™, steroids such as dexamethasone, and cholesterol-lowering drugs) with Invirase can change the amount of each drug in your blood. Your doctor may need to adjust the doses of your drugs to avoid under- or overdosing.

Invirasemay decrease the effectiveness of birth control pills, so alternative birth control methods should be used when you are taking Invirase.

Certain medications (including some acid reflux/heartburn drugs, antibiotics, antihistamines, sedatives, migraine medications, and antipsychotic drugs) should not be taken with Invirase. Do not take St. John’s Wort, garlic supplements, grapefruit juice, Zocor™, Mevacor™, or rifampin either.

Be sure your doctor knows about all the medications you are taking (including over-the-counter, prescription, street drugs, and herbs), even if you only use them occasionally.

For more information and additional resources to check interactions between the particular drugs you are taking, see our info sheet on drug interactions.

It is not uncommon to experience Invirase side effects. However, they are likely to be temporary and go away as your body adjusts to the medication. If you experience any of the side effects listed below, call your doctor for advice. Do not just stop taking your medication.

• Diarrhea
• Nausea
• Abdominal pain
• Intestinal gas (flatulence)
• Headaches
• Fatigue (unusual tiredness)
• Insomnia (inability to sleep)
• Mental confusion

More serious side effects:

• Liver toxicity: this may be indicated by elevated liver enzymes or yellowing of the skin and eyes (jaundice).
• Lipodystrophy, which may include elevated blood sugar (glucose), elevated lipid levels (cholesterol and triglycerides), and fat gain or loss in certain areas of the body. The exact causes of lipodystrophy are not known, but may include HIV and/or HIV drugs. It is unclear whether Invirase will cause or impact symptoms of lipodystrophy.

If you are experiencing persistent, unusual, or serious side effects, call your doctor right away.

One study of pharmacokinetics (how the drug is processed by the body), which included 12 women and 18 men, showed that Invirase behaves similarly in the bodies of women and men. But other research indicates that women eliminate the drug from their bodies more slowly than men, and therefore may have higher blood levels.

In several early studies, participants had Invirase added to their existing nucleoside reverse transcriptase inhibitor (NRTI) drug regimens. Most of these studies found that the addition of Invirase led to lower viral loads, higher CD4 cell counts, and reduced risk of progression to AIDS or death.

The CHEESE study compared Retrovir (zidovudine or AZT) plus Epivir (lamivudine or 3TC) plus a higher dose of Invirase to Retrovir plus Epivir plus Crixivan (indinavir) in 70 people, including 13 percent (or about 9) women. This trial found that the two drug regimens worked about equally well.

The MaxCmin1 study compared Norvir-boosted Invirase to Norvir-boosted Crixivan. This trial included 306 participants, 22 percent (or about 67) of whom were women. After 48 weeks, the drugs appeared to work about equally well, but more people in the Crixivan arm changed treatment due to side effects.

The MaxCmin2 trial compared Norvir-boosted Invirase to Kaletra (lopinavir/ritonavir), which already includes a small amount of Norvir. In this study, Kaletra appeared to be more effective, and fewer people taking Kaletra stopped treatment due to side effects.

Finally, the ACTG 359 study, which looked at different combinations of HIV drugs for “salvage therapy” in people who had already taken HIV drugs, suggested that women may respond better than men to second-line treatment. This trial included about 16 percent women, or 46 women out of 277 total participants. In this study, women had 25 percent higher Invirase blood levels, and were more likely to achieve undetectable viral loads (52 percent of women versus 33 percent of men).

In terms of side effects, most trials have shown that Invirase is less likely to cause side effects than other PIs. Some studies suggest that the metabolic side effects (lipodystrophy) associated with PIs may be somewhat different in women and men. However, it is still unclear if women are more likely to gain or lose body fat in certain areas than men.  It is also not clear whether Invirase is associated with lipodystrophy as much as lipodystrophy is seen in patients treated with other PIs.

Studies have shown that pregnant women who use HIV drugs can greatly reduce the risk of passing HIV on to their babies. Invirase™ has been used during pregnancy without any significant negative effect to mother or baby; however, long- term effects on the child are not known.

Check with your doctor about the best treatment options for you and your baby if you are thinking of getting pregnant.

People who are starting HIV treatment for the first time may develop Immune Reconstitution Inflammatory Syndrome or IRIS. IRIS can happen as a result of the immune system getting stronger and responding to an HIV-related infection such as Mycobacterium avium infection (MAC), cytomegalovirus (CMV), Pneumocystis jirovecii pneumonia (PJP), or tuberculosis (TB). People may have been treated for these infections in the past or may not even know they have them. If you notice any unusual symptoms soon after starting HIV drugs for the first time, let your doctor know right away so you can be evaluated and treated, if necessary.

1		Cohen Stuart, J.W.T., et. al. (1999). Randomized trial comparing saquinavir soft gelatin capsules versus indinavir as part of triple therapy (CHEESE study). AIDS, 13(7). F53-F58.
2		Easterbrook, P.J., et. al. (2001). Comparison of virologic, immunologic, and clinical response to five different initial protease inhibitor-containing and nevirapine-containing regimens. Journal of Acquired Immune Deficiency Syndromes, 27(4). 350-364..
3		Kirk, O., et. al. (2001). Clinical outcome among HIV-infected patients starting saquinavir hard gel compared to ritonavir or indinavir. AIDS, 15(8). 999-1008.
4		King J, Lundy SP, Kakuda T, Becker S, Acosta E. Pharmacokinetics of saquinavir with low-dose ritonavir or atazanavir twice daily in seronegative volunteers: ASPIRE II. Program and abstracts of the 13th Conference on Retroviruses and Opportunistic Infections; February 5-8, 2006; Denver, Colorado. Abstract 586.
5		Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents.  May 4, 2006.  Developed by the DHHS Panel on Antiretroviral Guidelines for Adults and Adolescents - A Working Group of the Office of AIDS Research Advisory Council.  Accessed at http://aidsinfo.nih.gov/ContentFiles/AdultandAdolescentGL.pdf .
6		www.hiv-druginteractions.org
7		http://www.hivinsite.ucsf.edu (drug interaction database)
8		What company makes Invirase™? Hoffmann - La Roche: 340 Kingsland Street, Nutley, NJ 07110 Telephone: (800) 526-6367