Invirase – brand name

saquinavir – generic name

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

Another version of this drug called Fortovase was discontinued in the US in 2006, but is still used in some other countries. Invirase, which is the preferred version of the drug, is the only version available in the US.

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 the PI Norvir (ritonavir) and other HIV drugs for the treatment of HIV infection in adults and adolescents over 16 years old.

Invirase comes in:

• 200 milligram (mg) hard-gel capsules
• 500 mg film-coated tablets

Invirase must be taken with a low dose of Norvir. Taking Norvir increases the effectiveness of Invirase. The recommended dose is two 500 mg Invirase tablets plus one 100 mg Norvir capsule twice a day.

Invirase should be taken within two hours of 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 Norvir and other HIV medications to treat HIV.

Tell your health care provider if you have liver or kidney problems, diabetes, or hemophilia.

Take a missed dose as soon as possible, but do not double up on your next dose.

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

Invirase, combined with Norvir, may be used for people who are taking HIV drugs for the first time. However, in most cases, this is not the preferred choice for initial (first-time) therapy. If you have not previously received any treatment for HIV, talk to your health care provider 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. However, Invirase plus Norvir may not work as well if HIV is resistant to certain other PIs.

You and your health care provider should use resistance testing and your treatment history to guide the use of Invirase and to determine which drugs will work best 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. This can lead to the drugs not working as well or an increased risk of side effects.

Invirase can interact with other medications. Taking Invirase with certain drugs can change the amount of each drug in your blood. Your health care provider may need to either adjust the doses of your drugs to avoid under- or overdosing or change the drugs you currently take.

Invirase plus Norvir should not be taken with the following drugs:

• Acid reflux/heartburn medication: Propulsid (cisapride)
• Antibiotics: Priftin (rifapentine), Rifadin (rifampin), Mycobutin (rifabutin)
• Antimigraine medications (ergot medications): Methergine, Methylergometrine (methylergonovine), Ergostat, Cafergot, Ercaf, Wigraine (ergotamine), Ergotrate, Methergine (ergonovine), D.H.E. 45, Migranal (dihydroergotamine)
• Antihistamines: Hismanal (astemizole), Seldane (terfenadine)
• Cholesterol-lowering drugs (statins): Zocor (simvastatin), Mevacor (lovastatin)
• Heart medications: Cordarone, Pacerone (amiodarone), Vascor (bepridil), Tambocor (flecainide), Rythmol (propafenone), Quinaglute/Quinidex (quinidine), antiarrhythmic drugs, other drugs that may prolong the QT or PR interval of the heart
• Antipsychotic: Orap (pimozide)
• Sedatives: Versed (midazolam), Halcion (triazolam)
• Herbal products: St. John's wort, garlic capsules
• Antifungal: Vfend (voriconazole)
• Enlarged prostate: Uroxatral (alfuzosin)
• HIV drugs: Aptivus (tipranavir)
• Pulmonary arterial hypertension treatment: Revatio (sildenafil)
• Prostate medication: Uroxatral (alfuzosin)
• Inhaled medications: Serevent, Advair (salmeterol), Nasal spray: Flonase (fluticasone)

If you are taking any of the following medications with Invirase plus Norvir, speak to your health care provider as your doses may need to be adjusted

• Anticonvulsants: Tegretol ( carbamazepine), Luminal (phenobarbital), Dilantin (phenytoin)
• Heart medication: Lanoxin (digoxin)
• Erectile dysfunction drugs: Viagra (sildenafil), Levitra (vardenafil), Cialis (tadalafil)
• Pulmonary arterial hypertension drugs: Tracleer (bosentan), Adcirca (tadalafil)
• HIV drugs: Viramune (nevirapine), Sustiva (efavirenz), Reyataz (atazanavir), Rescriptor (delavirdine), Crixivan (indinavir), Viracept (nelfinavir), Kaletra (lopinavir/ritonavir)
• Methadone

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

The drug colchicine needs dose adjustments when taken with Invirase. Colchicine should not be used at all with Invirase if you have kidney or liver problems.

Because there are so many possible drug interactions with Invirase plus Norvir, it is very important to go over all your medications with your health care provider. Be sure your health care provider 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 or go to:

http://www.hiv-druginteractions.org/
OR
http://hivinsite.ucsf.edu/insite?page=ar-00-02

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 health care provider 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
• Vomiting
• Pneumonia

More serious side effects:

• According to a February 2010 FDA announcement, taking Invirase plus Norvir may increase your risk for developing abnormal heart rhythms. In some cases this could lead to serious heart problems, including a condition called torsades de pointes (dangerous and irregular heart beat) and heart block (slowing of the heart beat). These problems can be seen on a test called an electrocardiogram (EKG). Symptoms include lightheadedness, fainting, or abnormal heart beats. The FDA is investigating to see if there is definite link between the use of Invirase plus Norvir and these heart problems. In the meantime, Invirase plus Norvir should not be used by people taking heart medications including quinidine, amiodarone, or antiarrhythmic drugs; or in people with a history of these types of heart conditions. The FDA suggests that people using Invirase plus Norvir speak with their health care providers about their cardiovascular (heart) history and current medications to determine if they should continue using Invirase plus Norvir.
• Liver toxicity: this may be indicated by elevated liver enzymes or yellowing of the skin and eyes (jaundice). People with liver diseases such as hepatitis B and C may have worsening liver problems.
• High blood sugar (hyperglycemia), diabetes, or worsening of diabetes may occur.
• Increased bleeding problems in some HIV+ people with hemophilia.
• 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. For more information on lipodystrophy, see our info sheet.

If you are experiencing persistent, unusual, or serious side effects, call your health care provider 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.

An Antiretroviral Pregnancy Registry has been established to collect information on pregnant women who take HIV drugs, including Invirase. If you are pregnant and taking Invirase or other HIV drugs, your health care provider can register you by calling 1-800-258-4263 or going to www.apregistry.com.

It is not known whether Invirase passes into breast milk. HIV+ women should not breast-feed because their babies could be infected with HIV through the breast milk.
Check with your health care provider about the best treatment options for you and your baby if you are thinking of getting pregnant.

Click this link for more information about pregnancy.

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 health care provider know right away so you can be evaluated and treated, if necessary.