Fortovase (saquinavir): a complete guide from AIDSmeds.com

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Fortovase® (saquinavir Soft Gel Cap, or SQV)

Pronunciations: FOR-toe-vase; sa-KWIH-nuh-veer

What is Fortovase?

Fortovase is an anti-HIV medication. It is in a category of HIV medications called protease inhibitors (PIs). Fortovase prevents T-cells that have been infected with HIV from producing new HIV.
Fortovase was manufactured by Hoffmann-La Roche. The U.S. Food and Drug Administration (FDA) approved it for the treatment of HIV infection in 1997.
Fortovase is a second version of saquinavir, the generic name for this protease inhibitor. The first version of saquinavir, Invirase®, was approved in 1995.
As of February 15, 2006, Hoffmann-La Roche discontinued the U.S. sale and distribution of Fortovase. Invirase is now the only form of saquinavir available. This is because the 500mg capsules of Invirase, combined with ritonavir, are better tolerated than the current Fortovase capsules (combined with ritonavir). Roche will discontinue the sale and distribution of Fortovase in other countries in the near future.

What is known about Fortovase?

The FDA-approved dose of Fortovase, if it is not used in combination with Norvir® (ritonavir), is six 200mg capsules every eight hours. However, most healthcare providers prefer to prescribe eight 200mg capsules every 12 hours – even though it is not approved by the FDA – as it is easier to take.
Fortovase has also been approved by the FDA for use in combination with Norvir® (ritonavir), another protease inhibitor that boosts Fortovase levels in the bloodstream. When used together, the Fortovase dose should be five 200mg capsules and the Norvir dose should be one 100mg capsule, taken at the same time twice a day.
Fortovase can be given to HIV-positive children. For children using Fortovase as their only protease inhibitor, the correct dose is 50mg per kilogram of body weight, every eight hours. If Fortovase is combined with Viracept® (nelfinavir) – the only two-protease inhibitor combination to be studied in HIV-positive children – the correct Fortovase dose is 33mg per kilogram of body weight, every eight hours. A liquid or powder formulation of Fortovase is not available. Only the adult capsules can be given to children. To learn about treatment options for children, click here.
Fortovase (either with or without Norvir) should be taken with food, preferably a full nutritious meal (e.g., breakfast and dinner). Taking Fortovase with food increases the amount of drug in the bloodstream, which makes Fortovase more effective against the virus.
Clinical trials have determined that Fortovase is safe and effective when combined with other drugs, most notably two nucleoside reverse transcriptase inhibitors (NRTIs). Clinical trials have also suggested that Fortovase, combined with Norvir, is an equally, if not more effective, option – and easier to take – than Fortovase taken without Norvir.
For HIV-positive adults beginning anti-HIV drug therapy for the first time, Fortovase combined with Norvir is listed as an "alternative" protease inhibitor option by the United States Department of Health and Human Services in its treatment guidelines. Fortovase, without Norvir, is not recommended. The protease inhibitor Kaletra® (lopinavir/ritonavir) is listed as the "preferred" option. To learn more about these recommendations and options, click here.
If your viral load becomes detectable while taking a drug regimen that contains Fortovase, your doctor can order a drug-resistance test to see which drugs your virus are becoming less sensitive to. If your doctor finds that your virus is becoming resistant to Fortovase, it might be possible to begin taking a low dose of Norvir – if you're not already on one – to boost the amount of Fortovase in the bloodstream. This may help overcome low-level resistance to Fortovase and help push viral load back down to undetectable levels.
Many of the currently available protease inhibitors are affected by cross-resistance. This means that, if you've tried and failed a drug regimen in the past that contained a protease inhibitor, your virus might be resistant to Fortovase. Similarly, if you take an anti-HIV drug regimen that contains Fortovase and your virus becomes resistant to the drug, your virus might also be resistant to many of the other protease inhibitors available. This is why it is very important to use drug-resistance testing to determine which drugs your virus are no longer responding to if you experience a rebound in your viral load while taking an anti-HIV drug regimen. Drug-resistance testing can also help you figure out which protease inhibitors your virus is still sensitive to.

What about drug interactions?

Fortovase is broken down (metabolized) by the liver, like many medications used to treat HIV and AIDS. This means that Fortovase can interact with other medications. Fortovase can lower or raise the levels of other medications in the body. Similarly, other medications can lower or raise the levels of Fortovase in the body. While many interactions are not a problem, some can cause your medications to be less effective or increase the risk of side effects.
Tell your doctors and pharmacists about all medicines you take. This includes those you buy over-the-counter and herbal or natural remedies, such as St. John’s Wort. Bring all your medicines when you see a doctor, or make a list of their names, how much you take, and how often you take them. Your doctor can then tell you if you need to change the dosages of any of your medications.
The following medications should not be taken while you are being treated with Fortovase:
Acid reflux/heartburn medications: Propulsid® (cisapride)
Antibiotics: Priftin® (rifapentine), Rifadin® (rifampin), and Mycobutin® (rifabutin)
Antimigraine medications: Ergostat®, Cafergot®, Ercaf®, Wigraine® (ergotamine) or D.H.E. 45® (dihydroergotamine)
Antihistamines: Hismanal® (astemizole) or Seldane® (terfenadine)
Cholesterol-lowering drugs (statins): Zocor® (simvastatin) and Mevacor® (lovastatin)
Antipsychotics: Orap® (pimozide)
Sedatives: Versed® (midazolam) and Halcion® (triazolam)
Anticonvulsants, such as Tegretol® ( carbamazepine), Luminal® (phenobarbital), and Dilantin® (phenytoin), may decrease the amount of Fortovase in the bloodstream. It might be necessary to increase your dose of Fortovase if you are taking any of these drugs.
Anti-HIV protease inhibitors can interact with Fortovase. Crixivan® (indinavir), Norvir® (ritonavir), Kaletra® (lopinavir/ritonavir), Viracept® (nelfinavir), Reyataz® (atazanavir), and Agenerase® and Lexiva® (amprenavir/fosamprenavir) – six protease inhibitors – can increase Fortovase levels in the bloodstream. Viracept can also increase Fortovase levels in the bloodstream. If Fortovase is combined with Norvir, the dose should be five 200mg Fortovase capsules plus one 100mg Norvir capsule twice a day. If Fortovase is combined with Viracept, the dose should be six 200 mg Fortovase capsules plus the usual Viracept dose. If Fortovase is combined with Kaletra, the dose should be five 200mg Fortovase capsules plus the usual Kaletra dose. No dosing has been recommended for Fortovase plus either Crixivan, Reyataz, Agenerase, or Lexiva.
Anti-HIV non-nucleoside reverse transcriptase inhibitors (NNRTIs) can also interact with Fortovase. Sustiva® (efavirenz) and Viramune® (nevirapine) can decrease the amount of Fortovase in the bloodstream. If either of these NNRTIs are combined with Fortovase, low-dose Norvir should also be used. A third NNRTI, Rescriptor® (delavirdine), significantly increases the amount of Fortovase in the bloodstream. If Rescriptor is used, the Fortovase dose should be reduced to four 200mg capsules three times daily.
Fortovase can interact with some medications used to treat TB, MAC, and other bacterial infections. Rifadin® (rifampin) decreases Fortovase levels in the bloodstream; these two drugs should not be used together. Mycobutin® (rifabutin) also decreases Fortovase levels in the bloodstream (a dosing change is only necessary if Norvir is also being used in the combination). Fortovase can increase Biaxin® (clarithromycin) levels and Biaxin can increase Fortovase levels in the bloodstream (neither dose needs to be changed).
Fortovase can interact with some medications used to treat thrush (candidiasis) and other fungal infections. Nizoral® (ketoconazole) can increase Fortovase levels and Fortovase can increase Nizoral levels in the bloodstream. A Nizoral dose change may only be necessary if you have excessive diarrhea, nausea, and abdominal discomfort
If Fortovase is combined with Norvir® (ritonavir), it can decrease the amount of methadone in the bloodstream, a drug commonly used to treat heroin addiction. It may be necessary to monitor blood levels of methadone and increase the dose, if needed.
It is not known what effect Fortovase has on oral contraceptives/birth-control pills. To reduce the risk of pregnancy, barrier protection (e.g., condoms) should be used.
Cholesterol-lowering drugs, also known as "statins," can interact with Fortovase. There are two statins that should not be used with Fortovase: Zocor® (simvastatin) and Mevacor® (lovastatin). Levels of these two drugs can become significantly increased in the bloodstream if they are combined with Fortovase, which increases the risk of side effects. The two statins that are considered to be the safest in combination with Fortovase are Pravachol® (pravastatin) and Lescol® (fluvastatin). It is also possible to take Fortovase with Lipitor® (atorvastatin), although Fortovase can increase Lipitor levels in the bloodstream. If Lipitor is prescribed, it's best to begin treatment with the lowest possible dose of the drug and then increase the dose if necessary. Little is known about the newest statin, Crestor® (rosuvastatin), although it is not expected to have any serious drug interactions with Fortovase or the other protease inhibitors.
Viagra® (sildenafil), Levitra® (vardenafil) and Cialis® (tadalafil) levels in the bloodstream likely increase when combined with Fortovase. In turn, it is best to use a lower dose of these drugs in order to reduce the risk of side effects.
Herbal products can also interact with Fortovase. St. John's wort should not be used with Fortovase, since it can greatly reduce the amount of Fortovase in the bloodstream. HIV-positive people should also be cautious about using garlic supplements or milk thistle with Fortovase – test tube studies suggest that both herbal products can interact with the same liver enzyme system (cytochrome P450 3A4) responsible for metabolizing Fortovase. This may alter the amount of Fortovase in the bloodstream. These and other herbal products should be used with caution, until further studies are conducted.
A number of other negative drug interactions are possible if Fortovase is combined with Norvir. To learn more about these drug interactions, click here.

What about side effects?

Short-term side effects include appetite loss, headaches, feeling crummy (malaise), diarrhea, nausea, and vomiting. Very often, these side effects improve within a few months/weeks of starting Fortovase.
Anti-HIV drug regimens containing protease inhibitors, including Fortovase, can cause increased fat levels (cholesterol and triglycerides) in the blood, abnormal body-shape changes (lipodystrophy; including increased fat around the abdomen, breasts, and back of the neck, as well as decreased fat in the face, arms, and legs), and diabetes. These side effects of anti-HIV drug therapy are reviewed in our lessons on Lipodystrophy, Facial Lipoatrophy, and Risks To Your Heart (Hyperlipidemia).

Who should not take Fortovase?

Before taking this medication, tell your doctor if you have kidney disease or liver disease. You may not be able to take Fortovase, or you may require a dosage adjustment or special monitoring during treatment if you have any of these conditions.
Fortovase is classified by the FDA as a pregnancy category B drug. Pregnancy category B means that animal studies have failed to demonstrate a risk to the fetus, but there are no adequate and well-controlled studies in pregnant women. HIV-positive women who become pregnant should discuss the benefits and possible side effects of anti-HIV treatment to help protect their babies from HIV (see our lesson called Pregnancy & HIV).
It is not known whether Fortovase passes into breast milk and what effects it may have on a nursing baby. However, to prevent HIV transmission of the virus to uninfected babies, it is recommended that HIV-positive mothers not breast-feed.

Where can I learn more about clinical trials that are using Fortovase?

If you would like to find out if you are eligible for any clinical trials that include Fortovase, there is an interactive web site run by ACRIA, the AIDS Community Research Initiative of America.
Another useful service for finding clinical trials is AIDSinfo.nih.gov, a site run by the U.S. National Institutes of Health. They have "health information specialists" you can talk to at their toll-free number at 1-800-HIV-0440 (1-800-448-0440).

Last Revised: 11/13/06