Lexiva (fosamprenavir)

October 2007     View PDF     En español
Reprinted from www.aidsmeds.com, US

What is Lexiva?
Lexiva is an anti-HIV medication. It is in a category of HIV medicines called protease inhibitors (PIs). Lexiva prevents cells infected by HIV from producing new virus. This reduces the amount of virus in your body.

Lexiva, developed by Vertex Pharmaceuticals and GlaxoSmithKline, was approved by the U.S. Food and Drug Administration on October 20, 2003.

In some parts of the world, fosamprenavir is sold under the brand name Telzir.

Lexiva is a “prodrug” of Agenerase (amprenavir), a protease inhibitor also marketed by GlaxoSmithKline. This means that the drug must be broken down inside the body before it can become active. Doing so increases the amount of drug in the blood, while at the same time decreasing the number of pills that must be swallowed every day. Because Lexiva is easier to take and may cause less side effects than Agenerase, it is now the preferred form of amprenavir.

Lexiva must be used in combination with at least two other anti-HIV drugs. For HIV-positive people who have tried other protease inhibitors in the past, it is recommended that Lexiva also be combined with low doses of Norvir (ritonavir) to boost the amount of Lexiva in the bloodstream (which makes the drug more effective against HIV that may be resistant to other protease inhibitors).

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What is already known about Lexiva?
Lexiva is very similar to Agenerase (amprenavir), and will likely not be effective in patients who are resistant to Agenerase.

The FDA has approved three different dosages for Lexiva, which can be taken with or without food:

two 700mg tablets twice daily,
two 700mg tablets in combination with one 100mg capsules of Norvir once daily, or
one 700mg tablet in combination with one 100mg capsule of Norvir twice daily.

For HIV-positive people who have tried other protease inhibitors in the past, the FDA-recommended dose is one 700mg Lexiva tablet in combination with one 100mg capsule of Norvir twice daily.

A liquid version of Lexiva was approved by the FDA in June 2007. There are three dosing options for children, depending on their body weight and age:

Children between 2 and 5 years of age: 30 milligrams of liquid Lexiva per kilogram (mg/kg) of body weight twice daily. Only for 2- to 5-year-olds starting HIV treatment for the first time (treatment naive); combining Lexiva with Norvir is not recommended.

Treatment-naive children 6 years of age or older: 30 mg/kg of body weight twice daily, or 18 mg/kg liquid Lexiva plus 3 mg/kg liquid Norvir twice daily.
• Treatment-experienced children 6 years of age or older: 18 mg/kg Lexiva plus 3 mg/kg Norvir twice daily.
• Clinical trials have determined that Lexiva is safe and effective when combined with other drugs, most notably two nucleoside reverse transcriptase inhibitors (NRTIs). Clinical trials have also concluded that Lexiva, combined with Norvir, is an effective option for people who have tried and failed other protease inhibitors in the past.
• There haven’t been any clinical trials comparing the effectiveness of Lexiva to the effectiveness of Agenerase. In turn, it’s not known if Lexiva is a more powerful version of amprenavir. However, in one small, short-term study, Lexiva caused fewer gastrointestinal side effects than Agenerase. This is probably because Agenerase capsules contain small amounts of propylene glycol (used in deodorants, cosmetics, fat-free ice cream, and other products), while Lexiva doesn’t. What’s more, rash was less likely to occur in people taking Lexiva than those taking Agenerase.

For HIV-positive adults beginning anti-HIV drug therapy for the first time, twice-daily Lexiva plus Norvir is listed as a “preferred” protease inhibitor option by the United States Department of Health and Human Services in its treatment guidelines. Once-daily Lexiva plus Norvir, or twice-daily Lexiva used without Norvir, are listed as “alternative” treatment options.

If your viral load becomes detectable while taking a drug regimen that contains Lexiva, 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 Lexiva, it might be possible to begin taking a low dose of Norvir—if you’re not already on one—to boost the amount of Lexiva in the bloodstream. This may help overcome low-level resistance to Lexiva 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 Lexiva. Similarly, if you take an anti-HIV drug regimen that contains Lexiva 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.

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What about drug interactions?
Lexiva is broken down (metabolized) by the liver, like many medications used to treat HIV and AIDS. This means that Lexiva can interact with other medications. Lexiva can lower or raise the levels of other medications in the body. Similarly, other medications can lower or raise the levels of Lexiva 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.

Based on what we know about the drug interactions with Lexiva, the following medications should not be taken while you are being treated with Lexiva:

Acid reflux/heartburn medications: Propulsid (cisapride)
Antimigraine medications: Methergine, Methylergometrine (methylergonovine); Ergostat, Cafergot, Ercaf, Wigraine (ergotamine); Ergotrate, Methergine (ergonovine); or D.H.E. 45, Migranal (dihydroergotamine)
Cholesterol-lowering drugs (statins): Zocor (simvastatin) and Mevacor (lovastatin)
Antipsychotics: Orap (pimozide)
Sedatives: Versed (midazolam) and Halcion (triazolam)

If Lexiva is combined with low-dose Norvir, the following medications should also be avoided:

Antifungals: Vfend (voriconazole)
Antihistamines: Hismanal (astemizole) or Seldane (terfenadine)
Heart medications: Cordarone (amiodarone), Vascor (bepridil), Tambocor (flecainide), Rythmol (propafenone), or Quinaglute/Quinidex (quinidine)
Enlarged prostate: Uroxatral (alfuzosin)

Anticonvulsants, such as Tegretol ( carbamazepine), Luminal (phenobarbital), and Dilantin (phenytoin), can decrease the amount of Lexiva in the bloodstream. It might be necessary to increase your dose of Lexiva if you are taking any of these drugs.

Based on what we know about the drug interactions with Lexiva, it is likely that other anti-HIV drugs can interact with Lexiva. Anti-HIV protease inhibitors can interact with Lexiva. Norvir (ritonavir), Kaletra (lopinavir/ritonavir), Reyataz (atazanavir), Crixivan (indinavir), and Viracept (nelfinavir) may all increase Lexiva levels in the bloodstream. If Lexiva is combined with either Norvir or Kaletra, the Lexiva dose should be reduced. At the same time, if Lexiva is combined with Kaletra, the Kaletra dose may need to be increased (Lexiva may decrease the amount of lopinavir in the bloodstream). Invirase (saquinavir) may decrease the amount of Lexiva in the bloodstream. If Lexiva is combined with Invirase, low-dose Norvir may be necessary to maintain Lexiva levels in the bloodstream.

Anti-HIV non-nucleoside reverse transcriptase inhibitors (NNRTIs) can also interact with Lexiva. Sustiva (efavirenz) and Viramune (nevirapine) may decrease the amount of Lexiva in the bloodstream. A third NNRTI, Rescriptor (delavirdine), can increase levels of Lexiva in the bloodstream. No dosing recommendations have been made, although low-dose Norvir may be necessary if Viramune or Sustiva are combined with Lexiva.

It’s possible that Ziagen (abacavir), an NRTI, can increase Lexiva levels in the bloodstream. However, there is no need to change the dose of either drug.

Lexiva can interact with some medications used to treat TB, MAC, and other bacterial infections. Rifadin (rifampin) can decrease Lexiva levels (these drugs should not be used together). Lexiva can increase Mycobutin (rifabutin) levels and Mycobutin may decrease Lexiva levels (the Mycobutin dose will likely need be reduced). Biaxin (clarithromycin) increases Lexiva levels, although no dosing changes will likely be necessary.

Lexiva can interact with some medications used to treat thrush (candidiasis) and other fungal infections. Lexiva can increase Nizoral (ketoconazole) levels in the bloodstream. Similarly, Nizoral can increase Lexiva levels in the bloodstream. However, no dosing changes will likely be necessary.

Lexiva may decrease the amount of oral contraceptives (taken by women to help avoid pregnancy) in the bloodstream. This means that there may be a higher risk of becoming pregnant if Lexiva and oral contraceptives are taken at the same time. To reduce the risk of pregnancy, barrier protection (e.g., condoms) should be used.

Cholesterol-lowering drugs, also known as “statins,” can interact with Lexiva. The two statins that are considered to be the safest in combination with Lexiva are Pravachol (pravastatin) and Lescol (fluvastatin). It may also be possible to take Lexiva with Lipitor (atorvastatin), Zocor (simvastatin) and Mevacor (lovastatin), although Lexiva can increase levels of these three drugs in the bloodstream. If Lipitor, Zocor, or Mevacor are 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 Lexiva or the other protease inhibitors.

Viagra (sildenafil), Levitra (vardenafil) and Cialis (tadalafil) levels in the bloodstream may increase when combined with Lexiva. 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 Lexiva. St. John’s wort should not be used with Lexiva, since it can greatly reduce the amount of Lexiva in the bloodstream. HIV-positive people should also be cautious about using garlic supplements or milk thistle with Lexiva—test tube studies suggest that both herbal products can interact with the same liver enzyme system (cytochrome P450 3A4) responsible for metabolizing Lexiva. This may alter the amount of Lexiva 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 Lexiva is combined with Norvir (ritonavir).

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What about side effects?
Short-term side effects include rash, appetite loss, headaches, feeling crummy (malaise), diarrhea, nausea, and vomiting. While these are the same side effects caused by Agenerase, many are less common with Lexiva. Very often, these side effects improve within a few months/weeks of starting Lexiva.

Anti-HIV drug regimens containing protease inhibitors, including Lexiva, 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.

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Who should not take Lexiva?
Lexiva is classified by the FDA as a pregnancy category C drug. Pregnancy category C means that animal studies have shown an adverse effect on the fetus and there are no adequate and well-controlled studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks. 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.

It is not known whether Lexiva passes into breast milk and what effect it may have on a nursing baby. To prevent transmission of the virus to uninfected babies, it is recommended that HIV-positive mothers not breast-feed.

Lexiva has not been studied in children younger than 2 years of age.

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Where can I learn more about clinical trials that are using Lexiva?
If you would like to find out if you are eligible for any clinical trials that include Lexiva, there is an interactive website 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).

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