Kaletra (ABT-378/r) Approved.

On September 15 the FDA approved Kaletra [TM] (formerly called ABT-378/r), a protease inhibitor, for use in combination with other antiretroviral agents for treatment of HIV infection. Kaletra was already in use by several thousand patients, through a preapproval expanded access program for persons who could not otherwise put together a satisfactory antiretroviral combination; Abbott Laboratories will continue to supply the drug through this program for up to two months as patients obtain coverage (for information about the expanded access program which is now being phased out, call 1-888-711-7193). Kaletra is already in a few pharmacies as we go to press, and should be widely available in about a week.

The U.S. price is $6,500 annually "wholesale acquisition cost" (Kaletra has not yet been approved in any other country). For patients who have no other way of affording the drug, there will be a patient assistance program similar the Abbott's program for Norvir; for information, patients can call 1-800-222-6885 Monday through Friday 8:00 a.m. to 4:30 p.m. Central time.

It is not known if most physicians will use this drug for first-line treatment, or keep it in reserve for cases of failure of other antiretrovirals (which is how it was used in the expanded access program). It is not known which strategy would be best overall. But in either case, many more physicians will now use the drug; and many of them will be less experienced in HIV treatment, and less knowledgeable about this drug, than the doctors in the early-access program.

If you are prescribed Kaletra, be sure that you receive a patient information sheet from Abbott Laboratories (probably titled Kaletra Patient Information--do not confuse this with general drug information sheets or printouts which some pharmacies may give you). The patient information material includes:

A long list of medicines that must not be used concurrently, "because they can cause serious problems or death if taken with Kaletra."

Other medicines and non -prescription products should not be taken with Kaletra because the interaction can make Kaletra (or the other medicine) less effective. This includes St. John's wort herbal products, sometimes used as a non-prescription antidepressant, which may lower Kaletra levels in the body and therefore might lead to HIV resistance to this and other antiretrovirals.

Other medicines require or may require dosage adjustment if taken concurrently. (This includes Viagra, some antiretrovirals, some antibiotics, and some other drugs.)

While Kaletra is well tolerated by most patients, there are cases of serious side effects that can be life threatening. For example, Abbott Laboratories recently warned physicians that some people in the expanded access program have developed pancreatitis (which might or might not have been caused by Kaletra). There can also be liver toxicities, especially in patients who already have liver disease. Blood tests can give early warning of these problems. The Kaletra Patient Information sheet lists these and other potential side effects.

If you cannot get the Kaletra Patient Information sheet from your pharmacy, it is on the Web, as the last four pages of the physicians' information at http://www.kaletra.com.

The main importance of Kaletra is that it can be effective even against some viruses which have become resistant to other approved protease inhibitors--and resistance to Kaletra may be slower to develop than resistance to the other protease inhibitors, because Kaletra has an unusually wide therapeutic window between the high levels achievable in blood, and the substantially lower levels which can suppress most HIV. However, resistance to Kaletra can develop, at least in patients already resistant to other protease inhibitors; and it is important not to lose this valuable drug by using it thoughtlessly or improperly. As with any antiretroviral, doctors need to prescribe Kaletra as part of appropriate combinations that are likely to keep HIV well suppressed, to minimize ongoing viral reproduction and the risk of resistance development. And patients need to use the drugs as directed, to avoid having blood levels too low to fully suppress the virus.

Notes:

Kaletra is a combination of two drugs: lopinavir, the main antiretroviral, combined with a low dose of ritonavir (Norvir[R]), another protease inhibitor made by Abbott. The ritonavir is used mainly to block the body's ability to destroy lopinavir; without ritonavir, the lopinavir would be metabolized too fast to be useful as an antiretroviral. The drugs are supplied in the proper ratio, so they are automatically administered together.

The usual adult dose is 400/100 (400 mg of lopinavir combined with 100 mg. of ritonavir--three capsules of Kaletra) taken twice daily with food (four capsules instead of three may be prescribed for certain patients). The capsules (or liquid form which is available as an alternative) should usually be refrigerated, but if necessary patients can keep them at room temperature for up to two months. Pediatric dosing has been approved for children from 6 months to 12 years of age.

For more information, see the drug "label" (the prescribing information for physicians), which is available at http://www.kaletra.com (or at http://www.abbott.com). Physicians should note that the "Microbiology" section of this label has clinical information about both phenotypic and genotypic HIV resistance testing.