Kaletra
Protease Inhibitor
Common Name: lopinavir/ritonavir (LPV/r)
Brand Name: Kaletra
Class: HIV protease inhibitor (PI)
Standard dose: Two 200/50 mg tablets twice a day or four 200/50 mg tablets once daily for first-time therapy (no once-daily dose if taken with Sustiva or Viramune). Three tablets twice a day may be considered for treatment-experienced people or those taking it with Sustiva or Viramune. Half-strength film-coated tablet available: 100 mg lopinavir and 25 mg ritonavir. Take with or without food, preferably with food to lessen side effects; liquid formula available. Take missed dose as soon as possible, but do not double up on your next dose.
AWP: $876.98 / month
Manufacturer contact: Abbott Laboratories,
www.kaletra.com, 1 (800) 222–6885
AIDSInfo:
1 (800) HIV–0440 (448–0440), www.aidsinfo.nih.gov
Potential side effects and toxicity: Diarrhea is the most common. Rash, nausea, vomiting, stomach pain, headache, muscle weakness, and increased cholesterol, triglycerides (fats in the blood), and elevated liver enzymes, a sign of liver damage—this may be more common in people with hepatitis B or C. As seen with other protease inhibitors (except unboosted Reyataz), there can be increased levels of cholesterol and triglycerides which may be associated with an increased risk of heart disease. Other possible side effects seen with protease inhibitors are lipodystrophy (body fat changes, including thinning of the face, arms and legs, with or without fat accumulation in the stomach, breasts and sometimes the upper back), onset of new cases or worsening of diabetes (see your doctor promptly) and increased bleeding in hemophiliacs. Immune Reconstitution Inflammatory Syndrome (IRIS) may occur as the immune system regains strength; report symptoms of illness, such as shingles and TB, to health care provider.
Potential drug interactions: Interacts with many—tell your provider all the drugs you are taking. Do not take with Tambocor, Rythmol, Cordarone, oral Versed (midazolam), Halcion, Uroxatral, rifampin, pimozide, ergot derivatives (such as Cafergot, Wigraine, Methergine, and D.H.E. 45), garlic supplements, or the herb St. John’s wort. Do not use Zocor, Vytorin or Mevacor; lipid-lowering alternatives are Lipitor, Lescol, and pravastatin, but they should be used with caution due to potential for liver toxicity. Oral solution contains alcohol, so do not use with Antabuse or Flagyl (metronidazole). Avoid certain calcium channel blockers (such as Norvasc, Procardia, and others).
Dosage of methadone may need to be increased when taken with Kaletra. Increase Kaletra dose to three tablets twice a day with food when using with Sustiva or Viramune in people who previously took HIV drugs, especially protease inhibitors. Not recommended to be taken with Lexiva. Kaletra may lower levels of Retrovir (zidovudine, AZT) and Ziagen. Videx should be taken an hour before or two hours after Kaletra, if Kaletra is taken with food. Mycobutin (rifabutin) dosage should be reduced to 150 mg every other day (or 150 mg three times per week) when used with Kaletra.
Phenobarbital, phenytoin or carbamazepine may lower blood levels of Kaletra. Reduces effectiveness of birth control pills; use alternative contraceptive. Mepron levels may be reduced with Kaletra. Avoid Sporanox (itraconazole) or Nizoral (ketoconazole) doses greater than 200 mg per day with Kaletra. Decreases Vfend (voriconazole) levels. People with kidney impairment may require lower Biaxin doses with Kaletra. Immunosuppressants require close monitoring with Kaletra. Kaletra may alter Coumadin levels. Steroids, especially Decadron, may decrease levels of Kaletra. Increases levels of fluticasone (active component of Advair, Flonase, Flovent) and trazodone. Cialis, Levitra, and Viagra levels are increased; doses should not exceed 10 mg Cialis or 2.5 mg Levitra per 72 hours, or 25 mg Viagra per 48 hours.
Tips: Kaletra once or twice daily is one of four protease inhibitors recommended by U.S. HIV treatment guidelines for first-time therapy, but the other three are easier to take. Also, Prezista and Reyataz were found to be more effective for people with more than 100,000 viral load in large studies last year. Still, HIV has a high barrier against developing resistance to Kaletra, a real plus. Kaletra has even been shown to work well all by itself (monotherapy), but this is still an experimental dose. Great viral load results out to 7 years in people on their first HIV regimen. Good results also seen in heavily treatment-experienced adults, even those with protease inhibitor resistance. Use Kaletra with caution in people with mild to moderate liver impairment. Four tablets once daily can increase side effects, especially diarrhea. However, avoid extreme heat and bright light. Carefully follow instructions on pediatric dosing. New change last year: should not be taken only once a day by children under 18. Avoid the oral solution during pregnancy. Please see package insert for more complete potential side effects and interactions.
Doctor
Kaletra (lopinavir/ritonavir) was approved as a capsule (dosed as three capsules twice daily) for use in combination with other antiretroviral drugs in the treatment of HIV infection in 2000. In 2005, Kaletra tablets were approved for dosing at two tablets twice daily. Studies in individuals who are new to HAART have demonstrated that Kaletra can be given in a once-daily dosing schedule (four tablets daily). Kaletra monotherapy has been studied, but I don’t believe this dosing is durable. A liquid preparation of Kaletra is available and the tablet form does not have to be refrigerated. Kaletra is the only co-formulated (one pill) protease inhibitor that takes advantage of the ritonavir boosting effect. I have generally believed that those patients with low CD4 cells and high viral loads (greater than 100,000 copies per ml) get better immunologic reconstitution with a boosted PI regimen. In general, studies have not proved this, but as an immunologist, I believe there may be a particle of truth to it. The major clinical adverse effect with Kaletra is diarrhea and, from a laboratory standpoint, elevated liver test results. Lipids take a hit with this drug. High triglycerides and cholesterol occur a little more commonly with Kaletra. This becomes important because we don’t want our patients dying from a heart attack when they have pushed back the “fatal tag” to HIV infection. With the ability to boost other protease inhibitors which have better side effect profiles and are more tolerable, Kaletra has found competition. Since the problems with Viracept in pregnancy, Kaletra has become our choice for treatment of pregnant women with HIV infection. In Africa (specifically Uganda), Kaletra (Alluvia) is virtually the only protease inhibitor used (second-line therapy). —Frank M. Graziano, M.D., Ph.D.
Activist
More bang for the buck, literally. Kaletra is the first and only co-formulated ritonavir-boosted PI—Kaletra doesn’t have to be boosted because it comes with Norvir/ritonavir already in it. This allows for fewer prescription co-pays. Kaletra is indicated for both treatment-naïve and treatment-experienced patients and its once-daily dosing gets it on the DHHS Guidelines Panel’s “preferred” list of PIs. Kaletra works well to reduce high viral loads and increase low CD4 counts, and also replaces Viracept as the only recommended PI for pregnant women. It now comes in a more heat-stable form (Meltrex formulation), an important consideration for HIV treatment in the developing world. —Morris Jackson
