Potential side effects and toxicity: Rash, diarrhea, nausea, vomiting, stomach pain, headache, muscle weakness, increased cholesterol and triglycerides (fats in the blood), and AST/ALT (liver function tests, a sign of liver damage; this may be more common in people with hepatitis B or C).
As seen with all other protease inhibitors are increased levels of cholesterol and triglycerides, except possibly unboosted Reyataz (atazanavir) and these increased levels may be associated with heart disease. Other possible side effects 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.
Potential drug interactions: Do not take with Versed, Halcion, Hismanol, Seldane, rifampin (however, recent studies show that increasing the total daily dose of Kaletra may be an option), ergot derivatives (such as Cafergot, Wigraine and Methergine, D.H.E. 45, in any form—serious interactions seen with dilation during gynecological exams), garlic supplements, or the herb St. John’s wort. Do not use Zocor or Mevacor; lipid-lowering alternatives are Lipitor, Lescol, and Pravachol, 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. Avoid certain calcium channel blockers.
Dosage of methadone may need to be increased when taken with Kaletra. Increase Kaletra dose to 4 capsules or three tablets twice-a-day with food recommended 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 and Ziagen. Videx should be given an hour before or two hours after Kaletra, as Kaletra should be 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 doses greater than 200 mg per day with Kaletra. People with kidney impairment may require lower Biaxin doses with Kaletra. Transplant medicines require close monitoring with Kaletra. Kaletra may alter coumadin levels. Steroids, especially Decadron, may decrease levels of Kaletra.
Protease inhibitors increase blood levels of Viagra, Cialis and Levitra. Use with caution. Initially the Viagra dose should be 12.5 mg (1/2 of 25 mg tablet) and increased as needed and tolerated. It’s recommended that people on PIs do not exceed 25 mg of Viagra in a 48-hour period because of potential for serious reaction. Use Cialis at reduced doses of 10 mg every 72 hours and Levitra at reduced doses of no more than 2.5 mg every 72 hours, with increased monitoring for adverse events.
Tips: See Norvir. The FDA recently approved the new tablet formulation of Kaletra with the same dosage but less pills and hopefully fewer side effects. The newer formulation doesn’t require refrigeration (especially important for resource-poor countries) and has fewer food restrictions. Three capsules equal two tablets, except for patients also taking Sustiva or Viramune; look for new data being released as this issue went to press. Doctors and patients report that Kaletra is very tolerable. Great viral load results out to 6 years in people on their first HIV regimen. Good results also seen in heavily treatment-experienced adults, when compared to Reyataz, even those with protease inhibitor resistance. Use Kaletra with caution in people with mild to moderate liver impairment. The taste may be unappealing due to Norvir. Once-a-day concentration levels of the tablets were not satisfactory in treatment-experienced patients. Using the capsules in a once-daily dosing resulted in a huge increase in side effects. Kaletra capsules and solution should be stored in the refrigerator, but are stable for up to 60 days at room temperature (77 F˚). However, avoid extreme heat and bright light.
Doctor
Lopinavir/ritonavir is currently the most widely prescribed protease inhibitor, and is listed as the protease inhibitor of choice for treatment-naïve patients in the DHHS Guidelines, due to its potency, safety, tolerability, and durability. The manufacturer now has six years’ data touting Kaletra’s efficacy and durability, as well as general lack of resistance. Like many PIs, its main side effect is diarrhea, which can be severe. Reformulation should reduce most of the GI effects. Another long-term toxicity in some patients is elevated triglycerides and total cholesterol. The long term effect of this toxicity is unclear, but a recent study suggests it will increase overall risk for cardiovascular disease. Sequencing is also unclear: Some providers use it up front due to long-term data on durability, efficacy, and resistance; others “save” the drug for use when other PIs fail. In PI-naïve patients, Kaletra may be used once-daily. —Chad J. Zawitz, MD
Activist
Still the PI with the most robust long-term data and a “preferred” drug for treatment naïve patients. A tablet formulation of Kaletra was approved in the United States in October 2005. Abbott hopes to replace the original capsule formulation with the new tablets soon. The new formulation requires two fewer tablets a day and no refrigeration. The most common side effects of Kaletra in the past have been diarrhea and increases in cholesterol and triglycerides. Abbott claims that the new formulation may have fewer GI side effects but no improvements in triglycerides. The Kaletra market share is being eroded by Reyataz and may be further decreased with the introduction of TMC-114.—Nelson Vergel
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