Kaletra

Common Name: lopinavir/ritonavir

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. Tablets should be swallowed whole, not chewed, broken, or crushed. Take with or without food, preferably with food to lessen side effects; liquid formula available. Take missed dose as soon as possible, unless it is almost time for your next dose. Do not double up on next dose.

AWP: $841.90 / month for tablets, $420.95 for 160 ml solution

Manufacturer contact: Abbott Laboratories, www.kaletra.com, 1 (800) 222-6885

Potential side effects and toxicity: Diarrhea is the most common and can be very severe. Rash, nausea, vomiting, stomach pain, headache, muscle weakness, 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 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; signs and symptoms of inflammation from previous infections may occur soon after anti-HIV treatment is initiated. Report symptoms of illness, such as shingles and TB, to a 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, 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 Advicor, Altoprev, Mevacor (lovastatin), Simcor, Vytorin, or Zocor (simvastatin) for the treatment of high lipids. Lipid-lowering alternatives are Crestor, Lescol, Lipitor, and Pravacol (pravastatin), but should be used with caution. Oral solution contains alcohol, so do not use with Antabuse or Flagyl (metronidazole). Use calcium channel blockers (such as Norvasc, Procardia, and others) with caution. Dosage of methadone may need to be increased when taken with Kaletra. Current guidelines state the Kaletra dose should total 500 mg lopinavir and 125 mg ritonavir twice daily when used with Sustiva or Viramune. That would mean 5 tablets of low-dose Kaletra twice daily. Because of high pill burden, physicians usually prescibe three tablets twice a day with food of the 200/50 mg dose when using with Sustiva or Viramune. Not recommended to be taken with Lexiva. Kaletra may lower levels of Retrovir (zidovudine, AZT) and Ziagen. Videx and Kaletra can be taken together, but without food. If Kaletra is taken with food, Videx should be taken an hour before or two hours after Kaletra. 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 methods. 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. Blood levels of immunosuppressants (cyclosporine, tacrolymus, and rapamycin) should be monitored, because their blood levels may increase when taken 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. Use caution with anti-convulsants: Tegretol (carbamazepine), phenobarbital, and Dilantin (phenytoin). Drug levels of bupropion are lowered; titrate dose based on clinical response. 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: In December 2009, Kaletra was downgraded from "preferred" to "alternative" therapy in U.S. HIV treatment guidelines for treatment-naive people, but is preferred for pregnant women. For people doing well on Kaletra, this should not be an issue. According to the guidelines, the need for 200 mg a day of Norvir (contained in Kaletra) and the higher rate of gastrointestinal side effects compared with boosted PIs using 100 mg Norvir make Kaletra an alternative for treatment-naive people. Four tablets once daily can increase side effects, especially diarrhea. Taking with food and anti-diarrheal medicine helps lessen diarrhea. Kaletra should not be taken only once a day by children under 18. Please see package insert for more complete potential side effects and interactions.

Doctor

Kaletra (lopinavir/ritonavir) was approved as a capsule for use in combination with other antiretrovirals in 2000. In 2005, Kaletra tablets were approved. A liquid preparation is available and the tablet does not have to be refrigerated -- both of these provide certain advantages. For some, it is the fact that Kaletra is also the only co-formulated protease inhibitor (lopinavir and ritonavir in the same tablet) that leads to choosing this over other options. This was the boosted PI that taught the field about the important advantages of using a ritonavir-boosted PI versus unboosted PIs, including seeing minimal, if any, drug resistance in PI-naive patients who did not maintain virologic suppression -- this "high genetic barrier" minimizing the risk of virologic resistance is an important reason why PIs are considered in some circumstances. The most common clinical adverse effect with Kaletra is diarrhea -- it is this "tolerability" issue that contributes to why Kaletra was deemed a less successful choice compared to Reyataz in a recent large study in people starting treatment. There are some lipid differences, as well, that are less favorable compared to Reyataz. In addition, a study comparing Kaletra to Prezista showed that while these two antivirals are similarly successful in patients who adhere to treatment, Kaletra was less successful than Prezista in maintaining suppression in those who miss doses over time. While it is ideal to take each dose each day, it is clear that this is not necessarily something everyone can do, and that has led to a second reason to reconsider the use of Kaletra. Finally, a few studies have shown that using Kaletra increases the risk of having a heart attack and this impact is not fully explained by the cholesterol changes which occur with the use of this drug. However, in pregnant women, Kaletra is still considered the treatment of choice in combination with two NRTIs. -- Cal Cohen, M.D.

Activist

Once the gold standard of protease-based regimens, Kaletra's GI and lipid problems have knocked it off the list of preferred regimens for new HIV patients. With its Norvir boost combined with the Kaletra in one pill that doesn't need to be refrigerated, it has an advantage over all the other PIs that need to be boosted with stand-alone Norvir (can we say marketshare insurance?) and can save on co-pays for patients who need a boosted protease inhibitor. But newer PIs, like Reyataz and Prezista, have replaced it as the preferred first line PI-based regimens. However, it still remains the preferred PI for pregnant women. -- Jeff Taylor