POSITIVELY AWARE MARCH/APRIL 2011
brand name: Kaletra
common name: lopinavir/ritonavir, or LPV/r
class: Protease inhibitor (PI)
manufacturer: Abbott Laboratories | www.kaletra.com, (800) 222–6885
Standard dose: Two 200/50 mg tablets twice a day or four 200/50 mg tablets once daily for people with less than 3 lopinavir resistance-related substitutions, as shown on a resistance test (no once-daily dose if taken with Sustiva or Viramune, or anticonvulsants). 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. Can be taken with or without food, with no dietary restrictions, but preferably taken 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 (400 mg/5 ml lopinavir and 100 mg/5ml ritonavir)
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 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
Do not take with alfuzosin, Revatio, 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 Advicor, Altoprev, Livalo, Mevacor, Simcor, Vytorin, or Zocor for the treatment of high lipids. Lipid-lowering alternatives are Crestor, Lescol, Lipitor, and Pravacol, but should be used with caution. Oral solution contains alcohol, so do not use with Antabuse or Flagyl. 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. 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 dosage should be reduced to 150 mg every other day (or 150 mg three times per week) when used with Kaletra. Effectiveness of birth control pills may be decreased; consider the use of alternative or additional contraception. Mepron levels may be reduced with Kaletra. Avoid Sporanox or Nizoral doses greater than 200 mg per day with Kaletra. Decreases Vfend levels. People with kidney impairment may require lower Biaxin doses with Kaletra. Blood levels of immunosuppressants should be monitored, because their blood levels may increase when taken with Kaletra. Kaletra may alter Coumadin levels; additional monitoring may be required. Steroids, especially Decadron, may decrease levels of Kaletra. Kaletra increases levels of fluticasone (active component of Advair, Flonase, and Flovent) and trazodone. Use caution with anti-convulsants: Tegretol, phenobarbital, and Dilantin, as they may lower blood levels of Kaletra. 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. Use with caution with bosentan, salmeterol, immunosuppressants (including transplant drugs), and colchicine; use lower dose of colchicine. Kaletra can decrease the effects of Malarone; consider alternative drug for malaria prophylaxis.
More information
In December 2009, Kaletra, like Lexiva, was downgraded from “preferred” to “alternative” therapy for treatment-naïve people in the U.S. HIV treatment guidelines. For people doing well on Kaletra, this should not be an issue. Kaletra is preferred, however, for pregnant women with twice-daily dosing only. Once-daily dosing cannot be taken by people with more than three Kaletra-related HIV mutations. 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-naïve people. Four tablets once daily can increase side effects, especially diarrhea. Taking with food and anti-diarrheal medicine helps lessen diarrhea. A few studies have shown an increased risk in heart attacks, not explained by cholesterol increases. Kaletra should not be taken only once a day by children under 18. See package insert for more complete information on potential side effects and interactions.
Doctor’s comments
Kaletra transformed our use of HAART, ushering in the widespread use of ritonavir-boosted PIs, not just for treatment-experienced patients, but for anyone using a PI. The advantages of boosting include less frequent dosing and a big barrier to resistance, especially if you have no PI resistance to start with. Kaletra was far easier and better tolerated than drugs like Crixivan, and more effective than Viracept, which was in common use at the time of its approval. It became the gold-standard PI and maintained that title for many years. However, Kaletra use has declined in the last few years, and it’s now considered a preferred PI only for pregnant women. It’s increasingly being replaced by Norvir-boosted Prezista and Reyataz, which can be taken with just 100 mg per day of Norvir compared to 200 mg in a daily dose of Kaletra. These drugs cause less diarrhea and lipid elevation than Kaletra. Kaletra still has the advantage of being the only co-formulated PI, meaning that you don’t have to take Norvir as a separate tablet. This can reduce co-pays, and it also makes it impossible to take the PI without the ritonavir needed to achieve adequate drug levels. —Joel Gallant, MD, MPH
Activist’s comments
No longer a preferred regimen in the treatment guidelines, Kaletra has the GI and lipid problems of many older PIs, as well as a host of drug interactions. Recent studies have shown it not to be as durable as Prezista, so it is losing ground to that and the more lipid-friendly Reyataz. All this despite Abbott’s efforts to combine it with their new non-refrigerated Norvir for convenience, and their shameful refusal to make that same non-refrigerated Norvir available to be combined with competing PIs for years in a desperate attempt to preserve market share. —Jeff Taylor
