Brand name: Kaletra

Generic name: lopinavir/ritonavir, or LPV/r

Class: Protease inhibitor (PI)

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

AWP: $904.99/month for tablets, $420.95 for 160 mL solution

Standard Dose: Two tablets (200 mg lopinavir/50 mg ritonavir) twice a day or four 200/50 mg tablets once daily for people with less than three lopinavir resistance-related mutations, 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, pregnant women during the second and third trimesters, or those taking it with Sustiva or Viramune. Can be taken by children older than 14 days. 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 (400 mg/5 mL lopinavir, 100 mg/5mL ritonavir) is available. Take missed dose as soon as possible, unless it is closer to the time of your next dose. Do not double up on your dose.

Potential side effects and toxicity: Diarrhea is the most common and can be severe, but may be less severe with the tablets. 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). See chart for potential drug class side effects.

Potential drug interactions: PIs interact with many other drugs. See package insert for the most complete list. Tell your provider or pharmacist about all medications, herbs, and supplements you are taking or thinking of taking, prescribed or not. Do not take with alfuzosin, Revatio, Tambocor, Rythmol, Cordarone, oral Versed (midazolam), Halcion, Incivek, rifampin, pimozide, 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 cholesterol. Alternatives are Crestor, Lescol, Lipitor, and Pravacol, but should be used with caution and started at the lowest dose possible; monitor closely for increased side effects from these medications. Oral solution contains alcohol, so do not use with Antabuse or Flagyl. Use calcium channel blockers (such as Norvasc and Procardia) with caution. Dosage of methadone may need to be increased. Because of high pill burden, physicians usually prescribe three tablets twice a day with food of the 200/50 mg dose when using with Sustiva or Viramune. Current guidelines state the Kaletra dose should total 500 mg lopinavir and 125 mg ritonavir twice daily when used with Sustiva or Viramune. Not recommended to be taken with Lexiva. Kaletra may lower levels of Retrovir (zidovudine) 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. If taking Kaletra with Viread or combinations containing tenofovir, you should be monitored for side effects from tenofovir as Kaletra increases its levels. Rifabutin 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. Monitor for side effects when taken with Noxafil. Decreases Vfend levels. People with kidney impairment may require lower Biaxin doses with Kaletra. Blood levels of immunosuppressants should be monitored, because levels may increase. Kaletra may alter Coumadin (warfarin) levels; additional monitoring may be required. Steroids, especially Decadron, may decrease levels of Kaletra. Kaletra increases levels of fluticasone (found in Advair, Flonase, and Flovent), use only if the benefits outweigh the risks, and monitor for signs of Cushing's syndrome (increased fat in the abdomen, fatty hump between the shoulders, rounded face, red/purple stretch marks on the skin, bone loss, possible high blood pressure, and sometimes diabetes). Kaletra increases levels of trazodone. Use caution with anti-convulsants Tegretol, phenobarbital, and Dilantin, as they may lower 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, and immunosuppressants, and use lower dose of colchicine. Kaletra can decrease the effects of Malarone. Use of the hepatitis C drug Victrelis (boceprevir) along with a Norvir-boosted PI can potentially reduce the effectiveness of both drugs -- combined use is not recommended.

More information: According to U.S. HIV treatment guidelines, the need for 200 mg a day of Norvir (contained in Kaletra) and the higher rate of gastrointestinal side effects compared to other 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. Kaletra should not be taken once a day by children under 18. Kaletra solution cannot be given to premature babies until 14 days after their due date because it contains propylene glycol, which infants can not eliminate very well from their bodies. 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 Norvir-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 position for many years. However, Kaletra use has been declining, 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 once daily 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, though that's likely to change soon with the imminent approval of cobicistat, a booster that can be more easily co-formulated with other PIs.

-- Joel Gallant, M.D., M.P.H.

Activist's Comments

Once the "lion" of the protease inhibitor class, Kaletra is no longer a preferred drug in DHHS treatment guidelines. Amazing clinical results for most helped it hold the title for quite some time, but the downsides started to weigh heavily as newer agents with fewer side effects came to market. Kaletra has interactions with many drugs, especially Viagra and some female contraceptives, plus it has the lipid problems of many of the older PIs. Pricing scandals and Abbott's unwillingness to work with other companies to co-formulate their Norvir boosting agent with another's drugs didn't help with community sentiment about their products, although their co-pay cards are pretty easy to use. Kaletra remains one of the best treatments for pregnant women. Otherwise, mixed reviews at best in this day and age.

-- Joey Wynn

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