Potential side effects and toxicity: Potential side effects include: headache, fatigue or weakness, malaise (general ill feeling), nausea, diarrhea, stomach pains, loss of appetite, yellowing of skin/eyes, changed skin color, dry mouth/sore throat, taste changes, painful urination, indigestion, joint pain, hives, and liver toxicity. Itchy/dry skin, ingrown toe nails and hair loss are unique to Crixivan. Kidney stones, which may lead to more serious problems, can also occur. If pain develops in the middle to lower stomach or the back, or if there is blood in the urine call your healthcare provider immediately. Drugs such as Bactrim and Dapsone are associated with hemolytic anemia, so be careful when using indinavir. Hemolytic anemia is the fast breakdown of red blood cells. It is rare but can lead to severe problems—monitoring red blood counts is necessary. An increase in bilirubin (a test of liver function) has been reported, but it is not associated with liver problems. It may sometimes cause yellowing of the skin or eyes. 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 Tambocor (flecainide), Rythmol (propafenone), Versed, Halcion, Hismanol, Seldane, rifampin, pimozide (a psychiatric drug), 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 (simvastatin) or Mevacor (lovastatin); lipid-lowering alternatives are Lipitor (atorvastatin), Lescol, and Pravachol (pravastatin), but they should be used with caution due to potential for liver toxicity.
Increase Crixivan to 1,000 mg every eight hours when taken with Viramune or Sustiva, or take Crixivan boosted by Norvir. Not recommended in combination with Reyataz. Reduce Crixivan to 600 mg every eight hours when taken with Rescriptor. Reduce Crixivan to 600 mg every eight hours when taken with Sporanax (itraconazole, 200 mg twice-a-day) or Nizoral (ketoconazole, 200 mg once-a-day) or ketoconazole.
The dose of rifampin (Mycobutin) should be reduced by 50% and increase Crixivan dose to 1000 mg every eight hours when taken together.
Protease inhibitors increase blood levels of Viagra (sidenafil citrate), Cialis (tadalafil) and Levitra (vardenafil). 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: Combining PIs continues to be a common practice today—some combinations with lower doses of Crixivan include: Crixivan 1200 mg with 1250 Viracept each twice-a-day; and Crixivan 600 mg with standard dose of Kaletra each twice-a-day. It is recommended that you drink at least 48 oz of fluids daily, preferably water or clear liquids (soda pop doesn’t count!) to decrease the chances of a kidney stone forming. Don’t forget to drink more water in summer or with increased sweating. Large amounts of coffee or alcohol can increase risk of stones due to increased dehydration. Stones may continue after stopping Crixivan. Grapefruit juice decreases Crixivan blood levels. Should be stored in original container and kept dry.
Doctor
Indinavir (IDV) was once the most widely prescribed protease inhibitor, and with good reason. It was very potent and many patients started on this agent years ago are still virologically suppressed. The main drawback initially was three times a day dosing on an empty stomach, but this was eliminated with the use of boosting with ritonavir. Additionally it had to be taken with large quantities of water to prevent the formation of painful kidney stones. Boosting has not eliminated the risk of stones, so it still requires large amounts of water. As with other protease inhibitors, gastrointestinal effects are common and hyperlipidemia is also a concern. In rare circumstances, this agent may lead to hyperbilirubinemia (a pigment made by the liver which can lead to jaundice), but this does not require discontinuation of the drug.—Chad J. Zawitz, MD
Activist
The PI that saved our lives and that we now ungratefully love to hate. When it first entered the market, it was a true hardhitter and the best PI at the time. We had to take it three times a day on an empty stomach, which would get even more complicated if you took it with ddI. Many blame Crixivan for the lipo belly, although this problem is not isolated only to this PI. Norvir bosting made it more convenient to take it twice a day with food, but its typical side effects increased (kidney stones, liver dysfunction, ingrown toe nails, hair loss, and insulin resistance/diabetes). These problems were added to the lipo belly and fat wasting when Crixivan was successfully used with ddI+d4T, a now defunct regimen that people avoid. It is the cheapest Norvir-boosted PI, but it has fallen out of grace in the developed world.—Nelson Vergel
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