Crixivan

Common Name: indinavir sulfate

Brand Name: Crixivan

Class: HIV protease inhibitor (PI)

Standard dose: Rarely used by itself (two 400 mg capsules every eight hours with no food or a low-fat snack). Almost always boosted with Norvir, both twice daily: 400 mg Crixivan + 400 mg Norvir; 800 mg + 100 mg; or 800 mg + 200 mg (all doses taken with food, and with plenty of water to avoid kidney sludge or stones). Take missed dose as soon as possible, unless it is almost time for your next dose. Do not double up on your next dose. Also available in 100 mg, 200 mg, and 333 mg capsules.

AWP: $548.12 / month for 400 mg, 180 capsules

Manufacturer contact: Merck and Co., www.crixivan.com, 1 (800) 850-3430

Potential side effects and toxicity: 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 health care provider immediately. 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 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: Do not take with Tambocor (flecainide), Rythmol (propafenone), Cordarone (amiodarone), midazolam, triazolam, 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.

Not recommended in combination with Reyataz. Reduce Crixivan to 600 mg every eight hours when taken with Rescriptor, itraconazole (200 mg twice a day), or ketoconazole (200 mg once a day). The dose of Mycobutin should be reduced to 150 mg daily or 300 mg three times a week and Crixivan dose increased to 1,000 mg every eight hours or use Norvir-boosted dose when taken together.

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.

Effectiveness of birth control pills may be decreased; consider the use of alternative or additional contraception. Additional monitoring may be required when taking Coumadin (warfarin), immunosuppressants, or calcium channel blockers (such as Norvasc, Procardia, and others). Use caution with anti-convulsants: Tegretol (carbamazepine), phenobarbital, and Dilantin (phenytoin). Crixivan may decrease levels of methadone, but withdrawal rarely occurs. Methadone doses may need to be increased. Also, increased levels of trazodone can occur with Crixivan. Increased levels of the inhaled and nasal sprays with fluticasone, a steroid for asthma or allergies (found in Advair, Flonase, and Flovent) can occur with Crixivan and therefore should be used with caution.

Tips: Drink at least 48 oz. of fluids daily, preferably water or clear liquids (soda pop doesn't count!) to decrease the chances of kidney stones. 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 and vitamin C (more than one gram a day) decreases Crixivan blood levels. Store in original container and keep dry. Please see package insert for more complete potential side effects and interactions.

Doctor

Crixivan (indinavir) was approved for use with other antiretroviral drugs for HIV infection in 1996. While this drug did provide a high degree of virologic suppression when used in several combinations, there are several reasons why its use is rare at the present time. The first issue that was evident was its complex dosing as well as dietary restrictions -- two capsules had to be ingested every eight hours on an empty stomach or at least adequately separate from food. That issue was addressed by the addition of the booster drug ritonavir, allowing indinavir to be taken twice daily instead. However, other concerns remained, including a risk of kidney stones comprised of the drug. Finally, this drug seemed to be associated more with increased abdominal fat (in the area surrounding the intestines, behind the abdominal muscle) versus any other PI, and that was the beginning of the widespread concern for a condition later called "lipodystrophy." As there are better, safer choices in the PI class, this drug is rarely used at this time. -- Cal Cohen, M.D.

Activist

The drug that ushered in the Protease Revolution, its every-eight-hour dosing on an empty stomach -- with enough water to float a boat -- saved lives even as those lives came to revolve around the drugs that made life possible. Now boosted with Norvir, like most other PIs, for more convenient dosing with food, the risk of kidney stones, lipid problems and fat redistribution (remember "Crix belly"?) mean that it can't compete with the newer and improved PIs. So it has become a footnote in HIV history -- remembered with mixed emotions by those whose lives it saved. -- Jeff Taylor