Norvir
Common Name: ritonavir
Brand Name: Norvir
Class: HIV protease inhibitor (PI)
Standard dose: New 100 mg tablets that don’t require refrigeration became available as PA went to press (photo not available); must be taken with a meal. Almost never used at its approved dose (a lead-in dosing, then six 100 mg tablets twice daily). Norvir is primarily used as a boosting agent for other PIs, at smaller doses of 100 to 400 mg, either once or twice a day. See drug label of the other PI. Take missed dose as soon as possible, unless it is almost time for your next dose. Do not double up on your next dose. Approved for children ages one month and older. Liquid formula available, but tastes unbelievably horrific.
AWP: $308.60 / for 30 capsules, $1,728.24 for 240 ml oral solution (80 mg/ml). Pricing for tablets unavailable at press time.
Manufacturer contact: Abbott Laboratories,
www.norvir.com, 1 (800) 222–6885
Potential side effects and toxicity: Most common side effects include weakness, stomach pain, upset stomach (nausea, diarrhea, and vomiting), tingling/numbness around the mouth, hands or feet, loss of appetite, taste disturbance, weight loss, headache, dizziness, pancreatitis (see NRTIs), and alcohol intolerance.
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.
Other potential side effects are liver problems, such as an increase in liver enzymes (AST, ALT, and GGT), hepatitis, or jaundice (yellowing of skin), and increased muscle enzyme (CPK) and uric acid. People with hepatitis B or C may be at increased risk.
Potential drug interactions: Norvir interacts with many other drugs. See the manufacturer package insert for the most complete list. Tell your provider of all drugs you are taking, prescribed or non-prescribed. Do not take with Tambocor, Rythmol, Cordarone, Versed (midazolam), Halcion (triazolam), Uroxatral, Rifadin (rifampin reduces Norvir levels by 35%), Orap (pimozide), ergot derivatives (such as Cafergot, Wigraine, Methergine, and D.H.E. 45), Vfend (voriconazole), 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. Norvir increases levels of fluticasone (active component of Advair, Flonase, Flovent). Trazodone concentrations may increase; a lower dose of trazodone is recommended. Norvir and Aptivus may decrease levels of methadone, but withdrawal rarely occurs. Methadone doses may need to be increased. Use caution with anti-convulsants: Tegretol (carbamazepine), phenobarbital, and Dilantin (phenytoin). Use calcium channel blockers (such as Norvasc, Procardia, and others) with caution. 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. The effectiveness of birth control pills may be decreased when taking Norvir; alternative or additional contraception methods with barrier should be used.
Levels of the street drug Ecstasy are greatly increased by Norvir, and at least one death has been attributed to the combination. GHB is also dangerous with Norvir. Tobacco and alcohol may lower blood levels of Norvir. Increases seen in Biaxin (clarithromycin) levels by 80%. Contains alcohol (but should not be enough to trigger relapse), so be cautious with Antabuse (disulfiram) or Flagyl (metronidazole)—greatly hastens intoxication.
Tips: There is great excitement for the new tablet formulation (which became available at press time) that doesn’t require refrigeration and high hopes for a co-pay assistance card. The real strength of Norvir is in combination with other PIs (used as a boosting agent), allowing for a lower dose of both (decreased pill burden) and, in many cases, a decrease in the frequency of doses. Abbott Laboratories increased the price of Norvir 400% in 2003 and has been on the hit list of medical providers and advocates since. Promising alternatives to Norvir boosting are in research. Stomach side effects are reduced by taking Norvir with high fat foods (such as peanut butter or avocado)—however, be careful because some other HIV medicines should not be taken with high fat foods. You can mix liquid solution in ice cream, milk (especially chocolate), or pudding to hide the taste. Label says mix one hour before taking. Blood concentration increases in people with hepatic (liver) impairment. Please see package insert for more complete potential side effects and interactions.
Doctor
Norvir (ritonavir) was originally approved in 1996 for use as an extraordinarily bitter liquid taken twice daily in combination with other antiretroviral drugs in the treatment of HIV infection. In 1999, a soft-gel capsule formulation of the drug was approved and the original formulation was used far less often. The nearly only use of this drug is due to an important drug interaction it has with other PIs—it blocks the enzyme that breaks down other protease inhibitors, which then provides higher and more effective blood levels of that PI. Most all use of protease inhibitor drugs is when they are “boosted” with low-dose ritonavir, as boosted PIs are more successful than their unboosted versions. However, it also blocks the metabolism of several other drugs, not just protease inhibitors, and that leads to an important consideration when prescribing other medications to people on boosted PIs. While the current capsule does not require refrigeration, it is sensitive to heat and must be kept at “room temperature,” not in a warm place or else the capsule can melt. [A reformulated tablet version was approved as PA went to press.] The search is ongoing for an alternative booster drug; however, there are several expected side effects such as diarrhea with even low-dose ritonavir, and some patients just do not feel well when taking it. However, low-dose ritonavir has made a profoundly important impact by improving the efficacy and durability of PI-based HAART. —Cal Cohen, MD
Activist
A necessary evil—without Norvir, many PIs would be useless or have a much less convenient dosing schedule. But the GI side effects (diarrhea, gassiness, stomach cramping, and did I mention diarrhea?) can destroy quality of life for many. With a list of drug interactions longer than some phone books, it’s a daunting drug to add to the multiple meds many HIVers have to take. Even though the Norvir contained in Abbott’s PI Kaletra has long been available in a non-refrigerated Meltrex forumulation, it took years for them to do the same thing for the just-approved Meltrex version of Norvir. Can we say “preserve Kaletra’s marketshare”? Additionally, Abbott’s egregious pricing history has made this a justly maligned drug—with many hoping for a new booster to replace it altogether so they can celebrate its demise. —Jeff Taylor
