Brand name: Norvir
Generic name: ritonavir, or RTV
Class: Protease inhibitor (PI)
Manufacturer: Abbott Laboratories, www.norvir.com, (800) 222-6885
AWP: $314.99/month for 30 tablets; $1,728.24 for 240 mL oral solution (80 mg/mL)
Standard Dose: Almost never used at its approved dose (a lead-in dosing, then six 100 mg tablets twice daily). Do not crush or chew tablets, always swallow whole. Norvir is primarily used as a boosting agent for other PIs (increases the levels of other PIs so that they can be taken less often), at smaller doses of 100 to 400 mg, either once or twice a day with a meal. See drug label of the other PI. Always take Norvir at the same time as the other PI prescribed by your provider. Take missed dose as soon as possible, unless it is closer to the time of your next dose. Do not double up on your next dose. Approved for children ages one month and older. Liquid formulation available, but it tastes horrible.
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; and alcohol intolerance. Other potential side effects are liver problems, such as an increase in liver enzymes (AST, ALT, and GGT), hepatitis, jaundice (yellowing of skin), and increased muscle enzyme (CPK) and uric acid. People with hepatitis B or C may be at increased risk. 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, Halcion, Rifadin, Orap, Vfend (voriconazole), 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. Cholesterol-lowering alternatives are Crestor, Lescol, Lipitor, and Pravacol (pravastatin), but should be used with caution and started at the lowest dose possible; monitor closely for increased side effects from these medications. 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). Trazodone concentrations may increase; a lower dose of trazodone is recommended. Norvir and Aptivus may decrease levels of methadone and methadone may need to be increased, but withdrawal rarely occurs. 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. Effectiveness of birth control pills may be decreased; consider the use of alternative or additional contraception. 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. Biaxin (clarithromycin) levels can increase by up to 80%. Use with caution with bosentan, salmeterol, and immunosuppressants; lower colchicine dose. 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: The real strength of Norvir is its use with other PIs as a boosting agent, allowing for a lower dose of both and, in many cases, less frequent dosing. A promising alternative to Norvir boosting called cobicistat is in research, and is expected to be approved this year (see cobicistat). In one study, similar efficacy, safety, and tolerability out to 48 weeks were seen with cobicistat- vs. Norvir-boosted Reyataz. Blood concentration is higher with Norvir tablets when taken with food (as required), and may cause more side effects. Stomach side effects are reduced by taking Norvir with high-fat foods (such as peanut butter) -- however, 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 liver impairment. Abbott Laboratories increased the price of Norvir 400% in 2003 and has been in the doghouse with both providers and advocates since. See package insert for more complete information on potential side effects and interactions.
Norvir enjoyed very brief use as a PI in its own right, but the people who took it at its full, virtually intolerable dose of 600 mg twice a day didn't enjoy it at all. The dose was then reduced to 400 mg twice a day taken with Invirase. That regimen's claim to fame was that it wasn't Crixivan and it wasn't full-dose Norvir, but it was still tough to take. Now, it's used only because of its interactions with the other PIs, at "booster" doses of 100-200 mg per day. This prolongs their half-lives, decreases dosing frequency, and reduces the risk of drug resistance. All PIs except Viracept can be boosted by Norvir, and the only PIs that can be given unboosted are Viracept and Reyataz. Of those, I would never prescribe an unboosted PI other than Reyataz, and I do that only for my patients whom I refer to as "ritonophobes," people who, perhaps because of a Pavlovian response to memories of high-dose Norvir, get nauseated just by looking at the bottle. Norvir now comes in a heat-stable tablet, so it no longer requires refrigeration. We're expecting approval of cobicistat, a non-Norvir booster, later this year, which should allow for co-formulation with PIs like Reyataz and Prezista, and which will also be used to boost elvitegravir, a new integrase inhibitor.
-- Joel Gallant, M.D., M.P.H.
Norvir is the ultimate "Catch-22" of the HIV drug world. Originally a protease inhibitor itself in the earliest days, it was unrealistic to tolerate it, much less stay on it for long periods of time. Then Abbott finds a boosting feature, and voilà, a new reason to market the "almost dead" drug again! Now at much lower doses, it acts as a booster for other drugs. The company has made many mistakes over the years in regard to pricing and not working with other companies to co-formulate this drug. Patients wanting a once-a-day protease inhibitor will have to continue to deal with the uncomfortable side effects and be careful with the long list of drugs which interact with Norvir; even the booster amounts can cause reactions. I used to get super angry when doctors would say "mild" diarrhea is one of the few effects, as if any diarrhea is easy to deal with, especially when you're out in public! Grrrrrrr.
-- Joey Wynn