POSITIVELY AWARE MARCH/APRIL 2011
brand name: Norvir
common name: ritonavir
class: Protease inhibitor (PI)
manufacturer: Abbott Laboratories | www.norvir.com, (800) 222–6885
Standard dose: 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 with a meal. 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 tablets; $1,728.24 for 240 ml oral solution (80 mg/ml)
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, or jaundice (yellowing of skin), and increased muscle enzyme (CPK) and uric acid. People with hepatitis B or C may be at increased risk. There can be increased levels of cholesterol and triglycerides which may be associated with an increased risk of 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 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
Norvir interacts with many other drugs. See the package insert for the most complete list. Tell your provider of all drugs you are taking, prescribed or non-prescribed. Do not take with alfuzosin, Revatio, Tambocor, Rythmol, Cordarone, oral Versed, Halcion, Uroxatral, Rifadin (rifampin—reduces Norvir levels by 35%), Orap, 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, Livalo, Mevacor, Simcor, Vytorin, or Zocor for the treatment of high lipids. Lipid-lowering alternatives are Crestor, Lescol, Lipitor, and Pravacol, but should be used with caution. Norvir increases levels of fluticasone (active component of Advair, Flonase, and 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. 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. Increases up to 80% have been seen in Biaxin (clarithromycin) levels. Use with caution with bosentan, salmeterol, immunosuppressants (including transplant drugs), and colchicine; use lower dose of colchicine.
More information
Norvir is now available in a tablet formulation that does not require refrigeration. Although the tablet is not bioequivalent to the capsule, no dosage adjustment is needed. Blood concentration is higher with the tablets when taken with food (as required), and may cause more side effects. 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 in the doghouse with both medical providers and advocates since. A promising alternative to Norvir boosting called cobicistat (GS 9350) is in research. In one study, similar efficacy, safety, and tolerability were seen with cobicistat compared to Norvir-boosted Reyataz, with Truvada backbone. However, this medication may cause kidney impairment. More research is underway. 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 liver impairment. See package insert for more complete information on potential side effects and interactions.
Doctor’s comments
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 in combination with Invirase. That regimen was mainly popular because it wasn’t Crixivan and it wasn’t full dose Norvir, but it was still tough to take. No one takes Norvir at those doses now. It’s used only because of its interactions with the other PIs, at “booster” doses of 100-200 mg per day, which prolong their half-lives, decrease dosing frequency, and reduce 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. Some drug companies are looking at alternative booster agents, which they hope will have the same boosting effect on PIs and other agents, but with advantages in terms of cost, tolerability, or the ability to co-formulate. —Joel Gallant, MD, MPH
Activist’s comments
A drug that set new lows in pharmaceutical greed when Abbott quadrupled its price back in 2003, and new highs in side effects with diarrhea, cramps, gas, increased cholesterol and lipids, and fat gain (remember “protease paunch”?), Norvir remains a necessary evil because of its unique ability to boost the level of protease inhibitors (and also other drugs like Viagra, but that’s another subject). It remains to be seen whether Gilead’s yet-to-be-approved booster cobicistat will be substantially better in terms of side effects than Norvir. In the meantime, patients who want the convenience of a once-a-day protease inhibitor, or need its boosting strength to overcome resistance, will have to continue to tough out the side effects and avoid or exercise caution with the long list of drugs with which it can interact. —Jeff Taylor
