Norvir

Protease Inhibitor

Common Name: ritonavir (RTV)

Brand Name: Norvir

Class: HIV protease inhibitor (PI)

Standard dose: Almost never used at its approved dose (a lead-in dosing, then six 100 mg soft gelatin capsules twice daily, preferably with food -- dose escalation is important to avoid side effects). 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. Take missed dose as soon as possible, but do not double up on your next dose. Approved for children ages one month and older. Liquid formula available, but tastes unbelievably horrific. (As PA went to press, Abbott filed with the FDA to register a new tablet formulation of Norvir that will not require refrigeration.)

AWP: $321.46 / month for 30 capsules

Manufacturer contact: Abbott Laboratories,
www.norvir.com, 1 (800) 222-6885

AIDSInfo:
1 (800) HIV-0440 (448-0440), www.aidsinfo.nih.gov

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 sometimes the 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; report symptoms of illness, such as shingles and TB, to 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. Do not take with Tambocor, Rythmol, Cordarone, oral Versed (midazolam), Halcion (triazolam), Uroxatral, Rifadin (rifampin), Orap (pimozide), ergot derivatives (such as Cafergot, Wigraine, Methergine, and D.H.E. 45), Antabuse (disulfiram) or Flagyl (metronidazole), garlic supplements, or the herb St. John's wort. Do not use Zocor or Mevacor; lipid-lowering alternatives are Lipitor, Lescol (fluvastatin), and Pravachol, but they should be used with caution due to potential for liver toxicity. Increases levels of fluticasone (active component of Advair, Flonase, Flovent) and trazodone (Desyrel). 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.

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; women and their male partners should consider the use of alternative contraception methods with barrier.
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%. Rifampin decreases Norvir levels by 35%. Contains alcohol (but should not be enough to trigger relapse), so be cautious with Antabuse (disulfiram) or Flagyl (metronidazole) -- greatly hastens intoxication.

Tips: The real strength of Norvir is in combination with other PIs (used as a boosting agent), allowing for a lower dose of both and in many cases decreasing the frequency of doses. 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, or pudding to hide the taste. The capsules contain castor oil and have bitter taste. Chocolate masks the taste. 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 for use in combination with other antiretroviral drugs in the treatment of HIV infection in 1996. In 1999, a soft-gel capsule formulation of the drug was approved and the original formulation was discontinued. This antiretroviral was difficult to take and few could tolerate it. Before the soft gel capsule, there was a time when only ritonavir liquid was available. This stuff was not palatable. "I'd rather eat re-fried cow pies than take that liquid," said one of my patients. I tried it and totally agreed. Even with the new formulation of the drug (no refrigeration needed), acceptance of this drug was poor. It was dead in the water. Drug interactions with other PIs saved this drug. Now ritonavir is used not so much for its antiretroviral activity, but more for its ability to inhibit the enzyme that breaks down other protease inhibitors (leading to higher blood levels of the PIs). This allows health care providers to lower the dose and frequency of the PI administration, while improving efficacy. Most all protease inhibitor drugs are now boosted with low-dose ritonavir. While the search is ongoing for another protease booster drug, low-dose Norvir has made a significant impact on the efficacy and durability of HAART therapy. -- Frank M. Graziano, M.D., Ph.D.

Activist

Norvir was initially used as a stand-alone PI when it came onto the market in 1997. Twelve pills a day, a bad side effect profile and a myriad of drug interactions made it of little use. But that didn't stop Norvir's manufacturer, Abbott Laboratories, from jacking up its price by 400% (I would be remiss if I didn't mention this egregious fact). Today, Norvir is primarily prescribed as a 100 mg booster of other PIs (except with Aptivus), thus lowering their dosing requirements and raising their blood levels. But in doing so, it stifles a natural liver function, keeping the liver from doing what it was designed to do: filter out and protect the body from harmful substances. Norvir can still cause gastrointestinal side effects, but taking it with foods high in fat, like peanut butter (provided the January 2009 salmonella scare abates) or avocado, can help reduce stomach issues. I won't even discuss the liquid version except to say that it exists. -- Morris Jackson

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