Norvir

The side effect potential of Norvir is much lower now that it is only used as a booster at low doses. Most common side effects include stomach pain, nausea, diarrhea, and vomiting. Other less common side effects may include fatigue; tingling/numbness around the mouth, hands, or feet; loss of appetite; and taste disturbances. Norvir can also increase cholesterol and triglyceride levels. Measure liver function before starting and then monitor, with perhaps closer monitoring for those with underlying liver problems, especially during the first several months. No dose adjustment necessary with mild to moderate liver disease, but Norvir is not recommended for those with severe liver impairment.

Norvir interacts with many drugs. Do not take with alfuzosin, amiodarone, flecainide, lurasidone, propafenone, oral midazolam, triazolam, pimozide, ranolazine, Revatio, rifapentine, rifampin, voriconazole, ergot derivatives, or the herb St. John’s wort. Do not use lovastatin or simvastatin or co-formulations containing these drugs (Advicor and Vytorin) for the treatment of high cholesterol. Cholesterol-lowering alternatives are atorvastatin, rosuvastatin, pravastatin, pitavastatin, and fluvastatin, but should be used with caution and started at the lowest dose possible; monitor for increased side effects. Norvir increases levels of nasal and inhaled fluticasone (found in Advair, Flonase, Breo Ellipta, Arnuity Ellipta, and Flovent), which may lead to Cushing’s syndrome. Use an alternative corticosteroid and monitor for signs of Cushing’s syndrome (increased abdominal fat, fatty hump between the shoulders, rounded face, red/purple stretch marks, bone loss, possible high blood pressure, and sometimes diabetes). Trazodone concentrations may increase; a lower dose of trazodone is recommended. Norvir may decrease levels of methadone, therefore titrate dose of methadone to clinical effect. Use caution with anticonvulsants such as carbamazepine, phenobarbital, and phenytoin. Use calcium channel blockers (amlodipine, nifedipine, and others) with caution. Norvir may alter warfarin levels; additional monitoring is required. Norvir use with other blood thinners (anticoagulants), such as Xarelto, is not recommended. Norvir can increase anticoagulant concentrations (and thereby increase risk of bleeding) or decrease their concentrations (and thereby decrease effectiveness). 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. Monitor for increased side effects of these medications, such as visual disturbances, low blood pressure, dizziness, and prolonged painful erection lasting longer than 4 hours. Effectiveness of oral contraceptives may be decreased; consider using other or alternative methods of contraception. Levels of the street drug ecstasy are greatly increased by Norvir, and at least one death has been attributed to the combination. Using Norvir with methamphetamines can result in up to 2–3 fold increase in methamphetamine concentrations and puts user at risk for overdose. GHB, another street drug, is also dangerous with Norvir. Clarithromycin levels can increase by up to 80%. Co-administer bosentan, salmeterol, and immunosuppressants with caution. If co-administered, a lower dose of colchicine is recommended. Norvir, when combined with another PI, may be taken with Sovaldi, Daklinza (dose may need adjustment), Epclusa (monitor for tenofovir toxicity if TDF is part of regimen), and Harvoni (if TDF is not part of HIV regimen). Norvir + PI should not be taken with Olysio, Viekira Pak, or Zepatier. Tell your provider or pharmacist about all medications, herbals, and supplements you are taking or thinking of taking, prescribed or not, as there are other drug interactions which are not listed here.

The advantage of Norvir is its use with other PIs as a boosting agent (officially in the drug class called “pharmacokinetic enhancers”). As such, it’s used to increase the levels of some HIV protease inhibitor (PI) medications. An alternative to Norvir was approved in 2014 (see Tybost page). Stomach side effects are reduced by taking Norvir with high-fat foods—however, some other HIV medicines should not be taken with high-fat foods.

Dr. David Hardy says:

Norvir was the second protease inhibitor approved to treat HIV, in early 1996. Over a short period of time its significant side effects of nausea, vomiting, severe queasiness, and explosive diarrhea (when taking 1,200 mg/day) reduced its use as a protease inhibitor. By the late 1990s, it was used as the first booster (taking 100-400 mg/day) for almost all other protease inhibitors (except Viracept) and markedly increased the potency and reduced the number of doses of protease inhibitors. Even at lower doses, some PLWH have side effects such as nausea, queasiness, and diarrhea.

Activist Moisés Agosto-Rosario says:

Once upon a time Norvir, or ritonavir, was approved as a treatment for HIV. It was one of the first PIs that slowed the death rates of HIV. For many, it was the rescuer from certain death. As with the other first generation PIs, it causes many debilitating side effects, including gastrointestinal problems and increased risk for liver toxicity. Because of the way it is metabolized, ritonavir increases the blood level of other drugs. It was hard to take because of its toxicities and drug interactions. Even though it failed as a treatment, it has proven to be, at a lower dose, an effective booster for newer and safer PIs.