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. Of note, Norvir is not interchangeable with Tybost. Also, Norvir tablets are not interchangeable with Norvir capsules. 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, increased appetite, 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. Taking Norvir with most other blood thinners (anticoagulants), such as Xarelto, is not recommended; however, it can be used with apixaban (Eliquis) with monitoring and an adjusted dose of apixaban. 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 four 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 a 2–3-fold increase in methamphetamine concentrations, increasing the risk for overdose. GHB, another street drug, as well as cocaine are 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 many other drug interactions that are not listed here.

The advantage of Norvir is its use at low doses with other protease inhibitors (PIs) as a boosting agent (officially in the drug class called “pharmacokinetic enhancers”). As such, it’s used to increase the levels of some PIs. 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. Melanie Thompson:

Ritonavir is now used only as a booster to raise the levels of other drugs, usually other protease inhibitors. Its main downside is the long list of drug interactions it causes, some of them dangerous. If you take ritonavir, always consult your HIV care provider before taking OTC drugs, and always inform anyone who is prescribing drugs for you that you are taking ritonavir. Sadly, not all care providers are familiar with its drug interactions. Pharmacists, on the other hand, are awesome at this. You can look up drug interactions at hiv-druginteractions.org.

The most common side effects are gastrointestinal, including diarrhea, nausea, and vomiting. Some liver toxicity also has been seen, and ritonavir raises triglyceride levels. Somewhat unusual but common side effects include tingling of the mouth and taste disturbance. These are all less at lower doses that are used for boosting.

The breaking news about ritonavir is that it is now packaged as a component of Paxlovid, a new oral COVID treatment (see page 17). People already taking ritonavir or cobicistat can add Paxlovid to the mix (only 5 days of treatment) as it should not cause additional drug interactions. It could cause some additional side effects, so this should be discussed with an HIV care provider, if possible; if you are prescribed Paxlovid by someone other than your HIV care provider, be sure they are aware of all of the medicines you take. HIVMA and IDSA have made some recommendations here: idsociety.org/globalassets/covid-19-real-time-learning-network/patient-populations/hiv/oral-covid-tx-considerations-for-people-with-hiv-and-hcv.pdf. The NIH COVID-19 and treatment guidelines panel has a statement on Paxlovid here: covid19treatmentguidelines.nih.gov/therapies/statement-on-paxlovid-drug-drug-interactions/.

Activist Michael Broder:

At therapeutic doses, Norvir may cause considerable nausea, vomiting, and diarrhea, so it was not an ideal choice for treatment. Boosting of PIs with low-dose Norvir became standard. A downside of boosting is that it may increase side effects of the boosted PI. And Norvir, even at low doses, may still cause GI side effects. Given newer options, there is little need for a boosted PI these days. If your provider recommends a Norvir-containing regimen, they may have a good reason, but make sure they tell you what it is.