What is Norvir (ritonavir)?
Norvir (ritonavir) is a type of antiviral drug called a protease inhibitor used to treat human immunodeficiency virus (HIV) infection.
During infection with HIV, the HIV virus multiplies within the body's cells. Viruses are released from the cells and spread throughout the body where they infect other cells. During the production of the viruses, new proteins are made. Some of the proteins are structural proteins, which are proteins that form the body of the virus. Other proteins are enzymes which manufacture DNA and other components for the new viruses. Protease is the enzyme that forms the new structural proteins and enzymes.
Norvir blocks the activity of protease and results in the formation of defective viruses that are unable to infect the body's cells. As a result, the number of viruses in the body (the viral load) decreases. Norvir does not prevent the transmission of HIV, and it does not cure HIV or AIDS.
Common side effects of Norvir include
- diarrhea,
- nausea and vomiting,
- changes in taste,
- abnormal skin sensations (burning, prickling and tingling),
- headache,
- weakness,
- insomnia (difficulty sleeping),
- fat redistribution,
- high cholesterol, and
- high triglycerides.
Serious side effects of Norvir include
- liver failure,
- inflammation of the pancreas (pancreatitis),
- heart block,
- severe allergic reactions,
- elevated blood glucose resulting in new onset diabetes,
- spontaneous bleeding in patients with hemophilia, and
- immune reconstitution syndrome (inflammatory response to combination antiretroviral therapy).
Norvir increases the blood levels of these drugs and may lead to serious side effects:
- amiodarone,
- quinidine,
- triazolam,
- midazolam,
- pimozide,
- ergot derivatives,
- alfuzosin,
- propafenone, and
- flecainide.
Norvir should not be combined with voriconazole because it reduces blood levels of voriconazole.
Norvir also increases the concentrations in blood of rifabutin and sildenafil. The blood concentrations of oral contraceptives, methadone, and theophylline are reduced by Norvir, and this could reduce the effectiveness of these drugs.
Norvir decreases the concentration of meperidine and reduces the effect of meperidine while increasing its side effects. Norvir may increase the blood concentration of lovastatin, simvastatin, and atorvastatin and may result in increased occurrence of muscle pain or rhabdomyolysis (muscle breakdown).
St. John's wort and rifampin decrease the concentration of Norvir in the body and may reduce the effectiveness of Norvir. Clarithromycin, ketoconazole, fluconazole, and fluoxetine may increase blood concentrations of Norvir and result in increased side effects from Norvir.
Norvir increases blood levels of sildenafil and the risk of side effects such as low blood pressure, prolonged erection, and fainting.
Use of Norvir during pregnancy has not been adequately evaluated. To monitor outcomes of pregnant women that received Norvir, an Antiretroviral Pregnancy Registry has been established. Physicians are encouraged to register patients by calling 1-800-258-4263. It is unknown if Norvir passes into breast milk. HIV-infected mothers should not breastfeed because of the potential risk of transmitting HIV to an infant.
What are the important side effects of Norvir (ritonavir)?
The most serious side effects are:
- liver failure,
- inflammation of the pancreas (pancreatitis),
- heart block, and
- severe allergic reactions.
Ritonavir also may elevate blood glucose resulting in new onset diabetes. Fat redistribution, elevated triglycerides, and elevated cholesterol levels also occur. Patients with hemophilia may experience spontaneous bleeding. Immune reconstitution syndrome which is an inflammatory response to infection may occur in patients treated with combination antiretroviral therapy.
Other important side effects include:
Norvir (ritonavir) side effects list for healthcare professionals
The following adverse reactions are discussed in greater detail in other sections of the labeling.
- Drug Interactions
- Hepatotoxicity
- Pancreatitis
- Allergic Reactions/Hypersensitivity
When co-administering Norvir with other protease inhibitors, see the full prescribing information for that protease inhibitor including adverse reactions.
Clinical Trial Experience
Because clinical trials are conducted under widely varying conditions, adverse reactions rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
Adverse Reactions In Adults
The safety of Norvir alone and in combination with other antiretroviral agents was studied in 1,755 adult patients. Table 2 lists treatment-emergent Adverse Reactions (with possible or probable relationship to study drug) occurring in greater than or equal to 1% of adult patients receiving Norvir in combined Phase II/IV studies.
The most frequently reported adverse drug reactions among patients receiving Norvir alone or in combination with other antiretroviral drugs were gastrointestinal (including diarrhea, nausea, vomiting, abdominal pain (upper and lower)), neurological disturbances (including paresthesia and oral paresthesia), rash, and fatigue/asthenia.
Table 2. Treatment-Emergent Adverse Reactions (With Possible or Probable Relationship to Study Drug) Occurring in greater than or equal to 1% of Adult Patients Receiving Norvir in Combined Phase II/IV Studies (N = 1,755)
Adverse Reactions | n | % |
Eye disorders | ||
Blurred vision | 113 | 6.4 |
Gastrointestinal disorders | ||
Abdominal Pain (upper and lower)* | 464 | 26.4 |
Diarrhea including severe with electrolyte imbalance* | 1,192 | 67.9 |
Dyspepsia | 201 | 11.5 |
Flatulence | 142 | 8.1 |
Gastrointestinal hemorrhage* | 41 | 2.3 |
Gastroesophageal reflux disease (GERD) | 19 | 1.1 |
Nausea | 1,007 | 57.4 |
Vomiting* | 559 | 31.9 |
General disorders and administration site conditions | ||
Fatigue including asthenia* | 811 | 46.2 |
Hepatobiliary disorders | ||
Blood bilirubin increased (including jaundice)* | 25 | 1.4 |
Hepatitis (including increased AST, ALT, GGT)* | 153 | 8.7 |
Immune system disorders | ||
Hypersensitivity including urticaria and face edema* | 114 | 8.2 |
Metabolism and nutrition disorders | ||
Edema and peripheral edema* | 110 | 6.3 |
Gout* | 24 | 1.4 |
Hypercholesterolemia* | 52 | 3.0 |
Hypertriglyceridemia* | 158 | 9.0 |
Lipodystrophy acquired* | 51 | 2.9 |
Musculoskeletal and connective tissue disorders | ||
Arthralgia and back pain* | 326 | 18.6 |
Myopathy/creatine phosphokinase increased* | 66 | 3.8 |
Myalgia | 156 | 8.9 |
Nervous system disorders | ||
Dizziness* | 274 | 15.6 |
Dysgeusia* | 285 | 16.2 |
Paresthesia (including oral paresthesia)* | 889 | 50.7 |
Peripheral neuropathy | 178 | 10.1 |
Syncope* | 58 | 3.3 |
Psychiatric disorders | ||
Confusion* | 52 | 3.0 |
Disturbance in attention | 44 | 2.5 |
Renal and urinary disorders | ||
Increased urination* | 74 | 4.2 |
Respiratory, thoracic and mediastinal disorders | ||
Coughing* | 380 | 21.7 |
Oropharyngeal Pain* | 279 | 15.9 |
Skin and subcutaneous tissue disorders | ||
Acne* | 67 | 3.8 |
Pruritus* | 214 | 12.2 |
Rash (includes erythematous and maculopapular)* | 475 | 27.1 |
Vascular disorders | ||
Flushing, feeling hot* | 232 | 13.2 |
Hypertension* | 58 | 3.3 |
Hypotension including orthostatic hypotension* | 30 | 1.7 |
Peripheral coldness* | 21 | 1.2 |
* Represents a medical concept including several similar MedDRA PTs |
Laboratory Abnormalities in Adults
Table 3 shows the percentage of adult patients who developed marked laboratory abnormalities.
Table 3. Percentage of Adult Patients, by Study and Treatment Group, with Chemistry and Hematology Abnormalities Occurring in greater than 3% of Patients Receiving Norvir
Study 245 Naive Patients | Study 247 Advanced Patients | Study 462 PI-Naive Patients | |||||
Variable | Limit | Norvir plus ZDV | Norvir | ZDV | Norvir | Placebo | Norvir plus Saquinavir |
Chemistry | High | ||||||
Cholesterol | > 240 mg/dL | 30.7 | 44.8 | 9.3 | 36.5 | 8.0 | 65.2 |
CPK | > 1000 IU/L | 9.6 | 12.1 | 11.0 | 9.1 | 6.3 | 9.9 |
GGT | > 300 IU/L | 1.8 | 5.2 | 1.7 | 19.6 | 11.3 | 9.2 |
SGOT (AST) | > 180 IU/L | 5.3 | 9.5 | 2.5 | 6.4 | 7.0 | 7.8 |
SGPT (ALT) | > 215 IU/L | 5.3 | 7.8 | 3.4 | 8.5 | 4.4 | 9.2 |
Triglycerides | > 800 mg/dL | 9.6 | 17.2 | 3.4 | 33.6 | 9.4 | 23.4 |
Triglycerides | > 1500 mg/dL | 1.8 | 2.6 | - | 12.6 | 0.4 | 11.3 |
Triglycerides Fasting | > 1500 mg/dL | 1.5 | 1.3 | - | 9.9 | 0.3 | - |
Uric Acid | > 12 mg/dL | - | - | - | 3.8 | 0.2 | 1.4 |
Hematology | Low | ||||||
Hematocrit | < 30% | 2.6 | - | 0.8 | 17.3 | 22.0 | 0.7 |
Hemoglobin | < 8.0 g/dL | 0.9 | - | - | 3.8 | 3.9 | - |
Neutrophils | ≤ 0.5 x 109/L | - | - | - | 6.0 | 8.3 | - |
RBC | < 3.0 x 1012/L | 1.8 | - | 5.9 | 18.6 | 24.4 | - |
WBC | < 2.5 x 109/L | - | 0.9 | 6.8 | 36.9 | 59.4 | 3.5 |
-Indicates no events reported. |
Adverse Reactions In Pediatric Patients
Norvir has been studied in 265 pediatric patients greater than 1 month to 21 years of age. The adverse event profile observed during pediatric clinical trials was similar to that for adult patients.
Vomiting, diarrhea, and skin rash/allergy were the only drug-related clinical adverse events of moderate to severe intensity observed in greater than or equal to 2% of pediatric patients enrolled in Norvir clinical trials.
Laboratory Abnormalities in Pediatric Patients
The following Grade 3-4 laboratory abnormalities occurred in greater than 3% of pediatric patients who received treatment with Norvir either alone or in combination with reverse transcriptase inhibitors: neutropenia (9%), hyperamylasemia (7%), thrombocytopenia (5%), anemia (4%), and elevated AST (3%).
Postmarketing Experience
The following adverse events (not previously mentioned in the labeling) have been reported during post-marketing use of Norvir. Because these reactions are reported voluntarily from a population of unknown size, it is not possible to reliably estimate their frequency or establish a causal relationship to Norvir exposure.
Body As A Whole
Dehydration, usually associated with gastrointestinal symptoms, and sometimes resulting in hypotension, syncope, or renal insufficiency has been reported. Syncope, orthostatic hypotension, and renal insufficiency have also been reported without known dehydration.
Co-administration of ritonavir with ergotamine or dihydroergotamine has been associated with acute ergot toxicity characterized by vasospasm and ischemia of the extremities and other tissues including the central nervous system.
Cardiovascular System
First-degree AV block, second-degree AV block, third-degree AV block, right bundle branch block have been reported .
Cardiac and neurologic events have been reported when ritonavir has been co-administered with disopyramide, mexiletine, nefazodone, fluoxetine, and beta blockers. The possibility of drug interaction cannot be excluded.
Endocrine System
Cushing's syndrome and adrenal suppression have been reported when ritonavir has been co-administered with fluticasone propionate or budesonide.
Nervous System
There have been postmarketing reports of seizure.
Skin And Subcutaneous Tissue disorders
Toxic epidermal necrolysis (TEN) has been reported.
What drugs interact with Norvir (ritonavir)?
When co-administering Norvir with other protease inhibitors (atazanavir, darunavir, fosamprenavir, saquinavir, and tipranavir), see the full prescribing information for that protease inhibitor including important information for drug interactions.
Potential For Norvir To Affect Other Drugs
Ritonavir is an inhibitor of cytochrome P450 3A (CYP3A) and may increase plasma concentrations of agents that are primarily metabolized by CYP3A. Agents that are extensively metabolized by CYP3A and have high first pass metabolism appear to be the most susceptible to large increases in AUC (greater than 3-fold) when co-administered with ritonavir. Thus, co-administration of Norvir with drugs highly dependent on CYP3A for clearance and for which elevated plasma concentrations are associated with serious and/or life-threatening events is contraindicated. Co-administration with other CYP3A substrates may require a dose adjustment or additional monitoring as shown in Table 4.
Ritonavir also inhibits CYP2D6 to a lesser extent. Co-administration of substrates of CYP2D6 with ritonavir could result in increases (up to 2-fold) in the AUC of the other agent, possibly requiring a proportional dosage reduction. Ritonavir also appears to induce CYP3A, CYP1A2, CYP2C9, CYP2C19, and CYP2B6 as well as other enzymes, including glucuronosyl transferase.
Established And Other Potentially Significant Drug Interactions
Table 4 provides a list of established or potentially clinically significant drug interactions. Alteration in dose or regimen may be recommended based on drug interaction studies or predicted interaction for magnitude of interaction.
Table 4. Established and Other Potentially Significant Drug Interactions
Concomitant Drug Class: Drug Name |
Effect on Concentration of Ritonavir or Concomitant Drug | Clinical Comment |
HIV-Antiviral Agents | ||
HIV-1 Protease Inhibitor: atazanavir darunavir fosamprenavir |
↑ amprenavir ↑ atazanavir ↑ darunavir |
See the complete prescribing information for fosamprenavir, atazanavir, darunavir for details on co-administration with ritonavir. |
HIV-1 Protease Inhibitor: indinavir |
↑ indinavir | Appropriate doses for this combination, with respect to efficacy and safety, have not been established. |
HIV-1 Protease Inhibitor: saquinavir |
↑ saquinavir | See the complete prescribing information for saquinavir for details on co-administration of saquinavir and ritonavir. |
Saquinavir/ritonavir in combination with rifampin is not recommended due to the risk of severe hepatotoxicity (presenting as increased hepatic transaminases) if the three drugs are given together. | ||
HIV-1 Protease Inhibitor: tipranavir |
↑ tipranavir | See the complete prescribing information for tipranavir for details on co-administration of tipranavir and ritonavir. |
Non-Nucleoside Reverse Transcriptase Inhibitor: delavirdine |
↑ ritonavir | Appropriate doses of this combination with respect to safety and efficacy have not been established. |
HIV-1 CCR5 – antagonist: maraviroc | ↑ maraviroc | See the complete prescribing information for maraviroc for details on co-administration of maraviroc and ritonavir-containing protease inhibitors. |
Integrase Inhibitor: raltegravir | ↓ raltegravir | The effects of ritonavir on raltegravir with ritonavir dosage regimens greater than 100 mg twice daily have not been evaluated, however raltegravir concentrations may be decreased with ritonavir coadministration. |
Other Agents | ||
Alpha 1-Adrenoreceptor Antagonist: alfuzosin |
↑ alfuzosin | Contraindicated due to potential hypotension . |
Antianginal: ranolazine |
↑ ranolazine | Contraindicated due to potential for serious and/or life-threatening reactions . |
Analgesics, Narcotic: tramadol, propoxyphene, methadone, fentanyl |
↑ analgesics | A dose decrease may be needed for these drugs when co-administered with ritonavir. |
Dosage increase of methadone may be considered. | ||
↓ methadone ↑ fentanyl |
Careful monitoring of therapeutic and adverse effects (including potentially fatal respiratory depression) is recommended when fentanyl is concomitantly administered with Norvir. | |
Anesthetic: meperidine |
↓ meperidine/ ↑ normeperidine (metabolite) |
Dosage increase and long-term use of meperidine with ritonavir are not recommended due to the increased concentrations of the metabolite normeperidine which has both analgesic activity and CNS stimulant activity (e.g., seizures). |
Antialcoholics: disulfiram/metronidazole |
Ritonavir formulations contain ethanol, which can produce disulfiram-like reactions when co-administered with disulfiram or other drugs that produce this reaction (e.g., metronidazole). | |
Antiarrhythmics: amiodarone, dronedarone, flecainide, propafenone, quinidine |
↑ antiarrhythmics | Contraindicated due to potential for cardiac arrhythmias . |
Antiarrhythmics: disopyramide, lidocaine, mexiletine |
↑ antiarrhythmics | Caution is warranted and therapeutic concentration monitoring is recommended for antiarrhythmics when co-administered with ritonavir, if available. |
Anticancer Agents: abemaciclib, dasatinib, ibrutinib, neratinib, nilotinib, venetoclax, vincristine, vinblastine |
↑ anticancer agents | For vincristine and vinblastine, consideration should be given to temporarily withholding the ritonavir containing antiretroviral regimen in patients who develop significant hematologic or gastrointestinal side effects when ritonavir is administered concurrently with vincristine or vinblastine. |
Clinicians should be aware that if the ritonavir containing regimen is withheld for a prolonged period, consideration should be given to altering the regimen to not include a CYP3A or P-gp inhibitor in order to control HIV-1 viral load. A decrease in the dosage or an adjustment of the dosing interval of nilotinib and dasatinib may be necessary for patients requiring co-administration with strong CYP3A inhibitors such as Norvir. Please refer to the nilotinib and dasatinib prescribing information for dosing instructions. | ||
Avoid use of venetoclax or ibrutinib with Norvir because Norvir is a strong CYP3A inhibitor and may increase the risk of tumor lysis syndrome. | ||
Avoid concomitant use of neratinib with Norvir. Avoid concomitant use of abemaciclib with strong or moderate CYP3A4 inhibitors (such as Norvir). | ||
Anticoagulant: warfarin |
↑↓ warfarin | Initial frequent monitoring of the INR during ritonavir and warfarin co-administration is recommended. |
Anticoagulant: rivaroxaban |
↑ rivaroxaban | Avoid concomitant use of rivaroxaban and ritonavir. Co-administration of ritonavir and rivaroxaban may lead to risk of increased bleeding. |
Anticonvulsants: carbamazepine, clonazepam, ethosuximide |
↑ anticonvulsants | A dose decrease may be needed for these drugs when co-administered with ritonavir and therapeutic concentration monitoring is recommended for these anticonvulsants, if available. |
Anticonvulsants: divalproex, lamotrigine, phenytoin |
↓ anticonvulsants | A dose increase may be needed for these drugs when co-administered with ritonavir and therapeutic concentration monitoring is recommended for these anticonvulsants, if available. |
Antidepressants: nefazodone, selective serotonin reuptake inhibitors (SSRIs): e.g. fluoxetine, paroxetine, tricyclics: e.g. amitriptyline, nortriptyline |
↑ antidepressants | A dose decrease may be needed for these drugs when co-administered with ritonavir. |
Antidepressant: bupropion | ↓ bupropion ↓ active metabolite, hydroxybupropion |
Patients receiving ritonavir and bupropion concurrently should be monitored for an adequate clinical response to bupropion. |
Antidepressant: desipramine |
↑ desipramine | Dosage reduction and concentration monitoring of desipramine is recommended. |
Antidepressant: trazodone |
↑ trazodone | Adverse events of nausea, dizziness, hypotension and syncope have been observed following co-administration of trazodone and Norvir. A lower dose of trazodone should be considered. |
Antiemetic: dronabinol |
↑ dronabinol | A dose decrease of dronabinol may be needed when co-administered with ritonavir. |
Antifungals: ketoconazole itraconazole voriconazole |
↑ ketoconazole ↑ itraconazole ↓ voriconazole |
High doses of ketoconazole or itraconazole (greater than 200 mg per day) are not recommended. |
Co-administration of voriconazole and ritonavir doses of 400 mg every 12 hours or greater is contraindicated due to the potential for loss of antifungal response. Co-administration of voriconazole and ritonavir 100 mg should be avoided, unless an assessment of the benefit/risk to the patient justifies the use of voriconazole. | ||
Anti-gout: colchicine |
↑ colchicine | Contraindicated due to potential for serious and/or life-threatening reactions in patients with renal and/or hepatic impairment. |
For patients with normal renal or hepatic function: | ||
Treatment of gout flares-co-administration of colchicine in patients on ritonavir: 0.6 mg (one tablet) for one dose, followed by 0.3 mg (half tablet) one hour later. Dose to be repeated no earlier than three days. |
||
Prophylaxis of gout flares-co-administration of colchicine in patients on ritonavir: If the original colchicine regimen was 0.6 mg twice a day, the regimen should be adjusted to 0.3 mg once a day. If the original colchicine regimen was 0.6 mg once a day, the regimen should be adjusted to 0.3 mg once every other day. |
||
Treatment of familial Mediterranean fever (FMF)co-administration of colchicine in patients on ritonavir: Maximum daily dose of 0.6 mg (may be given as 0.3 mg twice a day). |
||
Anti-infective: clarithromycin |
↑ clarithromycin | For patients with renal impairment, adjust clarithromycin dose as follows:
|
Antimycobacterial: bedaquiline |
↑ bedaquiline | Bedaquiline should only be used with ritonavir if the benefit of co-administration outweighs the risk. |
Antimycobacterial: rifabutin |
↑ rifabutin and rifabutin metabolite | Dosage reduction of rifabutin by at least three-quarters of the usual dose of 300 mg per day is recommended (e.g., 150 mg every other day or three times a week). Further dosage reduction may be necessary. |
Antimycobacterial: rifampin |
↓ ritonavir | May lead to loss of virologic response. Alternate antimycobacterial agents such as rifabutin should be considered. |
Antiparasitic: atovaquone |
↓ atovaquone | Clinical significance is unknown; however, increase in atovaquone dose may be needed. |
Antiparasitic: quinine |
↑ quinine | A dose decrease of quinine may be needed when co-administered with ritonavir. |
Antipsychotics: lurasidone |
↑ lurasidone | Contraindicated due to potential for serious and/or life-threatening reactions . |
pimozide | ↑ pimozide | Contraindicated due to potential for serious and/or life-threatening reactions such as cardiac arrhythmias . |
Antipsychotics: perphenazine, risperidone, thioridazine | ↑ antipsychotics | A dose decrease may be needed for these drugs when co-administered with ritonavir. |
Antipsychotics: quetiapine |
↑ quetiapine | Initiation of Norvir in patients taking quetiapine: |
Consider alternative antiretroviral therapy to avoid increases in quetiapine exposures. If coadministration is necessary, reduce the quetiapine dose to 1/6 of the current dose and monitor for quetiapine-associated adverse reactions. Refer to the quetiapine prescribing information for recommendations on adverse reaction monitoring. | ||
Initiation of quetiapine in patients taking Norvir: | ||
Refer to the quetiapine prescribing information for initial dosing and titration of quetiapine. | ||
β-Blockers: metoprolol, timolol |
↑ beta-blockers | Caution is warranted and clinical monitoring of patients is recommended. A dose decrease may be needed for these drugs when co-administered with ritonavir. |
Bronchodilator: theophylline |
↓ theophylline | Increased dosage of theophylline may be required; therapeutic monitoring should be considered. |
Calcium channel blockers: diltiazem, nifedipine, verapamil |
↑ calcium channel blockers | Caution is warranted and clinical monitoring of patients is recommended. A dose decrease may be needed for these drugs when co-administered with ritonavir. |
Digoxin | ↑ digoxin | Concomitant administration of ritonavir with digoxin may increase digoxin levels. Caution should be exercised when co-administering ritonavir with digoxin, with appropriate monitoring of serum digoxin levels. |
Endothelin receptor antagonists: bosentan |
↑ bosentan | Co-administration of bosentan in patients on ritonavir: |
In patients who have been receiving ritonavir for at least 10 days, start bosentan at 62.5 mg once daily or every other day based upon individual tolerability. | ||
Co-administration of ritonavir in patients on bosentan: | ||
Discontinue use of bosentan at least 36 hours prior to initiation of ritonavir. | ||
After at least 10 days following the initiation of ritonavir, resume bosentan at 62.5 mg once daily or every other day based upon individual tolerability. | ||
Ergot Derivatives: dihydroergotamine, ergotamine, methylergonovine |
↑ ergot derivatives | Contraindicated due to potential for acute ergot toxicity characterized by vasospasm and ischemia of the extremities and other tissues including the central nervous system . |
GI Motility Agent: cisapride |
↑ cisapride | Contraindicated due to potential for cardiac arrhythmias . |
Hepatitis C direct acting antiviral: glecaprevir/pibrentasvir |
↑ glecaprevir ↑ pibrentasvir |
It is not recommended to co-administer ritonavir with glecaprevir/pibrentasvir, or simeprevir. |
simeprevir | ↑simeprevir | |
Herbal Products: St. John's Wort (hypericum perforatum) |
↓ ritonavir | Contraindicated due to potential for loss of virologic response and possible resistance to Norvir or to the class of protease inhibitors . |
Lipid-modifying agents | ↑ lovastatin ↑ simvastatin |
Contraindicated due to potential for myopathy including rhabdomyolysis . |
HMG-CoA Reductase Inhibitor: lovastatin simvastatin |
||
atorvastatin rosuvastatin |
↑ atorvastatin ↑rosuvastatin |
Titrate atorvastatin and rosuvastatin dose carefully and use the lowest necessary dose. If Norvir is used with another protease inhibitor, see the complete prescribing information for the concomitant protease inhibitor for details on co-administration with atorvastatin and rosuvastatin. |
Microsomal triglyceride transfer protein (MTTP) Inhibitor: lomitapide |
↑ lomitapide | Lomitapide is a sensitive substrate for CYP3A4 metabolism. CYP3A4 inhibitors increase the exposure of lomitapide, with strong inhibitors increasing exposure approximately 27-fold. Concomitant use of moderate or strong CYP3A4 inhibitors with lomitapide is contraindicated due to potential for hepatotoxicity . |
Immunosuppressants: cyclosporine, tacrolimus, sirolimus (rapamycin) |
↑immunosuppressants | Therapeutic concentration monitoring is recommended for immunosuppressant agents when co-administered with ritonavir. |
Long-acting betaadrenoceptor agonist: salmeterol |
↑ salmeterol | Concurrent administration of salmeterol and ritonavir is not recommended. The combination may result in increased risk of cardiovascular adverse events associated with salmeterol, including QT prolongation, palpitations and sinus tachycardia. |
Oral Contraceptives or Patch Contraceptives: ethinyl estradiol |
↓ ethinyl estradiol | Alternate methods of contraception should be considered. |
PDE5 Inhibitors: avanafil sildenafil, tadalafil, vardenafil | ↑ avanafil ↑ sildenafil ↑ tadalafil ↑ vardenafil |
Sildenafil when used for the treatment of pulmonary arterial hypertension (Revatio®) is contraindicated due to the potential for sildenafil associated adverse events, including visual abnormalities, hypotension, prolonged erection, and syncope . |
Do not use ritonavir with avanafil because a safe and effective avanafil dosage regimen has not been established. | ||
Particular caution should be used when prescribing sildenafil, tadalafil or vardenafil in patients receiving ritonavir. Coadministration of ritonavir with these drugs may result in an increase in PDE5 inhibitor associated adverse events, including hypotension, syncope, visual changes, and prolonged erection. | ||
Use of PDE5 inhibitors for pulmonary arterial hypertension (PAH): | ||
Sildenafil (Revatio®) is contraindicated . | ||
The following dose adjustments are recommended for use of tadalafil (Adcirca®) with ritonavir: | ||
Co-administration of ADCIRCA in patients on ritonavir: In patients receiving ritonavir for at least one week, start ADCIRCA at 20 mg once daily. Increase to 40 mg once daily based upon individual tolerability. |
||
Co-administration of ritonavir in patients on ADCIRCA: Avoid use of ADCIRCA during the initiation of ritonavir. Stop ADCIRCA at least 24 hours prior to starting ritonavir. After at least one week following the initiation of ritonavir, resume ADCIRCA at 20 mg once daily. Increase to 40 mg once daily based upon individual tolerability. |
||
Use of PDE5 inhibitors for the treatment of erectile dysfunction: | ||
It is recommended not to exceed the following doses:
|
||
Sedative/hypnotics: buspirone, clorazepate, diazepam, estazolam, flurazepam, zolpidem |
↑ sedative/hypnotics | A dose decrease may be needed for these drugs when co-administered with ritonavir. |
Sedative/Hypnotics: triazolam, orally administered midazolam |
↑ triazolam ↑ midazolam |
Contraindicated due to potential for prolonged or increased sedation or respiratory depression . |
Sedative/hypnotics: Parenteral midazolam |
↑ midazolam | Co-administration should be done in a setting which ensures close clinical monitoring and appropriate medical management in case of respiratory depression and/or prolonged sedation. Dosage reduction for midazolam should be considered, especially if more than a single dose of midazolam is administered. |
Stimulant: methamphetamine |
↑ methamphetamine | Use with caution. A dose decrease of methamphetamine may be needed when co-administered with ritonavir. |
Systemic/Inhaled/ Nasal/Ophthalmic Corticosteroids: e.g., betamethasone budesonide ciclesonide dexamethasone fluticasone methylprednisolone mometasone prednisone triamcinolone |
↑ glucocorticoids | Coadministration with corticosteroids whose exposures are significantly increased by strong CYP3A inhibitors can increase the risk for Cushing’s syndrome and adrenal suppression. |
Alternative corticosteroids including beclomethasone and prednisolone (whose PK and/or PD are less affected by strong CYP3A inhibitors relative to other studied steroids) should be considered, particularly for long-term use. |
Summary
Norvir (ritonavir) is a type of antiviral drug called a protease inhibitor used to treat human immunodeficiency virus (HIV) infection. Norvir blocks the activity of a protein resulting in viruses unable to infect cells and decreasing the viral load in the body. Norvir does not prevent the transmission of HIV, and it does not cure HIV or AIDS.
Multimedia: Slideshows, Images & Quizzes
-
What Are HIV & AIDS? Symptoms, Treatment, and Prevention
HIV, or human immunodeficiency virus, causes acquired immunodeficiency syndrome, or AIDS. Learn about HIV symptoms, HIV test, HIV...
-
HIV AIDS: Myths and Facts
What is HIV versus AIDS? What are the symptoms of HIV? Is there an HIV cure? Discover myths and facts about living with HIV/AIDS....
-
A Timeline of the HIV/AIDS Pandemic
Get a historical overview of the HIV/AIDS pandemic from human contraction to the present through this slideshow of pictures.
-
Picture of HIV Lipodystrophy
HIV lipodystrophy describes a constellation of changes in subcutaneous and visceral fat distribution in patients on...
-
HIV & AIDS Quiz: HIV Testing & Symptoms
Now, more than ever, you should know about HIV/AIDS, especially its causes, symptoms treatments, and complications. Take the...
-
Picture of HIV/AIDS
Acronym for the Human Immunodeficiency Virus, the cause of AIDS (acquired immunodeficiency syndrome). See a picture of HIV/AIDS...
-
Picture of HIV-associated Dementia (HAD)
A 40-year-old woman diagnosed with HIV presented with confusion and decline in memory. See a picture of HIV-associated Dementia...
Related Disease Conditions
-
HIV Early Signs and Stages
HIV (human immunodeficiency virus) weakens your immune system. Some people with HIV don’t have any symptoms, but those that do may experience mononucleosis-like or flu-like symptoms. There are 3 stages of HIV.
-
HIV and AIDS
Second Source article from WebMD
-
Human Immunodeficiency Virus (HIV)
HIV (human immunodeficiency virus) infection left untreated causes AIDS (acquired immunodeficiency syndrome). The human immunodeficiency virus (HIV) is a type of virus called a retrovirus, which can infect humans when it comes in contact with tissues that line the vagina, anal area, mouth, or eyes, or through a break in the skin. HIV infection is generally a slowly progressive disease in which the virus is present throughout the body at all stages of the disease. Three stages of HIV infection have been described. The initial stage of infection (primary infection), which occurs within weeks of acquiring the virus, often is characterized by the flu- or mono-like illness that generally resolves within weeks. The stage of chronic asymptomatic infection (meaning a long duration of infection without symptoms) lasts an average of eight to 10 years without treatment. The stage of symptomatic infection, in which the body's immune (or defense) system has been suppressed and complications have developed, is called the acquired immunodeficiency syndrome (AIDS). The symptoms are caused by the complications of AIDS, which include one or more unusual infections or cancers, severe loss of weight, and intellectual deterioration (called dementia). When HIV grows (that is, by reproducing itself), it acquires the ability to change (mutate) its own structure. These mutations enable the virus to become resistant to previously effective drug therapy. The goals of drug therapy are to prevent damage to the immune system by the HIV virus and to halt or delay the progress of the infection to symptomatic disease. Therapy for HIV includes combinations of drugs that decrease the growth of the virus to such an extent that the treatment prevents or markedly delays the development of viral resistance to the drugs. The best combination of drugs for HIV are those that effectively suppress viral replication in the blood and also are well tolerated and simple to take so that people can take the medications consistently without missing doses.
-
HIV vs. AIDS
Human immunodeficiency virus causes HIV infection. Acquired immunodeficiency syndrome (AIDS) is a condition that results after HIV has extensively damaged a person's immune system. Risk factors for HIV and AIDS include use of contaminated needles or syringes, unprotected sex, STDs, receiving a blood transfusion prior to 1985 in the United States, having many sex partners, and transmission from a mother to her child.
-
HIV Medications List and Drug Charts
The ultimate goal of HIV treatment is getting the viral load down below detectable levels. As long as those viral load and antibody levels are below a proscribed range, people with HIV can stave off AIDS and other serious symptoms. Antiviral treatment options usually include combinations of two NRTIs, often referred to as "nucs," and a third drug, typically being a boosted protease inhibitor, a NNRTI, often called "non-nucs," and integrase strand transfer inhibitors.
-
HIV/AIDS Infection Transmission and Prevention
HIV (human immunodeficiency virus) is spread through contact with genital fluids or blood of an infected person. The spread of HIV can occur when these secretions come in contact with tissues such as those lining the vagina, anal area, mouth, eyes (the mucus membranes), or with a break in the skin, such as from a cut or puncture by a needle.
-
HIV/AIDS Testing: Diagnosis and Monitoring
HIV/AIDS diagnosis and monitoring have come a long way from the days when a diagnosis was a death sentence. Crucial parts of the effective treatment regimens developed in the last 40 years are consistent monitoring of the viral load (the amount of virus in the blood), and the immune cell count, which function as biological markers of the disease’s progression. Doctors also must test for drug resistance.
-
HIV/AIDS Facts: What Is HIV?
HIV (human immunodeficiency virus) is the precursor infection to AIDS (acquired immunodeficiency syndrome). HIV is transmitted through blood and genital secretions; most people get it through sexual contact or sharing needles for illegal IV drug use. HIV can be controlled by a strict drug regimen, but left unchecked, it leads to AIDS. In AIDS, the immune system collapses and the body falls prey to secondary, opportunistic infections and cancers that typically kill the person.
-
What Are the Side Effects of HIV Medications?
It’s important to know the potential side effects of all the drugs you take to control your HIV infection, as well as potential drug interactions. All of the NNRTIs (nonnucleoside analogue reverse transcriptase inhibitors), for example, are associated with important drug-drug interactions so they must be used with caution in patients on other medications. Learn more about the side effects of the drugs in standard treatment regimens.
-
When should you start HIV medication?
Nearly everyone who is infected with HIV (human immunodeficiency virus) should start antiviral medication therapy as soon as they are diagnosed. Older guidelines recommended delaying treatment to help reduce the potential for drug side effects and viral resistance to treatment. Current thinking theorizes that early treatment may preserve more of the body's immune function.
Treatment & Diagnosis
- HIV-AIDS FAQs
- HIV Treatment, Medications, and Prevention
- Retrovirus & Opportunistic Infections Part II
- Retroviruses and Opportunistic Infections Conf. 2/2006
- HIV Urine Test Approved
- HIV: Two Patients Face The Diagnosis
- HIV Treatment - To Interrupt or Not
- Unprotected Sex Between HIV-Infected Partners: What's the Harm?
- HIV Transmission and Progression to AIDS Continues
- Physical and Biochemical Changes in HIV Disease
- Babies On The Breast Of HIV Moms
- Does Circumcision Prevent HIV and AIDS?
- How Long Should You Wait to Get an HIV Test?
- What Liver Problems Does HIV Cause?
- Can HIV Cause Kaposi's Sarcoma?
- Do You Need Antiretroviral Therapy for HIV with No Symptoms?
- Does HIV Cause Colorectal Cancer?
- Does Anti-Retroviral Therapy for HIV Cause Diabetes?
- HIV Infection Facts, History, Causes, and Risk Factors
- HIV Tests, Symptoms, Signs, and Stages of Infection
- Baby "Cured" of HIV Infection
Medications & Supplements
Prevention & Wellness
- Newly Diagnosed with HIV/AIDS
- Human Immune Deficiency Virus (HIV/AIDS) Specific References
- HIV, AIDS, and Older People
- HIV: The Hidden Epidemic
- HIV and Tuberculosis - Facts
- AIDS & HIV...Maybe Forgotten, Not Gone from the USA!
- FDA Approves a Once Daily Protease Inhibitor for HIV Infection
- HIV: The Truth About, New HIV Test
- HIV/AIDS - World Trends

Report Problems to the Food and Drug Administration
You are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.
Professional side effects and drug interactions sections courtesy of the U.S. Food and Drug Administration