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

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:

 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.

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 Reactionsn%
Eye disorders
  Blurred vision1136.4
Gastrointestinal disorders
  Abdominal Pain (upper and lower)*46426.4
  Diarrhea including severe with electrolyte imbalance*1,19267.9
  Dyspepsia20111.5
  Flatulence1428.1
  Gastrointestinal hemorrhage*412.3
  Gastroesophageal reflux disease (GERD)191.1
  Nausea1,00757.4
  Vomiting*55931.9
General disorders and administration site conditions
  Fatigue including asthenia*81146.2
Hepatobiliary disorders
  Blood bilirubin increased (including jaundice)*251.4
  Hepatitis (including increased AST, ALT, GGT)*1538.7
Immune system disorders
  Hypersensitivity including urticaria and face edema*1148.2
Metabolism and nutrition disorders
  Edema and peripheral edema*1106.3
  Gout*241.4
  Hypercholesterolemia*523.0
  Hypertriglyceridemia*1589.0
  Lipodystrophy acquired*512.9
Musculoskeletal and connective tissue disorders
  Arthralgia and back pain*32618.6
  Myopathy/creatine phosphokinase increased*663.8
  Myalgia1568.9
Nervous system disorders
  Dizziness*27415.6
  Dysgeusia*28516.2
  Paresthesia (including oral paresthesia)*88950.7
  Peripheral neuropathy17810.1
  Syncope*583.3
Psychiatric disorders
  Confusion*523.0
  Disturbance in attention442.5
Renal and urinary disorders
  Increased urination*744.2
Respiratory, thoracic and mediastinal disorders
  Coughing*38021.7
  Oropharyngeal Pain*27915.9
Skin and subcutaneous tissue disorders
  Acne*673.8
  Pruritus*21412.2
  Rash (includes erythematous and maculopapular)*47527.1
Vascular disorders
  Flushing, feeling hot*23213.2
  Hypertension*583.3
  Hypotension including orthostatic hypotension*301.7
  Peripheral coldness*211.2
* 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 PatientsStudy 247 Advanced PatientsStudy 462 PI-Naive Patients
VariableLimitNorvir plus ZDVNorvirZDVNorvirPlaceboNorvir plus Saquinavir
ChemistryHigh
Cholesterol> 240 mg/dL30.744.89.336.58.065.2
CPK> 1000 IU/L9.612.111.09.16.39.9
GGT> 300 IU/L1.85.21.719.611.39.2
SGOT (AST)> 180 IU/L5.39.52.56.47.07.8
SGPT (ALT)> 215 IU/L5.37.83.48.54.49.2
Triglycerides> 800 mg/dL9.617.23.433.69.423.4
Triglycerides> 1500 mg/dL1.82.6-12.60.411.3
Triglycerides Fasting> 1500 mg/dL1.51.3-9.90.3-
Uric Acid> 12 mg/dL---3.80.21.4
HematologyLow
Hematocrit< 30%2.6-0.817.322.00.7
Hemoglobin< 8.0 g/dL0.9--3.83.9-
Neutrophils≤ 0.5 x 109/L---6.08.3-
RBC< 3.0 x 1012/L1.8-5.918.624.4-
WBC< 2.5 x 109/L-0.96.836.959.43.5
-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:
  • For patients with CLCR 30 to 60 mL per min the dose of clarithromycin should be reduced by 50%.
  • For patients with CLCR less than 30 mL per min the dose of clarithromycin should be decreased by 75%.
No dose adjustment for patients with normal renal function is necessary.
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:
  • Sildenafil: 25 mg every 48 hours
  • Tadalafil: 10 mg every 72 hours
  • Vardenafil: 2.5 mg every 72 hours
Use with increased monitoring for adverse events.
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.

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Medically Reviewed on 6/12/2020
References
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