Fluticasone Propionate with Ritonavir Interaction Details

Brand Names Associated with Fluticasone Propionate

Brand Names Associated with Ritonavir

Medical Content Editor Dr. Brian Staiger, PharmD
Last updated Nov 11, 2023

Interaction Effect

Increased glucocorticoid exposure and decreased plasma cortisol, and increased risk of Cushing syndrome and adrenal insufficiency

Interaction Summary

Coadministration of ritonavir with corticosteroids (systemic, inhaled, nasal, or ophthalmic) that are primarily metabolized by CYP3A can significantly increase glucocorticoid exposure and increase the risk of Cushing syndrome and adrenal suppression. Following coadministration of ritonavir and triamcinolone, case reports have described the occurrence of Cushing syndrome  and adrenal insufficiency without preceding Cushing syndrome . A pharmacokinetic study demonstrated interactions between ritonavir and prednisone . If concomitant use is required, alternative corticosteroids that are less affected by strong CYP3A inhibitors (eg, beclomethasone and prednisolone) should be considered, particularly for long-term use .

Severity

Major

Onset

Unspecified

Evidence

Established

How To Manage Interaction

Coadministration of ritonavir with corticosteroids (systemic, inhaled, nasal, or ophthalmic) that are primarily metabolized by CYP3A can significantly increase glucocorticoid exposure and increase the risk of Cushing syndrome and adrenal suppression. Alternative corticosteroids that are less affected by strong CYP3A inhibitors (eg, beclomethasone and prednisolone) should be considered, particularly for long-term use.

Mechanism Of Interaction

Inhibition of CYP3A-mediated metabolism by ritonavir

Literature Reports

A) A 58-year-old man taking darunavir 800 mg/ritonavir 100 mg for HIV management was diagnosed with adrenal insufficiency, without preceding Cushing syndrome, 4 weeks after a local injection of triamcinolone 30 mg for relief of back pain. He presented with cold-like symptoms, progressive fatigue, muscular weakness, nausea, and a recent 3.5 kg weight loss; HIV viral load was less than 20 copies/mL and CD4 count was within normal limits. An adrenocorticotropic hormone (ACTH) test confirmed adrenal insufficiency. The patient was transitioned to an alternative HIV regimen devoid of ritonavir, and treatment with hydrocortisone was initiated at 35 mg/day with a 4 week taper. Symptoms improved rapidly and a follow up ACTH test after 4 weeks showed nearly complete resolution of adrenal insufficiency .

B) In a pharmacokinetic study in 18 subjects, coadministration of fluticasone propionate aqueous nasal spray 200 mcg once daily for 7 days concomitantly with ritonavir 100 mg every 12 hours for 7 days resulted in an approximate 350-fold increase in the fluticasone AUC and an approximate 25-fold increase in fluticasone Cmax. A decrease of 86% was also noted in plasma cortisol AUC. Systemic corticosteroid effects, including Cushing syndrome and adrenal suppression, have been reported during postmarketing use of ritonavir in combination with inhaled or intranasally administered fluticasone propionate or budesonide .

C) A 58-year-old, HIV-positive, African American woman had iatrogenic Cushing syndrome following concomitant administration of epidural triamcinolone and ritonavir. The woman had a history of spinal stenosis, hypertension, and hyperlipidemia. Her HIV regimen consisted of emtricitabine/tenofovir, ritonavir 100 mg, and fosamprenavir 1400 mg daily; other medications included hydrochlorothiazide 25 mg/day, omeprazole 40 mg/day, pravastatin 80 mg/day, and hydrocodone/acetaminophen as needed. Four weeks after administration of epidural triamcinolone, she presented with generalized swelling (for 2 weeks), fatigue, profound weakness, dyspnea on exertion, tremor, insomnia, recent weight gain, and spinal stenosis. Physical examination revealed blood pressure of 199/89 mmHg (from a baseline of 110 to 120/70 to 80 mmHg), a temperature of 101.2 degrees F, and cushingoid facies and body habitus (eg, prominent dorsocervical hump and truncal obesity). Diffuse ecchymosis, pitting edema in the lower extremities, diaphoresis, and tremor were also noted. Her CD4 count was 150 (a decrease from 400 two months prior) and her baseline morning cortisol level was 0.9 mcg/dL. Cortisol levels rose slightly to 5.9 mcg/dL at 30 minutes and 8.1 mcg/dL at 60 minutes after receiving 250 mcg of IV cosyntropin, indicating suppression of the hypothalamic-pituitary-adrenal axis. Further corticosteroid injections were avoided and ritonavir was continued. At 6 weeks after discharge, swelling was significantly decreased, blood pressure returned to baseline, and the CD4 count increased to near baseline .

D) Ritonavir significantly increased the systemic exposure of prednisolone in a pharmacokinetic drug interaction study conducted in 10 HIV-seronegative, healthy volunteers. Each subject was given single oral doses of prednisone 20 mg at baseline, and after receiving ritonavir 200 mg twice a day on days 4 and 14 of a 2-week course of ritonavir. Compared with baseline, the geometric mean prednisolone AUC increased from 2261 to 3098 nanograms (ng) x hr/mL (geometric mean ratios (GMR)=1.37; 90% CI, 1.27 to 1.47; p=0.0002) and from 2261 to 2906 ng x hr/mL (GMR=1.28; 90% CI, 1.19 to 1.37; p=0.001) on days 4 and 14, respectively. Prednisolone apparent oral clearance (Cl/F) decreased from 9.84 L/hr at baseline to 6.45 L/hr (GMR=0.73; 90% CI, 0.68 to 0.78; p=0.0002) on day 4 of ritonavir, and from 8.84 to 6.88 L/hr (GMR=0.78; 90% CI, 0.64 to 0.92; p=0.0002) on day 14. Prednisolone half-life also increased from 2.96 hours at baseline to 3.92 hours on day 4 of ritonavir administration (GMR=1.33; 90% CI, 1.2 to 1.46; p=0.003). At day 14, there were no significant differences in prednisolone half-life compared with baseline. Cmax and Tmax were not significantly different between the groups (p greater than 0.05 for all comparisons) .

Fluticasone Propionate Overview

• Nonprescription (over the counter) fluticasone nasal spray is used to relieve symptoms of rhinitis such as sneezing and a runny, stuffy, or itchy nose and itchy, watery eyes caused by hay fever or other allergies (caused by an allergy to pollen, mold, dust, or pets). Prescription fluticasone nasal spray is used to relieve symptoms of nonallergic rhinitis such as sneezing and runny or stuffy nose which are not caused by allergies. Prescription fluticasone nasal spray (Xhance) is used to treat nasal polyps (swelling of the lining of the nose). Fluticasone nasal spray should not be used to treat symptoms (e.g., sneezing, stuffy, runny, itchy nose) caused by the common cold. Fluticasone is in a class of medications called corticosteroids. It works by blocking the release of certain natural substances that cause allergy symptoms.

Ritonavir Overview

• Ritonavir is used along with other medications to treat human immunodeficiency virus (HIV) infection. Ritonavir is in a class of medications called protease inhibitors. It works by decreasing the amount of HIV in the blood. Although ritonavir does not cure HIV, it may decrease your chance of developing acquired immunodeficiency syndrome (AIDS) and HIV-related illnesses such as serious infections or cancer. Taking these medications along with practicing safer sex and making other lifestyle changes may decrease the risk of transmitting the HIV virus to other people.

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Definitions

Severity Categories

Contraindicated

These drugs, generally, should not be used together simultaneously due to the high risk of severe adverse effects. Combining these medications can lead to dangerous health outcomes and should be strictly avoided unless otherwise instructed by your provider.

Major

This interaction could result in very serious and potentially life-threatening consequences. If you are taking this drug combination, it is very important to be under close medical supervision to minimize severe side effects and ensure your safety. It may be necessary to change a medication or dosage to prevent harm.

Moderate

This interaction has the potential to worsen your medical condition or alter the effectiveness of your treatment. It's important that you are monitored closely and you potentially may need to make adjustments in your treatment plan or drug dosage to maintain optimal health.

Minor

While this interaction is unlikely to cause significant problems, it could intensify side effects or reduce the effectiveness of one or both medications. Monitoring for changes in symptoms and your condition is recommended, and adjustments may be made if needed to manage any increased or more pronounced side effects.

Onset

Rapid: Onset of drug interaction typically occurs within 24 hours of co-administration.

Delayed: Onset of drug interaction typically occurs more than 24 hours after co-administration.

Evidence

Level of documentation of the interaction.

Established: The interaction is documented and substantiated in peer-reviewed medical literature.

Theoretical: This interaction is not fully supported by current medical evidence or well-documented sources, but it is based on known drug mechanisms, drug effects, and other relevant information.

How To Manage The Interaction

Provides a detailed discussion on how patients and clinicians can approach the identified drug interaction as well as offers guidance on what to expect and strategies to potentially mitigate the effects of the interaction. This may include recommendations on adjusting medication dosages, altering the timing of drug administration, or closely monitoring for specific symptoms.

It's important to note that all medical situations are unique, and management approaches should be tailored to individual circumstances. Patients should always consult their healthcare provider for personalized advice and guidance on managing drug interactions effectively.

Mechanism Of Interaction

The theorized or clinically determined reason (i.e., mechanism) why the drug-drug interaction occurs.

Disclaimer: The information provided on this page is for informational purposes only and should not be considered medical advice. Always consult with a qualified healthcare professional regarding your specific circumstances and medical conditions.

Where Does Our Information Come From?

Information for our drug interactions is compiled from several drug compendia, including:

• Gold Standard Drug Database
• Micromedex
• Lexicomp
• DrugBank

The prescribing information for each drug, as published on DailyMED, is also used. 

Individual drug-drug interaction detail pages contain references specific to that interaction. You can click on the reference number within brackets '[]' to see what reference was utilized.

The information posted is fact-checked by HelloPharmacist clinicians and reviewed quarterly.