Fluticasone Propionate with Tipranavir Interaction Details

Brand Names Associated with Fluticasone Propionate

Brand Names Associated with Tipranavir

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

Interaction Effect

Increased plasma fluticasone levels and decreased plasma cortisol concentrations

Interaction Summary

Coadministration of fluticasone and tipranavir/ritonavir may result in increased plasma fluticasone levels and significantly decreased plasma cortisol levels. Cushing's syndrome and adrenal suppression have been reported with concurrent use of ritonavir and inhaled or intranasal fluticasone during postmarketing surveillance. Therefore, concomitant use of fluticasone and tipranavir/ritonavir is not recommended unless the potential benefit outweighs the risk of systemic corticosteroid adverse effects. However, if used concurrently, use caution and monitor patients for signs and symptoms of corticosteroid excess such as weight gain, reddening of the face and neck, increased blood pressure, and increased body hair.

Severity

Major

Onset

Unspecified

Evidence

Probable

How To Manage Interaction

Coadministration of fluticasone and tipranavir/ritonavir may result in increased plasma fluticasone levels and significantly decreased plasma cortisol levels and therefore, is not recommended unless the potential benefit to the patient outweighs the risk of systemic corticosteroid side effects. However, if used concurrently, use caution and monitor patients for signs and symptoms of corticosteroid excess such as weight gain, reddening of the face and neck, increased blood pressure, and increased body hair.

Mechanism Of Interaction

Inhibition of CYP3A-mediated fluticasone metabolism

Literature Reports

A) A 30 year-old HIV-positive male developed Cushingoid facies approximately six months after starting therapy with ritonavir 600 mg twice daily, zidovudine 250 mg twice daily, and lamivudine 150 mg twice daily. Plasma cortisol levels were undetectable (less than 30 nmol/L), and an overnight metyrapone test was compatible with secondary adrenal failure or exogenous steroid use. Prior to ritonavir therapy, the cortisol level was normal (670 nmol/L). Upon further questioning, the patient admitted to using a topical corticosteroid product for two months. Discontinuation of the corticosteroid product did not resolve his Cushingoid facies, and his plasma cortisol level was still not detectable. The patient then admitted to using fluticasone nasal spray 200 mcg daily, which he did not consider a medication, for the previous five months. Ritonavir was replaced with nevirapine 200 mg twice daily, and the plasma cortisol level increased to 290 nmol/L within three weeks. Rechallenge with ritonavir caused the plasma cortisol level to rapidly decrease. Ritonavir was permanently discontinued, and the plasma cortisol level returned to normal, while the patient's Cushingoid facies diminished .

B) Coadministration of fluticasone propionate and ritonavir is not recommended based on a multiple-dose, crossover drug interaction study in 18 healthy volunteers. Fluticasone propionate aqueous nasal spray 200 mg daily was coadministered for 7 days with ritonavir 100 mg twice daily. Plasma fluticasone propionate concentrations following fluticasone propionate aqueous nasal spray alone were undetectable (less than 10 picogram (pg)/mL (20 picomol/L)). When concentrations were detectable peak levels (Cmax) averaged 11.9 pg/mL (26.8 picomol/L) and area under the concentration-time curve (AUC) averaged 8.43 pg hr/mL. Fluticasone propionate Cmax and AUC increased to 318 pg/mL (715 picomol/L) and 3102 pg hr/mL, respectively, after coadministration of ritonavir with fluticasone propionate aqueous nasal spray. Plasma cortisol AUC also significantly decreased (86%) .

C) Eighteen subjects taking fluticasone propionate aqueous nasal spray 200 mcg once daily for 7 days concomitantly with ritonavir 100 mg every twelve hours for 7 days have resulted in approximately 350-fold increase in AUC and approximately 25-fold increase in Cmax (95% confidence interval). The significant increase in fluticasone propionate plasma concentration resulted in a significant decrease (86%) in plasma cortisol AUC. Systemic corticosteroid effects, including Cushing's syndrome and adrenal suppression have been reported during postmarketing use in patients receiving ritonavir and inhaled or intranasally administered fluticasone propionate .

D) A 27 year-old HIV positive woman had iatrogenic Cushing's syndrome with concomitant use of inhaled fluticasone and ritonavir. The woman had been HIV positive since 1995. Her medication regimen consisted of lopinavir/ritonavir 800 mg/200 mg, saquinavir 1 g twice daily, fluticasone/salmeterol 250/25 inhaler (for a total daily dose of 1000 mcg/d fluticasone). She was also in a maintenance program of methadone and benzodiazepines for intravenous drug users. Ten months post-partum, she presented with weight gain consistent with hypercortisolism, and including mild proximal myopathy, central adiposity, dorsocervical fat pad, and violaceous abdominal and axillary striae; morning plasma cortisol level (< 30 nmol/L); suppressed plasma adrenocorticotrophic hormone (0.8 pmol/L); and inadequate response to synacthen with a plasma cortisol level of 144 nmol/L 30 minutes after intramuscular injection. Fluticasone was replaced with low-dose oral glucocorticoid therapy until normal adrenal function returned. Ritonavir is a known potent inhibitor of cytochrome P450 3A4 (CYP3A4), and is the probable mechanism of interaction with fluticasone, which is also metabolized through CYP3A4. In addition, the physiological changes due to pregnancy may be another reason for this drug interaction .

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.

Tipranavir Overview

• Tipranavir is used with ritonavir (Norvir) and other medications to treat human immunodeficiency virus infection (HIV). Tipranavir is in a class of medications called protease inhibitors. It works by decreasing the amount of HIV in the blood. Although tipranavir 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.