Archived – Important Safety Information Regarding a Drug Interaction Between Fluticasone Propionate (Flonase /Flovent /Advair ) and Ritonavir (Norvir /Kaletra )

Starting date:

January 22, 2004

Posting date:

January 30, 2004

Type of communication:

Dear Healthcare Professional Letter

Subcategory:

Drugs

Source of recall:

Health Canada

Issue:

Important Safety Information

Audience:

Healthcare Professionals

Identification number:

RA-17000730

This is duplicated text of a letter from GlaxoSmithKline Inc.
Contact the company for a copy of any references, attachments or enclosures.

Notice about Health Canada advisories

Health Canada Endorsed Important Safety Information on FLUTICASONE PROPIONATE (FLONASE^®/ FLOVENT^®/ ADVAIR^®) and RITONAVIR (NORVIR^®/KALETRA^®)^{Footnote 1}

January 22. 2004

Subject: IMPORTANT SAFETY INFORMATION REGARDING A DRUG INTERACTION BETWEEN FLUTICASONE PROPIONATE (FLONASE^®/ FLOVENT^®/ ADVAIR^®) AND RITONAVIR (NORVIR^®/KALETRA^®)^{Footnote 1}

Dear Health Care Professional,

Concomitant use of ritonavir (NORVIR^®, KALETRA^®) can greatly increase fluticasone propionate (FLONASE^®, FLOVENT^®, ADVAIR^®) plasma concentrations leading to systemic corticosteroid effects including Cushing's syndrome and adrenal suppression.

Concomitant use of fluticasone propionate and ritonavir should be avoided, unless the benefit to the patient outweighs the risk of systemic corticosteroid side effects.

GlaxoSmithKline Inc., in consultation with Health Canada, would like to inform you of the results of a drug interaction study conducted with FLONASE^® (fluticasone propionate) aqueous nasal spray and NORVIR^® (ritonavir, Abbott Laboratories).

A drug interaction study in healthy subjects has shown that ritonavir (a highly potent cytochrome P450 3A4 inhibitor) can greatly increase fluticasone propionate plasma concentrations, resulting in markedly reduced serum cortisol concentrations. During post-marketing use, there have been reports of clinically significant drug interactions in patients receiving fluticasone propionate and ritonavir, resulting in systemic corticosteroid effects including Cushing's syndrome and adrenal suppression. Therefore, concomitant use of fluticasone propionate and ritonavir should be avoided, unless the potential benefit to the patient outweighs the risk of systemic corticosteroid side effects.

The study also showed that other inhibitors of cytochrome P450 3A4 produce negligible (erythromycin) and minor (ketoconazole) increases in systemic exposure to fluticasone propionate without notable reductions in serum cortisol concentrations. However, there have been a few case reports, during worldwide post-marketing use, of adrenocortical suppression associated with the use of azole antifungals and inhaled fluticasone propionate. Therefore, care is advised when co-administering potent CYP3A4 inhibitors (e.g. ketoconazole) as there is potential for increased exposure to fluticasone propionate.

Corticosteroids metabolized primarily by CYP3A4 would potentially be affected by this interaction with ritonavir.

The information regarding this drug interaction will be incorporated into the FLONASE^® (fluticasone propionate) aqueous nasal spray, FLOVENT^® (fluticasone propionate) inhalation aerosol and dry powder for inhalation and ADVAIR^®(salmeterol xinafoate/fluticasone propionate) inhalation aerosol and dry powder for inhalation Product Monographs. This information has been incorporated into the Product Monograph for NORVIR^® (ritonavir, Abbott Laboratories) and is to be incorporated into the Product Monograph for KALETRA^® (lopinavir/ritonavir 4:1, Abbott Laboratories).

The identification, characterization, and management of drug-related adverse events are dependent on the active participation of health care professionals in adverse drug reaction reporting programs. Health care professionals are asked to report any suspected adverse reactions in patients receiving FLONASE^® (fluticasone propionate) aqueous nasal spray, FLOVENT^® (fluticasone propionate) inhalation aerosol and dry powder for inhalation or ADVAIR^®(salmeterol xinafoate/fluticasone propionate) inhalation aerosol and dry powder for inhalation directly to GlaxoSmithKline or to the Marketed Health Products Directorate:

Your professional commitment in this regard has an important role in protecting the well-being of your patients by contributing to early signal detection and informed drug use.

Any questions from health care professionals may be directed to our Medical Information department via GlaxoSmithKline Customer Service at 1-800-387-7374.

Sincerely,

original signed by

Anne Phillips, M.D., FRCPC
Vice President, Research & Development and Chief Medical Officer
GlaxoSmithKline Inc.

NORVIR^® and KALETRA^® are registered trademarks, used under license by Abbott Laboratories.
^® FLONASE, FLOVENT and ADVAIR are registered trademarks, used under license by GlaxoSmithKline Inc.