Cobicistat and Fluticasone (Oral Inhalation)
Determining the interaction of Cobicistat and Fluticasone (Oral Inhalation) and the possibility of their joint administration.
In the database of official manuals used in the service creation an interaction registered by statistical results of studies was found, which can either lead to negative consequences for the patient health or strengthen a mutual positive effect. A doctor should be consulted to address the issue of joint drug administration.
Consumer:Cobicistat may significantly increase the absorption of fluticasone into the blood stream. You may be more likely to experience side effects such as swelling, weight gain, high blood pressure, high blood glucose, muscle weakness, depression, acne, thinning skin, stretch marks, easy bruising, bone density loss, cataracts, menstrual irregularities, excessive growth of facial or body hair, and abnormal distribution of body fat, especially in the face, neck, back, and waist. Talk to your doctor if you have any questions or concerns. Your doctor may be able to prescribe alternatives that do not interact, or you may need a dose adjustment or more frequent monitoring by your doctor to safely use both medications. Other side effects that may occur include decreased ability to fight infections, increased risk of developing infections, and inadequate response to stress such as infection, surgery, trauma, or a severe asthma attack. Children may experience a reduced growth rate due to excessive effects of fluticasone. It is important to tell your doctor about all other medications you use, including vitamins and herbs. Do not stop using any medications without first talking to your doctor.
Professional:GENERALLY AVOID: Coadministration with potent inhibitors of CYP450 3A4 may increase the systemic exposure to fluticasone following intranasal administration or oral inhalation. Fluticasone undergoes extensive first-pass and systemic metabolism via CYP450 3A4, thus inhibition of the isoenzyme may significantly increase systemic bioavailability of the drug. However, the extent of interaction may depend on route of fluticasone administration and the specific formulation. In 18 healthy subjects, coadministration of fluticasone propionate nasal spray (200 mcg once daily) with the potent CYP450 3A4 inhibitor ritonavir (100 mg twice daily) for 7 days resulted in an approximately 25-fold increase in fluticasone Cmax and 350-fold increase in AUC, accompanied by an 86% decrease in mean plasma cortisol AUC. In another study, coadministration of a single dose of orally inhaled fluticasone propionate (1000 mcg) with ketoconazole (200 mg once daily) resulted in a 1.9-fold increase in plasma fluticasone exposure and a 45% decrease in plasma cortisol AUC, but had no effect on urinary excretion of cortisol. In a study using intranasal fluticasone furoate, 6 of 20 subjects who were coadministered ketoconazole (200 mg once a day for 7 days) had measurable but low levels of fluticasone furoate compared to 1 of 20 subjects who received placebo. There was an estimated 5% reduction in 24-hour serum cortisol levels with ketoconazole relative to placebo. Similarly, when fluticasone furoate-vilanterol oral inhalation (200 mcg-25 mcg once daily for 7 days) was coadministered with ketoconazole (400 once daily for 11 days) in healthy subjects, fluticasone AUC was increased 36% relative to coadministration with placebo, and the increase was associated with a 27% reduction in 24-hour weighted mean serum cortisol. A study of 17 lung transplant patients found that mean fluticasone trough level in subjects receiving fluticasone propionate (1 mg twice daily by oral inhalation for 14 days) with itraconazole was 2.5 times that observed in subjects not receiving itraconazole. Clinically, systemic glucocorticoid adverse effects may occur in association with the interaction. Adrenal suppression, Cushing's syndrome, osteoporosis, and exacerbation of diabetes mellitus have been reported during worldwide postmarketing use of orally inhaled or intranasal fluticasone, primarily in combination with ritonavir. However, there have also been a few case reports of adrenal suppression associated with concomitant use of inhaled fluticasone propionate and azole antifungal agents. Recovery of adrenal function was reportedly slow in some patients following discontinuation of fluticasone. Investigators suggest that this could be related to the highly lipophilic nature of fluticasone, which allows for prolonged seepage of drug into the circulation from fat stores.
MANAGEMENT: Concomitant use of most orally inhaled fluticasone preparations with potent CYP450 3A4 inhibitors is not recommended unless the potential benefit outweighs the risk of systemic side effects. Alternatives to fluticasone should be considered whenever possible. A less potent, less lipophilic, and/or shorter-acting agent such as beclomethasone or flunisolide may be appropriate. The lowest effective dosage of orally inhaled corticosteroid should be used, and further adjustments made as necessary according to therapeutic response and tolerance. Intranasal fluticasone and fluticasone furoate-vilanterol oral inhalation powder may be used cautiously in combination with potent CYP450 3A4 inhibitors except ritonavir. Patients should be monitored for signs and symptoms of hypercorticism such as acne, striae, thinning of the skin, easy bruising, moon facies, dorsocervical "buffalo" hump, truncal obesity, increased appetite, acute weight gain, edema, hypertension, hirsutism, hyperhidrosis, proximal muscle wasting and weakness, glucose intolerance, exacerbation of preexisting diabetes, depression, and menstrual disorders. Other systemic glucocorticoid effects may include adrenal suppression, immunosuppression, posterior subcapsular cataracts, glaucoma, bone loss, and growth retardation in children and adolescents. Following extensive use with a potent CYP450 3A4 inhibitor, a progressive dosage reduction may be required over a longer period if fluticasone is to be withdrawn from therapy, as there may be a significant risk of adrenal suppression. Signs and symptoms of adrenal insufficiency include anorexia, hypoglycemia, nausea, vomiting, weight loss, muscle wasting, fatigue, weakness, dizziness, postural hypotension, depression, and adrenal crisis manifested as inability to respond to stress (e.g., illness, infection, surgery, trauma). Systemic glucocorticoids may be necessary until adrenal function recovers.
- "Product Information. Veramyst (fluticasone nasal)." GlaxoSmithKline, Research Triangle Park, NC.
- "Product Information. Norvir (ritonavir)." Abbott Pharmaceutical, Abbott Park, IL.
- Valin N, De Castro N, Garrait V, Bergeron A, Bouche C, Molina JM "Iatrogenic Cushing's syndrome in HIV-infected patients receiving ritonavir and inhaled fluticasone: description of 4 new cases and review of the literature." J Int Assoc Physicians AIDS Care 8 (2009): 113-21
- Lonnebo A, Grahnen A, Jansson B, Brundin RM, Lingandersson A, Eckernas SA "An assessment of the systemic effects of single and repeated doses of inhaled fluticasone propionate and inhaled budesonide in healthy volunteers." Eur J Clin Pharmacol 49 (1996): 459-63
- Soldatos G, Sztal-Mazer S, Woolley I, Stockigt J "Exogenous glucocorticoid excess as a result of ritonavir-fluticasone interaction." Intern Med J 35 (2005): 67-8
- Nocent C, Raherison C, Dupon M, Taytard A "Unexpected effects of inhaled fluticasone in an HIV patient with asthma." J Asthma 41 (2004): 793-5
- Li AM "Ritonavir and fluticasone: Beware of this potentially fatal combination." J Pediatr 148 (2006): 294-5
- Woods DR, Arun CS, Corris PA, Perros P "Cushing's syndrome without excess cortisol." BMJ 332 (2006): 469-70
- Jinno S, Goshima C "Progression of Kaposi sarcoma associated with iatrogenic Cushing syndrome in a person with HIV/AIDS." AIDS Read 18 (2008): 100-4
- Daveluy A, Raignoux C, Miremont-Salame G, et al. "Drug interactions between inhaled corticosteroids and enzymatic inhibitors." Eur J Clin Pharmacol (2009):
- Samaras K, Pett S, Gowers A, McMurchie M, Cooper DA "Iatrogenic Cushing's syndrome with osteoporosis and secondary adrenal failure in HIV-infected patients receiving inhaled corticosteroids and ritonavir-boosted protease inhibitors: six cases." J Clin Endocrinol Metab 90 (2005): 4394-8
- Schmid C, Naef R, Speich R, Boehler A "Addition of inhaled fluticasone propionate to systemic immunosuppression after lung transplantation: Cushing's Syndrome in patients on itraconazole comedication." Transplantation 76 (2003): 263-4
- Boorsma M, Andersson N, Larsson P, Ullman A "Assessment of the relative systemic potency of inihaled fluticasone and budesonide." Eur Respir J 9 (1996): 1427-32
- Grahnen A, Eckernas SA, Brundin RM, Ling-Andersson A "An assessment of the systemic activity of single doses of inhaled fluticasone propionate in healthy volunteers." Br J Clin Pharmacol 38 (1994): 521-5
- Pessanha TM, Campos JM, Barros AC, Pone MV, Garrido JR, Pone SM "Iatrogenic Cushing's syndrome in a adolescent with AIDSs on ritonavir and inhaled fluticasone. case report and literature review." AIDS 21 (2007): 529-32
- Rouanet I, Peyriere H, Mauboussin JM, Vincent D "Cushing's syndrome in a patient treated by ritonavir/lopinavir and inhaled fluticasone." HIV Med 4 (2003): 149-50
- Parmar JS, Howell T, Kelly J, Bilton D "Profound adrenal suppression secondary to treatment with low dose inhaled steroids and itraconazole in allergic bronchopulmonary aspergillosis in cystic fibrosis." Thorax 57 (2002): 749-50
- Pearce RE, Leeder JS, Kearns GL "Biotransformation of fluticasone: in vitro characterization." Drug Metab Dispos 34 (2006): 1035-40
- Brus R "Effects of high-dose inhaled corticosteroids on plasma cortisol consentrations in healthy adults." Arch Intern Med 159 (1999): 1903-8
- Todd GR, Acerini CL, Ross-Russell, Zahra S, Warner JT, McCance D "Survey of adrenal crisis associated witwh inhaled corticosteroids in the United Kingdom." Arch Dis Child 87 (2002): 457-61
- Arrington-Sanders R, Hutton N, Siberry GK "Ritonavir-fluticasone interaction causing Cushing syndrome in HIV-infected children and adolescents." Pediatr Infect Dis J 25 (2006): 1044-1048
- Fardon TC, Lee DK, Haggart K, McFarlane LC, Lipworth BJ "Adrenal suppression with dry powder formulations of fluticasone propionate and mometasone furoate." Am J Respir Crit Care Med 170 (2004): 960-6
- Lipworth BJ "Systemic adverse effects of inhaled corticosteroid therapy - A systematic review and meta-analysis." Arch Intern Med 159 (1999): 941-55
- Vassiliadi D, Tsagarakis S "Unusual causes of Cushing's syndrome." Arq Bras Endocrinol Metabol 51 (2007): 1245-52
- Bernecker C, West TB, Mansmann G, Scherbaum WA, Willenberg HS "Hypercortisolism caused by ritonavir associated inhibition of CYP 3A4 under inhalative glucocorticoid therapy. 2 case reports and a review of the literature." Exp Clin Endocrinol Diabetes 120 (2012): 125-7
- Kedem E, Shahar E, Hassoun G, Pollack S "Iatrogenic Cushing's syndrome due to coadministration of ritonavir and inhaled budesonide in an asthmatic human immunodeficiency virus infected patient." J Asthma 47 (2010): 830-1
- Hillebrand-Haverkort ME, Prummel MF, ten Veen JH "Ritonavir-induced Cushing's syndrome in a patient treated with nasal fluticasone." AIDS 13 (1999): 1803
- "Product Information. Flonase (fluticasone)." Glaxo Wellcome, Research Triangle Park, NC.
- "Product Information. Breo Ellipta (fluticasone-vilanterol)." GlaxoSmithKline, Research Triangle Park, NC.
- Bhumbra NA, Sahloff EG, Oehrtman SJ, Horner JM "Exogenous Cushing syndrome with inhaled fluticasone in a child receiving lopinavir/ritonavir." Ann Pharmacother 41 (2007): 1306-9
- Kempsford R, Norris V, Siederer S "Vilanterol trifenatate, a novel inhaled long-acting beta2 adrenoceptor agonist, is well tolerated in healthy subjects and demonstrates prolonged bronchodilation in subjects with asthma and COPD." Pulm Pharmacol Ther 26 (2013): 256-64
- Molimard M, Girodet PO, Pollet C, et al. "Inhaled corticosteroids and adrenal insufficiency: prevalence and clinical presentation." Drug Saf 31 (2008): 769-74
- Sastre J "Pharmacology of fluticasone propionate." J Investig Allergol Clin Immunol 7 (1997): 382-4
- Gupta SK, Dube MP "Exogenous Cushing syndrome mimicking human immunodeficiency virus lipodystrophy." Clin Infect Dis 35 (2002): E69-71
- Johnson SR, Marion AA, Vrchoticky T, Emmanuel PJ, Lujan-Zilbermann J "Cushing syndrome with secondary adrenal insufficiency from concomitant therapy with ritonavir and fluticasone." J Pediatr 148 (2006): 386-388
- Kelly HW "Comparison of inhaled corticosteroids." Ann Pharmacother 32 (1998): 220-32
- "Product Information. Flovent (fluticasone)." Glaxo Wellcome, Research Triangle Park, NC.
- Naef R, Schmid C, Hofer M, Minder S, Speich R, Boehler A "Itraconazole comedication increases systemic levels of inhaled fluticasone in lung transplant recipients." Respiration 74 (2007): 418-22
- Gillett MJ, Cameron PU, Nguyen HV, Hurley DM, Mallal SA "Iatrogenic Cushing's syndrome in an HIV-infected patient treated with ritonavir and inhaled fluticasone." AIDS 19 (2005): 740-1
- Foisy MM, Yakiwchuk EM, Chiu I, Singh AE "Adrenal suppression and Cushing's syndrome secondary to an interaction between ritonavir and fluticasone: a review of the literature." HIV Med 9 (2008): 389-96
Generic Name: fluticasone
Brand name: ArmonAir RespiClick 113, Arnuity Ellipta, Flovent Diskus, Flovent HFA, Flovent, Flovent Rotadisk, ArmonAir RespiClick 55, ArmonAir RespiClick 232
Synonyms: Fluticasone inhalation
In the course of checking the drug compatibility and interactions, data from the following reference sources was used: Drugs.com, Rxlist.com, Webmd.com, Medscape.com.
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