Atazanavir / cobicistat

Mometasone

Not recommended association.

No pharmaceutical opinion available for this interaction.

Mechanism

Atazanavir / cobicistat can inhibit the metabolism (CYP 3A4) and increase the plasma concentration of Mometasone.

Atazanavir / cobicistat

Pharmacodynamic effects

Recommendations

Alternative solution(s)

Mometasone

Pharmacodynamic effects

Possible increase of adverse effects.

Recommendations

Avoid association. Choose an alternative.

Alternative solution(s)

Beclomethasone 100 μg = mometasone 200 μg.

Monitor

Mometasone toxicity : Cushing's syndrome (moon face, buffalo hump, obesity, striations, acne, hirsutism, hypertension, osteoporosis, glucose intolerance, increased risk of infections) and adrenal suppression (melanodermia, fatigue, weakness, hypotension, weight loss, digestive disorders).

Tests

Pharmacokinetic parameters

Comment

Ref #3412 : Case report of a 54 year-old VIH+ woman on tenofovir, raltegravir and darunavir/ritonavir who developed severe unrecognized exogenous Cushing’s syndrome from the concomitant administration with the potent inhaled glucocorticoid mometasone.

The accumulation of corticosteroids can cause Cushing's syndrome (moon face, excitation/insomnia, hypertension, increased appetite and weight, ease of doing bruising) and potentially a suppression of the hypothalamic-pituitary axis, which could lead to adrenal insufficiency.

The safest corticosteroid is beclomethasone (Qvar) since its metabolism is mainly by an esterification mechanism.

Ref #2550 and #2551 : A cross-sectional study (n = 11 783) suggests lower prevalence of adrenal insufficiency with beclomethasone than with other corticosteroids currently available on the market. Pharmacokinetic studies with beclomethasone and ritonavir or combination darunavir/ritonavir demonstrated that there were no clinically significant pharmacokinetic interactions. No variation of blood cortisol have been observed.

Reference
  • 2619
    Mometasone(Asmanex Twisthaler), Merck, Québec, Canada, 24 janvier 2018.
  • 2806
    Saberi P, Phengrasamy T and Nguyen DP. Inhaled corticosteroid use in HIV-positive individuals taking protease inhibitors : a review of pharmacokinetics, case reports and clinical management. HIV medicine 2013 : 1-11.
  • 2808
    Molimard M, Girodet PO, Pollet C et al. Inhaled corticosteroids and adrenal insufficiency: prevalence and clinical presentation. Drug Saf 2008; 31(9): 769-774.
  • 2551
    Boyd A, Hadigan C, Pau A. Darunavir/ritonavir Does Not Significantly Increase Plasma Concentrations of Orally Inhaled Beclomethasone in Healthy Volunteers. Conference on Retroviruses and Opportunistic Infections, Seattle, 2012, Abstract 611.
  • 2550
    Boyd A, Penzak S, Nieman L et al. Co-administration of Orally Inhaled Beclomethasone Dipropionate and HIV Protease Inhibitor Does Not Significantly Alter Adrenal Function in Healthy Volunteers. Conference on Retroviruses and Opportunistic Infections, Seattle, 2012, Abstract 610.
  • 3101
    Lougheed MD, Lemiere C, Ducharme F et al. Canadien Thoracic Society 2012 guideline update: Diagnosis and management of athsma in preschoolers, children and adults. Can Respir J 2012; 19 (2): 127-164.
  • 3412
    Eid M, Sangli SS, Chua Ong E and AM Fleckman. Severe Iatrogenic Cushing's Syndrome from Combined Mometasone and Ritonavir: First Adult Report. Endocrine Society's 96th Annual Meeting and Expo, 2014 June 21–24, Chicago USA. SAT-0756.