Atazanavir / cobicistat

Salmeterol

Contraindicated.

No pharmaceutical opinion available for this interaction.

Mechanism

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

Atazanavir / cobicistat

Pharmacodynamic effects

Recommendations

Alternative solution(s)

Salmeterol

Pharmacodynamic effects

Increased risk of cardiotoxicity (QT prolongation, torsades de pointes, cardiac arrest).

Recommendations

Contraindicated. Use alternative.

Alternative solution(s)

Formoterol and indacaterol. Suggested equivalent dosage : salmeterol 50 μcg BID = formoterol 12 μcg BID = indacaterol 75 μcg QD.

Monitor

Tests

Pharmacokinetic parameters

Comment

The combination of salmeterol with a potent CYP3A4 inhibitor is contraindicated. The increase in salmeterol plasma levels is associated with a risk of QT interval prolongation which may cause torsade de pointe and possibly cardiac arrest, particularly for patients with risk factors such as electrolyte disturbances, bradycardia, or taking other drugs that may prolong the QT interval.

Ref #2354 : A study on the administration of repeated doses of salmeterol and erythromycin in healthy subjects did not reveal any significant variation of clinical pharmacodynamic effects at doses of erythromycin 500 mg three times a day. However, a study evaluating the potential interaction of in 15 healthy subjects, coadmnistration for 7 days of salmeterol (50 μg BID) and strong CYP3A4 inhibitor ketoconazole (400 mg QD) resulted in a significant increase in plasma salmeterol exposure (Increases of 15-fold in AUC and 1.4-fold in Cmax). Three subjects were withdrawn from salmeterol and ketoconazole coadministration due to beta-adrenergic mediated systemic effects (2 with QTc prolongation and 1 with palpitations and sinus tachycardia). Due to the potential increased risk of cardiovascular adverse events, the concomitant use of salmeterol with strong CYP3A4 inhibitors is not recommended.

Reference
  • 3230
    Atazanavir/cobicistat (Evotaz), Bristol-Myers Squibb, Québec, Canada, 8 septembre 2017.
  • 2354
    Salmeterol (Serevent), GlaxoSmithKline, Ontario, Canada, 9 juil 2014.
  • 2497
    Salmeterol/Fluticasone (Advair), GlaxoSmithKline, Ontario, Canda, 29 juil 2014.
  • 2586
    Cazzola M, Testi R and Matera MG. Clinical Pharmacokinetics of Salmeterol. Clin Pharmacokinet 2002;41(1):19-30.
  • 2813
    Drew BJ, Ackerman MJ, Funk M, Gibler WB, Kligfield P, Menon V, Philippides GJ, Roden DM, Zareba W. Prevention of torsade de pointes in hospital settings: a scientific statement from the American Heart Association and the American College of Cardiology Foundation. J Am Coll Cardiol 2010 Mar 2; 55(9): 934-47.
  • 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.