Atazanavir / ritonavir

Mirtazapine

Dose adjustment and closer monitoring are required.

No pharmaceutical opinion available for this interaction.

Mechanism

Atazanavir / ritonavir can inhibit the metabolism (CYP 3A4 and 2D6) and increase the plasma concentration of Mirtazapine.

Possible additive effects for the prolongation of the QT interval .

Atazanavir / ritonavir

Pharmacodynamic effects

Increased risk of QT interval prolongation.

Recommendations

Use with caution during the use of drugs that prolong the QT interval, especially in patients with risk factors.

Alternative solution(s)

Mirtazapine

Pharmacodynamic effects

Possible increase of adverse effects.

Increased risk of QT interval prolongation.

Recommendations

Start with the lowest dose possible, or in patients already on treatment, a dose reduction may be necessary.

Monitor closely clinical efficacy and appearance of adverse effects.

In patients already being treated with this combination and tolerating it, if deemed appropriate, keep actual treatment and exercise close monitoring of adverse effects.

Alternative solution(s)

Monitor

Mirtazapine adverse effects: drowsiness, dry mouth, increased appetite, gain of weight, constipation, dizziness and headaches.

QT interval in patients with possible electrolyte disorders or other risk factors for QT prolongation.

ECG

Tests

Pharmacokinetic parameters

Comment

Ref #2626 : Mirtazapine product monograph recommends caution when co-administered with CYP2D6 inhibitors or strong CYP3A4 inhibitors. Indeed, co-administration of mirtazapine (30 mg single dose) and ketoconazole, a strong CYP 3A4 inhibitor (200 mg BID for 6.5 days) resulted in an increase of approximately 50% and 40%, respectively, in mirtazapine AUC and Cmax.

Ref #2839 : Using a physiologically based pharmacokinetic modelling approach, the interaction with ritonavir resulted in a 52% increase in mirtazapine AUC.

Ref #2613 : Additionally, the atazanavir product monograph recommends caution when prescribing it in combination with drugs that may prolong the QT interval.

Comment
Reference
  • 2580
    Mirtazapine (Remeron), Organon Inc., Quebec, Canada, 4 mai 2021.
  • 122
    Ritonavir (Norvir), Corporation AbbVie, Quebec, Canada, 5 juillet 2021.
  • 2839
    Siccardi M, Marzolini C, Seden K et al. Prediction of drug-drug interactions between various antidepressants and efavirenz or boosted protease inhibitors using a physiologically based pharmacokinetic modelling approach. Clin Pharmacokit 2013; 52:582-592.
  • 2626
    Spina E, Trifirò G, Caraci F. Clinically significant drug interactions with newer antidepressants. CNS Drugs. 2012 Jan 1;26(1):39-67.
  • 2613
    Atazanavir (Reyataz), Bristol-Myers Squibb, Quebec, Canada, 26 octobre 2018.