Cobicistat

Felodipine

Dosage adjustment may be necessary.

No pharmaceutical opinion available for this interaction.

Mechanism

Cobicistat can inhibit the metabolism (CYP 3A4) and increase the plasma concentration of Felodipine.

Cobicistat

Pharmacodynamic effects

Recommendations

Alternative solution(s)

Felodipine

Pharmacodynamic effects

Possible increase of adverse effects.

Recommendations

Use this combination with caution.

Start treatment with lower dose possible.

Reduce the dose of the CCB if judged necessary and gradually increase according to clinical response and tolerance.

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

Or choose an alternative.

Alternative solution(s)

Diuretics, ACE inhibitors and some ARBs (if no contranindications).

Monitor

Adverse effects associated with calcium channel blockers : headache, peripheral edema, gastrointestinal effects, fatigue, hypotension, palpitations, tachycardia or bradycardia (diltiazem and verapamil), dizziness, nervousness, vertigo and drowsiness.

When possible, monitor the effects on blood pressure, heart rate and ECG.

Advise patient to consult quickly if lower limb edema, sudden weight gain, difficulty breathing, chest pain or tightness, or hypotension (dizziness, orthostatic effects).

Tests

Pharmacokinetic parameters

Comment

Ref #2776 : Coadministration of another extended release formulation of felodipine with itraconazole resulted in approximately 8-fold increase in the AUC, more than 6-fold increase in the Cmax, and 2-fold prolongation in the half-life of felodipine. The monograph recommends avoiding the combination of felodipine with potent CYP3A4 inhibitors.

Ref #2407: In one study, patients who received indinavir 800 mg + ritonavir 100 mg BID with amlodipine 5 mg QD had an increase in amlodipine AUC of approximately 90%. Other patients received indinavir 800 mg + ritonavir 100 mg BID with diltiazem 120 mg QD and a 26.5% increase in diltiazem AUC was observed. 13 patients in the study, two subjects had an increase in diltiazem AUC of 4 times the normal. By cons, no serious adverse effects on the cardiovascular system was observed.
The searchers therefore recommend, if co-administration is indicated, to initiate treatment with low doses increasing doses with caution according to clinical response and the occurrence of adverse effects.

Reference
  • 2949
    Cobicistat (Tybost), European public assessment report (EPAR) Product Information, London, United Kingdom, 4 juin 2015.
  • 2776
    Felodipine (Plendil), AstraZeneca, Ontario, Canada, 15 janvier 2015.
  • 2407
    Glesby MJ, Aberg JA, Kendall MA, et al. Pharmacokinetic interactions between indinavir plus ritonavir and calcium channel blockers. Clin Pharmacol Ther, 2005, 78(2): 143-53.