Darunavir / cobicistat

Vardenafil

Dosage adjustment is recommended.

No pharmaceutical opinion available for this interaction.

Mechanism

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

Darunavir / cobicistat

Pharmacodynamic effects

Recommendations

Alternative solution(s)

Vardenafil

Pharmacodynamic effects

Possible increase of adverse effects.

Recommendations

Use this combination with caution.

Use a single maximum dose of vardenafil of 2.5 mg every 72 hours according to the US product monograph.

Monitor closely for adverse effects.

The canadian monograph contraindicates this combination.

Alternative solution(s)

Sildenafil or tadalafil.

Monitor

Vardenafil toxicity: hypotension, tachycardia, headache, dizziness, flushing, visual changes (difficulty distinguishing blue and green) and syncope.

Tests

Pharmacokinetic parameters

Comment

The monographs of vardenafil and ritonavir contraindicate the coadministration with a potent CYP 3A4 inhibitor.

The product monographs of Prezcobix and Symtuza do not recommend the use of these with vardenafil.

Ref #1384 : Indeed, vardenafil AUC has increased by 49-fold when using a 5 mg vardenafil dose associated with ritonavir 600 mg BID, a potent inhibitor of cytochrome 3A4.

Caution:
- Liver impairment (Child Pugh B) : increases AUC to 160% and
- kidney failure (Clcr < 30 ml/min) : increases AUC to 20-30% and
- age > 65 years old : increases 52% of AUC.

See ritonavir and vardenafil.

Reference
  • 3071
    Darunavir/cobicistat (Prezcobix), Janssen, Ontario, Canada, 7 avril 2017.
  • 1384
    Vardenafil (Levitra), Bayer, Ontario, Canada, 4 juin 2016.
  • 3390
    Vardenafil (Levitra), Bayer Healthcare, New Jersey, USA, april 2014.
  • 3437
    Darunavir/cobicistat/emtricitabine/tenofovir alafenamide (Symtuza), Janssen Inc, Ontario, Canada, 3 octobre 2018.