Cobicistat

Tadalafil (Adcirca)

Dosage adjustment is recommended.

No pharmaceutical opinion available for this interaction.

Mechanism

Cobicistat can decrease the metabolism (CYP3A4) and increase the plasma concentration of Tadalafil (Adcirca).

Cobicistat

Pharmacodynamic effects

Recommendations

Alternative solution(s)

Tadalafil (Adcirca)

Pharmacodynamic effects

Possible increase of adverse effects.

Recommendations

Use this combination with caution.

In patients taking this antiretroviral treatment for at least one week, tadalafil may be initiated at a dose of 20 mg QD and increased to 40 mg QD based on tolerability.

In patients already on tadalafil, stop tadalafil at least 24 hours prior to starting this antiretroviral treatment.

After at least one week following initiation of this antiretroviral treatment, resume tadalafil at a dose of 20 mg QD and increase to 40 mg QD based on tolerability.

Monitor closely clinical efficacy and appearance of adverse effects.

Alternative solution(s)

Monitor

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

Treatment efficacy: symptoms reduction as well as the improvement of fonctional capacity (measured for example by the "6 minutes walk distance" (6MWD).

Tests

Pharmacokinetic parameters

Comment

Tadalafil AUC is increased by 124% when using a dose of tadalafil 20 mg associated with ritonavir (Norvir) 200 mg BID. When a 20 mg dose of tadalafil is administered with ritonavir 500 to 600 mg BID at steady state; there is an increase of only 32% in the AUC and a 30% decrease in the Cmax of tadalafil.

Also with ketoconazole (400 mg), a potent CYP3A4 inhibitor, associated with tadalafil 20 mg: there is an increase in tadalafil AUC and Cmax of 312% and 22% respectively. With ketoconazole (200 mg) and a dose of tadalafil 10 mg, rather there is an increase of 107% and 15% in tadalafil AUC and Cmax.

Precautions: hepatic and renal impairment (CrCl 31-50 ml/min: increases 2 times tadalafil AUC). Age >65 years may also increase tadalafil concentration.

Ref #2914: case report of recurrent priapism with combination of tadalafil and fosamprenavir/ritonavir.

Reference
  • 2949
    Cobicistat (Tybost), European public assessment report (EPAR) Product Information, London, United Kingdom, 4 juin 2015.
  • 2376
    Tadalafil (Adcirca), Eli Lilly, Ontario, Canada, 22 novembre 2016.
  • 2914
    Loulergue P, Gaillard R, Mir O. Interaction involving tadalafil and CYP3A4 inhibition by ritonavir. Scand J Infect Dis 2011 Mar; 43(3): 239-40.
  • 3151
    AIDS info, Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents Living with HIV. Disponible : https://aidsinfo.nih.gov/contentfiles/lvguidelines/adultandadolescentgl.pdf. Publié le 17 oct. 2017. Consulté le 11 janvier 2018.