https://interactions.guidetherapeutiquevih.com/en/interaction-details?id=2119

Ritonavir

Sildenafil (Viagra)

Modification of dose and/or administration time necessary.

No pharmaceutical opinion available for this interaction.

Mechanism

Ritonavir can decrease the metabolism (CYP3A4) and increase the plasma concentration of Sildenafil (Viagra).

Ritonavir

Pharmacodynamic effects

–

Recommendations

–

Alternative solution(s)

–

Sildenafil (Viagra)

Pharmacodynamic effects

Possible increase of adverse effects.

Recommendations

Start at the lowest possible dose (12.5 mg) and increase up to a maximum of 25 mg per 48 hours according to response and adverse effects.

If already used, reduce the dose to a maximum of 25 mg per 48 hours.

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.

Give extra caution to patients with hepatic or renal insufficiency, or older than 65 years.

Alternative solution(s)

–

Monitor

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

Tests

–

Pharmacokinetic parameters
Parameters
Reference number
# patients
AUC
Cmax
Tmax
T1/2
Dose
Frequency
HIV
PK parameters
Duration (days)
Sildenafil (Viagra)
734
28
+ 11x
+ 3.9x
+ 3.1 h
+ 1.8 h
100 mg
2x 1 dose *
-
 
 
Ritonavir
734
28
 
 
 
 
300-500 mg †
BID
-
± 0%
7 †
Comment

Ref #734 : * A dose on day 1 and another on day 7 or 8 according to randomization.
† 300, 400 and 500 mg BID on days 2, 3 and 4-8, respectively.
Sildenafil AUC increased by 11-fold when using a 100 mg dose of sildenafil associated with ritonavir 500 mg BID and 3.1-fold with saquinavir 1200 mg TID, two potent inhibitors of cytochrome 3A4.
See saquinavir/ritonavir + sildenafil (Viagra).

Ref # 2193: Another study showed that sildenafil plasma levels are similar when a dose of 25 mg is combined with darunavir/ritonavir 400/100 mg BID compared to a dose of sildenafil 100 mg alone.

Caution: Liver impairment (Child Pugh A and B): increases AUC to 84% and kidney failure (Clcr < 30 ml/min): increases AUC to 100% and age > 65 years old can also increase the concentrations of sildenafil.

Contraindicated with sildenafil (Revatio). See sildenafil (Revatio).

Reference
  • 122
    Ritonavir (Norvir), Corporation AbbVie, Quebec, Canada, 5 juillet 2021.
  • 734
    Muirhead GJ, Wulff MB, Fielding A, et al. Pharmacokinetic interactions between the HIV protease inhibitors ritonavir and saquinavir and Viagra (sildenafil citrate). Br J Clin Pharmacol 2000;50:99-107.
  • 2193
    Sekar V, Lefebvre E, De Marez T, De Pauw M, De Paepe E, Vangeneugden T, Hoetelmans RM. Effect of Repeated Doses of Darunavir plus Low-Dose Ritonavir on the Pharmacokinetics of Sildenafil in Healthy Male Subjects : Phase I Randomized, Open-Label, Two-Way Crossover Study.Clin Drug Investig. 2008;28(8):479-85.
  • 244
    Sildénafil (Viagra), Pfizer, Québec, Canada, 26 mai 2015.
  • 2375
    Sildenafil (Revatio), Pfizer, Quebec, Canada, 30 oct 2017.