https://interactions.guidetherapeutiquevih.com/en/interaction-details?id=11298

Atazanavir / ritonavir

Sildenafil (Viagra)

Modification of dose and/or administration time necessary.

No pharmaceutical opinion available for this interaction.

Mechanism

Atazanavir / ritonavir can inhibit the metabolism (CYP 3A4) and increase the plasma concentration of Sildenafil (Viagra).

Atazanavir / 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

–

Comment

Studies confirming increased PDE-5 inhibitor concentrations with coadministration of PIs and pharmacokinetic enhancers have been well documented since these ED agents first became available for clinical use. At least two published case reports describe deaths associated with interactions involving PDE-5 inhibitors and a PI in combination with ritonavir. Such consequences make recommendations for PDE-5 inhibitor dose reduction and slow dose titration essential when these ED agents are co-prescribed with strong CYP 3A4 inhibitors such as PIs, ritonavir, or cobicistat.

Ref #3726 : In this cohort study of 235 men with erectile dysfunction receiving treatment with a PDE-5 inhibitor and antiretroviral therapy with potential for interactions. The majority of men receiving ART boosted with ritonavir or cobicistat demonstrated interactions.

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%
Kidney failure (Clcr < 30 ml/min): increases AUC to 100%
Age > 65 years old can also increase the concentrations of sildenafil.

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

Comment
Reference
  • 1382
    Atazanavir (Reyataz), Bristol-Myers Squibb, Quebec, Canada, 26 octobre 2018.
  • 2573
    Ritonavir (Norvir), Corporation AbbVie, Quebec, Canada, 5 juillet 2021.
  • 244
    Sildénafil (Viagra), Pfizer, Québec, Canada, 26 mai 2015.
  • 2375
    Sildenafil (Revatio), Pfizer, Quebec, Canada, 30 oct 2017.
  • 3726
    Cota JM, Benavides TM, Fields JD, Jansen N, Ganesan A, et al. High frequency of potential phosphodiesterase type 5 inhibitor drug interactions in males with HIV infection and erectile dysfunction. PLoS One. 2021 May 6; 16 (5): e0250607.
  • 2374
    Aschmann YZ, Kummer O, Linka A, Wenk M, Azzola A, Bodmer M, Krähenbühl S, Haschke M.. Pharmacokinetics and pharmacodynamics of sildenafil in a patient treated with human immunodeficiency virus protease inhibitors. Therapeutic Drug Monitoring 2008;30(1):130-4.
  • 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.
  • 3727
    Hall MC, Ahmad S. Interaction between sildenafil and HIV-1 combination therapy. Lancet 1999. June 12; 353(9169) : 2071-2072.
  • 3728
    Kobayashi M, Takata Y, Goseki Y, Mizukami H, Hara S, Kuriiwa F, et al. A sudden cardiac death induced by sildenafil and sexual activity in an HIV patient with drug interaction, cardiac early repolarization, and arrhythmogenic right ventricular cardiomyopathy. Int J Cardiol 2015; 179: 421-423.