HIV-1 protease inhibitor; modern use is as a PK booster (CYP3A4 inhibitor) for other PIs and Paxlovid. Most potent oral CYP3A4 inhibitor available. Major DDI source — extensive contraindication list (statins, ergots, sedatives, alpha-blockers).
Half-Life (t½)
PO: 4h
Dosing Guidelines
PO: Typical 100 mg (Range: 100–600 mg)
Target Organ Systems
cardiovascular
digestive
Interactions
Atorvastatin (major): CYP3A4 inhibition (potent PI booster). Pham 2009 (PMID:19667285): tipranavir/ritonavir at steady state raised atorvastatin AUC 9.36× and Cmax 8.61× vs atorvastatin alone. Use lowest atorvastatin dose; avoid simvastatin / lovastatin entirely with ritonavir-containing regimens.
Simvastatin (contraindicated): CYP3A4 inhibition (potent PI booster). Fichtenbaum 2002 (PMID:11873000): RTV/SQV combination raised simvastatin AUC 32× (3059% increase) over 14 days. Combination contraindicated. With ritonavir-based regimens, use rosuvastatin or pravastatin (not CYP3A4 substrates).
Tacrolimus (contraindicated): CYP3A4 inhibition. Badri 2015 (PMID:25708713): ritonavir-containing regimen raised tacrolimus AUC 57×, t½ from 32 to 232 h (n=12 healthy). Empirically reduce tacrolimus to 0.5-1 mg every 1-2 weeks with ritonavir; trough monitoring mandatory.
Midazolam (contraindicated): CYP3A4 inhibition (most potent oral inhibitor). Greenblatt 2009 (PMID:20002087): low-dose ritonavir 100 mg × 3 raised midazolam AUC 28.4× and reduced oral CL to 4.2% of control (n=13 healthy). Combination contraindicated.
Sildenafil (contraindicated): CYP3A4 inhibition (TDI). Muirhead 2000 (PMID:10930961) n=14 healthy males, ritonavir 500 mg BID × 7d (full-dose), 100 mg sildenafil: AUC 11× (95% CI 9.0–12.0), Cmax 3.9×. Ki ≈ 5/(11−1) = 0.50 µM at full-dose Cp_perp 5 µM. Booster-dose effect smaller. Sildenafil label caps at 25 mg/48 h with strong CYP3A4 inhibitors.
Alprazolam (major): CYP3A4 inhibition (TDI). Greenblatt 2000 (PMID:10801241) double-blind crossover: ritonavir 200 mg × 4 doses (booster-equivalent) reduced alprazolam CL to 41% (P<.001), t½ 13→30 h. AUC ratio 2.44×; Ki ≈ 1.5/(2.44−1) = 1.0 µM at booster Cp_perp 1.5 µM. Note: chronic exposure produces less interaction (induction offset).
Fentanyl (major): CYP3A4 inhibition. Olkkola 1999 (PMID:10485779) n=12 crossover, ritonavir 200/300 mg TID, IV fentanyl 5 µg/kg: CL fell 67% (15.6→5.2 mL/min/kg), AUC0-18h 4.8→8.8 ng·h/mL (1.83×). Full AUC ratio ≈ 3×. Ki ≈ 1.5/2 = 0.75 µM. IV bypasses gut CYP3A4 — Ki reflects hepatic only; PO would be larger.
Amlodipine (warn): CYP3A4 inhibition. Courlet 2021 (PMID:33452585) NONMEM pop-PK n=55 PLWH on RTV-boosted darunavir: amlodipine AUC +96% (ratio 1.96). Ki ≈ 1.5/0.96 = 1.56 µM at booster Cp_perp 1.5 µM. Confound: darunavir as co-perpetrator. Halve amlodipine dose with boosted PI regimens.