Coadministration of paroxetine (20 mg once daily) and fosamprenavir/ritonavir (700/100 mg twice daily) decreased paroxetine Cmax and AUC by 51% and 55% respectively. There was no change in amprenavir Cmax, AUC or Cmin when compared to historical data. The mechanism of this interaction is unknown. Dose titration of paroxetine based on a clinical assessment of antidepressant response is recommended. Patients on stable dose of paroxetine who start treatment with fosamprenavir and ritonavir should be monitored for antidepressant response.
Telzir Summary of Product Characteristics, ViiV Healthcare UK Ltd, January 2021.

Coadministration is expected to decrease paroxetine concentrations. Any paroxetine dose adjustment should be guided by clinical effect (tolerability and efficacy).
Lexiva Prescribing Information, ViiV Healthcare, October 2020.

The effect of fosamprenavir/ritonavir (700/100 mg twice daily) on paroxetine (20 mg once daily) pharmacokinetics and vice versa was studied in 23 HIV- subjects. Addition of fosamprenavir/ritonavir to paroxetine significantly decreased paroxetine AUC by 55%, Cmax by 51 % and elimination half-life by 25%; the free fraction of paroxetine increased by 30%, but the Cmax of free (unbound) decreased by 40%. AUC, Cmax, Cmin and half life of amprenavir and ritonavir were similar to historical controls. The reduction in total paroxetine exposure is partly explained by protein displacement of paroxetine. The interaction is likely to be clinically relevant and titration to a higher dose of paroxetine may be necessary to achieve the needed antidepressant effect.
Interaction study of the combined use of paroxetine and fosamprenavir-ritonavir in healthy subjects. van der Lee MJ, Blenke AA, Rongen GA, et al. Antimicrob Agents Chemother, 2007, 51(11): 4098-4104.

The interaction between paroxetine and FPV/RTV was investigated in two groups of healthy subjects. One group received paroxetine alone (20 mg once daily) for 10 days, followed by a wash out period of 16 days and then paroxetine with FPV/RTV (700/100 mg twice daily) for 10 days. The second group received the study medications in the reverse order. Results from the groups were combined with 22 subjects completing the study. Addition of FPV/RTV to paroxetine was found to reduce paroxetine exposure by ~60%. GMR values for paroxetine (with FPV/RTV vs alone) were 0.42 for AUC, 0.40 for Cmax and 0.75 for half life. FPV and RTV exposures were similar to historical controls (APV AUC 42 mg/L.h, Cmax 5.9 mg/L, Ctrough 2.5 mg/L, half-life 11.0 h; RTV AUC 4.9 mg/L.h, Cmax 1.0 mg/L, Ctrough 0.15 mg/L, half-life 3.9 h). The effect of APV/RTV on paroxetine may be explained by decreased absorption and/or increased metabolism of paroxetine. Titration of paroxetine to a higher dose may be needed for optimal antidepressant effect.
Combined use of paroxetine and fosamprenavir/ritonavir: a pharmacokinetic interaction study in healthy volunteers. Burger, D et al. 6th International Workshop on Clinical Pharmacology of HIV Therapy, Quebec, April 2005, abstract 13.