No pharmaceutical opinion available for this interaction.
Rifapentin can induce the metabolism (CYP 3A4) and decrease the plasma concentration of Dolutegravir.
Primarily metabolized via UGT1A1 with some contribution from CYP3A. Renal elimination of unchanged drug was low (< 1% of the dose). UGT1A9 and 1A3, P-gp and BCRP (in vitro)
OCT2 and MATE 1
Possible decrease of clinical efficacy and risk of possible development of resistance to antiretroviral class.
Co-administration with rifapentine once daily (1HP) : Increase dolutegravir dose to 50 mg BID for Tivicay and administer an additional 50 mg dose of dolutegravir 12 hours after Triumeq or Dovato.
Co-administration with rifapentine once weekly (3HP) : No dose adjustment is necessary.
Monitor for clinical efficacy.
Avoid combination in patients with resistance to integrase inhibitors.
Juluca : Concomitant administration contraindicated.
Hydrolysed by esterase and renal and fecal excretion.
3A4, 2C8/9 and P-gp
Rifabutin : see dolutegravir + rifabutin.
Dolutegravir plasma level
Viral load HIV
Rifapentine once daily (1 HP)
Ref #3647 : In this study, 25 HIV-positive patients with indications of latent tuberculosis received rifapentine/isoniazid 600/300 mg QD (1 HP) and dolutegravir 50 mg BID for one month. Dolutegravir concentrations were always higher to those of dolutegravir alone at a standard dose of 50 mg QD. 24 patients had a viral load <50 copies/mL on day 28 (all on day 42). No serious adverse effects have been reported.
Ref #3649 : In this retrospective analysis in PLWH with latent tuberculosis, all patients (44/44) taking 1HP and dolutegravir containing regimen maintained viral loads <200 copies/mL at months 3-6 after the completion of LTBI treatment.
Rifapentine once a week (3 HP)
Ref #3646 : In this study, 60 HIV-positive patients received rifapentine/isoniazid 900/900 mg once weekly QD (3 HP) and dolutegravir 50 mg QD for 3 months. Dolutegravir concentrations decreased by 47% however all but one of the trough values measured during the 12 weeks were above the 90% maximum inhibitory concentration for dolutegravir (300 ng/mL). All patients had an undetectable viral load (<40 copies/mL). No adverse reactions related to rifapentine or isoniazid above grade 3 have been reported.
Ref #3343 : This study was stopped prematurely due to serious toxicities, possibly related to high isoniazid exposure (67-92% higher than expected), observed in 2 of 3 subjects receiving 3 doses of weekly isoniazid/rifapentine (wHP) with once daily dolutegravir. Limited PK data from these subjects showed decreased dolutegravir exposure by 46% and Cmin values by 74% with wHP co-administration. Researchers suggest to avoid co-administration.
Ref #3649 : In this retrospective analysis in PLWH with latent tuberculosis, 96.7% of patients (178/184) taking 3HP and bictegravir containing regimen maintained viral loads <200 copies/mL at months 3-6 after the completion of LTBI treatment.