Dolutegravir

Rifampin

Dosage adjustment is recommended.

No pharmaceutical opinion available for this interaction.

Mechanism

Rifampin can increase the metabolism (UGT 1A1) and decrease the plasma concentration of Dolutegravir.

Dolutegravir

Pharmacodynamic effects

Possible decrease of clinical efficacy.

Recommendations

Tivicay : In patients who have never received integrase inhibitors, increase dolutegravir dose to 50 mg BID.

Triumeq or Dovato : Administer an additional dose of 50 mg dolutegravir 12 hours after Triumeq or Dovato.

Monitor for clinical efficacy.

Avoid combination in patients with resistance to integrase inhibitors.

Juluca : Concomitant administration contraindicated.

Alternative solution(s)

Rifampin

Pharmacodynamic effects

Recommendations

Alternative solution(s)

Rifabutin (See rifabutine and dolutégravir)

Monitor

Tests

CD4+

Viral load HIV

Pharmacokinetic parameters
Parameters
Reference number
# patients
HIV
Dose
AUC
Cmin
Duration (days)
T1/2
Cmax
Frequency
Dolutegravir
2724 2724 3424 3424
11 11 14 14
- - - -
50 mg 50 mg 50 mg 100 mg
+ 33% * - 54% ** - 57% - 26% †
+ 22% * - 72% ** - 86% - 76% †
28 21 7 7
- 60% *      
+ 18% * - 43% ** - 35% + 9% †
QD+BID * QD QD QD
Rifampin
2724 2724 3424 3424
11 11 14 14
- - - -
600 mg 600 mg 600 mg 600 mg
       
       
14 14 7 7
       
       
QD QD QD QD
Comment

Dolutegravir 50 mg BID with rifampin compararable to dolutegravir 50 mg QD.

Ref # 2724:
* Comparison is rifampin taken with dolutegravir 50 mg BID compared with dolutegravir QD.
** Comparison is rifampin taken with dolutegravir 50 mg BID compared with dolutegravir 50 mg BID alone.
3 periods tudy with healthy subjects : Dolutegravir 50 mg QD (7 days), Dolutegravir 50 mg BID (7 days) and Dolutegravir 50 mg BID with rifampin (14 days).
One subject had a grade 2 lymphopenia and a rash.

Ref # 2868: The monograph recommends to give dolutegravir 50 mg BID for patients who have no resistance to integrase inhibitors. For patients with resistance to integrase inhibitors, it is suggested to choose an alternative to Rifampin.

Ref #3422 : In this sub-study with 12 HIV-TB co-infected patients, the treatment of dolutegravir 50 mg BID with rifampin 600 mg QD appears to show good efficacy with adequate dolutegravir Cmin. Although only two patients had concentrations of dolutegravir <640 ng/mL, it is suggested that this dose be used only in patients with wild-type HIV. Rifampin had no effect on lamivudine and tenofovir concentrations.

Ref #3424 : † When comparing PK parameters of dolutegravir 100 mg QD in co-administration with rifampin to dolutegravir 50mg QD alone.
Despite the significant decrease in dolutegravir Cmin, concentrations of dolutegravir 100 mg QD with rifampin were above the protein bindingadjusted IC of 64 ng/mL. Further study of this dose are needed.

Reference
  • 2868
    Dolutegravir (Tivicay), ViiV Healthcare, Quebec, Canada, 31 janv. 2020.
  • 3120
    Dolutégravir/abacavir/lamivudine (Triumeq), ViiV Healthcare, Québec, Canada, 31 janv. 2020.
  • 3441
    Dolutegravir/Rilpivirine (Juluca), ViiV Healthcare ULC, Quebec, Canada, 5 fév. 2020.
  • 3497
    Dolutegravir/Lamivudine (Dovato), ViiV Soins de santé ULC, Québec, Canada, 29 septembre 2020.
  • 2724
    Dooley KE, Sayre P, Borland J, et al. Safety, tolerability, and pharmacokinetics of the HIV integrase inhibitor dolutegravir given twice daily with rifampin or once daily with rifabutin: results of a phase 1 study among healthy subjects. J Acquir Immune Defic Syndr. 2013 Jan; 62(1): 21–27.
  • 3442
    Dooley KE, Kaplan R, Mwelase N et al. Safety and efficacy of dolutegravir-based ART in TB/HIV coinfected adults at week 24. CROI 2018, Boston, MA USA, March 4–7, 2018. Abstract #33.
  • 3422
    Le M, Cournil A, Eymard-Duvernay S, Kouanfack C, Lem S et al. Lack of Pharmacokinetic and virological efficacy of dolutegravir (50 mg BID) containing regimen in association with rifampin in HIV-infected patients using Dried Blood Spot: ANRS-12313 NAMSAL sub-study in Cameroon. 19th International Workshop on Clinical Pharmacology of Antiviral Therapy. May 22-24 2018, Baltimore, USA, Abstract 7.
  • 3424
    Wang X, Cerrone M, Ferretti F, Day-Weber I, Nadia C et al. Pharmacokinetics of Dolutegravir 100 MG Once-Daily with Rifampicin. 19th International Workshop on Clinical Pharmacology of Antiviral Therapy. May 22-24 2018, Baltimore, USA, Abstract 11.