https://interactions.guidetherapeutiquevih.com/en/interaction-details?id=10652

Dolutegravir

Rifabutin

Potential interaction.

No pharmaceutical opinion available for this interaction.

Mechanism

Rifabutin may induce CYP 3A4 and UGT1A1 and decrease plasma concentration Dolutegravir.

Dolutegravir

Pharmacodynamic effects

Possible decrease of clinical efficacy.

Recommendations

Tivicay, Triumeq ou Dovato : No dosage adjustment is necessary.

A dosage increase could be considered following a low TDM result.

Juluca : Take 25 mg of rilpivirine with Juluca tablet during co-administration.

See comments for further details.

Alternative solution(s)

–

Rifabutin

Pharmacodynamic effects

–

Recommendations

–

Alternative solution(s)

–

Monitor

–

Tests

Dolutegravir plasma level

Pharmacokinetic parameters
Parameters
Reference number
# patients
HIV
Dose
Frequency
Duration (days)
AUC
Cmax
Cmin
Ctr
Dolutegravir
2723 3779
9 12
- +
50 mg 50 mg
QD QD
14  
- 5%  
+ 15% - 45%
- 30% *  
  - 59%
Rifabutin
2723 3779
9 12
- +
300 mg 300 mg
QD QD
14  
   
   
   
   
Comment

Ref #2723 : * This decrease is unlikely to be clinically significant effect in integrase inhibitor-naive patients.

Ref #3662: To characterize the pharmacokinetics of dolutegravir when co-administered with rifabutin, this analysis includes data from two existing studies in a model describing the population pharmacokinetics of dolutegravir. Simulations showed that rifabutin decreased the volume of distribution of dolutegravir by 33.1%, but did not affect the area under the concentration-time curve. They also demonstrated that when 50 mg of dolutegravir is co-administered with rifabutin QD, the probability of achieving trough concentrations above the IC90 of 0.064 mg/L was greater than 99%.

Ref #3773 : In a case series of 4 patients coinfected with HIV and tuberculosis receiving dolutegravir and rifabutin and undergoing pharmacokinetic (PK) analysis, all patients had lower than expected dolutegravir concentrations even those receiving higher than recommended doses. The authors consider that therapeutic drug monitoring (TDM) for dolutegravir is advisable.

Comment
Reference
  • 2723
    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, 62(1): 21-27.
  • 2869
    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.
  • 3662
    Kawuma AN, Wasmann RE, Dooley KE, Maartens G and P Denti. Drug-drug interaction between rifabutin and dolutegravir: A population pharmacokinetic model. Br J Clin Pharmacol. 2023 Mar; 89 (3): 1216-1221.
  • 2868
    Dolutegravir (Tivicay), ViiV Soins de santé ULC, Quebec, Canada, 31 janv. 2020.
  • 3120
    Dolutégravir/abacavir/lamivudine (Triumeq), ViiV Soins de santé ULC, Québec, Canada, 22 nov. 2021.
  • 3441
    Dolutegravir/Rilpivirine (Juluca), ViiV Soins de santé ULC, Quebec, Canada, 5 juillet 2023.
  • 3497
    Dolutegravir/Lamivudine (Dovato), ViiV Soins de santé ULC, Québec, Canada, 27 juin 2023.
  • 3773
    Mendoza MA, Alshaer MH, Roldan G, Castro JG, Ashkin D, et al. Effect of Rifabutin in Dolutegravir Dosing: A Case Series. J Int Assoc Provid AIDS Care. 2022, vol 21: 1-6.
  • 3779
    Le X, Guo X, Sun J, Liu L , Shen Y, et al. Pharmacokinetic features of dolutegravir with rifampicin and rifabutin among patients coinfected with human immunodeficiency virus and tuberculosis/mycobacterium avium complex. International Journal of Infectious Diseases. 116 (2022) 147-150.