Isoniazid + Efavirenz = Precautionary

Effect on Concentration

Isoniazid
Decrease
Applies within class?
No
Efavirenz
Decrease
Applies within class?
No

Pharmacologic Effects

Isoniazid
Effect
N/A
Applies within class?
No
Efavirenz
Effect
N/A
Applies within class?
No

Interaction History

Unknown or No Reaction, 29-Aug-2018;

Last Updated 15-Oct-2023

Summary

When 400 mg of efavirenz once daily is given with anti-TB drugs, there is a slight decrease in EFV concentration. Moreover, studies show a decrease in INH exposure with EFV, however, a high TB treatment success rate is maintained. HIV viral loads remained suppressed and EFV concentrations were maintained within therapeutic limits.

Sources

Pharmacokinetics of Rifampin and Isoniazid in Tuberculosis-HIV-Coinfected Patients Receiving Nevirapine- or Efavirenz-Based Antiretroviral Treatment. ^

Study Design

A substudy of the ANRS 12146-CARINEMO trial assessed the impact on the pharmacokinetics of RIF and INH when NNRTI-based antiretroviral therapy was co-administered 4-6 weeks after the start of TB treatment. Thirty eight patients were included, of which 17 received efavirenz 600mg once daily in combination with stavudine and lamivudine. RIF was dosed at 10mg/kg/day and INH 5 mg/kg/day.

Study Results

The results showed a statistically significant 29% decrease in INH exposure was observed with EFV. A geometric mean ratio (90%CI) of 0.71 (0.55-0.92) for INH AUC (with/without EFV) was reported. Cmax and half-life were not significantly affected.

Study Conclusions

The study suggested that these PK changes were not clinically significant, with a high TB treatment success rate.

References

Bhatt NB, Barau C, Amin A. Pharmacokinetics of rifampin and isoniazid in tuberculosis-hiv-coinfected patients receiving nevirapine- or efavirenz-based antiretroviral treatment. Antimicrobial Agents And Chemotherapy . 2014; 6: 3182-3190.

Pharmacokinetics of Rifampin and Isoniazid in Tuberculosis-HIV-Coinfected Patients Receiving Nevirapine- or Efavirenz-Based Antiretroviral Treatment. ^

Study Design

A substudy of the ANRS 12146-CARINEMO trial assessed the impact on the pharmacokinetics of RIF and INH when NNRTI-based antiretroviral therapy was co-administered 4-6 weeks after the start of TB treatment. Thirty eight patients were included, of which 17 received efavirenz 600mg once daily in combination with stavudine and lamivudine. RIF was dosed at 10mg/kg/day and INH 5 mg/kg/day.

Study Results

The results showed a statistically significant 29% decrease in INH exposure was observed with EFV. A geometric mean ratio (90%CI) of 0.71 (0.55-0.92) for INH AUC (with/without EFV) was reported. Cmax and half-life were not significantly affected.

Study Conclusions

The study suggested that these PK changes were not clinically significant, with a high TB treatment success rate.

References

Cerrone, M, Wang, X, Neary, M. Pharmacokinetics of efavirenz 400mg with isoniazid/ rifampicin in people with hiv. Conference On Retroviruses And Opportunistic Infections. Boston. 2018; March 2018.

Efavirenz versus Isoniazid ^

Study Design

This open-label study investigated the pharmacokinetics (PK), efficacy, CYP2B6 pharmacogenetics of efavirenz (EFV)400 + Isoniazid/Rifampicin (INH/RIF) in patients living with HIV/AIDS (PLWH) without TB (TB-), receiving tenofovir disoproxil fumarate (TDF), emtricitabine (FTC) and EFV 600mg with a viral load (VL)< 50 copies/mL. They were switched to TDF/FTC/ EFV400. Weekly therapeutic drug monitoring (TDM), steady-state PK profiles of EFV400 without (PK1) and with INH/RIF following 4 (PK2) and 12 (PK3) weeks of co-administration, safety, virologic efficacy, polymorphisms in CYP2B6 (516C>T; 938T>C) were evaluated.

Study Results

All had viral load (VL) <50 at baseline, which was maintained throughout the study. Geometric mean ratios (GMR) PK2/PK1, n=22 (90%CI) of EFV400 Cmax, AUC, and C24h were 0.91 (0.83-0.99), 0.91 (0.86-1.13), 0.85 (0.72-0.99). GMR (90%CI) of PK3/PK2 and PK3/PK1 (n=17) Cmax, AUC, and C24h were 0.97 (0.88- 1.06), 0.94 (0.88-1.06), 0.91 (0.78-1.05) and 0.85 (0.78-0.94), 0.86 (0.80-1.09), 0.77 (0.64-0.94). 11/22 subjects were carriers of 516T (10) and/or 938C (3) slow metabolizers alleles.

Study Conclusions

INH/RIF co-administration in TB-PLWH with a VL<50 was associated with limited changes in EFV400 exposure (<23%). Results from this cohort conclude that EFV400 can be co-administered with anti-TB treatment. This should be confirmed in TB+ PLWH.

References

Cerrone, M, Wang, X, Neary, M. Pharmacokinetics of efavirenz 400mg with isoniazid/ rifampicin in people with hiv. Conference On Retroviruses And Opportunistic Infections. Boston. 2018; March 2018.

Efavirenz versus Isoniazid ^

Study Design

This open-label study investigated the pharmacokinetics (PK), efficacy, CYP2B6 pharmacogenetics of efavirenz (EFV)400 + Isoniazid/Rifampicin (INH/RIF) in patients living with HIV/AIDS (PLWH) without TB (TB-), receiving tenofovir disoproxil fumarate (TDF), emtricitabine (FTC) and EFV 600mg with a viral load (VL)< 50 copies/mL. They were switched to TDF/FTC/ EFV400. Weekly therapeutic drug monitoring (TDM), steady-state PK profiles of EFV400 without (PK1) and with INH/RIF following 4 (PK2) and 12 (PK3) weeks of co-administration, safety, virologic efficacy, polymorphisms in CYP2B6 (516C>T; 938T>C) were evaluated.

Study Results

All had viral load (VL) <50 at baseline, which was maintained throughout the study. Geometric mean ratios (GMR) PK2/PK1, n=22 (90%CI) of EFV400 Cmax, AUC, and C24h were 0.91 (0.83-0.99), 0.91 (0.86-1.13), 0.85 (0.72-0.99). GMR (90%CI) of PK3/PK2 and PK3/PK1 (n=17) Cmax, AUC, and C24h were 0.97 (0.88- 1.06), 0.94 (0.88-1.06), 0.91 (0.78-1.05) and 0.85 (0.78-0.94), 0.86 (0.80-1.09), 0.77 (0.64-0.94).

Study Conclusions

INH/RIF co-administration in TB-PLWH with a VL<50 was associated with limited changes in EFV400 exposure (<23%). Results from this cohort conclude that EFV400 can be co-administered with anti-TB treatment. This should be confirmed in TB+ PLWH.

References

Cerrone, M, Wang, X, Neary, M. Pharmacokinetics of efavirenz 400mg with isoniazid/ rifampicin in people with hiv. Conference On Retroviruses And Opportunistic Infections. Boston. 2018; March 2018.

Isoniazid and efavirenz drug interaction in pregnant women with HIV ^

Study Design

Prospective, double-blind, placebo-controlled, randomized, noninferiority IMPAACT trial in pregnant women who are HIV positive and &8805; 18 years old were included in the study if gestational age was 14 to 34 weeks, on HIV treatment for prevention of mother-to-child transmission, and weighing 35 kg. At study entry, women were randomized either to arm A (immediate 28 weeks of 300-mg isoniazid daily treatment, then placebo) or arm B (deferred isoniazid treatment, placebo until week 12 postpartum, then 28 weeks of 300 mg isoniazid)

Study Results

The overall median (interquartile range) of AUC 024 was 66.8 mgh/L (45.2114 mgh/L) when isoniazid was present and 55.4 mgh/L (39.798.1 mgh/L) when absent, corresponding to a 1.2-fold increase in efavirenz AUC024 due to the presence of isoniazid.

Study Conclusions

Results from this study concludes that isoniazid co-administered with efavirenz can decrease the clearance of efavirenz, especially in individuals who are CYP2B6 slow metabolizers.

References

Gausi, K, Wiesner, L, Norman, J, Wallis, C, Onyango-Makumbi, C, Chipato, T, Haas, D, Browning, R, Chakhtoura, N, Montepiedra, G, Aaron, L, McCarthy, K, Bradford, S, Vhembo, T, Stranix-Chibanda, L, Masheto, G, Violari, A, Mmbaga, B, Aurpibul, L, Bhosale, R, Nevrekhar, N, Rouzier, V, Kabugho, E, Mutambanengwe, M, Chanaiwa, V, Nyati, M, Mhembere, T, Tongprasert, F, Hesseling, A, Shin, K, Zimmer, B, Costello, D, Jean-Philippe, P, Sterling, T, Theron, G, Weinberg, A, Gupta, A, Denti, P. Pharmacokinetics and drug-drug interactions of isoniazid and efavirenz in pregnant women living with hiv in high tb incidence settings: importance of genotyping. American Society For Clinical Pharmacology And Therapeutics. 2020; 4: 1034-1044.

Efavirenz versus Isoniazid ^

Study Design

This open-label study investigated the pharmacokinetics (PK), efficacy, CYP2B6 pharmacogenetics of efavirenz (EFV)400 Isoniazid/Rifampicin (INH/RIF) in patients living with HIV/AIDS (PLWH) without TB (TB-), receiving tenofovir disoproxil fumarate (TDF), emtricitabine (FTC) and EFV 600mg with a viral load (VL) 50 copies/mL. They were switched to TDF/FTC/ EFV400. Weekly therapeutic drug monitoring (TDM), steady-state PK profiles of EFV400 without (PK1) and with INH/RIF following 4 (PK2) and 12 (PK3) weeks of co-administration, safety, virologic efficacy, polymorphisms in CYP2B6 (516CT; 938TC) were evaluated.

Study Results

All had viral load (VL) 50 at baseline, which was maintained throughout the study. Geometric mean ratios (GMR) PK2/PK1, n22 (90CI) of EFV400 Cmax, AUC, and C24h were 0.91 (0.83-0.99), 0.91 (0.86-1.13), 0.85 (0.72-0.99). GMR (90CI) of PK3/PK2 and PK3/PK1 (n17) Cmax, AUC, and C24h were 0.97 (0.88- 1.06), 0.94 (0.88-1.06), 0.91 (0.78-1.05) and 0.85 (0.78-0.94), 0.86 (0.80-1.09), 0.77 (0.64-0.94).

Study Conclusions

INH/RIF co-administration in TB-PLWH with a VL50 was associated with limited changes in EFV400 exposure (23). Results from this cohort conclude that EFV400 can be co-administered with anti-TB treatment. This should be confirmed in TB PLWH.

References

Gausi, K, Wiesner, L, Norman, J, Wallis, C, Onyango-Makumbi, C, Chipato, T, Haas, D, Browning, R, Chakhtoura, N, Montepiedra, G, Aaron, L, McCarthy, K, Bradford, S, Vhembo, T, Stranix-Chibanda, L, Masheto, G, Violari, A, Mmbaga, B, Aurpibul, L, Bhosale, R, Nevrekhar, N, Rouzier, V, Kabugho, E, Mutambanengwe, M, Chanaiwa, V, Nyati, M, Mhembere, T, Tongprasert, F, Hesseling, A, Shin, K, Zimmer, B, Costello, D, Jean-Philippe, P, Sterling, T, Theron, G, Weinberg, A, Gupta, A, Denti, P. Pharmacokinetics and drug-drug interactions of isoniazid and efavirenz in pregnant women living with hiv in high tb incidence settings: importance of genotyping. American Society For Clinical Pharmacology And Therapeutics. 2020; 4: 1034-1044.

Efavirenz versus Isoniazid ^

Study Design

This open-label study investigated the pharmacokinetics (PK), efficacy, CYP2B6 pharmacogenetics of efavirenz (EFV)400 Isoniazid/Rifampicin (INH/RIF) in patients living with HIV/AIDS (PLWH) without TB (TB-), receiving tenofovir disoproxil fumarate (TDF), emtricitabine (FTC) and EFV 600mg with a viral load (VL) 50 copies/mL. They were switched to TDF/FTC/ EFV400. Weekly therapeutic drug monitoring (TDM), steady-state PK profiles of EFV400 without (PK1) and with INH/RIF following 4 (PK2) and 12 (PK3) weeks of co-administration, safety, virologic efficacy, polymorphisms in CYP2B6 (516CT; 938TC) were evaluated.

Study Results

All had viral load (VL) 50 at baseline, which was maintained throughout the study. Geometric mean ratios (GMR) PK2/PK1, n22 (90CI) of EFV400 Cmax, AUC, and C24h were 0.91 (0.83-0.99), 0.91 (0.86-1.13), 0.85 (0.72-0.99). GMR (90CI) of PK3/PK2 and PK3/PK1 (n17) Cmax, AUC, and C24h were 0.97 (0.88- 1.06), 0.94 (0.88-1.06), 0.91 (0.78-1.05) and 0.85 (0.78-0.94), 0.86 (0.80-1.09), 0.77 (0.64-0.94). 11/22 subjects were carriers of 516T (10) and/or 938C (3) slow metabolizers alleles.

Study Conclusions

INH/RIF co-administration in TB-PLWH with a VL50 was associated with limited changes in EFV400 exposure (23). Results from this cohort conclude that EFV400 can be co-administered with anti-TB treatment. This should be confirmed in TB PLWH.

References

Gausi, K, Wiesner, L, Norman, J, Wallis, C, Onyango-Makumbi, C, Chipato, T, Haas, D, Browning, R, Chakhtoura, N, Montepiedra, G, Aaron, L, McCarthy, K, Bradford, S, Vhembo, T, Stranix-Chibanda, L, Masheto, G, Violari, A, Mmbaga, B, Aurpibul, L, Bhosale, R, Nevrekhar, N, Rouzier, V, Kabugho, E, Mutambanengwe, M, Chanaiwa, V, Nyati, M, Mhembere, T, Tongprasert, F, Hesseling, A, Shin, K, Zimmer, B, Costello, D, Jean-Philippe, P, Sterling, T, Theron, G, Weinberg, A, Gupta, A, Denti, P. Pharmacokinetics and drug-drug interactions of isoniazid and efavirenz in pregnant women living with hiv in high tb incidence settings: importance of genotyping. American Society For Clinical Pharmacology And Therapeutics. 2020; 4: 1034-1044.

Pharmacokinetics of Rifampin and Isoniazid in Tuberculosis-HIV-Coinfected Patients Receiving Nevirapine- or Efavirenz-Based Antiretroviral Treatment. ^

Study Design

A substudy of the ANRS 12146-CARINEMO trial assessed the impact on the pharmacokinetics of RIF and INH when NNRTI-based antiretroviral therapy was co-administered 4-6 weeks after the start of TB treatment. Thirty eight patients were included, of which 17 received efavirenz 600mg once daily in combination with stavudine and lamivudine. RIF was dosed at 10mg/kg/day and INH 5 mg/kg/day.

Study Results

The results showed a statistically significant 29 decrease in INH exposure was observed with EFV. A geometric mean ratio (90CI) of 0.71 (0.55-0.92) for INH AUC (with/without EFV) was reported. Cmax and half-life were not significantly affected.

Study Conclusions

The study suggested that these PK changes were not clinically significant, with a high TB treatment success rate.

References

Gausi, K, Wiesner, L, Norman, J, Wallis, C, Onyango-Makumbi, C, Chipato, T, Haas, D, Browning, R, Chakhtoura, N, Montepiedra, G, Aaron, L, McCarthy, K, Bradford, S, Vhembo, T, Stranix-Chibanda, L, Masheto, G, Violari, A, Mmbaga, B, Aurpibul, L, Bhosale, R, Nevrekhar, N, Rouzier, V, Kabugho, E, Mutambanengwe, M, Chanaiwa, V, Nyati, M, Mhembere, T, Tongprasert, F, Hesseling, A, Shin, K, Zimmer, B, Costello, D, Jean-Philippe, P, Sterling, T, Theron, G, Weinberg, A, Gupta, A, Denti, P. Pharmacokinetics and drug-drug interactions of isoniazid and efavirenz in pregnant women living with hiv in high tb incidence settings: importance of genotyping. American Society For Clinical Pharmacology And Therapeutics. 2020; 4: 1034-1044.

Pharmacokinetics of Rifampin and Isoniazid in Tuberculosis-HIV-Coinfected Patients Receiving Nevirapine- or Efavirenz-Based Antiretroviral Treatment. ^

Study Design

A substudy of the ANRS 12146-CARINEMO trial assessed the impact on the pharmacokinetics of RIF and INH when NNRTI-based antiretroviral therapy was co-administered 4-6 weeks after the start of TB treatment. Thirty eight patients were included, of which 17 received efavirenz 600mg once daily in combination with stavudine and lamivudine. RIF was dosed at 10mg/kg/day and INH 5 mg/kg/day.

Study Results

The results showed a statistically significant 29 decrease in INH exposure was observed with EFV. A geometric mean ratio (90CI) of 0.71 (0.55-0.92) for INH AUC (with/without EFV) was reported. Cmax and half-life were not significantly affected.

Study Conclusions

The study suggested that these PK changes were not clinically significant, with a high TB treatment success rate.

References

Gausi, K, Wiesner, L, Norman, J, Wallis, C, Onyango-Makumbi, C, Chipato, T, Haas, D, Browning, R, Chakhtoura, N, Montepiedra, G, Aaron, L, McCarthy, K, Bradford, S, Vhembo, T, Stranix-Chibanda, L, Masheto, G, Violari, A, Mmbaga, B, Aurpibul, L, Bhosale, R, Nevrekhar, N, Rouzier, V, Kabugho, E, Mutambanengwe, M, Chanaiwa, V, Nyati, M, Mhembere, T, Tongprasert, F, Hesseling, A, Shin, K, Zimmer, B, Costello, D, Jean-Philippe, P, Sterling, T, Theron, G, Weinberg, A, Gupta, A, Denti, P. Pharmacokinetics and drug-drug interactions of isoniazid and efavirenz in pregnant women living with hiv in high tb incidence settings: importance of genotyping. American Society For Clinical Pharmacology And Therapeutics. 2020; 4: 1034-1044.