Efavirenz + Medroxyprogesterone = Precautionary

Effect on Concentration

Efavirenz
Unknown
Applies within class?
No
Medroxyprogesterone
Decrease
Applies within class?
No

Pharmacologic Effects

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

Interaction History

N/A

Last Updated 24-Apr-2019

Summary

HIV patients on EFV-based HIV therapy were found to have lower progesterone levels in women on DMPA injections as a form of contraceptive. A more frequent dosing interval for the DMPA injection should be considered in these patients and caution should be exercised.

Sources

Efavirenz versus Depot medroxyprogesterone acetate ^

Study Design

This was a multicenter, single arm, study among women (n = 42) in sub-Saharan Africa stable on Efavirenz (EFV)-based antiretroviral therapy (ART) and Rifampicin (RIF)-based TB treatment. Plasma medroxyprogesterone acetate (MPA) concentrations were determined pre-dose and 2, 4,6, 8, 10 and 12 weeks after Depot medroxyprogesterone acetate (DMPA) 150 mg injection and measured plasma progesterone levels from week 2 onwards. The primary outcome measure was the proportion of women with sub-therapeutic MPA levels (<0.1 ng/mL) at week 12. MPA PK parameters were calculated using non-compartmental methods and compared with historical ART-naïve controls without TB who received DMPA.

Study Results

Five women [11.9% (95% CI 4.0-25.6%)] had MPA <0.1 ng/mL at week 12 with one of the five having MPA <0.1 ng/ml at week 10 compared to one of 16 (6,3%) at week 12 among the historical controls. No participant had progesterone levels >5 ng/mL (suggesting ovulation) throughout the study including at week 12. Compared to historical controls, median area under the concentration-time curve over 12 weeks (AUC0-12) was lower (7.63 vs. 12.38 ng*wk/mL, p=0.004) and apparent clearance was higher (19,681 vs. 12,117 L/ wk, p=0.004).

Study Conclusions

MPA clearance was higher than in controls, leading to sub-therapeutic concentrations of MPA in some women at 10 and 12 weeks post-dose, though progesterone levels typically associated with ovulation were not observed. It may be prudent to dose DMPA more frequently than every 12 weeks in women on EFV.

References

Mngqibisa, R, Cohn, SE, Kendall, MA, et al. Potential concern for timing of dmpa injection among women treated for hiv and tb. Conference On Retroviruses And Opportunistic Infections. Seattle . ; March 2019.