Dolutegravir + Ethinylestradiol/Norgestimate = Precautionary

Effect on Concentration

Dolutegravir
Unknown
Applies within class?
No
Ethinylestradiol/Norgestimate
No change
Applies within class?
No

Pharmacologic Effects

Dolutegravir
Effect
N/A
Applies within class?
No
Ethinylestradiol/Norgestimate
Effect
N/A
Applies within class?
No

Interaction History

N/A

Last Updated 22-Nov-2022

Summary

The highest clinical dose of DTG did not have an effect on this contraceptive hormonal combination (CHC). There were no pharmacokinetic results of the effect of this CHC on DTG.

Sources

Dolutegravir vs ethinyl estradiol/norgestimate ^

Study Design

This was a randomized, 2-period, double-blind, placebo-controlled cross-over study conducted within a single menstrual cycle in healthy female subjects. All subjects received Ortho-Cyclen (ethinyl estradiol (EE) 0.035mg and norgestimate 0.25mg) throughout the study and were randomized to receive dolutegravir (DTG) 50mg BID (highest clincial dose) or placebo with food every 12 hours for 10 days, then on day 11 all subjects received Ortho-Cyclen only. From days 12 to 21 subjects were switched to placebo or DTG (the opposite of what they received in the first 10 days) . Serial PK and safety was assessed throughout. PD was assessed by luteinizing hormone, follicle stimulating hormone, and progesterone levels.

Study Results

The PK of EE and norelgestromin (major active metabolite of norgestimate) were not altered by concomitant DTG. The geometric least squares mean ratios of the AUC(0-t) (90% CI) were 1.03 (0.964, 1.11) and 0.975 (0.910, 1.04) for EE and norelgestromin, respectivley with coadministration of DTG. There were no clinically relevant changes to PD measures. There were no clinically significant changes in lab values, vital signs, or ECG observed.

Study Conclusions

References

I Song, S Mark, J Borland, S Chen, T Wajima, A Peppercorn, S Piscitelli. Dolutegravir has no effect on pharmacokinetics of methadone or oral contraceptives with norgestimate and ethinyl estradiol. The 20th Conference On Retroviruses And Opportunistic Infections. Atlanta, GA, USA. ; 2013.