Recommendations for the Use of Antiretroviral Drugs in Pregnant Women with HIV Infection and Interventions to Reduce Perinatal HIV Transmission in the United States

The information in the brief version is excerpted directly from the full-text guidelines. The brief version is a compilation of the tables and boxed recommendations.

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Non-Nucleoside Reverse Transcriptase Inhibitors

Doravirine (Pifeltro, DOR)

Last Updated: December 7, 2018; Last Reviewed: December 7, 2018

There are insufficient human data on the use of doravirine in pregnancy to inform a drug-associated risk determination for birth defects and miscarriage.

Animal Studies

Carcinogenicity
Doravirine was not carcinogenic in long-term oral carcinogenicity studies in mice and rats at exposures up to 6 times and 7 times, respectively, the exposure seen in humans who received the recommended dose. A statistically significant incidence of thyroid parafollicular cell adenoma and carcinoma was observed among female rats who received a high dose of doravirine; however, this incidence was similar to the incidence observed among historical controls of the same species. Doravirine was not genotoxic in a battery of in vitro or in vivo mutagenicity assays.1

Reproduction/Fertility
In rats, doravirine did not affect fertility, reproductive performance, or early embryonic development at exposures (area under the curve [AUC]) that were approximately 7 times the exposure seen in humans who received the recommended dose.1

Teratogenicity/Adverse Pregnancy Outcomes
No adverse embryo-fetal effects were observed in rats and rabbits at doravirine exposures (AUC) that were approximately 9 times (in rats) and 8 times (in rabbits) the exposures seen in humans who received the recommended dose. Similarly, no adverse developmental findings were reported in a prenatal/postnatal study in rats at doravirine exposures that were approximately 9 times the exposure seen in humans who received the recommended dose.1

Placental and Breast Milk Passage
Embryo-fetal studies in rats and rabbits demonstrate placental passage of doravirine. Fetal plasma concentrations observed on gestation day 20 were up to 40% (in rabbits) and 52% (in rats) of maternal concentrations. Doravirine was excreted into the milk of lactating rats at concentrations approximately 1.5 times the maternal concentrations measured 2 hours post-dose on lactation day 14.1

Human Studies in Pregnancy

Pharmacokinetics
No pharmacokinetic studies of doravirine in pregnant women have been reported.

Placental and Breast Milk Passage
No data are available on placental or breast milk passage of doravirine in humans.

Teratogenicity/Adverse Pregnancy Outcomes
No data are available to inform the risk for birth defects following exposure to doravirine.

Excerpt from Table 10a

Note: When using FDCs, refer to other sections in Appendix B and Table 10 for information about the dosing and safety of individual drug components of the FDC during pregnancy.

Generic Name
(Abbreviation)
Trade Name
Formulation Dosing Recommendations Use in Pregnancy
Doravirine
(DOR)
Pifeltro

(DOR/3TC/TDF)
Delstrigo
DOR (Pifeltro):
  • 100 mg tablet
DOR/3TC/TDF (Delstrigo):
  • DOR 100 mg plus 3TC 300 mg plus TDF 300 mg tablet
Standard Adult Doses
DOR (Pifeltro):
  • 100 mg once daily with or without food
DOR/3TC/TDF (Delstrigo):
  • 1 tablet once daily with or without food
PK in Pregnancy:
  • No PK studies in human pregnancy.
Dosing in Pregnancy:
  • Insufficient data to make dosing recommendation.
For guidance about use of combination products in pregnancy, please see the specific sections on other components (i.e., 3TC, TDF)
No human data are available on placental transfer of DOR, but animal studies suggest that DOR crosses the placenta.

Insufficient data to assess for teratogenicity in humans. No evidence of teratogenicity in rats or rabbits.
a Individual ARV drug doses may need to be adjusted in patients with renal or hepatic insufficiency (for details, see the Adult and Adolescent Guidelines, Appendix B, Table 8).

Key to Acronyms: 3TC = lamivudine; ARV = antiretroviral; DOR = doravirine; FDC = fixed-dose combination; PK = pharmacokinetic; TDF = tenofovir disoproxil fumarate

References

  1. Doravirine [package insert]. Food and Drug Administration. 2018. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210806s000lbl.pdf.

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