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Baricitinib
Olumiant® (baricitinib) tablets
1mg, 2mg, 4mgbaricitinib
1mg, 2mg, 4mgThis information is provided in response to your request. Resources may contain information about doses, uses, formulations and populations different from product labeling. See Prescribing Information above, if applicable.
Does Olumiant® (baricitinib) affect male fertility?
In animal studies, baricitinib did not have an effect on male reproductive organs or sperm endpoints; however, there is a potential to decrease fertility.
Prescribing Information
See important safety information, including boxed warning, in the attached prescribing information.
Combined Male and Female Animal Fertility Study
Male rats were dosed with 0, 5, 15, or 50 mg/kg of baricitinib (BARI) daily for 6 weeks including 4 weeks prior to cohabitation with female rats treated with 0, 5, 25, or 100 mg/kg.1
The no-observed-adverse-effect level (NOAEL) for male fertility was 15 mg/kg based on rat studies.1
Effects on Reproductive Organs and Sperm in Animals
Histologic studies found no change in male rat reproductive organs, and no effects on sperm motility, concentration, and morphology at any BARI dose level.1
Effects on Fertility and Early Embryonic Development in Animals
Results by Doses
Fertility (achievement of pregnancy) was reduced in male and female rats that received BARI at oral doses of 50 and 100 mg/kg/day respectively (approximately 62 and 93 times the maximum recommended human dose [MRHD] in males and females, respectively, on an area under the curve [AUC] basis).2
Fertility was unaffected in male and female rats at oral doses of 15 mg/kg and 25 mg/kg, respectively (approximately 13 and 26 times the MRHD on an AUC basis).2
The number of viable embryos was unaffected in female rats that received BARI at an oral dose of 5 mg/kg/day and were mated to males that received the same dose (approximately 6 times the MRHD on an AUC basis).2
Potential Cause of Decreased Fertility
Based on the study design, it could not be determined if fertility results were attributable to toxicities in one sex or both.2 However, since there were no effects on spermatogenesis or semen/sperm endpoints in male rats, the decreased overall mating performance was likely the result of fertility effects in female rats including
- decreased corpora lutea and implantation sites
- increased preimplantation loss, and
- adverse effects on intrauterine survival.1
The NOAEL was 5 mg/kg for female fertility and early embryonic development based on rat studies.1
Effects on Reproductive Performance
Reproductive performance was unaffected in male and female rats that received baricitinib at oral doses up to 50 and 100 mg/kg/day respectively (approximately 62 and 93 times the MRHD in males and females, respectively, on an AUC basis).2
Use in Males of Reproductive Potential
Clinical Trial Data Related to Male Patients and Procreation
In all BARI clinical trials, male patients agreed to use 2 forms of birth control (1 must be highly effective) while engaging in sexual intercourse with female partners of childbearing potential
- while enrolled in the study, and
- for at least 28 days following the last dose of study treatment.1
Washout Period Prior to Conception
Eli Lilly cannot provide recommendations on whether male patients should continue or interrupt BARI treatment before conception as this has not been studied.1
Treatment-Emergent Adverse Events
A treatment-emergent adverse event (TEAE) is an adverse event (AE) that either occurred or worsened in severity after the first dose of study treatment and did not necessarily have a causal relationship to study treatment.1
Rheumatoid Arthritis
All BARI RA Analysis Set
The All-BARI-Rheumatoid Arthritis (RA) analysis set included 3770 patients with RA who received BARI at a variety of doses from 1 phase 1, 3 phase 2, and 5 phase 3 studies (RA-BEGIN, RA-BEAM, RA-BUILD, RA-BEACON, and RA-BALANCE). Data include a long-term extension study (RA-BEYOND) with
- 14,744 patient-years of exposure (PYE) to BARI
- 15,114 patient years (PY) overall observation including time on BARI and follow up
- median exposure of 4.6 years, and
- maximum exposure of 9.3 years.3
In this safety analysis, sperm-related AEs such as spermatogenesis abnormal (Medical Dictionary for Regulatory Activities [MedDRA] preferred term) have not been reported.1
Sperm analysis was not routinely conducted throughout the studies, and male participants were required to use birth control throughout the duration of the study as described above.1
Alopecia Areata
The All-BARI-Alopecia Areata (AA) dataset includes 1244 patients with AA who received BARI at a variety of doses from the phase 2/3 BRAVE-AA1 and phase 3 BRAVE-AA2 studies. Data include
- 1362.2 PYE to BARI
- a mean exposure of 400 days, and
- a maximum exposure of 903 days.4
In this safety analysis, sperm-related AEs such as spermatogenesis abnormal (MedDRA preferred term) have not been reported.1
Postmarketing Spontaneous Reports
The following information is valid for data received up through December 13, 2021. The data do not represent the number of AEs in a treated population. They merely represent the number of a particular AE reported to the company. The following MedDRA preferred terms have not been reported to the Eli Lilly and Company spontaneous AE database
- spermatogenesis abnormal, and
- paternal exposure during pregnancy.1
Spontaneous reporting of AEs can be highly variable and is not controlled clinical information on which to assess causality of a drug to an AE. Spontaneous reporting has limitations due to bias in reporting including incomplete information concerning the patient. When verification of product manufactured by Lilly is not obtainable, these cases are included in the spontaneous database.1
Paternal Exposure During Pregnancy in Clinical Trials
For more information on cases of paternal exposure during pregnancy in the BARI clinical program, please refer to the medical response on the use of BARI during pregnancy and/or lactation.
Enclosed Prescribing Information
References
The published references below are available by contacting 1-800-LillyRx (1-800-545-5979).
1Data on file, Eli Lilly and Company and/or one of its subsidiaries.
2Olumiant [package insert]. Indianapolis, IN: Eli Lilly and Company; 2022.
3Taylor PC, Takeuchi T, Burmester GR, et al. Safety of baricitinib for the treatment of rheumatoid arthritis over a median of 4.6 and up to 9.3 years of treatment: final results from long-term extension study and integrated database. Ann Rheum Dis. 2022;81(3):335-343. https://doi.org/10.1136/annrheumdis-2021-221276
4King B, Mostaghimi A, Shimomura Y, et al. Integrated safety analysis of baricitinib in adults with severe alopecia areata from two randomized clinical trials. Poster presented at: Annual Meeting of the American Academy of Dermatology Association (AAD); March 25-29, 2022; Boston, MA. Accessed April 29, 2022. https://aad-eposters.s3.amazonaws.com/AM2022/poster/33966/Integrated+safety+analysis+of+baricitinib+in+adults+with+severe+alopecia+areata+from+two+randomized+clinical+trials.pdf
Date of Last Review: April 13, 2022