For clinicians

Methotrexate

MTX

Looking for the plain-language version? See the patient version of this page.

Bottom lineBottom line: discontinue before conception in women (teratogen). The three guidelines give different intervals: ACR 2020 within 3 months (strong), EULAR 2024 1 to 3 months, BSR 2023 at least 1 month. Paternal use is the key divergence with drug labelling: ACR 2020, EULAR 2024 and BSR 2023 all consider low-dose (<=25 mg/week) paternal exposure compatible on current evidence, while some drug labels and agencies still advise stopping 3 to 6 months pre-conception.

By reproductive phase

PhasePositionDetailEvidence
Pre-conceptionStop pre-conceptionDiscontinue before conception. The interval differs by guideline: ACR 2020 within 3 months (strong), EULAR 2024 1 to 3 months, BSR 2023 at least 1 month (GRADE 1A). Continue folic acid; ensure effective contraception until stopped. The patient-facing version of this page states a single figure of at least 3 months before conception, matching the ACR 2020 strong recommendation, rather than presenting the range across guidelines. Timing for an individual, including anyone for whom delay carries its own cost, is set by the treating physician. The guideline positions below are unchanged.[1, 2, 3]●●●○moderate evidencestrong
1st trimesterAvoidAvoid; recognised teratogen (methotrexate embryopathy) and abortifacient.[1, 2]●●●○moderate evidencestrong
2nd/3rd trimesterAvoidAvoid throughout pregnancy.[1, 2]●●●○moderate evidencestrong
BreastfeedingAvoidACR 2020 conditionally recommends against methotrexate while breastfeeding, noting possible accumulation in neonatal tissues despite minimal transfer into milk. BSR 2023 states it cannot be recommended (GRADE 2C, SOA 99%). EULAR 2024 lists methotrexate (<=25 mg/week) among agents that may be considered during lactation only if no compatible alternative is available (4/C). The phase row follows ACR and BSR. Data are limited; individualise.[2]●●○○low evidenceconditional
PaternalContinueEULAR 2024 lists methotrexate <=25 mg/week among drugs that can be continued in male patients trying to conceive, with no demonstrated clinically relevant impact on offspring (2b/C). ACR 2020 concurs conditionally; BSR 2023 gives GRADE 1B (SOA 99.3%), the strongest of the three. Some drug labels and agencies still advise a 3 to 6 month stop.[1, 2, 3, 4, 5]●●○○low evidenceconditional

Guideline comparison

GuidelinePositionStrength
ACR 2020Strongly recommend against before pregnancy (discontinue within 3 months prior to conception) and during pregnancy (stop; folic acid 5 mg/day) (Table 3: strongly against / strongly against). The narrative records that timing data are conflicting and do not permit a more specific recommendation, describing one menstrual cycle as the minimum and 3 months as the most common period, and notes that time off the drug also allows disease stability to be observed. Conditionally recommend against in breastfeeding (may accumulate in neonatal tissues despite minimal transfer into milk). Paternal: conditionally recommend continuing (data show no evidence of mutagenicity or teratogenicity).[1]Strong against (maternal); conditional continue (paternal)
EULAR 2024Teratogenic; discontinue before pregnancy (2a/B). The narrative specifies discontinuation before conception at 1 to 3 months for methotrexate (1.5 months for mycophenolate, 3 months for cyclophosphamide); Table 1 does not restate the interval. In lactation, MTX <=25 mg/week may be considered only if no compatible alternative exists (4/C). Continuable in men at <=25 mg/week (2b/C).[2]Oxford LoE/GoR as shown
BSR 2022/23Stop >=1 month pre-conception; not compatible in first or second/third trimester or with breastfeeding. Compatible with paternal exposure (<=25 mg/week).[3]Verified against BSR Table 1
=Guideline divergence. VERIFIED DIVERGENCE (pre-conception interval). The three guidelines give three different intervals and must not be presented as one blended range. ACR 2020 strongly recommends discontinuation within 3 months prior to conception. EULAR 2024 specifies 1 to 3 months in its narrative, though Table 1 does not restate the interval. BSR 2023 gives at least 1 month (GRADE 1A, SOA 98%) and records 3 months as its own previous recommendation, citing the 2006 Ostensen consensus. All three read at source 2026-08-03.
=Guideline divergence. VERIFIED DIVERGENCE (lactation). ACR 2020 conditionally recommends against methotrexate while breastfeeding, citing possible accumulation in neonatal tissues despite minimal transfer into milk. BSR 2023 states it cannot be recommended (GRADE 2C, SOA 99%). EULAR 2024 places methotrexate <=25 mg/week among agents with limited lactation data that may be considered only where no compatible alternative can be used (4/C), a position its task force reached after extended discussion and lists as a research priority. The breastfeeding phase row follows ACR and BSR and reads avoid. Phase rows on this site are otherwise EULAR-driven, so this row is a deliberate departure, directed 2026-08-03.
=Guideline divergence. VERIFIED DIVERGENCE (paternal exposure). All three guidelines permit continuation of low-dose methotrexate (<=25 mg/week) in men trying to conceive: ACR 2020 conditionally, EULAR 2024 at 2b/C, BSR 2023 at GRADE 1B (SOA 99.3%). This remains at odds with some drug labels and agencies advising a 3 to 6 month stop.

Key points

PointEvidence
Recognised teratogen; must be discontinued before conception with effective contraception in place.[1, 2]●●●○moderate evidencestrong
EULAR 2024 lists paternal MTX <=25 mg/week as continuable (2b/C). iFAME-MTX (verified primary text) is a prospective semen-parameter study: conventional semen parameters and sperm DNA fragmentation index did not differ significantly before versus after MTX exposure, and MTX-polyglutamates in spermatozoa were very low. Note it assessed fertility markers, not pregnancy outcomes.[2, 4]●●○○low evidenceconditional

Monitoring

References

  1. Sammaritano LR, et al. 2020 ACR Guideline for the Management of Reproductive Health in RMD. Arthritis Rheumatol. 2020;72(4):529-556. https://acrjournals.onlinelibrary.wiley.com/doi/10.1002/art.41191
  2. Ruegg L, et al. EULAR recommendations for antirheumatic drugs in reproduction, pregnancy, and lactation: 2024 update. Ann Rheum Dis. 2025;84(6):910-926. https://ard.eular.org/article/S0003-4967(25)00818-0/fulltext
  3. Russell MD, et al. BSR guideline on prescribing drugs in pregnancy and breastfeeding: immunomodulatory drugs and corticosteroids. Rheumatology (Oxford). 2023;62(4):e48-e88. https://academic.oup.com/rheumatology/article/62/4/e48/6783012
  4. Perez-Garcia LF, et al. Methotrexate in men with immune-mediated inflammatory disease and an active desire to become a father (iFAME-MTX). Ann Rheum Dis. 2023. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10359513/
  5. EULAR 2024 update, section III (antirheumatic drugs in male patients): drugs continuable in men trying to conceive include methotrexate <=25 mg/week. https://doi.org/10.1016/j.ard.2025.03.011