Is mesalazine (5-aminosalicylic acid) safe to use during pregnancy?

Mesalazine Safety in Pregnancy

Mesalazine is safe to use during pregnancy and should be continued to maintain disease remission, as active inflammatory bowel disease poses greater risks to pregnancy outcomes than the medication itself. 1, 2

Key Safety Evidence

The FDA drug label explicitly states that published data from meta-analyses, cohort studies, and case series have not reliably shown an association between mesalamine use during pregnancy and major birth defects, miscarriage, or adverse maternal or fetal outcomes. 2

• The Toronto Consensus Guidelines (2016) found that mesalamine use was not associated with significantly increased risk of congenital abnormalities (OR 1.16; 95% CI 0.76-1.77), stillbirth (OR 2.38; 95% CI 0.65-8.72), spontaneous abortion (OR 1.14; 95% CI 0.65-2.01), or preterm delivery (OR 1.35; 95% CI 0.85-2.13). 1

• A prospective controlled cohort study of 165 women exposed to mesalamine during pregnancy showed no increase in major malformations (0.8% vs 3.8% in controls, P=0.23), confirming mesalamine does not represent a major teratogenic risk. 3

Critical Importance of Maintaining Therapy

Active IBD during pregnancy poses substantially greater risks than mesalamine exposure, including preterm delivery, low birth weight, and spontaneous abortion. 1

• Among patients with ulcerative colitis who decreased dose or discontinued 5-ASA therapy during pregnancy, the flare rate was 56.3% compared to only 26.5% in those who continued treatment (OR 3.6; 95% CI 1.0-12.4). 1

• Disease activity during pregnancy is associated with low birth weight (OR 2.05) and preterm birth (OR 2.64, increasing to OR 3.6 in moderate to severe disease). 1

Dosing Recommendations

Therapeutic doses of at least 2 grams daily should be maintained throughout pregnancy to prevent disease flares. 1

• The British Society of Gastroenterology recommends mesalamine doses of at least 2 g daily for patients with left-sided or more extensive ulcerative colitis (strong recommendation, moderate-quality evidence). 1

• Studies demonstrate a dose-dependent protective effect with minimum effective doses of 1.2-2 g daily. 1

Important Formulation Consideration

Avoid mesalamine formulations containing dibutyl phthalate (DBP) during pregnancy due to theoretical teratogenic concerns. 1, 4

• DBP-containing formulations (such as Asacol and Mesasal in some countries) should be switched to non-DBP formulations before conception when possible. 1

• If already pregnant on a DBP-containing formulation, switching must be individualized based on gestational age (beyond first trimester, switching provides minimal benefit) and disease stability. 1

• Switching formulations carries theoretical risk of precipitating disease flare, so adequate time should be allowed to ensure sustained remission before conception. 1

Rare Adverse Event

One case report documented severe fetal anemia and hydrops fetalis potentially related to high-dose mesalamine (4 g daily), though this remains an isolated finding. 5

• This single case involved a fetus with severe anemia (hemoglobin 51 g/L) at 31 weeks gestation in a mother taking 4 g mesalamine daily. 5

• The fetus required four intrauterine transfusions but was ultimately born healthy at 37 weeks after maternal medication discontinuation. 5

• This extremely rare complication should not alter standard recommendations for mesalamine use in pregnancy, as the benefits of disease control far outweigh this theoretical risk. 1, 2

Breastfeeding Safety

Mesalamine is safe during breastfeeding, with only small amounts detected in breast milk (relative infant dose <0.1%). 2

• While isolated case reports describe diarrhea in breastfed infants, mesalamine and its metabolite N-acetyl-5-aminosalicylic acid appear in human milk in minimal quantities. 2

Clinical Management Algorithm

For women with IBD planning pregnancy or already pregnant:

1. Continue mesalamine maintenance therapy at therapeutic doses (≥2 g daily) throughout pregnancy 1, 2

2. Switch from DBP-containing formulations to non-DBP alternatives before conception if disease is stable 1

3. Ensure folic acid supplementation (1 mg daily) if using sulfasalazine, starting at least 3 months before conception 6

4. Monitor disease activity closely as active disease poses greater pregnancy risks than medication exposure 1

5. Coordinate care with gastroenterology throughout pregnancy to optimize disease management 1