Fingolimod (Gilenya▼): increased risk of congenital malformations; new contraindication during pregnancy and in women of childbearing potential not using effective contraception

Fingolimod is associated with an increased risk of major congenital malformations including cardiac, renal, and musculoskeletal defects, when used in pregnancy. Women of childbearing potential must use effective contraception during fingolimod treatment and for 2 months after discontinuation.

Advice for healthcare professionals:

New contraindication

  • fingolimod increases the risk of major congenital malformations when used in pregnancy
  • exposure in pregnancy is thought to lead to an estimated additional 2–3 cases major congenital malformation per 100 livebirths compared with the general population (a two-fold increase)
  • fingolimod is contraindicated during pregnancy and in women of childbearing potential not using effective contraception

Management of women of childbearing potential before and during fingolimod treatment

  • advise women that fingolimod increases the risk of congenital abnormalities and provide them with the new pregnancy-specific patient reminder card
  • exclude pregnancy before starting fingolimod and repeat pregnancy testing at suitable intervals during treatment (depending on contraceptive used and personal circumstance – see guidance below)
  • ensure that an effective form of contraception is used during treatment and for 2 months after discontinuation
  • stop fingolimod 2 months before a pregnancy is planned and consider alternative treatments

Management if pregnancy exposed

  • should a woman on fingolimod become pregnant, stop treatment immediately and refer to an obstetrician for close monitoring during pregnancy, including ultrasound assessments
  • exposed pregnancies should be enrolled to the prospective registry for outcome monitoring


Fingolimod (Gilenya) is a sphingosine 1-phosphate receptor modulator. It is authorised to treat highly active relapsing-remitting multiple sclerosis in patients aged 10 years and older whose disease has failed to respond to at least 1 disease-modifying therapy or where disease is severe and rapidly evolving (see full indication in Summary of Product Characteristics).

As of May 2019, more than 284,000 people with multiple sclerosis have been treated with Gilenya worldwide in clinical trials and routine clinical practice (more than 677,700 patient-years). In the UK, 9025 patients have received fingolimod since it was marketed in 2011.[footnote 1]

Risk of congenital malformations

At the time of licence of fingolimod in 2011, little clinical data were available about safety of use in pregnancy. The product information for fingolimod noted that animal data suggested a risk of foetal harm and therefore advised that women should not become pregnant while taking fingolimod. A registry was introduced to prospectively collect outcome data of any pregnancies exposed to fingolimod.

A recent EU review analysed post-marketing data, including from the registry, and concluded that fingolimod exposure in pregnancy is associated with a two-fold increase in the risk of congenital malformations compared with the observed rate of 2–3% in the general population reported by the European network of population-based registries for the epidemiological surveillance of congenital anomalies [EUROCAT]. Prospective data were included from 1,465 women exposed to fingolimod during pregnancy.

Reported malformations include congenital heart disease, such as tetralogy of Fallot, atrial and ventricular septal defects, and renal and musculoskeletal abnormalities.

Advice on contraception use and need for pre-pregnancy counselling

The Association of British Neurologists’ guidelines (2019)[footnote 2] on pregnancy in multiple sclerosis recommends that all women of childbearing potential should have regular pre-pregnancy counselling starting at or soon after diagnosis. Women considering pregnancy should also be advised to discuss their plans with their physician before trying to conceive.

Before starting fingolimod, women of childbearing potential must be informed of the risk of teratogenicity and have a negative pregnancy test. They must use effective contraception during treatment with fingolimod and for 2 months after stopping it. Due to its long half-life, use of fingolimod during the 8 weeks leading up to the last menstrual period may result in exposure of a subsequent pregnancy. Women should be advised to tell their doctor immediately if they think they may be pregnant.

When using any medicine with teratogenic potential, a woman should be advised of the risks and encouraged to use the most effective contraceptive method taking into account her personal circumstances. See Drug Safety Update March 2019 for guidance on contraceptive methods and frequency of pregnancy testing to reduce inadvertent exposures during pregnancy in a woman taking a medicine of teratogenic potential. Fingolimod has been shown not to interact with oral contraceptives containing ethinylestradiol and levonorgestrel, and an effect on other progestogens is not expected.

New patient reminder card for women of childbearing potential

The educational materials (physician’s checklist and patient’s guide) are being updated to include new information on the risk of congenital defects and required mitigation measures. A new pregnancy-specific patient reminder card will be introduced to provide further information on this risk to women of childbearing potential and to tell them to contact their doctor immediately if they experience disease worsening after stopping fingolimod. Women exposed to fingolimod while pregnant will also be encouraged to enrol in the pregnancy exposure registry.

Hard copies of the revised education materials and the new pregnancy-specific patient reminder card will be distributed to prescribers of fingolimod and copies can be requested by other healthcare professionals from the manufacturer. Electronic copies will also be made available on the electronic medicines compendium (eMC).

Risk of rebound of disease activity with discontinuation

Highly active disease has been reported in a small number of patients for up to 6 months after discontinuing fingolimod. Physicians should monitor patients discontinuing fingolimod for any return of disease activity (see July 2017 Drug Safety Update and section 4.4 of the Summary of Product Characteristics).

Report suspected adverse drug reactions on a Yellow Card

Please continue to report any suspected adverse drug reactions (ADRs) associated with fingolimod via the Yellow Card Scheme. Remember only a suspicion is needed to report – if in doubt, please complete a Yellow Card.

Any suspected ADRs associated with fingolimod exposure in pregnancy should also be reported via the Yellow Card Scheme. Due to its long half-life fingolimod exposure during pregnancy may occur if used during the 8 weeks leading up to the last menstrual period. For more about the importance of reporting suspected adverse drug reactions associated with medicines in pregnancy see Drug Safety Update July 2018.

Pregnancies exposed to fingolimod should also be enrolled in the fingolimod pregnancy registry for outcome monitoring.

Suspected ADRs after discontinuation of multiple sclerosis therapies should also be reported to the Yellow Card Scheme. Healthcare professionals, patients, and caregivers can report suspected side effects via the website or via the Yellow Card App. Download the app today via iTunes Yellow Card for iOS devices or via PlayStore Yellow Card for Android devices.

Further information

Article citation: Drug Safety Update volume 13, issue 2: September 2019: 2.

Post-publication note:

Liver monitoring requirements and discontinuation criteria for fingolimod have been updated following reports of serious liver injury. Fatal cases of encephalitis and meningitis caused by herpes simplex and varicella zoster viruses have also been reported during fingolimod treatment – please see Drug Safety Update January 2021 for more information.

  1. Dobson R, et al. UK consensus on pregnancy in multiple sclerosis: ‘Association of British Neurologists’ guidelines. Pract Neurol 2019; 19: 106–114. 

  2. Data provided to the MHRA from the Marketing Authorisation Holder. 8 August 2019. 

Published 19 September 2019