Drug transporter protein -mediated drug interactions during pregnancy and offspring outcome; with special emphasis on second-generation antipsychotics and
SSRIs (PgP and BCRP interactions and pregnancy)

Study identification

• PURI:
  https://redirect.ema.europa.eu/resource/33382
• EU PAS number:
  EUPAS13051
• Study ID:
  33382
• Official title and acronym:
  Drug transporter protein -mediated drug interactions during pregnancy and offspring outcome; with special emphasis on second-generation antipsychotics and SSRIs (PgP and BCRP interactions and pregnancy)
• DARWIN EU® study:
  No
• Study countries:
  Finland
• Study description:
  Background. Drug transporter proteins play an important role in the bioavailability and toxicity of drugs. P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) are the two important efflux transporter proteins in the human placenta. It is not known if drug transporter protein -mediated drug interactions account for the possible teratogenicity of drugs or if such interactions can also predispose to neonatal drug toxicity.Objectives. To investigate if concomitant use of two or more drug transporter substrates or a substrate and an inhibitor during first trimester is associated with an increased risk of offspring major congenital malformations. Specifically, we will assess the risk of overall malformations in offspring of women using SGAs, and the risk of cardiac malformations in offspring of women using SSRIs or bupropion, and the risk of severe or prolonged neonatal adaptation problems.Methods. This is a population-based cohort study based on the Drugs and Pregnancy project database in Finland. Data are derived from national health registers: the Medical Birth Register, the Register on Induced Abortions, the Malformation Register and the Prescription Register and Special Refund Entitlement Register. Data in these registers have been collected during Jan 1st 1996 - Dec 31st 2011 and include all births (live and still births), pregnancy terminations due to major congenital malformation, and information on drug purchases during pregnancy and 3 months before pregnancy. To this database we will further link data on individual drugs and their relation (substrate, inhibitor) to P-gp and BCRP from the University of Washington Metabolism and Transport Drug Interaction Database (DIDB). Offspring of women with concomitant use of two or more drug transporter substrates, or a combination of a substrate and an inhibitor, are compared to offspring of women using only one drug transporter specific substrate, and to unexposed.
• Study status:
  Finalised

Research institutions and networks

Institutions

Finnish Institute for Health and Welfare (THL)

Finland

Teratology Information Service, Helsinki (TIS Helsinki), HUSLAB

Finland

Department of Clinical Pharmacology Helsinki University and Helsinki University Hospital

Study timelines

Date when funding contract was signed

Actual: 02/01/2015

Study start date

Planned: 31/08/2016

Actual: 19/11/2018

Data analysis start date

Planned: 30/11/2016

Date of interim report, if expected

Planned: 31/05/2017

Date of final study report

Planned: 30/05/2018

Actual: 10/12/2019

Sources of funding

Other

More details on funding

Finnish Medical Agency, National Institute of Health and Welfare, Social Insurance Institution

Study protocol

Initial protocol

Research protocol_APR_25_2016

Regulatory

• Was the study required by a regulatory body?:
  No
• Is the study required by a Risk Management Plan (RMP)?:
  Not applicable