The Summary of the Product Characteristics (SPC) represents the source of official and legitimate drug information for the healthcare professionals within the European Union. Specific information concerning the use in pregnancy, breastfeeding and fertile age, besides the effects on fertility, are described in a special section of the SPC, whose content is established by the European Commission for the drugs authorised by centralised procedure.1
It is therefore very important that the SPC content about the use in pregnancy and during breastfeeding is clear and updated. Prescribing a drug in pregnancy always entails a delicate decision. Even though teratogenic effects of drugs cause approximately 1% of congenital malformations, the general tendency among healthcare professionals and patients is to overestimate this prevalence.2 In certain situations, the benefit for the mother and the foetus could exceed the risk, however both the healthcare professional and the woman could be induced to avoid the administration simply because the available information is uncertain or ambiguous.3
A study1 specifically evaluated the section dedicated to pregnancy and breastfeeding for 534 SPCs of drugs authorised by centralised procedure and updated on April 18, 2011, excluding those whose principal indications were for use in post-menopause, paediatric use, exclusive use in the male population, for contraceptive use and for use within the assisted reproductive technologies.
The authors provided some specifications to extract and interpret the information in a standardised way, specifically: a) if the drug can cross the placental barrier and if it is excreted in breast milk; b) the existence of preclinical and clinical studies or clinical experience about the drug use in pregnancy or during breastfeeding; c) the effects of the drugs on fertility; d) the use in women of fertile age; e) the presence of specific recommendations for use in pregnancy and breastfeeding. The results have been provided separately for the information concerning use in pregnancy and during breastfeeding.
Use in pregnancy
Among the 534 SPCs analysed, 477 (89.3%) do not mention placenta-crossing, 46 (8.6%) indicate that the drug can cross the placental barrier, 7 (1.3%) indicate that the drug is not able to cross the placental barrier and 4 (0.7%) declare that the information concerning placenta-crossing is not available.
The existence of preclinical studies for the evaluation of teratogenic effects is reported by 408 SPCs (76.4%). In 78 SPCs (14.6%) there is no mention about the existence of teratogenic studies on pre-clinic models, whilst in 153 (28.6%) no information is provided about the existence of similar studies in human subjects. Among the 106 SPCs (19.8%) that report clinical studies or clinical experience in pregnant women, 15 (14.2%) do not provide information about the potential adverse effects for the embryo, foetus or newborn in case of exposure to the drug.
In 505 SPCs (94.6%) it is recommended to avoid the use in pregnancy, in 20 SPCs (3.7%) the use is allowed, whilst in 9 (1.7%) there is no recommendation. In case of inadvertent use in pregnancy, 448 SPCs (87.3%) do not provide information on the management of the exposure.
Information concerning the effects on fertility are absent in 422 SPCs (79.0%).
Use during breastfeeding
Of the 534 SPCs analysed, 115 (21.5%) do not report any information about the possibility that the drug is excreted in the breast milk. Among the 88 SPCs (16.5%) that report the excretion of the drug in the breast milk, 78 (88.6%) do not provide information about the possible adverse effects for the breastfed newborns.
In 492 SPCs (92.1%), breastfeeding is not allowed even though 83 of these SPCs (16.9%) do not provide information about the drug excretion in the breast milk.
The data of this study demonstrate that there is insufficient information concerning the use of drugs in pregnancy and during breastfeeding in the European SPCs. The use of drugs in pregnancy is contraindicated in over 90% of the SPCs examined. In many cases, however, this restriction is not guided by the risk of documented effects on the foetus, but from the lack of information. It is probable that this tendency often reflects a defensive medicine strategy employed both by the pharmaceutical industry and by the prescribers.3 However, even though caution in prescribing drugs is recommendable, it is important to consider that under-prescribing some drugs in pregnancy could have significant consequences both for the mother and for the foetus.4 It would be beneficial, when information are provided, to be able to distinguish between the situations where risk is well documented from those where the risk is unknown for lack of evidence.
For this reason, it is essential that the regulatory agencies promote and retrieve information about drug exposure in pregnant and breastfeeding women and that the information included in the SPCs are update consequently. In case of uncertainty it is important to invite the prescribers and the patients to find out more information from specialists and dedicated structures that offer informative services about the use of drugs.
Monitoring Unit of Drug Adverse Reactions, University Hospital Pisa, Pharmacovigilance Centre Tuscany
Drugs & Pregnancy
By Renata Bortolus, University Hospital Verona and Marco Tuccori, University Hospital Pisa, Pharmacovigilance Centre Tuscany.
- Brit J Clin Pharmacol 2015;79:537-44.
- Expert Opini Pharmacother 2003;4:949-61.
- Drug Saf 2008;31:799-806.
- Eur J Obstet Gynecol Reproduct Biol 2004;114:182-8.