[Use of antiepileptic drugs during breastfeeding : What do we tell the mother?] / Antiepileptika in der Stillzeit : Wie beraten wir die Mütter?

BACKGROUND: Knowledge about the passage of various antiepileptic drugs into breast milk and its consequences for the infant is limited. Faced with this uncertainty, breastfeeding is often discouraged for these patients. The aim of this study was to comprehensively review the available data regarding antiepileptic drugs during breastfeeding, to compare these data with information provided by the summary of product characteristics (SmPCs), and to provide recommendations for the use of these drugs in breastfeeding women. MATERIAL AND METHODS: We performed a systematic literature review on breastfeeding data for 23 antiepileptic drugs. A breastfeeding compatibility score was developed and validated. The estimated score based on the literature review was compared with the estimated score based on recommendations provided by the SmPCs. RESULTS: We identified 75 articles containing exposure and safety data for 15 antiepileptic agents during breastfeeding. The comparison between the score values based on the literature review and on the SmPCs revealed a very low degree of concordance (weighted kappa: 0.08). CONCLUSION: Phenobarbital, primidone, carbamazepine, valproate and levetiracetam are probably compatible with breastfeeding. Treatment with phenytoin, ethosuximide, clonazepam, oxcarbazepine, vigabatrin, topiramate, gabapentin, pregabalin, lamotrigine and zonisamide can be authorized during breastfeeding, provided breastfed infants are carefully monitored for side effects. Since data on the use of mesuximide, clobazam, rufinamide, felbamate, lacosamide, sultiame, perampanel and retigabine are insufficient to adequately assess the risk for breastfed infants, use in breastfeeding women is in principle not recommended and should be carefully evaluated on a case by case basis. In practice, a risk-benefit analysis should be performed for each mother under antiepileptic treatment wishing to breastfeed her child, so that individual risk factors can adequately be taken into account when counseling the patient.

[Antiepileptics in women of childbearing age and during pregnancy: comparison of specialized information with the current state of knowledge in Germany and Switzerland]. / Antiepileptika bei Frauen im gebärfähigen Alter und in der Schwangerschaft : Vergleich der Fachinformationen in Deutschland und der Schweiz mit dem aktuellen Wissensstand.

BACKGROUND: Healthcare professionals regularly read the summary of product characteristics (SmPC) as one of the various sources of information on the risks of drug use in women of childbearing age and during pregnancy. The aim of this article is to present an overview of the teratogenic potential of various antiepileptic drugs and to compare these data with the information provided by the SmPCs. METHODS: A literature search on the teratogenic risks of 19 antiepileptic agents was conducted and the results were compared with the information on the use in women of childbearing age and during pregnancy provided by the SmPCs of 38 commercial products available in Switzerland and Germany. RESULTS: The teratogenic risk is discussed in all available SmPCs. Quantification of the risk for birth defects and the numbers of documented pregnancies are mostly missing. Reproductive safety information in SmPCs showed poor concordance with risk levels reported in the literature. Recommendations concerning the need to monitor plasma levels and possibly perform dose adjustments during pregnancy to prevent treatment failure were missing in five Swiss and two German SmPCs. DISCUSSION: The information regarding use in women of childbearing age and during pregnancy provided by the SmPCs is heterogeneous and poorly reflects the current state of knowledge. Regular updates of SmPCs are warranted in order for these documents to be of reliable use for health care professionals.

Pregnancy outcome following maternal exposure to statins: a multicentre prospective study.

OBJECTIVE: This contribution addresses the risk associated with exposure to statins during pregnancy. DESIGN: Multicentre observational prospective controlled study. SETTING: European Network of Teratology Information Services. POPULATION: Pregnant women who contacted one of 11 participating centres, seeking advice about exposure to statins during pregnancy, or to agents known to be nonteratogenic. METHODS: Pregnancies exposed during first trimester to statins were followed up prospectively, and their outcomes were compared with a matched control group. MAIN OUTCOME MEASURES: Rates of major birth defects, live births, miscarriages, elective terminations, preterm deliveries and gestational age and birthweight at delivery. RESULTS: We collected observations from 249 exposed pregnancies and 249 controls. The difference in the rate of major birth defects between the statin-exposed and the control groups was small and statistically nonsignificant (4.1% versus 2.7% odds ratio [OR] 1.5; 95% confidence interval [95% CI] 0.5-4.5, P = 0.43). In an adjusted Cox model, the difference between miscarriage rates was also small and not significant (hazard ratio 1.36, 95% CI 0.63-2.93, P = 0.43). Premature birth was more frequent in exposed pregnancies (16.1% versus 8.5%; OR 2.1, 95% CI 1.1-3.8, P = 0.019). Nonetheless, median gestational age at birth (39 weeks, interquartile range [IQR] 37-40 versus 39 weeks, IQR 38-40, P = 0.27) and birth weight (3280 g, IQR 2835-3590 versus 3250 g, IQR 2880-3630, P = 0.95) did not differ between exposed and non-exposed pregnancies. CONCLUSIONS: This study did not detect a teratogenic effect of statins. Its statistical power remains insufficient to challenge current recommendations of treatment discontinuation during pregnancy.

[Off-label use of psychotropic medications in pediatric wards: a prospective study]. / Utilisation hors autorisation de mise sur le marché (AMM) des psychotropes en pédiatrie: une étude prospective.

PURPOSE: The aim of this study was to investigate the use of psychotropic medications for both labeled and off-labeled indications in a French paediatric teaching hospital. METHODS: A prospective analysis of all psychotropic drug prescriptions was conducted during a 6-month interval. Details were recorded from the computerized prescription order entry system. They included demographic data (sex, age and weight) and psychotropic medications (name, dosage, schedule, route of administration and indication). The physicians specified the indication when prescribing the psychotropic medication. All prescriptions were assessed for off-label use. Off-label prescriptions were defined as: use of a different dose or dose schedule, use for an indication not included in the license or approved for adults only, drug use outside the age range of the product license, use of medicines for which no paediatric information was available, use when the product was contraindicated, use of drug preparations that were manufactured by the hospital pharmacy, use of licensed drugs that were modified by the hospital pharmacy and use of new drugs available under a special manufacturing license. Each prescription was compared with data available in the National French Formulary. RESULTS: A total of 1629 drug prescriptions were written for 472 patients. Sixty-eight percent of all drug prescriptions were for off-label uses: indication not included in the license or approved for adults only in 40%, no paediatric information available in 37%, different dose or dose schedule in 7%, licensed drugs that were modified by the hospital pharmacy in 5%, administration to children outside the age range of the product license in 4%, drug preparations that were manufactured by the hospital pharmacy in 4%, contraindication in 2% and new drugs available under a special manufacturing license in 1%. Sixty-six percent of the patients were prescribed a psychotropic drug in an off-label manner. Over half of the off-label prescriptions were given to adolescents (62%), followed by children (29%), infants (8%) and neonates (1%). The percentage of off-label prescriptions by age was: neonates 91%; adolescents 74%; children 59% and infants 58%. The percentage of off-label prescriptions by medication class are presented in decreasing order of prescription frequency: anxiolytics 65%; antipsychotics 69%; antidepressants 92%; antiepileptics 51%; stimulants 30%; antiparkinsonians 100% and hypnotics 100%. The 5 drugs most commonly prescribed off label were risperidone (12%), clobazam (12%), amitriptyline (11%), hydroxyzine (10%) and diazepam (7%). Nearly half (47%) of all off-label prescriptions were associated with 3 indications: anxiety (24%), disruptive behaviour (12%) and pain (11%). CONCLUSION: The high rates of off-label prescription documented here and elsewhere highlight the need for further controlled clinical trials to evaluate the risks and benefits of psychotropic medication in children and adolescents.