Antiemetic Prescription Fills in Pregnancy: A Drug Utilization Study Among 762,437 Pregnancies in Norway

Abstract

Objective To determine antiemetic prescription fill patterns during pregnancy in Norway, with special focus on the use of ondansetron and recurrent use in subsequent pregnancies. Methods We conducted a population-based registry study based on data from the Medical Birth Registry of Norway linked to the Norwegian Prescription Database for 762,437 pregnancies >12 gestational weeks ending in live or non-live births between 2005 and 2017. Prescription fills of medications used for nausea and vomiting of pregnancy were summarized in treatment pathways to determine drug utilization patterns. Logistic regression analyses were used to estimate associations between maternal and pregnancy characteristics and antiemetic prescription fills. Results The prescription fill rate for antiemetic medication during pregnancy was 7.6%. However, prescription fill rates were 35.5% in the second pregnancy after filling an antiemetic prescription in the first pregnancy and 53.5% for women who filled antiemetic prescriptions in the previous 2 pregnancies. Among pregnancies with antiemetic prescription fills, 62.2% were dispensed metoclopramide, 28.2% meclizine, and 17.2% promethazine. First-line treatment started with monotherapy in 97.4% of these pregnancies, which was the only treatment received in 78.7%. Prescriptions for ondansetron were filled in 0.3% of pregnancies, with 76.9% being initially filled in the first trimester. Ondansetron as first-line prescription medication and/or use in the first trimester was associated with proxies for more severe nausea and vomiting of pregnancy, including a diagnosis of hyperemesis gravidarum, multiple gestations, a higher obstetric comorbidity index, and concomitant use of medication for gastroesophageal reflux disease and nervous system medications. Women who filled an antiemetic prescription in their first pregnancy were less likely to have subsequent pregnancies than women who did not fill an antiemetic prescription in their first pregnancy (OR 0.93, 95% CI 0.90–0.96). Conclusion Complex patterns of antiemetic prescription fills in pregnancy may mirror the challenge of optimal management of nausea and vomiting of pregnancy in clinical practice, especially for women with severe symptoms.

Antiemetic treatment of hyperemesis gravidarum in 1,064 Norwegian women and the impact of European warning on metoclopramide: a retrospective cohort study 2002–2019

“…In contrast, we found a substantial, but non-persisting, drop in pre-hospital use of metoclopramide. A similar, temporary decline in metoclopramide prescription fills in pregnancy was seen from 2014 in the NorPD-study [ 21 ]. Our results suggest that the EMA warning in the HG treatment guidelines were implemented in clinical practice more extensively at the hospital compared to primary care.…”

“…A possible explanation is that while use of metoclopramide pre-hospital apparently recovered after the initial drop, women were only offered five days of treatment and hospitalized if further treatment was required. In the NorPD-study, treatment duration exceeding 5 days was registered for virtually all metoclopramide prescriptions 2015–2017 [ 21 ]. However, the median treatment duration reported corresponds to the smallest package size available in Norway (20 tablets; 6.7 days), and therefore gives no indication of whether administration complied with the five-day limit.…”

“…This is a well-defined hospital cohort including women with severe HG with no bias introduced by selection. A strength of the study is the level of detail of treatment information compared to registry studies where over the counter and in-patient treatment is unavailable [ 21 ]. In addition, consecutive documentation of information in routine hospital charts reduce risk of recall bias.…”

“…The dopamine antagonists prochlorperazine and chlorpromazine were preferred [ 9 , 10 , 20 ]. Between 2004 and 2017, 60% of all antiemetic prescription fills during pregnancy in the Norwegian Prescription Database (NorPD) were for metoclopramide [ 21 ], but changes in treatment provision for patients with HG related to the metoclopramide warning has not previously been investigated.…”

What changes in prescription patterns of antiemetic medications in pregnant women in France?

“…Another study conducted in the French Echantillon Généraliste des Bénéficiaires (EGB), between 2010 and 2013, showed that 13.8% of pregnant women received metoclopramide during pregnancy and 13% received domperidone [18]. In Germany [4], the Netherlands [19], and Norway [20], pregnant women appeared to be less exposed to these medications with respectively 5%, 23%, and 7.6% concerned. In the United States [5], between 2001 and 2015, 23% of women received these medications during pregnancy.…”