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International audience; PURPOSE: This post-authorisation safety study estimated the risk of anaphylaxis in patients receiving intravenous (IV) iron in Europe, with interest in iron dextran and iron non-dextrans. Studies conducted in the United States have reported risk of anaphylaxis to IV iron ranging from 2.0 to 6.8 per 10 000 first treatments. METHODS: Cohort study of IV iron new users, captured mostly through pharmacy ambulatory dispensing, from populations covered by health and administrative data sources in five European countries from 1999 to 2017. Anaphylaxis events were identified through an algorithm that used parenteral penicillin as a positive control. RESULTS: A total of 304 210 patients with a first IV iron treatment (6367 iron dextran), among whom 13–16 anaphylaxis cases were identified and reported as a range to comply with data protection regulations. The pooled unadjusted incidence proportion (IP) ranged from 0.4 (95% confidence interval [CI], 0.2–0.9) to 0.5 (95% CI, 0.3–1.0) per 10 000 first treatments. No events were identified at first dextran treatments. There were 231 294 first penicillin treatments with 30 potential cases of anaphylaxis (IP = 1.2; 95% CI, 0.8–1.7 per 10 000 treatments). CONCLUSION: We found an IP of anaphylaxis from 0.4 to 0.5 per 10 000 first IV iron treatments. The study captured only a fraction of IV iron treatments administered in hospitals, where most first treatments are likely to happen. Due to this limitation, the study could not exclude a differential risk of anaphylaxis between iron dextran and iron non-dextrans. The IP of anaphylaxis in users of penicillin was consistent with incidences reported in the literature.

Purpose To determine risk of respiratory tract infections, urinary tract infections and candidiasis in secukinumab users compared to ustekinumab users among individuals with psoriasis in Sweden. Methods This was a Swedish population‐based register‐linked new‐user cohort study on individuals with psoriasis and psoriasis arthritis treated with secukinumab (2015‐2017) and ustekinumab (2009‐2017). Ever‐never exposure definition was used, that is, each individual's follow‐up time was attributed to the drug they were first exposed to. Risk of severe respiratory and urinary tract infections and candidiasis (diagnosis codes from out‐patient specialist visits and in‐patient hospitalisations) and respiratory and urinary tract infections treated in primary care (proxied by dispensation of antibiotics) was determined by adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) using Cox regression. We also give crude incidence rates and rate ratios. Results In total, 1955 new users of secukinumab (n = 848) and ustekinumab (n = 1107) were identified. There was a slightly increased risk of respiratory and urinary tract infections treated in primary care among secukinumab users compared to ustekinumab users (HR: 1.22, 95% CI: 1.03‐1.43). Non‐significant differences in estimated risk of severe respiratory and urinary tract infections (HR: 0.96, 95% CI: 0.57‐1.61) and candidiasis (HR: 1.80, 95% CI: 0.84‐3.84) treated in the hospital setting were observed. Conclusion We observed a slightly increased risk of respiratory and urinary tract infections treated in primary care among secukinumab users compared to ustekinumab users. Larger studies with longer follow‐up are needed to draw conclusions on relative safety.

Aim: We aimed to describe opioid maintenance treatment (OMT) to pregnant women in Norway and study the background characteristics of the pregnant women compared to the general population of pregnant women and to a previous clinical cohort study of OMT in pregnancy. Methods: Population-based cohort study with linked data from the Norwegian Medical Birth Registry, the Norwegian Prescription Database, the Norwegian Patient Registry, and Statistics Norway. The study population consisted of women giving birth between 2005-2015 in Norway. We defined OMT pregnancies as pregnancies where the woman was dispensed OMT medications (methadone, buprenorphine, or buprenorphine/ naloxone) at least once during pregnancy. Results: The study population consisted of 420,808 women with 645,440 pregnancies ending in a live birth in Norway in 2005-2015 (the general pregnant population). Of these, 261 women (0.6‰) had altogether 306 OMT pregnancies. The mean number of pregnancies was 28 OMT pregnancies per year and quite stable during the study period. Women with OMT pregnancies were older, smoked tobacco more frequently, had lower education, and fewer of them had a partner, compared to the general population of pregnant women. In most pregnancies, the women were treated with buprenorphine (n=183 (59.8%)), while in 120 (39.2%) pregnancies, the woman received methadone. From 2008, buprenorphine replaced methadone as the most frequently used drug. In only 38 (12.4%) pregnancies, OMT treatment was initiated in pregnancy. In 201 (66%) pregnancies, the woman used OMT medications in all trimesters. For these women, the mean amount of dispensed drug was 3.4 DDD/day (85 mg/day) in pregnancy for methadone and 1.9 DDD/day (15.2 mg/day) for buprenorphine. Conclusion: The number of OMT pregnancies per year has been low and stable in the period 2005-2015. Following Norwegian recommendations, there has been a shift from treatment with methadone towards buprenorphine. The women receiving OMT during pregnancy had more risk factors for adverse outcomes than the general pregnant population but were quite similar to the previous clinical cohort.

Introduction During clinical trials, mirabegron, a β3-adrenoreceptor agonist, was associated with increased vital signs vs placebo in patients with overactive bladder. Objective The purpose of this study was to compare incidence rates of adverse cardiovascular (CV) outcomes following mirabegron or antimuscarinic use. Methods We conducted an observational post-marketing safety study utilising real-world data. The study population was identified within five sources: Danish and Swedish National Registers, Clinical Practice Research Datalink (UK), Optum (USA) and Humana (USA). Episodes of time when patients were new users of mirabegron or antimuscarinics (October 2012–December 2018) were sourced from prescriptions and matched on propensity scores. Occurrences of major adverse cardiovascular events (MACE), acute myocardial infarction (AMI), stroke, CV mortality and all-cause mortality were identified. Outcome incidence rates and hazard ratios from Cox models were estimated. Results Overall, 152,026 mirabegron and 152,026 antimuscarinic episodes were matched. The population consisted of 63.1% women and 72.6% were ≥ 65 years old. There were no appreciable differences in the incidence rates of MACE, AMI or stroke between users of mirabegron and antimuscarinics. Incidence rates of CV mortality (hazard ratio 0.83, 95% confidence interval 0.73–0.95) and all-cause mortality (hazard ratio 0.80, 95% confidence interval 0.76–0.84) were no higher with mirabegron vs antimuscarinics. Results restricted to episodes at high risk for CV events or stratified by age (< 65 years, ≥ 65 years) or prior overactive bladder medication use were consistent with overall findings. Conclusions This large, multinational study found no higher risk of MACE, AMI, stroke, CV mortality or all-cause mortality among users of mirabegron relative to users of antimuscarinics. Supplementary Information The online version contains supplementary material available at 10.1007/s40264-021-01095-7., Plain Language Summary During clinical trials, mirabegron, which is a treatment for overactive bladder, was associated with small increases in heart rate and blood pressure. This study was conducted to compare the frequency of cardiac events following the use of mirabegron or antimuscarinics, a group of treatments also used to treat overactive bladder. We obtained the data for this study from four countries: Denmark, Sweden, the UK and the USA. We identified people who were new users of mirabegron or antimuscarinics from 2012 to 2018 using prescription or dispensing records. Occurrences of major cardiac events, heart attack, stroke, death due to cardiac events and death from any cause were evaluated. Overall, we identified 152,026 times when mirabegron or antimuscarinics were each used as new treatments. Most of the people in the study were women (63.1%) and at least 65 years old (72.6%). There were no notable differences between the treatment groups with regard to how often major cardiac events, heart attack or stroke occurred. Further, death due to cardiac events and death from any cause were no higher with mirabegron compared with antimuscarinics. We obtained similar results when the data were assessed for patients who were at high risk for cardiac events or split by age (less than 65 years or at least 65 years) or a history of overactive bladder medication use. In conclusion, this large study involving data from several countries found no higher risk of major cardiac events, heart attack, stroke or death among people prescribed mirabegron compared with antimuscarinics. Supplementary Information The online version contains supplementary material available at 10.1007/s40264-021-01095-7.

Objective: This post-authorization safety study (EU PAS Register Number: EUPAS16088) was designedto compare the incidence of cancer outcomes in patients treated with mirabegron versus antimuscarinicmedications.Methods: Cohorts of mirabegron initiators during 2012–2018 were propensity-score matched to antimuscarinicmedication initiators within real-world data sources (Danish National Registers, SwedishNational Registers, Clinical Practice Research Datalink [UK], Optum [US], and Humana [US]). Incidentcancer cases were identified during follow-up from direct linkage to cancer registers or validatedthrough medical record review or through physician questionnaires. Comparisons of sex-specific compositecancer outcomes (cancer of the lung/bronchus, colon/rectum, melanoma of skin, urinary bladder,non-Hodgkin lymphoma, kidney/renal pelvis, pancreas, prostate in men and breast and uterus inwomen) were made overall and for person-time in the first year and after the first year following startof treatment, for all ages and for the subgroup 65 years.Results: Among the 80,637 mirabegron initiators matched to 169,885 antimuscarinic medication initiators,68% were at least 65 years of age and 66% were women. Over 5000 incident cancer cases wereobserved overall. Incidence rates were higher for men than women for composite and individual canceroutcomes. The pooled fixed effects hazard ratios for composite cancer outcomes (all ages) were1.05 (95% confidence interval [CI]: 0.98–1.14) for women and 1.06 (95% CI: 0.98–1.14) for men. Resultswere similar in persons 65 years.Conclusions: The results suggest no association between mirabegron use and risk of cancer, comparedwith antimuscarinic medications, in either men or women.Registration: EU PAS Register Number: EUPAS16088

Introduction: During clinical trials, mirabegron, a β3-adrenoreceptor agonist, was associated with increased heart rate and systolic/diastolic blood pressure vs placebo in patients with overactive bladder (OAB). We studied the association between mirabegron and cardiovascular (CV) outcomes in an observational post-marketing safety study using real-world data. Methods: The study population was identified within five data sources: Danish and Swedish National Registers, Clinical Practice Research Datalink (UK), Optum (US), and Humana (US). Episodes of time when patients were new users of mirabegron or antimuscarinic medications (AMs) from 2012 to 2018 were sourced from prescription/dispensing information and matched on propensity scores. Major adverse CV events (MACE), acute myocardial infarction (AMI), stroke, and CV and all-cause mortality were identified from register linkage or validated through medical record review or physician questionnaires. Incidence rates of these outcomes during person-time of current use were estimated along with hazard ratios (HRs) from Cox models. Results: In total, 152,026 mirabegron episodes were matched to an equal number of AM episodes. The study population was 63.2% female and 72.6% were ≥65 years old. Baseline CV risk factors were similar between matched groups. There were no appreciable differences in the incidence rates of MACE, AMI, and stroke among current users of mirabegron relative to AMs (Table). The incidence rates of CV mortality (HR: 0.83, 95% confidence interval [CI]: 0.73, 0.95) and all-cause mortality (HR: 0.80, CI: 0.76, 0.84) were no higher with mirabegron vs AMs. Results restricted to episodes at high risk for CV events or stratified by age ( Conclusions: This large, multinational study found no higher risk of MACE, AMI, stroke, or CV or all-cause mortality among current users of mirabegron relative to users of AMs.

ObjectivesWe aimed to calculate cumulative hepatitis C virus (HCV) treatment coverage among individuals enrolled in opioid agonist therapy (OAT) in Norway between 2013 and 2017 and to document the treatment transition to direct-acting antiviral (DAA) agents. Moreover, we aimed to describe adherence to DAAs in the same cohort.DesignProspective cohort, registry data.SettingSpecialist healthcare service (secondary)Participants and outcomesThis observational study was based on data from The Norwegian Prescription Database. We studied dispensed OAT and HCV treatment annually to calculate the cumulative frequency, and employed secondary sources to calculate prevalence, incidence and HCV treatment coverage from 2013 to 2017, among the OAT population. Factors associated with adherence to DAAs were identified a priori and subject to logistic regression.Results10 371 individuals were identified with dispensed OAT, 1475 individuals of these were identified with dispensed HCV treatment. Annual HCV treatment coverage increased from 3.5% (95% CI: 3.2 to 4.4) in 2013 to 17% (95% CI: 17 to 20) in 2017, giving a cumulative HCV coverage among OAT patients in Norway of 38.5%. A complete shift to interferon-free treatment regimens occurred, where DAAs accounting for 32% of HCV treatments in 2013 and 99% in 2017. About two-thirds of OAT patients were considered adherent to their DAA regimens across all genotypes. High level of OAT continuity was associated with improved adherence to DAAs (adjusted OR 1.4, 95% CI: 1 to 2, p=0.035).ConclusionsA large increase in HCV treatment coverage attributed by a complete shift to interferon-free regimens among the Norwegian OAT population has been demonstrated. However, treatment coverage is inadmissibly too low and a further substantial scale-up in HCV treatment is required to reach the universal targets of controlling and eliminating the HCV endemic.

Background Treatment with direct-acting antiviral agents (DAAs) offers an opportunity to eliminate hepatitis C virus (HCV) endemic among people who inject drugs (PWID) and people enrolled in opioid agonist therapy (OAT) programs. The objective of this study was to estimate and to compare HCV treatment uptake after the introduction of DAAs among patients receiving OAT in Sweden and Norway. We also aimed to evaluate predictors of DAAs treatment among OAT patients in both countries. Methods This observational study was conducted with data from The Swedish Prescribed Drug Register and The Norwegian Prescription Database. We studied dispensed medications to calculate HCV treatment among OAT patients from 2014 to 2017 in Sweden and Norway. HCV prevalence was estimated from primary and secondary sources. Dispensations of medicines from different therapeutic areas, which served as proxy for co-morbidities in 2017, were conditionally adjusted for age, gender, and OAT medications. Logistic regression was used to evaluate these parameters. Results In total 3529 individuals were identified with dispensed OAT in the Swedish cohort and 7739 individuals in the Norwegian cohort. HCV treatment was utilized by 407 persons in Sweden and 920 in Norway during the study period. Annual HCV and DAA treatment uptake increased in both countries. The estimated cumulative HCV treatment uptake at the end of 2017 was 31% in Norway and 28% in Sweden. DAA treatment was associated with increased age (aOR 1.8; 95% CI 1.0–3.2) and the dispensation of drugs used for diabetes (aOR 3.2; 95% CI 1.8–5.7) in Sweden. In Norway, lipid modifying agents and antibacterials were associated with decreased odds (aOR 0.4; 95%CI 0.2–0.9, aOR 0.8; 95%CI 0.6–1.0). Conclusions An increase in DAA treatment and HCV treatment uptake was observed among Swedish and Norwegian OAT patients whilst introducing new direct-acting antiviral treatment regimens. However, more than two thirds of the OAT population in Norway and Sweden were untreated at the beginning of 2018. A further scale-up is crucial in order to control and eliminate the HCV endemic among OAT patients.

Background It is estimated that up to a third of patients on opioid agonist therapy (OAT) have attention deficit hyperactivity disorder (ADHD). Treatment by ADHD medication, including a centrally acting stimulant (CAS) or atomoxetine is one of the essential approaches. This study evaluates the use of dispensed ADHD medications in the Norwegian OAT population in the period from 2015 to 2017. Types and doses of ADHD medications, co-dispensations of other potentially addictive drugs like benzodiazepines, z-hypnotics, gabapentinoids, and non-OAT opioids, as well as direct-acting antivirals (DAA) against hepatitis C infection, are investigated. Methods Information about all dispensed ADHD medication, OAT opioids, and the defined potentially addictive drugs were recorded from the Norwegian Prescription Database. Dispensation rates, the types, and the doses of dispensed ADHD medications were estimated by summarizing the number of dispensations, and the dispensed doses. Logistic regression analyses were employed to assess the associations between ADHD medication, and OAT opioid use, and dispensations of other potentially addictive drugs and DAAs against hepatitis C infection. Results A total of 9235 OAT patients were included. The proportion of patients who were dispensed ADHD medication increased from 3.5 to 4.6% throughout the study period. The three most dispensed CAS were short- and intermediate-acting methylphenidate (55%), lisdexamphetamine (24%), and dexamphetamine (17%) in 2017. Buprenorphine, rather than methadone, as OAT opioid (adjusted odds ratio: 1.6, CI: 1.2–2.1) was associated with being dispensed ADHD medication. Among patients who received CAS and OAT opioids each calendar year, the dispensed doses of methylphenidate increased from 63 mg/day in 2015 to 76 mg/day in 2017 (p = 0.01). Sixty percent of patients receiving ADHD medications were also dispensed other addictive drugs concomitantly in 2017. Similar results were found in 2015 and 2016. Conclusion Co-prescription of ADHD medications was low among patients on OAT in Norway, considering a high prevalence of ADHD in this patient group. On the other hand, concurrent dispensations of multiple addictive drugs were common in this population. Understanding the underlying reasons for such prescribing is essential, and research on how to optimize ADHD medication of patients with ADHD receiving OAT is needed.

Background The extent to which iatrogenically-immunosuppressed individuals benefit from indirect effects of childhood vaccination with pneumococcal conjugate vaccines (PCVs) is unknown. We determined how the sequential introduction of PCV7 (2006) and PCV13 (2011) in the Norwegian childhood vaccination program has affected the epidemiology of invasive pneumococcal disease (IPD) in individuals treated with immunosuppressants in ambulatory care. Methods We conducted a case-cohort study comprising 7926 IPD cases reported to the Norwegian Surveillance System for Communicable Diseases in 2005-2014 and 249998 individuals randomly selected from the National Registry in 2012. We defined immunosuppressive treatment groups based on dispensed prescriptions retrieved from the Norwegian Prescription Database. Incidences and age-adjusted relative risks (RR) were estimated. Results IPD incidences decreased in all groups. The PCV13 incidence decreased by 5-12% across groups. The non-PCV13 incidence increased by 4-10%, mostly in individuals on chemotherapy (overlapping 95% confidence intervals). In the PCV13 era, the RR for IPD was highest (significant) and the percentage of cases caused by the polysaccharide vaccine PPV23 serotypes lowest (numerical) in individuals on chemotherapy (RR = 20.4, PPV23 = 52%), followed by individuals on corticosteroids (RR = 6.2, PPV23 = 64%), other immunosuppressants (RR = 5.6, PPV23 = 68%), and no immunosuppressants (RR = 1 [reference], PPV23 = 74%). Conclusions IPD incidences declined after PCV introduction in both immunocompetent and iatrogenically-immunosuppressed individuals, underscoring the benefit of childhood vaccination for the entire population. Still, individuals treated with immunosuppressants in ambulatory care are at increased risk of IPD caused by a more diverse group of serotypes.

INTRODUCTION AND OBJECTIVE:The β3-adrenergic agonist mirabegron is an alternative to antimuscarinics (AMs) for treatment of overactive bladder. During mirabegron development, a greater number of ca...

Purpose There is an increasing number of children with in utero exposure to opioids. Knowledge about opioid safety in pregnancy, particularly for outcomes later in childhood is scarce. It has been suggested that opioids can modulate immune system and increase the risk of infections. Our goal was to study the impact of in utero opioid exposure on the immune system and the risk of infections in childhood. Methods This population-based cohort study used nationwide registers from Denmark, Norway, and Sweden. Among pregnant women we identified users of opioids for two different indications, opioids used in opioid maintenance therapy (OMT) and opioids used for treatment of pain. We followed the exposed children and studied susceptibility for infections measured as number of antibiotic prescriptions expressed as Incidence rate ratios (IRRs) and diagnoses in specialist health care expressed as hazard ratios (HRs). Results After adjustment we did not observe increased risk for filling antibiotic prescriptions in children exposed to OMT opioids compared with OMT discontinuers (IRR, 1.08; 95% CI 0.81-1.44 in Norway and Sweden, and IRR, 0.74; 95% CI 0.63-0.88 in Denmark), or for diagnosis of infection in specialist health care (HR 0.83; 95% CI 0.55-1.26 in Norway and Sweden, and 0.82; 95% CI 0.62-1.10 in Denmark). Conclusions In this population-based cohort study, we did not observe increased risk of infections among children prenatally exposed to OMT opioids when compared to OMT discontinuers, nor long-term analgesic opioids exposed when compared to short-term analgesic opioids exposed.

Publisher's version (útgefin grein)., Objective Diabetes in pregnancy and consequently the need for treatment with antidiabetic medication (ADM) has become increasingly prevalent. The prevalence and patterns of use of ADM in pregnancy from 2006 onward in seven different countries was assessed. Research design and methods Data sources included individually linked data from the nationwide health registers in Denmark (2006-2016), Finland (2006-2016), Iceland (2006-2012), Norway (2006-2015), Sweden (2006-2015), state-wide administrative and claims data for New South Wales, Australia (2006-2012) and two US insurance databases: Medicaid Analytic eXtract (MAX; 2006-2012, public) and IBM MarketScan (2012-2015, private). The prevalence of ADM use was calculated as the proportion of pregnancies with at least one filled prescription of an ADM in the 90 days before pregnancy or within the three trimesters of pregnancy. Results Prevalence of any ADM use in 5 279 231 pregnancies was 3% (n=147 999) and varied from under 2% (Denmark, Norway, and Sweden) to above 5% (Australia and US). Insulin was the most used ADM, and metformin was the most used oral hypoglycemic agent with increasing use over time in all countries. In 11.4%-62.5% of pregnancies with prepregnancy use, ADM (primarily metformin) was discontinued. When ADM treatment was initiated in late pregnancy for treatment of gestational diabetes mellitus, insulin was most often dispensed, except in the US, where glibenclamide was most often used. Conclusions Prevalence and patterns of use of ADM classes varied between countries and over time. While insulin remained the most common ADM used in pregnancy, metformin use increased significantly over the study period., g This study was funded by NordForsk as part of the Nordic Pregnancy Drug Safety Studies project (Project No: 83539) and the Research Council of Norway as part of the International Pregnancy Drug Safety Studies (InPreSS) (Project No: 273366) both awarded to KF at Norwegian Institute of Public Health (NIHP). Linkage of the Australian data was supported by an Australian National Health and Medical Research Council Project grant (No. 1028543). GB was supported by the Swedish Society of Medicine (InPreSS grant) and the Stockholm County Council (clinical postdoctoral appointment). HZ was funded by a Scientia Fellowship awarded by UNSW. BTB, SH-D and KFH were supported by the grant R01HD097778 from the Eunice Kennedy Shriver National Institute for Child Health & Human Development. YY’s salary is paid by unrestricted grants from the Lundbeck Foundation (R232-2016-2462 and R265-2017-4069), unrelated to this work. The study funders were not involved in the design of the study; the collection, analysis, and interpretation of data; writing the report; or the decision to submit the report for publication.

The aim of the study was to examine if there was an association between use of anxiolytics and hypnotics in pregnancy and language competence in the offspring at age 3 years.The Norwegian Mother and Child Cohort Study (MoBa) is a prospective pregnancy cohort where the mothers were asked to report on their medication use at pregnancy week 17-18, 30, and at 6 months postpartum. A woman was defined as a user of anxiolytics and hypnotics during pregnancy if she had reported use of benzodiazepines or benzodiazepine-related drugs during pregnancy. Children's language competence was measured at age three by maternal report on a validated language grammar scale. We used ordinal logistic regression with estimated standard errors allowing for clustering of multiple pregnancies.Forty-five thousand and two hundred sixty-six women with 51,748 pregnancies were included in the study. The women reported use of anxiolytics and/or hypnotics in 395 pregnancies (0.8 %). The odds ratios of being in a group with lower language competence were 1.2 (0.9-1.5) and 1.7 (1.0-2.8) for short-term and long-term anxiolytics and hypnotics use, respectively. When adjusting for SSRI use during pregnancy, the odds ratios were 1.1 (0.83-1.41) and 1.4 (0.84-2.33), respectively. Children whose mothers took no anxiolytics and hypnotics during or before pregnancy were reference group.The results refute any strong association between prenatal use of anxiolytics and hypnotics and lower language competence in the offspring at age 3 years.

Objectives To investigate the prescribing of systemic drugs for the treatment of acne in adolescents in the period 2005-15. Methods The study population consisted of 14-24-year-old users of tetracyclines, isotretinoin or hormonal therapy retrieved from the Norwegian Prescription Database. The 1 year period prevalence was calculated as the number of patients who had redeemed at least one prescription during the year divided by the mean population. If the user had no prescriptions in the preceding 12 months he/she was defined as a new user. The incidence rate was defined by the number of new users during the year divided by the mean population. Results Increased prescribing rates for systemic tetracyclines and isotretinoin were observed in the period 2005-15, while a decreased prescribing rate for hormonal therapy was observed from 2007. The majority (75%) of the tetracycline prescriptions were prescribed by general practitioner specialists or physicians with no specialty/under training for a specialty. The average durations of treatment in men and women who only used tetracyclines were 3.3 and 2.8 months, respectively. For men and women that switched to isotretinoin, the average durations of treatment were 4.3 and 3.9 months. Conclusions The increased use of systemic tetracyclines in general, and the prolonged use of tetracyclines in patients who later switch to isotretinoin, raise the question of whether isotretinoin treatment should be considered at an earlier stage to reduce the use of systemic tetracyclines.

Aims: To study information on prescribed drug use (opioids, antidepressants and benzodiazepines (BZD)) recorded in the Norwegian Prescription Database (NorPD) and to compare this information with selfreported drug use among pregnant women in the Norwegian Mother and Child Cohort Study (MoBa).Materials and methods: The study population consisted of 28 479 women who participated in MoBa and who answered all questionnaires in pregnancy and whose pregnancy started after 1 March 2004. Data on dispensed drugs in NorPD were extracted for three different time windows: a) the pregnancy period, b) 30 days prior to pregnancy in addition to pregnancy, c) 60 days prior to pregnancy in addition to pregnancy. Data on self- reported drug use in MoBa were used as the reference standard in the validity analysis. Sensitivity and specificity were calculated.Results: Sensitivity of drug use as recorded in NorPD for the pregnancy period was highest for antidepressants (66.9%) and BZD-antiepileptics (100%) and lowest for BZD-anxiolytics (44.8%) and BZDhypnotics (27.8%). Expansion of the time windows for dispensed drugs in the NorPD to include intervals 30 and 60 days before pregnancy led to higher sensitivity, but lower specificity of all classes of drugs. For opioids, sensitivity increased from 48.8% to 53.6%, while specificity decreased from 98.7 to 97.6%. For antidepressants and BZD-anxiolytics, specificity decreased for both from 99.7 to 99.4%.Conclusion: Using self-reported data as reference standard, the prescription data provides valid information on current exposures to BZD-antiepileptics and antidepressants in pregnant women if time windows are selected with adequate consideration depending on the investigated problem. However, validity is lower for other benzodiazepines and opioids.