Fluconazole (all routes except local only) - Cumulative dose > 150 mg - Medication and Pregnancy KB

Fluconazole (all routes except local only) - Cumulative dose > 150 mg

Exposed non-exposed, cohort studies

Study	Country Study period Study design	Data source	Exposure definition	Non-exposure definition	Exposition period	Sample size (exposed/unexposed) Or (case / control)	Remarks	Risk of bias
Inman (> 150mg) 1994	United Kingdom 1988 - 1989 retrospective cohort	A prescription-event monitoring (PEM) carried out at the Drug Safety Research Unit (DSRU).	Pregnancies in which Fluconazole (two or more doses of 150 mg) was prescribed after the last monthly period (LMP).	unexposed, sick Pregnancies in which Fluconazole was prescribed before the last monthly period (LMP).	during pregnancy (anytime or not specified)	2 / 192
Inman (> 150mg) 1994	United Kingdom 1988 - 1989 retrospective cohort		The patients were identified by means of copies of prescriptions supplied to the Drug Safety Research Unit (DSRU) in confidence by the Prescription Pricing Authority.		during pregnancy (anytime or not specified)	2 / 192
Molgaard-Nielsen (300 - 6000mg) 2013	Denmark 1996 - 2011 population based cohort retrospective	Registry-based cohort of liveborn infants in Denmark	Women who fill prescriptions for oral fluconazole (>150 mg, i.e: 300 -6000 mg) during the first trimester.	unexposed (general population or NOS) Women who did not fill prescriptions for oral azole antifungal agents during the first trimester.	1st trimester	3270 / 968236	Oral exposure. Dose response studied. The 2 high doses (300 mg and 350-6000 mg) were pooled.
Molgaard-Nielsen (300 - 6000mg) 2013	Denmark 1996 - 2011 population based cohort retrospective	Registry-based cohort of liveborn infants in Denmark	Prescriptions for oral fluconazole that were filled by the women during pregnancy was obtained from the National Prescription Registry.		1st trimester	3270 / 968236
Molgaard-Nielsen (> 350-5600) 2016	Denmark 1997 - 2013 population based cohort retrospective	Nationwide register-based cohort study in Denmark	Exposure to oral fluconazole (350-5600 mg) during the specific time windows: gestational week 7 to 22 and week 7 to birth for spontaneous abortion and stillbirth, respectively.	unexposed (general population or NOS) Non exposure to fluconazole during the specific time windows: gestational week 7 to 22 and week 7 to birth for spontaneous abortion and stillbirth, respectively.	during pregnancy (anytime or not specified)	472 / 1400113	Use of Oral Fluconazole. Analysis of dose response: low dose (150-300 mg) vs high dose (350-5600 mg).
Molgaard-Nielsen (> 350-5600) 2016	Denmark 1997 - 2013 population based cohort retrospective	Nationwide register-based cohort study in Denmark	Information on prescriptions for oral fluconazole (a prescription-only drug) was obtained from the National Prescription Register.		during pregnancy (anytime or not specified)	472 / 1400113
Pasternak (>300 mg) 2018	Sweden and Norway 2005 - 2015 population based cohort retrospective	Nationwide registers of Sweden and Norway.	Oral fluconazole exposure (>300 mg) at any time during pregnancy, as defined by filled prescriptions.	unexposed (general population or NOS) No fluconazole exposure at any time during pregnancy, as defined by filled prescriptions.	during pregnancy (anytime or not specified)	4543 / 106690	Oral exposure. Dose effect analysis.
Pasternak (>300 mg) 2018		Nationwide registers of Sweden and Norway.	Prescription database.		during pregnancy (anytime or not specified)	4543 / 106690	Oral exposure. Dose effect analysis.

Case-control studies

Study	Country Study period Study design	Data source	Case	Control	Exposition	Exposition period	Sample size (exposed/unexposed) Or (case / control)	Remarks	Risk of bias
Berard (> 150 mg) 2019	Canada 1998 - 2015 nested case control	The Quebec Pregnancy Cohort	Case of spontaneous abortion or stillbirth or major malformations.	Pregnancies not ending in spontaneous abortion or stillbirth (random sampling control) or major malformations (all live-births used as controls).	The Quebec Prescription Drug Insurance database. The filled prescription data were validated comparing them with maternal reports (the positive predictive value of prescription drug data to be ≥ 87% and the negative predictive value to be ≥ 92%).	1st trimester, during pregnancy (anytime or not specified)	29458 / 291410
Berard (> 150 mg) 2019	Canada 1998 - 2015 nested case control	The Quebec Pregnancy Cohort	Identification from the medical claims databases: Régie de l’assurance maladie du Québec (RAMQ) (outpatient diagnoses, procedures, women’s and physicians’ socioeconomic status), hospitalization archive database (MED-ÉCHO: diagnoses and procedures) and the Institut de la statistique du Québec (ISQ).			1st trimester, during pregnancy (anytime or not specified)	29458 / 291410

Risk of bias: : NA; : low; : moderate; : serious; : critical; : unclear;

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