First trimester exposure to topiramate and the risk of oral clefts in the offspring: A systematic review and meta-analysis

Alsaad, Abdulaziz M.S.; Chaudhry, Shahnaz Akthar; Koren, Gideon

doi:10.1016/j.reprotox.2015.03.003

Cited by 54 publications

(34 citation statements)

References 26 publications

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“…A meta‐analysis of all studies reporting on women exposed to topiramate during pregnancy included 3420 patients and 1 204 981 controls. The odds ratio of oral cleft following first trimester exposure to topiramate was 6.26 (95% CI 3.13–12.51; P = 0.00001) Evidence level 2++ …”

Section: Information Giving During Pregnancymentioning

confidence: 92%

Care of Women with Obesity in Pregnancy

Denison¹,

Aedla²,

Keag³

et al. 2018

BJOG

184

187

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Section: Information Giving During Pregnancymentioning

confidence: 92%

Care of Women with Obesity in Pregnancy

Denison¹,

Aedla²,

Keag³

et al. 2018

BJOG

184

187

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“…Pregnancy register data from UK, US and Australia failed to find an association with malformation status of the child (16,20,24) as did a small population based study (21). There is consistent evidence of a specific risk of oral clefts following in utero exposure to topiramate (25,26). There is no evidence of an increased rate of malformation in children exposed to gabapentin (21,27), oxcarbazepine (21) or zonisamide (16), however data is limited for conclusions to be drawn.…”

Section: Introductionmentioning

confidence: 93%

The treatment of epilepsy in pregnancy: The neurodevelopmental risks associated with exposure to antiepileptic drugs

Bromley

2016

Reproductive Toxicology

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A number of antiepileptic drugs (AEDs) have been confirmed as teratogens due to their association with an increased malformation rate. The majority of research to date does not find an association between prenatal exposure to monotherapy carbamazepine, lamotrigine or phenytoin and neurodevelopmental outcome in comparison to control children and noted higher abilities in comparison to children exposed to valproate; but further work is needed before conclusions can be drawn. Data for levetiracetam was limited to one study, as was the evidence for topiramate. Sodium valproate exposure appeared to carry a dose dependent risk to the developing brain, with evidence of reduced levels of IQ, poorer verbal abilities and increased rate of autistic spectrum disorder both in comparison to control children and children exposed to other AEDs. The severity of the neurodevelopmental deficits associated with prenatal exposure to valproate highlight the critical need to consider neurodevelopmental outcomes as a central aspect of teratological research.

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“…In March 2011, labeling for all topiramate formulations was revised to report human data of an increased risk of oral cleft (cleft lip with/without cleft palate, CL/P) following first‐trimester exposure to topiramate monotherapy (Pregnancy Category D) . In a recent meta‐analysis of published studies that included nearly 3500 first trimester exposures to topiramate across all doses and all indications and more than 1.2 million controls, the risk of CL/P was increased sixfold with topiramate . Clinicians should counsel women of reproductive age regarding the potential increased risk of CL/P associated with topiramate exposure in the first trimester of pregnancy.…”

Section: Tolerability/safetymentioning

confidence: 99%

Topiramate in Migraine Prevention: A 2016 Perspective

Silberstein

2016

Headache

103

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Topiramate has activity at multiple molecular targets, which may account for why it is effective in migraine and most other, more specific, anticonvulsants are not. Based on randomized controlled trials, topiramate reduces migraine frequency and acute medication use, improves quality of life, and reduces disability in patients with episodic migraine and in those with chronic migraine with or without medication overuse headache. Its efficacy in chronic migraine is not improved by the addition of propranolol. Topiramate's ability to prevent progression from high-frequency episodic migraine to chronic migraine remains unclear. Consistent with clinicians' perceptions, migraineurs are more sensitive to topiramate-associated side effects than patients with epilepsy. Paresthesia is a common occurrence early in treatment but is rarely cause for terminating topiramate treatment. Cognitive problems occur much less frequently than paresthesia but are more troublesome in terms of treatment discontinuation. Cognitive complaints can often be managed by slowly increasing the topiramate dose in small increments to allow habituation. As with other carbonic anhydrase inhibitors, topiramate has metabolic effects that favor the development of metabolic acidosis and possibly renal stones. Because migraineurs have an increased risk of renal stones independent of topiramate exposure, clinicians should counsel all migraine patients to maintain hydration. Abrupt onset of blurring, other visual disturbances, and/or ocular pain following topiramate's initiation should be evaluated promptly since this may indicate rare but potentially sight-threatening idiosyncratic events. Postmarketing evidence has shown that first-trimester exposure to topiramate monotherapy is associated with increased occurrence of cleft lip with or without cleft palate (Pregnancy Category D). Even though topiramate's long half-life would seemingly support q.d. dosing, randomized controlled migraine trials used b.i.d. administration of immediate-release (IR) topiramate, which has more favorable plasma concentration-time profile (ie, lower peak concentrations and higher trough concentrations) than q.d. IR dosing. Given the sensitivity of migraineurs to topiramate-related adverse events, particularly cognitive effects, pharmacokinetic profiles should be considered when optimizing migraine outcomes. The extended-release (XR) formulations Qudexy XR (Upsher-Smith Laboratories) and Trokendi XR (Supernus Pharmaceuticals) were specifically designed to achieve the adherence benefits of q.d. dosing but with more favorable (ie, more constant) steady-state plasma concentrations over the 24-hour dosing interval vs IR topiramate b.i.d. Intriguing results from a study in healthy volunteers showed consistently less impairment in neuropsychometric tests of verbal fluency and mental processing speed with an XR topiramate formulation (Trokendi XR) vs IR topiramate b.i.d. These findings suggest a pharmacodynamic effect associated with significantly reducing plasma concentration fluctuatio...

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First trimester exposure to topiramate and the risk of oral clefts in the offspring: A systematic review and meta-analysis

Cited by 54 publications

References 26 publications

Care of Women with Obesity in Pregnancy

Care of Women with Obesity in Pregnancy

The treatment of epilepsy in pregnancy: The neurodevelopmental risks associated with exposure to antiepileptic drugs

Topiramate in Migraine Prevention: A 2016 Perspective

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