Posts Tagged valproate

[BLOG POST] Which are the safest epilepsy drugs in pregnancy? – Neurochecklists Updates

Maternal use of antiepileptic agents during pregnancy and major congenital malformations in children

Bromley RL, Weston J, Marson AG.

JAMA 2017; 318:1700-1701.

Abstract

CLINICAL QUESTION:

Is maternal use of antiepileptic drugs during pregnancy associated with major congenital malformations in children?

BOTTOM LINE:

Certain antiepileptic drugs were associated with increased rates of congenital malformations (eg, spina bifida, cardiac anomalies). Lamotrigine (2.31% in 4195 pregnancies) and levetiracetam (1.77% in 817 pregnancies) were associated with the lowest risk and valproate was associated with the highest risk (10.93% in 2565 pregnancies) compared with the offspring of women without epilepsy (2.51% in 2154 pregnancies).

Also see

Weston J, Bromley R, Jackson CF, et al. Monotherapy treatment of epilepsy in pregnancy: congenital malformation outcomes in the child. Cochrane Database Syst Rev 2016; 11:CD010224.

Both references are cited in the neurochecklist:

Antiepileptic drugs (AEDs): teratogenicity

Abstract link 1

Abstract link 2

Drugs firms ‘creating ills for every pill’. Publik15 on Flickr. https://www.flickr.com/photos/publik15/3415531899

via Which are the safest epilepsy drugs in pregnancy? – Neurochecklists Updates

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[Abstract] Antiepileptic drug clearances during pregnancy and clinical implications for women with epilepsy

Abstract

Objective To characterize the magnitude and time course of pregnancy-related clearance changes for different antiepileptic drugs (AEDs): levetiracetam, oxcarbazepine, topiramate, phenytoin, and valproate. A secondary aim was to determine if a decreased AED serum concentration was associated with increased seizure frequency.

 

Methods Women with epilepsy were enrolled preconception or early in pregnancy and prospectively followed throughout pregnancy and the first postpartum year with daily diaries of AED doses, adherence, and seizures. Study visits with AED concentration measurements occurred every 1–3 months. AED clearances in each trimester were compared to nonpregnant baseline using a mixed linear regression model, with adjustments for age, race, and hours postdose. In women on monotherapy, 2-sample t test was used to compare the ratio to target concentrations (RTC) between women with seizure worsening each trimester and those without.

 

Results AED clearances were calculated for levetiracetam (n = 18 pregnancies), oxcarbazepine (n = 4), topiramate (n = 10), valproate (n = 5), and phenytoin (n = 7). Mean maximal clearances were reached for (1) levetiracetam in first trimester (1.71-fold baseline clearance) (p = 0.0001), (2) oxcarbazepine in second trimester (1.63-fold) (p = 0.0001), and (3) topiramate in second trimester (1.39-fold) (p = 0.025). In 15 women on AED monotherapy, increased seizure frequency in the first, second, and all trimesters was associated with a lower RTC (p < 0.05).

 

Conclusion AED clearance significantly changes by the first trimester for levetiracetam and by the second trimester for oxcarbazepine and topiramate. Lower RTC was associated with seizure worsening. Early therapeutic drug monitoring and dose adjustment may be helpful to avoid increased seizure frequency.

 

via Antiepileptic drug clearances during pregnancy and clinical implications for women with epilepsy | Neurology

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[WEB SITE] Women with Epilepsy Achieve Same Pregnancy Rate as Peers

  • by Judy George, Contributing Writer, MedPage Today. 

Women with epilepsy were at no disadvantage in getting pregnant as their peers without epilepsy, the prospective Women with Epilepsy: Pregnancy Outcomes and Deliveries (WEPOD) study found.

About 60% of women in both groups became pregnant within a year of discontinuing contraception, according to Page Pennell, MD, of Brigham and Women’s Hospital in Boston and co-authors.

Median time to pregnancy, sexual activity, and ovulatory rates were similar in each group, too, they reported online in JAMA Neurology.

These findings have two meanings, Pennell noted. First, they tell neurologists “that their female patients with epilepsy in their practice who want to become pregnant will have no additional difficulties becoming pregnant just because of their epilepsy,” she said.

But an equally important message is that women with epilepsy are at risk of unplanned pregnancy.

“It is important to always keep this in mind when choosing which medications to prescribe and to recommend supplemental folic acid,” Pennell told MedPage Today. “Other studies have reported that beginning supplemental folic acid prior to pregnancy is important to lower the risk of neurodevelopmental problems and autistic features in the children of women with epilepsy on anti-epileptic drugs.”

Maternal use of valproate (Depakote) in pregnancy has been tied to autism and impaired cognitive development in children, prompting FDA warnings about using the drug during pregnancy. A European Medicines Agency committee recently advised that valproate use be restricted in fertile women unless they participate in a pregnancy prevention program.

Research indicates that prenatal exposure to newer anti-epileptic drugs like levetiracetam (Keppra) or topiramate (Topamax) is not linked to reduced cognitive abilities in children, but a recent study indicates that women on anti-seizure medications who did not take folic acid supplements before conception had a substantially increased risk of having offspring with autistic traits.

Previous studies also have suggested that women with epilepsy may have lower fertility especially if they use multiple anti-seizure medications, but WEPOD is the first prospective study of pregnancy that included controls, the authors noted. All women in WEPOD planned their pregnancy in advance, distinguishing it from pregnancy registry or population studies.

In WEPOD, the researchers followed women with a steady male partner who wanted to become pregnant within a year of ending contraception, excluding women with a history of infertility or related disorders.

Patients recorded sexual activity and menstrual bleeding through a custom smartphone application, a web-based interface, or a paper diary. Patients in the epilepsy group also tracked their medication use and seizures.

A total of 88 women with epilepsy and 109 healthy controls enrolled in the WEPOD study throughout four U.S. academic centers. Most participants (72.1%) were white. The average age of women with epilepsy was about 32, and the average age of controls was about 31. Most women with epilepsy used monotherapy to control seizures: 44.8% used lamotrigine (Lamictal) and 28.7% used levetiracetam.

In total, 60.7% of women with epilepsy achieved pregnancy, as did 60.2% of controls.

After controlling for key covariates like age, body mass index (BMI), parity, and race, the median time to pregnancy was similar in each group: 6 months (95% CI 3.8-10.1) for women with epilepsy, and 9 months (95% CI 6.5-11.2; P=0.30) for controls. In both groups, the same proportion (81.5%) of pregnancies resulted in a live birth. No epilepsy factors were significant.

These findings allow neurologists “to provide hope, backed up by data, that if a woman with epilepsy does not have a prior gynecologic diagnosis related to infertility, then she will have the same likelihood of achieving pregnancy and same pregnancy outcomes as her female peers,” Pennell said.

The study does not answer whether women with epilepsy have different rates of infertility or polycystic ovary syndrome (PCOS) because women with these diagnoses were excluded, the authors noted. While prior research indicates that PCOS occurs more frequently in women with epilepsy, the researchers did not include these women in the study to give physicians information about the “more common clinical scenario of women with epilepsy without a preexisting diagnosis of infertility or associated disorders” who want to become pregnant.

The authors listed several other limitations: Some women may have become pregnant before they could be recruited. And it’s possible the researchers did not account for unmeasured differences between women with epilepsy and controls that may have occurred because the study used multiple sources of recruitment.

 

via Women with Epilepsy Achieve Same Pregnancy Rate as Peers | Medpage Today

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[WEB SITE] Moms-to-be, take note. European experts advise against epilepsy drug in pregnancy

The compound, valproate, is also used for migraine and bipolar disorder, and doctors already advised against prescribing the medicine for pregnant women in France.

Updated: Feb 10, 2018 13:45 IST

Valproate medicines are licenced under different names by national drugs authorities.

Valproate medicines are licenced under different names by national drugs authorities.(Shutterstock)

An expert committee of Europe’s medicines watchdog recommended Friday that a drug used to treat epilepsy and linked to malformations in children not be used in pregnancy. The compound, valproate, is also used for migraine and bipolar disorder, and doctors already advised against prescribing the medicine for pregnant women in France. France’s medicines regulator, known by the acronym ANSM, asked the London-based European Medicines Agency (EMA) to conduct a risk review.

The EMA’s Pharmacovigilance Risk Assessment Committee (PRAC) said in a statement Friday it was recommending that valproate not be used by pregnant women for any of the three medical conditions. For women suffering from epilepsy, however, it may be impossible for some to stop after becoming pregnant, it said. These may have to continue treatment, though with “appropriate specialist care”. The experts also advised against prescribing the drug for women “from the time they become able to have children”, unless using contraception.

Valproate medicines are licenced under different names by national drugs authorities. The committee recommendations will now go to another body of the EMA, which deals with concerns over drugs that are not centrally authorised in the EU. Last April, a preliminary study showed that valproate caused “severe malformations” in as many as 4,100 children in France since the drug was first marketed in the country in 1967.
Women who took the drug during pregnancy to treat epilepsy were four times more likely to give birth to babies with congenital malformations, said a report of the French National Agency for the Safety of Medicines (ANSM) and the national health insurance administration. Birth defects included spina bifida — a condition in which the spinal cord does not form properly and can protrude through the skin — as well as defects of the heart and genital organs. The risk of autism and developmental problems was also found to be higher.
via Moms-to-be, take note. European experts advise against epilepsy drug in pregnancy | fitness | Hindustan Times

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[WEB SITE] European experts advise against epilepsy drug in pregnancy

PARIS, France (AFP) — An expert committee of Europe’s medicines watchdog recommended Friday that a drug used to treat epilepsy and linked to malformations in children not be used in pregnancy.

The compound, valproate, is also used for migraine and bipolar disorder, and doctors already advised against prescribing the medicine for pregnant women in France.

France’s medicines regulator, known by the acronym ANSM, asked the London-based European Medicines Agency (EMA) to conduct a risk review.

The EMA’s Pharmacovigilance Risk Assessment Committee (PRAC) said in a statement Friday it was recommending that valproate not be used by pregnant women for any of the three medical conditions.

For women suffering from epilepsy, however, it may be impossible for some to stop after becoming pregnant, it said. These may have to continue treatment, though with “appropriate specialist care”.

The experts also advised against prescribing the drug for women “from the time they become able to have children”, unless using contraception.

Valproate medicines are licenced under different names by national drugs authorities.

The committee recommendations will now go to another body of the EMA, which deals with concerns over drugs that are not centrally authorised in the EU.

Last April, a preliminary study showed that valproate caused “severe malformations” in as many as 4,100 children in France since the drug was first marketed in the country in 1967.

Women who took the drug during pregnancy to treat epilepsy were four times more likely to give birth to babies with congenital malformations, said a report of the French National Agency for the Safety of Medicines (ANSM) and the national health insurance administration.

Birth defects included spina bifida — a condition in which the spinal cord does not form properly and can protrude through the skin — as well as defects of the heart and genital organs.

The risk of autism and developmental problems was also found to be higher.

via European experts advise against epilepsy drug in pregnancy

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[WEB SITE] Newer Epilepsy Drugs May Be Safer During Pregnancy: MedlinePlus

Newer Epilepsy Drugs May Be Safer During Pregnancy

Small British study says two drugs don’t harm a child’s mental development, but popular older one does

THURSDAY, Sept. 1, 2016 (HealthDay News) — Women who take the new epilepsy drugs levetiracetam and topiramate during pregnancy don’t run the risk of harming their infant’s mental development, British researchers report.

But the commonly prescribed anti-seizure drug valproate was linked with lower IQs in children, especially when taken at higher doses, researchers say.

“The treatment of epilepsy in women who are considering a pregnancy or are pregnant involves optimizing the health of the mother as well as keeping the risk to the fetus as low as possible,” said lead researcher Rebecca Bromley, a research fellow at the Institute for Human Development at the University of Manchester.

In the study, children exposed to levetiracetam (Keppra) or topiramate (Topamax) in the womb did not differ from children not exposed to these drugs. And they had better outcomes than the children exposed to valproate (Depakote) in terms of their IQ, thinking and language skills, Bromley said.

“These data can be used by doctors and women to help them make their decisions about which medication is best for them,” she added.

For the study, Bromley and her colleagues used the U.K. Epilepsy and Pregnancy Register to identify 171 women with epilepsy who had a child between 5 and 9 years old. During their pregnancy, 42 of the women took levetiracetam, 27 took topiramate, and 47 took valproate, the researchers said.

Bromley’s team compared the women with epilepsy with 55 women who did not take epilepsy drugs during pregnancy. The children had their IQ measured and took tests on verbal and nonverbal comprehension and how fast they could process visual information.

The researchers found that children of women who took levetiracetam or topiramate did not have lower IQs or other thinking-skill problems, compared with kids of mothers who did not take these drugs, no matter what dose of these drugs were taken.

Children whose mothers took valproate, however, had the lowest IQs of the study, Bromley said. These kids scored, on average, 11 points lower on the IQ test.

Among children whose mothers took valproate, 19 percent had IQs lower than the average score of 100, compared with 6 percent among kids whose mothers did not take any epilepsy drugs during pregnancy, the researchers found.

Because the registry the researchers used does not include all women with epilepsy, the findings might not apply to all women with the conditions, Bromley noted. She also said that topiramate, one of the newer drugs, has been associated with an increased risk of birth defects, such as cleft lip and palate.

The study was funded by Epilepsy Research U.K. and the report was published online Aug. 31 in the journal Neurology.

Dr. Ian Miller is a pediatric neurologist and medical director of the comprehensive epilepsy program at Nicklaus Children’s Hospital in Miami. “This study means that we have a little bit more information for women who become pregnant while taking epilepsy medicines,” he said.

The exact risks of taking any medicine during pregnancy are very difficult to know, he added.

“As a result, many questions remain,” Miller said. “But this study gives doctors a reason to choose topiramate or levetiracetam, which did not show a measurable effect on the child’s development, rather than valproate, which did.”

Women who are on valproate because they already tried other medications and “moved on because those medications were less effective, will face some difficult decisions,” he said.

“Any woman of childbearing potential should discuss this aspect of their medical management with their doctor, especially in light of these new findings,” Miller added.

SOURCES: Rebecca Bromley, Ph.D., research fellow, Institute for Human Development, University of Manchester, England; Ian Miller, M.D., pediatric neurologist, and medical director, comprehensive epilepsy program, Nicklaus Children’s Hospital, Miami; Aug. 31, 2016, Neurology, online

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Source: Newer Epilepsy Drugs May Be Safer During Pregnancy: MedlinePlus

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[WEB SITE] ProtectYour Pregnancy: Certain neurologic conditions are treated with drugs that may be dangerous or inappropriate for women of reproductive age. We asked experts about the risks and the alternatives. : Neurology Now

Gorman, Megan Othersen

Brandy Parker-McFadden had always considered herself one of the lucky ones, and by any measure she was. Diagnosed with epilepsy at age 15 after her first convulsive seizure, Parker-McFadden, now 40, has had just three seizures in the 25 years since. “I took my medications faithfully and went on with my life,” she says. “I grew up, I got married, and I had a baby—and then two more. Through it all, my epilepsy was well controlled with medication. From the outside, it was almost as though I didn’t have it.”

This was thanks in large part to valproate, an antiseizure medication prescribed by her neurologist that is often used to treat epilepsy and bipolar disorder and to prevent migraines. So when her neurologist instructed her obstetrician to increase the dosage during her first pregnancy to ensure that the medicine remained at a therapeutic level within her body, Parker-McFadden didn’t question it.

That was 12 years ago, in 2003. Parker’s firstborn, Samuel, is now 11.

“Samuel was born right around the time we got the first information on cognitive risks to babies exposed to valproate in utero,” says Kimford J. Meador, MD, a professor of neurology and neurological sciences at Stanford University Medical Center in California, clinical services director of the Stanford Comprehensive Epilepsy Program, and a Fellow of the American Academy of Neurology (FAAN). “There were hints in the epilepsy pregnancy registries [online databases cataloging the experiences of pregnant women taking epilepsy drugs], but what wasn’t fully known until 2004 is that one in 10 children exposed to valproate in utero will have a major complication—plus a 7- to 10-point drop in IQ. Verbal intelligence, in particular, is affected.”

Continue —>  ProtectYour Pregnancy: Certain neurologic conditions are tre… : Neurology Now

WEB EXTRA: For more information about pregnacy and epilepsy, visithttp://bit.ly/NN-pregnancy-epilepsy.

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