- Discussing Diclegis With Your Doctor
- What to ask your doctor
- What is Diclegis?
- Is it safe?
- Will it cure my morning sickness?
- More About Morning Sickness
- Should I take Diclegis first before trying other ways to treat morning sickness?
- Further discussion
- Know exactly when and how you should take it
- Explain your specific symptoms
- Talk with your doctor about the medication’s history for your own peace of mind
- Know what to expect
- Guidelines Recommend It, But Evidence That Prescription Drug For Morning Sickness Works Is Lacking
- More evidence common morning sickness drug may not work
- Kim Kardashian’s first trimester nausea: The truth behind Diclegis
- Pregnancy Nausea Medication May Not Work All That Well
- Drug approval in 2013
- Questions remain
- Talk to your doctor
Discussing Diclegis With Your Doctor
Morning sickness strikes most moms-to-be in some way. Maybe you feel slightly nauseated when you first wake up, or perhaps certain smells make you sick, or, if you’ve got a severe case, you might not be able to keep anything down morning, noon, or night. Most expectant moms think they have to weather morning sickness symptoms for the first trimester and maybe longer. But there could be some welcome relief in sight — an FDA-approved medication called Diclegis.
Diclegis is a prescription drug that may ease pregnancy-related nausea and vomiting. But before you run to your doctor for a prescription, use this guide to figure out the questions you need to ask and the important points you should discuss with your obstetrician. Then, you can work together to determine whether Diclegis is right for you.
What to ask your doctor
Start your conversation by getting answers to some of the following important questions about the drug.
What is Diclegis?
Available only by prescription, Diclegis is used to control nausea and vomiting of pregnancy (NVP). It has two main ingredients: vitamin B6 and the antihistamine doxylamine. For years, doctors have recommended that women manage morning sickness with B6 and doxylamine, but you had to take them separately, using medications that weren’t specifically formulated to treat pregnant women’s nausea. Diclegis combines these two ingredients in a formulation specifically designed and approved for use during pregnancy.
Is it safe?
Diclegis has undergone extensive testing and has been approved by the Food and Drug Administration (FDA). A similar version of the drug for expectant mothers has been available in Canada for 30 years. Drowsiness is the most common side effect associated with Diclegis.
Will it cure my morning sickness?
Diclegis can be very effective at reducing symptoms as long as you stay on the medication, but your morning sickness may return if you stop taking it.
More About Morning Sickness
Your Health Morning Sickness and Nausea During Pregnancy Your Health 7 Things I Wish I Had Known About Morning Sickness Pregnancy 10 Products to Help with Pregnancy Nausea and Morning Sickness Your Health Morning Sickness and Nausea During Pregnancy Your Health 7 Things I Wish I Had Known About Morning Sickness Pregnancy 10 Products to Help with Pregnancy Nausea and Morning Sickness
Should I take Diclegis first before trying other ways to treat morning sickness?
Your doctor will likely recommend that you try dietary and lifestyle changes to ease your symptoms before considering medication. If you’ve tried that, and your nausea isn’t getting better, it may be time to start Diclegis.
Once you’re armed with the answers to your questions, talk to your doctor about the particulars of using the medication.
Know exactly when and how you should take it
Talk to your doctor about how much Diclegis to take and when to take it, including when to stop using the medication. Do not take more than four tablets (one in the morning, one in the mid-afternoon, and two at bedtime) in one day. Take the medication on an empty stomach with a glass of water.
Explain your specific symptoms
Let your doctor know whether your symptoms are getting in the way of your daily life. You may be asked to take a questionnaire — the Pregnancy-Unique Quantification of Emesis (PUQE) — that can reveal the severity of your symptoms to see whether you could benefit from Diclegis. If you’re suffering from continual vomiting, you may have hyperemesis gravidarum, a more serious condition that can lead to weight loss and dehydration. In that case, it isn’t known if Diclegis will be safe or effective. Your doctor may recommend hospitalization so you can be treated intravenously with liquids and medication.
Talk with your doctor about the medication’s history for your own peace of mind
A drug similar to Diclegis was sold in the US 50 years ago. It was pulled off the shelves following concerns about safety, but the FDA found the concerns unfounded. After extensive testing, the FDA has concluded that Diclegis is safe for women and their developing babies.
Know what to expect
You may still have some nausea or discomfort while taking Diclegis, but studies show that the medication helps ease morning-sickness symptoms, allowing you to eat healthy, go to work, and enjoy your pregnancy.
Thankfully, morning-sickness symptoms for most women usually pass around week 14. So with time, you’ll be feeling much better and can focus on planning for your baby.
Guidelines Recommend It, But Evidence That Prescription Drug For Morning Sickness Works Is Lacking
Kim Kardashian might have sworn by it, but Dr. Nav Persaud says there’s no evidence that the only prescription drug approved to treat morning sickness works.
Kardashian in 2015 endorsed the medication, sold as Diclegis in the United States, in a 2015 Instagram post that spurred the Food and Drug Administration to send a warning letter to Duchesnay, the Canadian company that makes the drug. Kardashian, who was paid by Duchesnay, failed to include any information about the drug’s risks. (Duchesnay’s latest celebrity spokeswoman is “lifestyle expert” Emily Maynard Johnson, best known for her appearances on “The Bachelor” and “The Bachelorette.”)
That’s the least of the problems with Diclegis, says Persaud, a family practice doctor at the University of Toronto. The FDA and Health Canada, the FDA’s counterpart in that country, never should have approved the drug because it doesn’t work, he says.
“I used to prescribe it,” Persaud told me. “And then when I started looking into it, I completely stopped.”
Morning sickness is thought to strike in three out of four pregnancies (it is not to be confused with the far more serious and rarer hyperemesis gravidarum, persistent nausea and vomiting that leads to pregnant women losing 5% or more of their body weight). Diclegis, which sells for about $6 per pill for women with insurance coverage–they might need to take up to four tablets a day–is a combination of two inexpensive over-the-counter drugs: vitamin B6, also called pyridoxine, and doxylamine, an antihistamine sold as Unisom SleepTabs. CVS sells Unisom for about 28 cents per tablet; the chain’s own brand of doxylamine sells for less than 20 cents per pill. You can buy B6 for as little as 4 1/2 cents a pill at CVS.
The B6/doxylamine combo has a somewhat checkered past in the United States. From 1956 to 1983, it was sold as Bendectin by the now-defunct Merrell Dow Pharmaceuticals. According to one estimate Bendectin was prescribed in 25% to 30% of pregnancies during that period. But Merrell Dow voluntarily pulled the drug off the market in 1983 because of mounting lawsuits from women who claimed it caused birth defects, even though the scientific evidence at the time suggested otherwise. Two decades later, Duchesnay re-introduced the B6/doxylamine combination in the United States with the brand name Diclegis, each pill of which is imprinted with the outline of a pregnant woman. The B6/doxylamine combination never came off the market in Canada, where it’s been sold for 60 years.
Persaud’s pursuit of evidence about the drug’s safety and effectiveness began several years ago when he realized he didn’t have the answers to a patient’s questions about Diclectin, its brand name in Canada.
In 2014, he coauthored a re-analysis of safety data supporting the use of doxylamine for nausea and vomiting in pregnancy. The earlier analysis had concluded that doxylamine not only was safe but actually cut the risk of birth defects by about a quarter. Persaud and his coauthors found no such benefit associated with doxylamine.
This month, Persuad coauthored a report in the journal PLoS ONE about an unpublished B6/doxylamine trial whose findings had helped convince the FDA to approve Diclegis in 2013. He had seen references to the study in other paper, but it took years before the FDA responded to his Freedom of Information Act request and provided him with the data. The trial, conducted at 14 U.S. clinics, involved 2,308 women in the first 12 weeks of pregnancy who were experiencing nausea or vomiting. Persaud and his coauthor concluded that the integrity of data from the study were “questionable.” That and other concerns about the study, such as a high drop-out rate and flaws in its design, preclude making firm conclusions about the safety or effectiveness of vitamin B6 and/or doxylamine, the authors wrote. Claims about their effectiveness and treatment guidelines and regulatory decisions based on this previously unpublished trial should be revisited, they said.
Dr. Laura Riley, director of labor and delivery at Massachusetts General Hospital, said she was glad to see Persaud’s study. “I am a firm believer that the best remedy for N/V (nausea and vomiting) is SweetTARTS and acupuncture,” Riley told me in an email. “No studies to back it up, but no side effects, either!” (Actually, some research suggests acupuncture might help, but I couldn’t find any studies about the candy.)
In a prepared statement, Michael Gallo, vice president of regulatory and medical affairs at Duchesnay, said, “The conclusions expressed in the report published in PLoS ONE are highly inconsistent with the large and comprehensive body of evidence regarding this combination drug.” The statement called B6/doxylamine “the most studied drug combination used in pregnancy.”
Diclegis/Diclectin is approved only in the United States, Canada and Israel, but Duchesnay estimates that 35 million women around the world have used the B6/doxylamine combo to treat nausea and vomiting in pregnancy.
Persaud says he understands why B6/doxylamine has been so widely prescribed. “There’s a pregnant woman in your office, she’s saying she’s suffering. You put the two together, and the result is a prescription.”
Medical societies in the United States and Canada recommend that pregnant women first try non-drug measures, such as eating frequent, small meals to avoid a full stomach and avoiding spicy or fatty foods, although there’s little published evidence of their effectiveness.
If non-drug approaches don’t work, a 2015 “practice bulletin” from the American College of Obstetricians and Gynecologists (ACOG) says vitamin B6 or vitamin B6 plus doxylamine “is safe and effective and should be considered first-line pharmacotherapy.” In 2014, an article in American Family Physician, the official publication of the American Academy of Family Physicians, said there was better evidence supporting the use of B6 than B6 plus doxylamine for the prevention or treatment of morning sickness.
Unlike ACOG and the American Family Physician, which did not mention Diclegis by name, the Society of Obstetricians and Gynecologists of Canada specifically names Diclectin as the first-line medication to use if non-drug measures don’t work.
Last week, though, Canadian Family Physician (CFP), the official publication of the College of Family Physicians of Canada, backtracked on recommendations from the Canadian OB/GYN group that it had previously published.
“We agree with the conclusions of Persaud and his colleagues that there is not, at this time, clear evidence that the combination of doxylamine-pyridoxine is more effective in the management of NVP than pyridoxine alone,” wrote an editor and two members of the journal’s advisory board. “Science and journals such as CFP that publish science in service to good care are not static entities.”
More evidence common morning sickness drug may not work
(Reuters Health) – – A pill millions of women have used for morning sickness may not actually help relieve nausea, according to a new study that some doctors say reinforces their decision to stop prescribing the drug.
The U.S. Food and Drug Administration (FDA) approved the drug, pyridoxine-doxylamine (Diclegis, Diclectin), based on results from a clinical trial. But previously unpublished data from the trial show the drug worked no better than a placebo at reducing nausea and vomiting in pregnant women, researchers report in PLOS One.
“I have stopped prescribing this medication,” said lead study author Dr. Nav Persaud, a researcher and family physician at St. Michael’s Hospital and the University of Toronto.
“Based on all the information available, I don’t think that it works,” Persaud said by email.
For the current study, researchers analyzed findings from a 9,000-page clinical trial report from Health Canada that provided more information about the medicine than results from the trial that were published in 2010.
The 2010 report included 101 women who took the drug for two weeks and 86 women who took a placebo, or dummy pill.
While these results suggested that the drug worked better than a placebo, the current analysis found that this difference was too small to be clinically meaningful for patients.
That’s because women rated nausea symptoms on a 13-point scale and achieved only a 0.7-point greater reduction with the drug than with a placebo. Unpublished records from the trial indicate that the drug needed to achieve at least a 3-point greater reduction in nausea and vomiting to be considered better than a placebo.
Health Canada and the FDA should revoke marketing approval for the medicine, and until this happens doctors shouldn’t prescribe it, Persaud and colleagues argue.
“It is surprising that the FDA and those who determine clinical practice guidelines would make recommendations based on a single clinical trial that lacks a robust conclusion of efficacy,” said Dr. Marlena Fejzo, an obstetrician and gynecologist at the University of Southern California and the University of California, Los Angeles, who wasn’t involved in the study.
“Most patients do not take the decision of using a medication in pregnancy lightly, and deserve to know that their provider is basing their recommendations on a single study that had opposing interpretations with respect to medication effectiveness,” Fejzo said by email.
The drug was developed in the 1970s, and an older version of the medicine was in use as far back as the 1950s. Early in 2017, Persaud coauthored a re-analysis of a clinical trial from the 1970s; like the current study, last year’s re-analysis found missing data and called into question the effectiveness of the medication.
Many doctors still consider the drug among their best options for treating morning sickness and continue to prescribe it for women.
In December, in a practice bulletin published in Obstetrics & Gynecology, the American College of Obstetricians and Gynecologists (ACOG) reaffirmed its recommendation that doctors prescribe Diclegis first before considering alternative medications to ease nausea.
ACOG is aware of the current study and still considers Diclegis to be safe and effective for morning sickness, said Dr. Mark Turrentine, chair of ACOG’s committee that drafted the nausea treatment recommendations.
“If the U.S. Food and Drug Administration, the authors of the original studies, or the drug manufacturer, correct or retract any of the evidence used to develop ACOG’s guidance, we will reassess,” Turrentine said by email.
Up to four in five pregnant women experience nausea, and half of them endure vomiting and retching, ACOG notes in its practice guidelines. The condition often peaks early in pregnancy, and can ease without treatment, but in severe cases women can become dehydrated and malnourished and require hospitalization.
Women may relieve symptoms by taking ginger capsules, wearing acupressure wrist bands, or swapping their prenatal vitamins for a supplement that contains only folic acid, ACOG advises.
Other drugs that ACOG recommends for morning sickness include: dimenhydrinate (Dramamine, Gravol), diphenhydramine (Benadryl), prochlorperazine (Compro), and promethazine (Phenergan). Pregnant women are generally advised to check with their doctor before taking any medication, however – especially in the first trimester.
SOURCES: bit.ly/2DIxnks PLOS One, online January 17, 2018, and bit.ly/2DJv94f Obstetrics & Gynecology, online December 21, 2017.
Our Standards:The Thomson Reuters Trust Principles.
Kim Kardashian’s first trimester nausea: The truth behind Diclegis
It was only a matter of time before Kim Kardashian posted a picture on her Instagram account with a bottle of Diclegis, basically announcing her brand partnership with Duchesnay, the manufacturer of the prescription medication for nausea and vomiting in pregnancy. Duchesnay had been tweeting for ages that they were so relieved Kim had found help with Diclegis — so much so that I was wondering if Ms. Kardashian was possibly having the longest first trimester known to womankind.
While the FDA was all over the Instagram post, I suppose they didn’t jump on the promoted tweets (which sure looked like advertising to me), because the link in the tweet took you to a page that actually listed side effects and contraindications. Although I think promoted tweets with a celebrity name is a pretty sly way around the rules. How many people really click through and read the fine print versus bring up a screen shot of the promoted tweet and ask their doctor for the medication that helped Kim?
But the FDA aside, I find Ms. Kardashian’s claim that she found the drug on her own somewhat surprising. She has an OB, and honestly I have a hard time imagining her doctor not bringing it up if she mentioned an issue with nausea and or vomiting. The cynic in me wonders if her doctor only mentioned the over-the-counter (OTC) option.
Yes, while you can buy Diclegis as a prescription it is just a combination of two readily over-the-counter (OTC) medications — vitamin B6 and doxylamine (an antihistamine) with slightly different dosing. When taken together doxylamine and vitamin B6 are mildly to moderately effective for nausea and vomiting in pregnancy. The difference between the prescription and the OTC is a minor variation in dose, and the prescription is delayed-release so it is only taken once a day. However, there has been no head to head comparison between the OTC and prescription, so we have no idea if the delayed-release offers any advantage beyond the convenience of once daily dosing.
The big difference between the OTC option and Diclegis is price. You can buy 100 doxylamine 25 mg tablets for $12.79 and 100 vitamin B6 tablets 25 mg for $7.29 (see below), and you can bet the manufacturers are still making a profit. Diclegis, if you have a coupon, is $345 for 60 tablets. The dose is two tablets a day, but some women need four tablets so the cost for could be $690 a month (with a discount coupon!). Some may get it covered by insurance, but even then co-payments are likely to be $20 or more. You will pay at most $25.20 a month for OTC (less if you don’t need four pills a day and/or take advantage of the buy one get the other 50% off at Walgreens). The other advantage of the OTC route is you can start with vitamin B6 and if that doesn’t work then add in the doxylamine. After all, we recommend a step-wise approach to nausea and vomiting.
Let’s compare OTC doxylamine/vitamin B6 with Diclegis. The OTC dosing is not identical but close enough and before 2013 (when Diclegis wasn’t available) we managed just fine using these slightly different doses. Check out this table:
While doxylamine and vitamin B6 may help many pregnant women, for most Diclegis is an unnecessary medication. I’m not saying unnecessary to downplay nausea and vomiting — I suffered terribly in my pregnancy with nausea, so I am very empathetic. I’m saying unnecessary because at that price and without studies showing medical benefit of a delayed-release formulation the prescription should only be considered if the OTC version isn’t working, Perhaps for some women the delayed-release might be better and since there are more studies on doxylamine/vitamin B6 than other options it makes sense to step up to this after trying the OTC option and before other prescriptions are tried.
If your insurer pays for you to take Diclegis and you haven’t tried and failed the OTC combination that’s several hundred dollars that could have been spent elsewhere. Your insurer will make up the difference somewhere, typically by higher co-payments for delivery.
Every single OB/GYN and pharmacist I know believes Diclegis came out with the delayed-release formulation to break into the amazingly pharma-friendly U.S. health care market because they knew they could do minimal work and charge insurers a bazillion dollars. In fact, when I retire and no longer have to worry about conflicts of interest I will invest in big pharma because they literally get away with crippling the American health care system. OK, probably not because I want my kids to be able to afford health care, and I want to sleep at night, but you get the idea.
Diclegis is nothing special — it’s no brand new wonder drug. If it had been studied head to head with the OTC products and found to be clearly superior, that would be different. It’s hard to make sense of a regulatory agency that is primed for this kind of manipulation.
Meanwhile, I’m just waiting to see what birth control pill or IUD Ms. Kardashian is going to talk about once her seemingly eternal pregnancy comes to fruition I’m sure she has learned a marketing lesson and instead of an Instagram photo shoot complete with full makeup and fake eyelashes (because that is exactly how Diclegis makes you feel, right?! ) it will be casually dropped in conversation on her show or in an interview. Hey, maybe you will be able to buy a digital version in her game!
I wonder how many Birkin Bags the insurance companies (and hence your dollars) are buying for Ms. Kardashian through the middlemen at Duchesnay. And remember, no matter how much they are paying Ms. Kardashian the folks at Duchesnay are making exponentially more. Remember, $5.75 for a pill that makes a profit at $0.21.
Jennifer Gunter is an obstetrician-gynecologist and author of the Preemie Primer. She blogs at her self-titled site, Dr. Jen Gunter.
Image credit: Tinseltown / .com
Pregnancy Nausea Medication May Not Work All That Well
How effective is the most commonly prescribed drug for nausea during pregnancy?
Not so great, say researchers from St. Michael’s Hospital in Canada. They are questioning the effectiveness of pyridoxine-doxylamine, which is sold under the brand name Diclegis in the United States.
In an article published today in the journal PLOS ONE, the research team shared previously unpublished information from a randomized clinical trial conducted in 2009, called DIC-301.
The U.S. Food and Drug Administration (FDA) relied on DIC-301 to approve Diclegis, which has been prescribed to millions of women around the world.
But after obtaining a copy of the manufacturer’s full clinical trial report from Health Canada, the researchers from St. Michael’s said they found evidence that the drug isn’t clinically effective.
The clinical trial report specified that the findings would only be considered clinically important if there was a three-point reduction in symptoms — a threshold that the results didn’t meet.
The clinical trial found that on a 13-point scale, women who took the drug reported reductions in symptoms that were only 0.7 points greater than those who took a placebo.
While that difference is statistically significant, it’s not large enough to be noticeable to patients, Dr. Nav Persaud, MSc, lead investigator and a family physician at St. Michael’s, told Healthline.
“One of the most important things about this study is that it explains exactly why many women who have taken this medication would believe that it works and many of the physicians who have prescribed it would believe that it works,” he said.
“When you look at the symptom scores for women who are given a placebo, they start around 9 on the first day of the study, and by two weeks later, the symptom score is 4 out of 13, and a minimum score on that scale is 3, which would indicate no symptoms,” he added.
In other words, whether women were given a placebo or the drug, they went from having relatively high symptoms at the start of the trial to having low or no symptoms by the end.
The simplest explanation, Persaud said, was that participants’ nausea and vomiting was self-limited, which means it would have resolved without treatment.
He noted that while the clinical trial didn’t show that pyridoxine-doxylamine was effective, it also didn’t find any safety issues associated with the drug.
Drug approval in 2013
Diclegis is manufactured by Duchesnay Inc., a pharmaceutical company that focuses on products for pregnant patients.
The drug had been sold under a different name when it was pulled from the market in 1983 after lawsuits were filed stating the medication caused birth defects.
Advocates for Diclegis say the fears stated in the lawsuits were unfounded.
In the early 2000s, Duchesnay Inc. approached the FDA to obtain approval for Diclegis.
The FDA requested evidence from a clinical trial and approved the drug in 2013, after trial DIC-301 was completed.
“The FDA took into account the totality of the evidence submitted when deciding whether Diclegis could be approved, including data from the more recent phase three, randomized, double-blind, placebo-controlled trial conducted by the company that owns Diclegis, and other supportive data,” the FDA told Healthline in a written statement.
“Based on the available data, the FDA determined that Diclegis has been shown to be safe and effective for the treatment of nausea and vomiting in pregnant women who do not respond to conservative management,” the statement continued.
Healthline also heard from Fiona Story, senior director of communications at Duchesnay Inc., who stated the safety and efficacy of Diclegis have been demonstrated in multiple studies.
Story said trial DIC-301 was designed in collaboration with the FDA through a special protocol assessment.
“The clinical trial achieved a statistically significant endpoint using the method of analysis requested by the FDA in accordance with all FDA requirements,” Story said.
In response to the comments from the FDA and Story, Persaud drew attention to the discrepancy between the pre-specified threshold for clinical importance and the findings in trial DIC-301.
“A difference of three points on the 13-point symptoms scale was pre-specified as the minimal clinically important difference, but the reported difference was less than 1 point,” Persaud said.
“If it is true that the manufacturer and the FDA agreed on the design of the study, then they both agreed ahead of time that three points was the minimal clinically important difference,” he continued.
In the past, Persaud has also raised concerns about other studies on the efficacy of pyridoxine and doxylamine for treating nausea and vomiting in pregnancy.
For example, he published an article last year calling the methodological integrity of an older trial on pyridoxine and doxylamine into question.
Persaud would like the FDA to revisit its regulatory decision on Diclegis and more clearly articulate its basis for believing the drug is effective.
“It’s one thing to say, as the FDA does, that it’s based on the totality of the evidence,” he said, “but you know, as someone who has taken quite a bit of time to try to sift through all of the evidence for this medication, I actually couldn’t tell you exactly what they mean.”
In its statement to Healthline, the FDA noted that it’s reviewing Persaud’s article.
“The FDA is reviewing the findings of the paper. The FDA remains committed to informing the public in a timely manner when the agency identifies concerns about approved drug products,” the statement read.
Talk to your doctor
Diclegis is currently the first-line pharmacological treatment recommended by the American College of Obstetricians and Gynecologists (ACOG) for nausea and vomiting in pregnancy.
“This month, ACOG released its updated Practice Bulletin ‘Nausea and Vomiting of Pregnancy’ and maintains that vitamin B6 (pyridoxine) alone or vitamin B6 (pyridoxine) plus doxylamine in combination is safe and effective and should be considered first-line pharmacotherapy,” Dr. Mark Turrentine, chair of ACOG’s Committee on Practice Bulletins — Obstetrics, told Healthline.
“If the U.S. Food and Drug Administration, the authors of the original studies, or the drug manufacturer correct or retract any of the evidence used to develop ACOG’s guidance, we will reassess and consider the conclusions at that time,” he added.
In his own clinical practice, Persaud has stopped prescribing Diclegis.
“I used to prescribe it routinely for women who have nausea and vomiting during pregnancy, but I have completely stopped prescribing this medication,” he said.
“And my recommendation would be to speak to your healthcare providers about effective treatment for nausea and vomiting during pregnancy. Based on the information that I’ve reviewed, this medication doesn’t seem to be effective,” he added.
According to Persaud, several other drugs are available for the treatment of nausea and vomiting in pregnancy.
Photo: NS YAPR/Getty Images
Last night, Kim Kardashian posted on Instagram that she’s taking Diclegis, a prescription morning-sickness drug to help with the nausea she’s still experiencing while carrying Yeezy Jr. As she told Us Weekly at the CFDA awards in early June, “I’ve had really bad morning sickness, day sickness, night sickness — I can barely get out of bed.” Diclegis is the only FDA-approved drug to treat morning sickness, known in the medical community as Nausea and Vomiting of Pregnancy (NVP). Kardashian wrote, “I felt a lot better and most importantly, it’s been studied and there was no increased risk to the baby.” The photo is drawing criticism both because Kim recently said that her Instagram account is “off limits” to advertisers, and since the drug has a controversial past.
Diclegis, which is a combination of OTC antihistamine doxylamine and vitamin B6, was pulled from the market in 1983 following lawsuits claiming it caused birth defects, ABC News reported. Manufacturer Merrell Dow maintained the drug (then called Bendectin) was safe, but discontinued it in the face of prohibitive insurance and legal costs. Numerous studies have confirmed its safety since then and the U.S. Food and Drug Administration approved Diclegis — the same formula made by a different company — in 2013 as a Pregnancy Category A drug, which means the medication failed to demonstrate health risks to the fetus in well-controlled human trials. It’s the highest rating available, and some experts believe the drug shouldn’t have been discontinued in the first place. Case in point: The Canadian company Kardashian is partnering with, Duchesnay, has manufactured a generic version of the drug since 1983.
“Diclegis is really safe,” says Jill Rabin, M.D., professor of obstetrics and gynecology at Hofstra North Shore-LIJ School of Medicine. “It’s absolutely the only antinausea medication approved for use in pregnancy by the FDA.” Other drugs, like Dramamine, Zofran, and Thorazine are Category B, Dr. Rabin says, meaning there’s no known risk in animal trials but no adequate studies in pregnant women. And she points to studies that found the rate of birth defects in the U.S. stayed the same after Bendectin was discontinued, while hospitalizations for morning sickness doubled.
“‘Morning sickness’ is a misnomer because 95 percent of women with NVP experience symptoms beyond the morning,” Dr. Rabin says. “It can have a huge impact on people’s lives.” And, yes, you could buy Diclegis’s two active ingredients at the drugstore, but she cautions against it. “There are medication errors possible because there are multiple active and inactive ingredients in the separate forms.” Plus, Diclegis is a time-released formula that peaks five to seven hours after you take it, so going the DIY route wouldn’t help you when you wake up feeling like death.
As with any medication, caveats apply. Duchesnay USA says Diclegis hasn’t been studied in women with hyperemesis gravidarum, the rare, hellish form of morning sickness with vomiting so persistent it can lead to weight loss. (Kate Middleton had it in both of her pregnancies.) And they advise that pregnant women try to manage their morning-sickness symptoms. It should be used with caution in women who have asthma or other health conditions, and shouldn’t be taken with alcohol, sleep aids, or other antihistamines.
Diclegis (doxylamine succinate and pyridoxine hydrochloride) has been approved by the FDA for the treatment of nausea and vomiting associated with pregnancy. On April 8, 2013, the FDA announced approval of Diclegis (doxylamine succinate and pyridoxine hydrochloride) for nausea and vomiting associated with pregnancy. It may be used in pregnant women with nausea and vomiting that does not improve with conservative management strategies; however, it has not been studied in pregnant women with hyperemesis gravidarum,1 a condition that causes extreme, persistent nausea often associated with dehydration.2
The components of Diclegis have been used since 1976 to treat morning sickness in the United States and around the world. Currently, Diclegis is the only FDA-approved treatment for nausea and vomiting associated with pregnancy.1,3
Pharmacology and Pharmacokinetics
The mechanism of action of Diclegis is unknown.1
Peak plasma concentrations of the doxylamine component occur in 7.5 hours, and the pyridoxine component, 5.5 hours. Elimination half-life is 12.5 hours for the doxylamine component, and in 0.5 hours for the pyridoxine component. Steady-state concentrations of doxylamine are reached within 24 to 48 hours. Pyridoxine does not reach steady-state concentrations due to its short half-life.1
Dosage and Administration
Each tablet contains 10 mg of doxylamine succinate and 10 mg of pyridoxine hydrochloride, should not be chewed or crushed, and should be taken on an empty stomach with a glass of water. Patients should start with 2 tablets daily at bedtime, adding a single-tablet morning dose if symptoms are inadequately controlled. If further symptoms occur, patients may add a single-tablet midafternoon dose to the regimen, reaching the 4-tablet maximum daily dose.1
Two meta-analyses evaluated the results of several cohort and case control studies carried out between 1961 and 1985, and failed to detect any teratogenicity to the components of Diclegis related to use during the first trimester of pregnancy. Further studies in pregnant rhesus monkeys confirmed the safety of these medications.1
In a clinical trial of pregnant, adult women between 7 and 14 weeks’ gestation, 131 patients received between 2 and 4 tablets daily and 125 patients received placebo for 14 days. Investigators evaluated the degree of nausea with a survey called the Pregnancy Unique-Quantification of Emesis (PUQE) that rated the degree of emesis from 3 (no emesis) to 15 (6 or more hours of nausea, 7 or more instances of vomiting, and 7 or more instances of dry heaves daily). Treatment with placebo led to a 3.9-point mean decrease in the PUQE score by day 15, while patients treated with Diclegis experienced an additional 0.7-point mean decline in PUQE scores over patients treated with placebo (95% CI: 0.2-1.2; P <.0006).1,4
Contraindications, Warnings, and Precautions
Diclegis is contraindicated in patients with a hypersensitivity to ethanolamine-based antihistamines, pyridoxine hydrochloride, or any inactive components of Diclegis. Patients should avoid tasks such as operating machinery or driving. Alcohol should be avoided because it may increase the sedation potential of Diclegis. Medical conditions such as asthma, increased intraocular pressure, narrow-angle glaucoma, certain stomach problems, and bladder obstruction problems should be discussed with a health care professional before initiating treatment because the anticholinergic properties of doxylamine may affect these conditions.1
Although Diclegis is a category A medication for use in pregnancy, it should not be used during breast-feeding because the doxylamine component may cause sedation and worsening of respiratory conditions in infants. Excitement and irritability may also occur with doxylamine exposure in infants. In clinical trials, 14.3% of patients using Diclegis experienced somnolence versus 11.7% of patients using placebo, meaning investigators would have to treat ≈38 patients with Diclegis instead of placebo for 1 additional case of somnolence to occur. Other adverse events observed in postmarketing experience include tachycardia, blurred vision, vertigo, irritability, migraine, urinary retention, and rash.1
Michael R. Page earned his PharmD from the Ernest Mario School of Pharmacy at Rutgers University. He has worked as a community pharmacist at CVS Pharmacy and is currently clinical editor in clinical and scientific affairs at Pharmacy Times.
- Diclegis (doxylamine succinate and pyridoxine hydrochloride) . Bryn Mawr, PA: Duchesnay USA, Inc; 2013.
- US National Library of Medicine. Hyperemesis gravidarum. www.nlm.nih.gov/medlineplus/ency/article/001499.htm. Accessed June 2013.
- US Food and Drug Administration. FDA approves Diclegis for pregnant women experiencing nausea and vomiting. www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm347087.htm. Accessed June 2013.
- Koren G, Clark S, Hankins GD, et al. Effectiveness of delayed-release doxylamine and pyridoxine for nausea and vomiting of pregnancy: a randomized placebo controlled trial. Am J Obstet Gynecol. 2010;6(571):e1-e7.