diclegis

The Only FDA-Approved Drugs for Nausea and Vomiting During Pregnancy

In 1956, the FDA approved a medication called Bendectin for the treatment of nausea and vomiting during pregnancy. This drug, which was known as Diclectin in Canada, Debendox in the UK and Australia, and Lenotan in other countries, combined two active ingredients: pyridoxine (a B vitamin) and doxylamine succinate (an antihistamine). In essence, it was a combination of a vitamin and an over-the-counter sleep aid.

Active Ingredients and Dosages

• Diclegis: Each tablet contains 10 mg of doxylamine succinate and 10 mg of pyridoxine hydrochloride, delivered in a delayed-release form.
• Bonjesta: Each tablet provides 20 mg of doxylamine succinate and 20 mg of pyridoxine hydrochloride, with an extended-release formulation.
• Over-the-Counter Alternatives: Doxylamine (the active ingredient in Unisom) is available in 25 mg tablets, and pyridoxine is available in doses ranging from 25 mg to 500 mg.

For those seeking an over-the-counter equivalent to Diclegis or Bonjesta, you can start with 25 mg of doxylamine and 25 mg of pyridoxine at bedtime, as doxylamine has sedative properties. If needed, you can add a half tablet (12.5 mg) of each in the morning and again at midday, adjusting based on the balance of benefits and side effects.

Indication

Diclegis is prescribed for the treatment of nausea and vomiting in pregnant women who haven’t responded to dietary changes or other non-medication treatments.

Limitations of Use

It is not known whether Diclegis is safe and effective for women with severe nausea and vomiting of pregnancy, known as hyperemesis gravidarum. Women with this condition may require hospitalization.

A Brief History

Originally, Bendectin included a third ingredient, dicyclomine hydrochloride, which was later removed after failing to meet the efficacy standards set by the Food, Drug, and Cosmetic Act of 1975. While Bendectin was being prescribed in the U.S., thalidomide was used in Europe, leading to a wave of birth defects. Although thalidomide was never approved in the U.S., concerns about Bendectin arose, and lawsuits followed, despite studies showing no increased risk of birth defects. The FDA confirmed its safety in 1980, but due to escalating legal and insurance costs, Merrell Dow Corporation pulled it from the market in 1983.

For years, women managed their pregnancy nausea by buying pyridoxine from the vitamin aisle and doxylamine from the sleep aid section. This combination has become one of the most studied regimens for pregnancy-related nausea. In 1999, the FDA assigned it a Category A rating, the safest possible rating, indicating no increased risk of birth defects.

In 2013, the FDA approved the same combination under the name Diclegis, manufactured by Duchesnay, the same company that had been producing it in Canada. However, Diclegis comes with a hefty price tag of around $570 for a one-month supply, often not covered by insurance. For a fraction of that cost, around $10, women can purchase the over-the-counter equivalents.

In 2016, the FDA approved Bonjesta, a long-acting version of the same medication, also produced by Duchesnay. Bonjesta features a multilayered coating that releases the medication gradually over time, reducing the need for multiple daily doses.

Acknowledging Hyperemesis Gravidarum

The packaging of both Diclegis and Bonjesta notes that these medications have not been studied in women with hyperemesis gravidarum (HG). This is because, at the time the original studies were conducted, nausea and vomiting in pregnancy were not differentiated between morning sickness and HG. However, today, the acknowledgment of HG marks progress in recognizing and addressing this severe condition.

Currently, Diclegis and Bonjesta are the only FDA-approved medications for morning sickness, and the combination of Vitamin B6 (pyridoxine) and doxylamine (Unisom) is the first-line treatment in clinical guidelines. The primary difference lies in the dosage.

A Few Key Considerations

While doxylamine is rated Category A for safety—meaning it is unlikely to cause birth defects—the evidence supporting its efficacy is not particularly strong. There are more effective medications available that can better help reduce vomiting. Additionally, a high-dose vitamin B combination, including B1 (thiamin) and B12 (cobalamin), might offer more benefits than vitamin B6 alone. It’s also crucial to remember that vitamin B9 (folic acid or methylfolate) is particularly important during the first nine weeks of pregnancy when the heart and palate are forming.

It’s important to keep in mind that the Category A safety rating primarily indicates that Diclegis is not a teratogen, meaning it won’t cause birth defects. However, there are several safety considerations for the mother. Diclegis contains doxylamine, a first-generation antihistamine that crosses the blood-brain barrier, leading to drowsiness and other anticholinergic effects. Because of this, the manufacturer advises caution when using Diclegis in women with conditions such as asthma, increased intraocular pressure, narrow-angle glaucoma, stenosing peptic ulcer, pyloroduodenal obstruction, and urinary bladder-neck obstruction.

A rather unusual fact noted in the Diclegis package insert is the potential for “Interference with urine drug screening.” Women are advised that Diclegis may result in false-positive urine drug screenings for methadone, opiates, and PCP.

Another key point is that taking Diclegis with food decreases its absorption, so it’s best taken on an empty stomach—a challenge made easier when dealing with HG.

Regarding Efficacy: Does Diclegis Work?

In the study that led to Diclegis receiving FDA approval, 19% of patients remained on 2 tablets daily, 21% took 3 tablets daily, and 60% required 4 tablets daily over the two-week trial period. By the end of the study, the average reduction in PUQE (Pregnancy-Unique Quantification of Emesis) score was just 0.7 points. Only you can decide if taking multiple pills throughout the day, which may cause drowsiness, is worth this modest benefit.

However, multiple studies have shown that ondansetron and other medications are superior to Diclegis in terms of efficacy. If reducing vomiting is a priority, consider starting with other more effective options that are also proven to be as safe in pregnancy.

Do these medications help with HG? Share your experiences with these two ingredients at info@hgpharmacist.com, and we’ll share the feedback.