Nausea and vomiting during pregnancy is a common condition that affects the health of a pregnant woman and her developing baby. It can diminish a woman’s quality of life and significantly contribute to health care costs and time lost from work. Modifications in diet and medications to prevent or reduce nausea and vomiting in pregnancy are beneficial to prevent hyperemesis gravidarum. Treatment in the early stages may prevent more serious complications, including hospitalization. Safe and effective treatments are available for more severe cases, and mild cases of nausea and vomiting of pregnancy may be resolved with lifestyle and dietary changes. Nausea and vomiting of pregnancy should be distinguished from nausea and vomiting related to other causes.

Pyridoxine is recommended as a first line treatment for pregnant women who have mild nausea and infrequent vomiting. Individuals who have nausea with frequent vomiting, or have inadequate relief from dietary changes, avoidance of triggering factors, and pyridoxine may benefit from the addition of an antihistamine such as dimenhydrinate, diphenhydramine, prochlorperazine, or promethazine. Both pyridoxine and doxylamine are available over-the-counter (OTC). Both drugs, taken alone or together, have been found to be safe during pregnancy with no known harmful effects to the developing baby.

Bonjesta and Diclegis are fixed dose combinations of doxylamine and pyridoxine approved by the Food and Drug Administration (FDA) for the treatment of nausea and vomiting of pregnancy in women who have not responded to conservative management.

Definitions

"Conservative management" refers to changes to diet and lifestyle that might help a patient feel better. Examples include taking vitamins, adjusting meal times or changing the types of foods eaten.

"Hyperemesis gravidarum" (HG) refers to the most severe form of nausea and vomiting of pregnancy. HG may be diagnosed when a woman has lost 5 percent of her pre-pregnancy weight and/or has other problems related to dehydration or loss of body fluids. Women with hyperemesis gravidarum often need acute treatment in a hospital setting to stop the vomiting and restore body fluids.

"Nausea" refers to an uneasy feeling in one’s stomach that might indicate the need to vomit. Other symptoms that can accompany nausea include weakness, sweating, or dizziness.

"Vomiting" refers to the act of ejecting stomach contents from the mouth in an uncontrolled manner. Vomiting is a common action associated with morning sickness during the early stages of pregnancy.

Medical Necessity Criteria for Initial Authorization

The Plan considers Bonjesta or Diclegis (doxylamine/pyridoxine) medically necessary when ALL of the following criteria are met:

1. The member is 18 years of age or older; AND
2. The member has a diagnosis of pregnancy-related nausea and vomiting, confirmed by laboratory work and/or medical records; AND
3. The prescribing provider submits documentation or attestation stating that the member is unable to use, or has inadequate relief from lifestyle modifications such as dietary changes or avoidance of triggers; AND
4. The member is unable to use, or has not benefited from the individual components (OTC doxylamine and pyridoxine) taken concomitantly as separate products; AND
5. The requested medication is being prescribed for use within Food and Drug Administration (FDA) approved dosing or as supported by evidence-based literature; AND
6. Medical records and supporting lab work are provided for review to validate the above-listed requirements.

If the above prior authorization criteria are met, Bonjesta or Diclegis (doxylamine/pyridoxine) will be approved for 9 months.

Dosage and Administration

• If this dose adequately controls symptoms the next day, continue taking one tablet daily at bedtime only. However, if symptoms persist on Day 2, increase the daily dose to one tablet in the morning and one tablet at bedtime.
• The maximum recommended dose is two tablets per day, one in the morning and one at bedtime.

Diclegis

• Initially, take two DICLEGIS delayed- release tablets orally at bedtime (Day 1). If this dose adequately controls symptoms the next day, continue taking two tablets daily at bedtime.
• If symptoms persist into the afternoon of Day 2, take the usual dose of two tablets at bedtime that night then take three tablets starting on Day 3 (one tablet in the morning and two tablets at bedtime).
• If these three tablets adequately control symptoms on Day 4, continue taking three tablets daily. Otherwise, take four tablets starting on Day 4 (one tablet in the morning, one tablet mid-afternoon, and two tablets at bedtime).
• The maximum recommended dose is four tablets (one in the morning, one in the mid-afternoon, and two at bedtime) daily.

Experimental or Investigational / Not Medically Necessary

Bonjesta or Diclegis (doxylamine/pyridoxine) for any other indication is considered not medically necessary by the Plan, as it is deemed to be experimental, investigational, or unproven.

References

1. ACOG (American College of Obstetrics and Gynecology): Nausea and Vomiting of Pregnancy FAQs. Available at: https://www.acog.org/womens-health/faqs/morning-sickness-nausea-and-vomiting-of-pregnancy
2. American College of Obstetricians and Gynecologists (ACOG) Committee on Practice Bulletins- Obstetrics. ACOG Practice Bulletin No. 189: nausea and vomiting of pregnancy. Obstet Gynecol. 2018;131(1):e15-e30.
3. Bonjesta (doxylamine and pyridoxine) [prescribing information]. Bryn Mawr, PA: Duchesnay USA; June 2018.
4. Campbell K, Rowe H, Azzam H, Lane CA. The management of nausea and vomiting of pregnancy. J Obstet Gynaecol Can. 2016;38(12):1127-1137. doi:10.1016/j.jogc.2016.08.009
5. Diclegis ((doxylamine succinate and pyridoxine hydrochloride) [prescribing information]. Bryn Mawr, PA: Duchesnay USA; June 2018.
6. Herrell HE. Nausea and vomiting of pregnancy. Am Fam Physician 2014 Jun 15;89(12):965-970.
7. 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;203(6):571.e1-571.e5717. doi:10.1016/j.ajog.2010.07.030
8. Koren G, Clark S, Hankins GD, et al. Maternal safety of the delayed-release doxylamine and pyridoxine combination for nausea and vomiting of pregnancy; a randomized placebo controlled trial. BMC Pregnancy Childbirth. 2015;15:59. doi:10.1186/s12884-015-0488-1
9. Micromedex® (electronic version). IBM Watson Health, Greenwood Village, Colorado, USA. Available at: https://www.micromedexsolutions.com. Accessed August 16, 2021.

Clinical Guideline Revision / History Information

Original Date: 10/14/2021
Reviewed/Revised: 12/01/2021, 06/23/2022, 06/29/2023