Nausea and vomiting
of pregnancy

Nausea and vomiting of pregnancy (NVP) is a common condition that affects a woman’s health and that of her fetus. It can diminish a woman’s quality of life and can also significantly contribute to healthcare costs and time lost from work.1-6 Bonjesta® is approved to treat nausea and vomiting when conservative management fails. Please see below for full indication and limitation of use.

Symptoms

Symptoms of NVP may include:

  • Nausea
  • Vomiting
  • Retching
  • Gagging

These symptoms can vary from mild to severe:

Mild
No symptoms
Nausea (2-3 hours per day)
No vomiting
No retching

Moderate
Nausea 4–6 hours per day
Vomiting 1–2 times per day
No retching
Nausea 4–6 hours per day
Vomiting 1–2 times per day
Retching 3–4 times per day

Severe
Nausea Over 6 hours per day
Vomiting 5–6 times per day
Retching 5–6 times per day

You can use the Pregnancy Unique Quantification of Emesis (PUQE) test found below to assess the severity of a patient’s symptoms. This test is based on the number of episodes of nausea, vomiting and retching over a 12-hour period.

The most severe form of NVP, hyperemesis gravidarum, occurs in 0.3–3% of women and involves:*

  •  Severe and persistent vomiting
  • Loss of ≥5% of pre-pregnancy body weight
  • Ketonuria
  • Electrolyte abnormalities
  • Dehydration
  • Potential vitamin and mineral deficiencies
  • Hyperemesis gravidarum is the most common cause of hospitalization during early pregnancy and the second most common reason for hospitalization (behind pre-term labor) after the first trimester of pregnancy.
  • Bonjesta® has not been studied and is not indicated in women with hyperemesis gravidarum.

NVP is a common condition, occurring in up to 85% of women.

95% of these women may experience symptoms that last well beyond the morning.


Clinical course7,8

Percentage Patients
  • Onset of symptoms: as early as 4–6 weeks
  • Peaks ~10 weeks
  • Generally subsides by 14–16 weeks
  • For ~10% of women, symptoms persist throughout pregnancy

Pathophysiology9,10

  • The pathogenesis of NVP remains unclear and there is no consensus on its etiology
  • Various theories have been proposed, including:
    • Hormonal stimulus
    • Evolutionary adaptation (protecting the woman and her fetus from potentially dangerous foods)
    • Psychological predisposition
  • Appears to be a multifactorial disorder:
    • Family or personal history of NVP (genetic predisposition)
    • Increased placental mass
    • Level of reproductive hormones (estrogen)
    • Peak in human chorionic gonadotropin (hCG)
    • H. pylori infection (for hyperemesis gravidarum)
    • History of motion sickness or migraines

The timing of peak NVP symptoms correlates closely with hCG levels:11,12

Timing peak NVP

Impact of NVP

Physiological impact8, 13
NVP may result in varying degrees of the following physiological effects on patients:

  • Poor nutrition or malnutrition
  • Poor sleep quality
  • Dehydration or electrolyte imbalance
  • Mild to severe NVP affects patients’ ability to take or keep down prenatal multivitamins
    • This increases the baby’s risk of folic acid deficiency-related malformations, such as neural tube defects
  • Mild to severe NVP can impact patients’ ability to gain weight

A prospective study of 160 women reported that the severity of nausea was comparable to that induced by chemotherapy8.

Societal impact and humanistic burden 2,3

  • 55% of women suffering from NVP report feeling frustrated, helpless, resentful and depressed
  • An estimated 30–40% of pregnant women are unable to fully participate in many family and social functions, as well as in household activities due to their NVP

Economic burden4-6
Hospitalizations:

  • 285,354 emergency department visits in the U.S. in 2014 due to NVP
  • 20,000 hospital admissions
    • Average length of stay: 3 days
    • Mean cost exceeding $4,000
  • Time lost from paid employment
    • Average of 14 days lost from work per employed women
    • Restricted activity at work and impaired job performance
  • Estimated total economic burden of NVP in 2012 in the US: $1,778,473,782
    • $1,827 Average cost to manage care for one woman with NVP
    • Costs increase with increasing severity of NVP

References

  1. Whitehead SA et al. J Obstet Gynaecol.1992;12:364-369
  2. Miller F. Am J Obstet Gynecol. 2002;186:S182-3.
  3. Mazzotta P et al. J Psychosom Obstet Gynaecol. 2001;22:7-12.
  4. Agency for Healthcare Research and Quality. Healthcare Cost and Utilization Project (HCUP). Rockville, MD.2014.
  5. Attard CL et al. Am J Obstet Gynecol. 2002;186:S220-7
  6. Piwko C et al. J Popul Ther Clin Pharmacol. 2013;20:e149-60.
  7. Vellacott ID et al. Int J Gynaecol Obstet. 1988;27(1):57-62.
  8. Lacroix R et al. Am J Obstet Gynecol. 2000;182:931-937.
  9. Bustos M et al. Auton Neurosci. 2017;202:62-72.
  10. Niebyl JR. N Eng J Med. 2010;363(16):1544-1550.
  11. Braunstein GD et al. J Clin Endocrinol Metab. 1976;42(6):1123-1126.
  12. Gadsby R et al. Br J Gen Pract. 1993;43:245-248.
  13. Heitmann K et al. BMC Pregnancy Childbirth. 2017;17:75.

Indication and important safety information

INDICATION

Bonjesta® is a fixed-dose combination drug product of 20 mg doxylamine succinate, an antihistamine, and 20 mg pyridoxine hydrochloride, a vitamin B6 analog, indicated for the treatment of nausea and vomiting of pregnancy in women who do not respond to conservative management.

LIMITATIONS OF USE

Bonjesta® has not been studied in women with hyperemesis gravidarum.

IMPORTANT SAFETY INFORMATION

Contraindications: Bonjesta® is contraindicated in women with any of the following conditions:

  • Known hypersensitivity to doxylamine succinate, other ethanolamine derivative antihistamines, pyridoxine hydrochloride or any inactive ingredient in the formulation;
  • Monoamine oxidase (MAO) inhibitors intensify and prolong the adverse central nervous system effects of Bonjesta®.

Warnings and Precautions:

  • Somnolence: Bonjesta® may cause somnolence due to the anticholinergic properties of doxylamine succinate, an antihistamine. Women should avoid engaging in activities requiring complete mental alertness, such as driving or operating heavy machinery, while using Bonjesta® until cleared to do so by their healthcare provider.
  • Central nervous system (CNS) depressants: Use of Bonjesta® is not recommended if a woman is concurrently using CNS depressants, such as alcohol or sedating medications, including other antihistamines (present in some cough and cold medications), opiates, and sleep aids. The combination of Bonjesta® and CNS depressants could result in severe drowsiness leading to falls or other accidents.
  • Concomitant Medical Conditions: Use Bonjesta® with caution in women with (1) asthma, (2) increased intraocular pressure, (3) narrow angle glaucoma, (4) a stenosing peptic ulcer, (5) pyloroduodenal obstruction, or (6) bladder-neck obstruction.
  • Interference with Urine Screen for Methadone, Opiates and Phencyclidine Phosphate (PCP): There have been reports of false positive urine screening tests for methadone, opiates, and PCP with doxylamine succinate/pyridoxine hydrochloride use. Women should be informed that use of Bonjesta® may result in false positive urine drug screening for methadone, opiates and PCP.

Adverse Reactions: The most common adverse reaction (≥5 percent and exceeding the rate in placebo) with combination 10 mg doxylamine succinate and 10 mg pyridoxine hydrochloride tablets is somnolence.

Drug-Food Interactions: A food-effect trial demonstrated that the delay in the onset of action of Bonjesta® may be further delayed, and a reduction in absorption may occur when tablets are taken with food. Therefore, Bonjesta® should be taken on an empty stomach with a glass of water.

Use in Specific Populations:

  • Pregnancy: Bonjesta® is intended for use in pregnant women. 
  • Lactation: Women should not breastfeed while using Bonjesta® because the antihistamine component (doxylamine succinate) in Bonjesta® can pass into breast milk. Excitement, irritability, and sedation have been reported in nursing infants presumably exposed to doxylamine succinate through breast milk. Infants with apnea or other respiratory syndromes may be particularly vulnerable to the sedative effects of Bonjesta® resulting in worsening of their apnea or respiratory conditions.
  • Pediatric Use: The safety and effectiveness of Bonjesta® in children under 18 years of age have not been established. Fatalities have been reported from doxylamine overdose in children. Children appear to be at a high risk for cardiorespiratory arrest.

Overdosage: Bonjesta® is an extended-release formulation; therefore, signs and symptoms of intoxication may not be apparent immediately. Signs and symptoms of overdose may include restlessness, dryness of mouth, dilated pupils, sleepiness, vertigo, mental confusion, and tachycardia. At toxic doses, doxylamine exhibits anticholinergic effects, including seizures, rhabdomyolysis, acute renal failure and death. If treatment is needed, it consists of gastric lavage or activated charcoal, whole bowel irrigation and symptomatic treatment. If you suspect an overdose or seek additional information about overdose treatment, call a poison control center at 1-800-222-1222.

To report suspected adverse reactions, contact Duchesnay Inc. at 1-855-722-7734 or medicalinfo@duchesnayusa.com or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.