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Common Medications

Although no drug is generally encouraged and few are considered completely safe during pregnancy, the risk of these medications must be balanced against the potential complications associated with prolonged starvation and dehydration. These both present risks for both mother and child. Focusing on treating the individual symptoms and easing the incredible misery of HG are top priorities.

To look up a drug for more information about its use or safety:

Important Note: The class of drugs known as serotonin antognists (Zofran/ondansetron, Anzemet/dolasetron, Kytril/granisetron) are dose-dependent drugs. Both benefits and side-effects increase with the dose. They are similar, yet do not have the exact same results in all women. Please note that some women with nausea/vomiting improve greatly on the higher doses, thus avoiding IV's and expensive nutritional therapies. Gradual reduction in dose, then frequency is critical to avoid relapse. It's important to intervene early with effective medications in women who show a clinical course that may lead to hyperemesis, or in women who have a history of HG.

Remember: Individual responses to medications vary greatly. There is no single isolated cause or "cure" for the nausea and vomiting in all women. Treatment should focus on the primary triggers of nausea/vomiting such as motion sensitivity. If there are numerous triggers, medications that directly target the vomiting center in the brain (serotonin antagonists) are likely most effective. If a woman is vomiting constantly, oral dosing of medications may not be effective. A few doses IV followed by a trial of oral medication is important. Women often report a medication is not working orally, but will if given IV or subcutaneously.

Mother's Note: If you have pre-existing medical conditions (diabetes, heart disease, etc.), a history of medication reactions, or are a smoker, please inform your physician before taking medications.

SEROTONIN ANTAGONISTS

Highly selective antagonist of 5-HT3 receptors in the vagus, CTZ (chemotrigger zone) and gut. Mostly Class B drugs.

Possible side-effects: Headache, mild liver function abnormalities, constipation*, diarrhea
* Proactive, daily bowel management is very important. For information on managing these symptoms, download this article (1.34 Mb PDF).

Often effective in mothers who have multiple triggers (smell, motion, etc.), a history of hormone sensitivity, and/or moderate to severe vomiting. If a woman has a history of HG that responded to serotonin antagonists, it should be used early and as a first line drug to minimize severity.

IMPORTANT: Effects are dose dependent. Expensive intravenous therapies and termination may sometimes be avoided if higher doses are used. Best taken on a strict schedule and weaned very slowly when asymptomatic for two weeks. It is not uncommon for women to require this medication until delivery. Different brands may have different effects and dissolvability.


Drug Name Min/Max Dosage Notes Research Studies
Zofran, Zuplenz
(Ondansetron)
4 to 8 mg every 6 hours

Given via SQ pump, oral tablet, NEW Researchquick dissolve film, or IV.

Some women require dosing throughout pregnancy to avoid relapse or stabilize symptoms.

Patient assistance program
1-888-825-5249

Zofran is available as a generic.

Available in oral dissolvable tablets or film, and liquid. Suppository available outside US.

Widely available around the world.

Monitor closely for constipation. Proactively treat with a daily regimen of stool softeners and laxatives as needed.

Some mothers find the generic oral dissolvable tablets do not dissolve as well.

Antiemetic medications in pregnancy: a prospective investigation of obstetric and neurobehavioral outcomes.

Ondansetron in pregnancy and risk of adverse fetal outcomes. (2013)

Secular Trends in the Treatment of Hyperemesis Gravidarum. American Journal of Perinatology, (2007)

The safety of ondansetron for nausea and vomiting of pregnancy: a prospective comparative study.

Pharmacokinetics of Three Formulations of Ondansetron

More research articles on PubMed.

 

Kytril, Sancuso
(Granisetron)
1 mg every 12 hours (IV or orally)

Allows twice a day dosing

Also available in transdermal patch form as Sancuso.NEW Research
Very expensive. Patient assistance program available.

Kytril is now available as a generic.NEW Research

Research articles on PubMed.
Mirtazapine (Remergil, Remeron)   May interact with sedatives, antihistamines, and tricyclic antidepressants.

Has both anti-vomiting and anti-depressant effects.

Rohde A, et al.
Mirtazapine (Remergil) for treatment resistant hyperemesis gravidarum: rescue of a twin pregnancy.

Mirtazapine use in resistant hyperemesis gravidarum: report of three cases and review of the literature.

More research articles on PubMed.

Aloxi
(palonosetron)
Dose not established in HG. 0.25 mg IV given for chemo. Half-life: 40 hr. & only given once in 5 days.
Reimbursement Support Network.
Research articles on PubMed.
Anzemet
(Dolasetron)
Dose not established in HG. 50-150 mg orally daily is reported. Slightly less expensive than similar drugs.
Patient assistance program available.
Research articles on PubMed.

SUBSTANCE P/NEUROKININ 1 (NK1) RECEPTOR ANTAGONIST

This is a NEW class of drugs so minimal safety data is available. No studies for it's use in pregnancy are available. We caution the use of this medication class at this point.

(See below for FDA-Assigned Pregnancy Categories)

Research Links:

Drug Name Min/Max Dosage Notes Research Studies
EmendNEW Research (Aprepitant)

80-125 mg per day is dose for chemotherapy

Oral and IV formulations available.

Typical protocol for chemo patients includes combining with a serotonin antagonists and steroids for best relief. None for HG yet.

CORTICOSTEROIDS

Cortisone/Corticosteroids - Not recommended until after 8-10 weeks
Some possible side-effects include blood sugar instability, weight loss, nausea and vomiting.

Steroids are used for refractory hyperemesis gravidarum; however, there is some concern over fetal brain development with prolonged dosing at high levels and use during the first trimester. No studies have proven a link and the HER Foundation has not heard such reports from women with HG.

Complications including reduced birth weight, increased risk of preeclampsia, and increased risk of oral and lip clefts have been reported when corticosteroids were administered during early pregnancy. However, the Collaborative Perinatal Project monitored 50,282 mother-child pairs, 34 of which had first-trimester exposure to cortisone. No evidence of a relationship to congenital defects was observed. If these drugs are used during pregnancy, the potential risks should be discussed. Babies born to women receiving large doses of corticosteroids during pregnancy should be monitored for signs of adrenal insufficiency and appropriate therapy initiated, if necessary.

The typical treatment is a steroid burst with a rapid taper similar to what is used in acute asthma attacks. [Most studies of asthma patients using steroids show no adverse fetal effects.]

Women with hypothyroidism may have an exaggerated response to corticosteroids; thus any steroid should be used with caution in these mothers. Also, women with Type 1 Diabetes may require as much as a 40% increase in their insulin when high dose steroids are started.

Drug Classification:
Methylprednisolone is classified as pregnancy category C. Prednisone is classified as category B but cortisone is classified as pregnancy category D. This probably reflects the fact that cortisone is more commonly used during pregnancy than is prednisone and therefore, more reports of problems have been associated with cortisone than prednisone, not that it is a more potent teratogen. Corticosteroids cross the placenta. [From: Clinical Pharmacology 2000]

(See below for FDA-Assigned Pregnancy Categories)

Research Links:

Drug Name Min/Max Dosage Notes Research Studies
Medrol or Solu-Medrol (Methylprednisolone or Prednisone) Typical oral dosage is 48 mg per day for three to five days, followed by slow tapering over two to three weeks.

Limit to one month of therapy if possible.

See Goodwin article on right for more on dosing.
Consideration should be given to using with serotonin antagonists and/or during weaning from steroids to prevent relapse. T. Murphy Goodwin, MD
Corticosteroid therapy in hyperemesis gravidarum


Termination is not the treatment of choice for severe hyperemesis gravidarum: Successful management using prednisolone

ANTIHISTAMINES

Common side-effects: Drowsiness, dry mouth, blurred vision, constipation, urinary retention, restlessness, insomnia, sedation, upset stomach, nervousness, headache.

Mostly Class B drugs

Effective for MILD cases of nausea and vomiting during pregnancy or as adjunctive therapy with more potent medications. Women mostly sensitive to motion may benefit most. Antihistamines with sedative effects can be helpful for sleep.

Research Links:

Drug Name Min/Max Dosage Notes Research Studies
Bonine, Antivert, Marezine
(Meclizine/Buclizine/Cyclizine)
Follow directions on the label. See Medline Plus  
Dramamine
(Dimenhydrinate)
50-100 mg every 4-6 hours Used for motion sickness.  
Doxylamine
(Unisom)
25 mg orally at bedtime,
1/2 tablet every 6 hours as needed
Component of Bendectin/Diclectin.

Often taken with vitamin B6.
 
Diclectin, DiclegisNEW Research
(doxylamine plus pyridoxine)
Average dose is 1 tablet in morning, one in afternoon and two at night.

May be given in higher doses up to 12 tablets daily - see research links on right.
Differs from Unisom/B6 combo because it is a delayed release formula.

The return to the USA of doxylamine-pyridoxine delayed release combination (Diclegis®) for morning sickness.

Research articles on PubMed.

Benadryl
(Diphenhydramine or Gravol)
25 mg IVP/orally every 4–6 hours      
Tigan
(Trimethobenzamide)
25 mg orally every 6-8 hours
200 mg IM every 6-8 hours
   
Vistaril, Atarax
(Hydroxyzine)
25 mg orally every 6 hours Syrup available
Helpful for insomnia
 

ANTIDOPAMINERGICS: PHENOTHIAZINES

Common side-effects: Drowsiness, hypotension, dry mouth, constipation, urinary retention, rash, extrapyramidal symptoms (EPS), restlessness, confusion, fatigue.

Mostly Class C drugs.

May be helpful in mild and moderate cases or used in conjunction with other medications. Consider co-administration of antihistamines to minimize side-effects.

(Extrapyramidal symptoms include: involuntary movements, tremors and rigidity, body restlessness, muscle contractions and changes in breathing and heart rate.)

Drug Name Min/Max Dosage Notes Research Studies
Compazine, Stemetil
(Prochlorperazine)
5–10 mg orally, IM, or IV every 6–8 hours

Rectal 25 mg every 6–8 hours
Risk of EPS additive with metoclopramide (Reglan). Treat EPS symptoms with Benadryl (can prophylax with Benadryl). Phenothiazines lower seizure threshold.  
Phenergan
(Promethazine)
12.5–25 mg IVP/orally, IM/PR every 4-6 hours NEW Research Warning: IV or injected doses can cause tissue damage. More info available on fda.gov.

Side-effects common and may limit use.
 
Thorazine
(Chlorpromazine)
12.5–25 orally/IM every 4–6 hours
Rectal 50–100 mg every 6–8 hours
May increase risk of fetal malformations.

May cause muscle spasms in neck/face and/or difficulty with speech.
 
Haldol
(Haloperidol)
1–2 mg orally/IM every 8 hours Extrapyramidal symptoms (EPS) more common. May cause constipation.  

ANTIREFLUX MEDICATIONS

Common side-effects: Headache, dizziness, difficulty sleeping, constipation, diarrhea.

This class of drugs is helpful both for reflux and for prevention of gastric irritation which worsens nausea. They should be considered whenever a woman is vomiting frequently and/or cannot eat and drink sufficiently. Studies suggest they are safe during pregnancy. Mostly Class B drugs. [This list is not inclusive of all medications available.]

Research Links:

Drug Name Min/Max Dosage Notes Research Studies
Zantac
(Ranitidine)
50 mg IV every 8 hours or 150 mg orally daily or twice a day    
Tagamet
(Cimetidine)
  Not recommended during pregnancy due to antiandrogenic effects in humans. Illinois Teratogen Information Service
Gastroesophogeal Reflux (GERD) Medications in Pregnancy
Pepcid
(Famotidine)
20 mg IVP/orally every 12 hours    
Prevacid
(Lansoprazole)
30-60 mg/day   Bruce T. Vanderhoff, M.D, et. al. (AAFP) July 15, 2002
Proton Pump Inhibitors: An Update.

Nikfar S, et. al.
Use of proton pump inhibitors during pregnancy and rates of major malformations: a meta-analysis.

PROKINETIC AGENTS

Reglan blocks dopamine receptors in the CTZ (chemoreceptor trigger zone) and increases the CTZ threshold & decreases the sensitivity of visceral nerves that transmit afferent impulses from the GI tract to the vomiting center.

May be helpful in women who typically vomit after eating/drinking. Their main symptoms often are GI specific (v. motion sickness or sensitivity to light/sound) and these women may or may not respond to other medications such as Zofran. These drugs are sometimes used in conjunction with meds such as Zofran. Use with antihistamines to minimize side-effects. Side-effects are very common and can be severe, especially when given quickly through an IV.

Common side-effects: Drowsiness, dizziness, abdominal pain, diarrhea, restlessness, EPS, depression

(Extrapyramidal symptoms include: involuntary movements, tremors and rigidity, body restlessness, muscle contractions and changes in breathing and heart rate.)

Drug Name Min/Max Dosage Notes Research Studies
Reglan or Maxeran
(Metoclopramide)
10–20 mg IV/orally every 6 hours

May be given orally, SQ pump, IV
NEW ResearchFDA recommends this drug be taken for up to 12 weeks. Risks of serious side-effects increase thereafter.

Additive CNS side effects when used with phenothiazines.

Side-effects common and may limit use.

Class B drug.
L. Buttino Jr., et. al.
Home subcutaneous metoclopramide therapy for hyperemesis gravidarum.

Mati Berkovitch
The safety of metoclopramide during pregnancy

L. Buttino Jr., et. al.
Home Infusion of Reglan
Propulsid
(Cisapride)
10 mg orally every 6 hours, before meals and at bedtime (maximum dose 20 mg every 6 hours) No CNS side effects. Limited availability in US.  

ANTICHOLINERGICS/ANTISPASMODICS

Common side-effects: Confusion; dizziness, lightheadedness (continuing) or fainting; eye pain; skin rash or hives.

Should not be used in treatment of hyperemesis gravidarum. These agents slow gastric emptying and prolong GI transit time. Since slowed gastric emptying is part of the etiology of HG, these agents are inappropriate.

Drug Name Min/Max Dosage Notes Research Studies
Scopolamine, Belladonna
(Hyoscine Hydrobromide)
     

MISCELLANEOUS

Drug Name Min/Max Dosage Notes Research Studies
Pyridoxine
(Vitamin B6, Hexa-Betalin)
20-75 mg/day Paresthesias may occur if taken in high doses. Doses up to 150 mg are being used.

Note: reactions to vitamins are uncommon but possible. See article from Kuwata Y., et al.
Kuwata Y., et. al.
Serious adverse drug reaction in a woman with hyperemesis gravidarum after first exposure to vitamin B complex containing vitamins B1, B6 and B12.
Reprivex 3 tablets daily Each tablet contains 25mg of Vitamin B6 (as Pyridoxine Hydrochloride) and 100mg of Ginger Root PE 5% Gingerois (zingiber Officinalis) This medication was introduced in 2006. A prescription is NOT required for this medication.
Ginger 250 mg orally every 6 hours or a glass of ginger ale as needed May be helpful in mild cases.  
Emetrol
(Fructose, Dextrose, and Phosphoric Acid)
One or two tablespoonfuls upon arising and every three hours as needed. May be helpful in mild cases.  
Marijuana
(Cannabis)
or the pharmaceutical extract: Marinol
(Dronabinol)
Dose not established for HG. Medical Marijuana is currently legal in the following states (US): Alaska, California, Washington, Oregon, Hawaii, Colorado, Arizona, Maine. Eran Kozer, et. al.
Effects of prenatal exposure to marijuana.

International Association for Cannabis as Medicine
Does cannabis/THC do harm to the fetus if it is used during pregnancy?

Washington Hemp Education Network
Cannabis Indications
Benzodiazepine Derivatives:
Valium
(Diazepam)
Dose not established for HG. Class D drug. Ditto A, Morgante G, la Marca A, De Leo V.
Evaluation of treatment of hyperemesis gravidarum using parenteral fluid with or without diazepam.
Neuroleptic:
Inapsine
(Droperidol)
Gerald G. Briggs
Briggs (LBMMC) Hyperemesis Protocol
Use with diphenhydramine to avoid side-effects.

Category C drug.
Nageotte MP, Briggs GG, Towers CV, Asrat T.
Droperidol and diphenhydramine in the management of hyperemesis gravidarum.

Gerald G. Briggs
Droperidol-diphenhydramine for hyperemesis gravidarum.


** IM = Intramuscular (injection)
** IV = Intravenous
** IVP = Intravenous push (injected into an IV)
** PR = Per rectum
** SQ = subcutaneous (injected under the skin)

FDA-Assigned Pregnancy Categories for Drugs (United States Classification)

  • Category A
    Adequate and well-controlled studies have failed to demonstrate a risk to the fetus in the first trimester of pregnancy (and there is no evidence of risk in later trimesters).
     
  • Category B
    Animal reproduction studies have failed to demonstrate a risk to the fetus and there are no adequate and well-controlled studies in pregnant women.
     
  • Category C
    Animal reproduction studies have shown an adverse effect on the fetus and there are no adequate and well-controlled studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks.
     
  • Category D
    There is positive evidence of human fetal risk based on adverse reaction data from investigational or marketing experience or studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks.
     
  • Category X
    Studies in animals or humans have demonstrated fetal abnormalities and/or there is positive evidence of human fetal risk based on adverse reaction data from investigational or marketing experience, and the risks involved in use of the drug in pregnant women clearly outweigh potential benefits.

Excerpted from Drug Information for the Health Care Professional, USP-DI, Volume 1A, 11th ed., 1991.

Updated on: Jan. 31, 2014

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