Individual responses to medications vary greatly due to many factors including genetics and hydration.
Target the triggers of nausea/vomiting such as motion sensitivity while ensuring adequate hydration and metabolic balance.
If a woman is vomiting constantly, oral dosing of medications will likely be ineffective and alternates such as transdermal (patch/cream), subcutaneous (subQ), or intravenous (IV) routes should be considered along with hydration.
Intramuscular injections (shots) should be avoided during HG, especially in those with loss of muscle mass.
Top 5 Medication Strategies
Serotonin Antagonists
Highly selective antagonist of 5-HT3 receptors in the vagus, CTZ (chemotrigger zone) and gut. Mostly Class B drugs. Found to improve symptoms in > 80% of women. Use cautiously with metoclopramide (Reglan), and avoid use with other serotonin antagonists (e.g. SSRI’s, antidepressants) to prevent serotonin syndrome.
Zofran (ondansetron) & Kytril Tips:
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 these medications.
More common side-effects: Headache, mild/moderate (reversible) liver function test abnormalities, constipation*, diarrhea
* Proactive, daily bowel management is very important.
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 considered as a first line drug to minimize symptom severity. Dosing throughout pregnancy may prevent relapse or stabilize symptoms.
IMPORTANT: Best taken on a strict schedule and weaned very slowly.
| Drug Name | Min/Max Dosage | Notes | Research Studies |
|---|---|---|---|
| Zofran, Zuplenz (Ondansetron) (** Update on Zofran safety) | 4 to 8 mg every 6 hours (or 2 to 4 mg every 3 hours) Given via SQ pump, oral tablet, quick dissolve film or tablet (ODT), or IV. Suppository available outside US. Can be compounded into a suppository or cream. Quick dissolving tablets are sometimes prescribed vaginally. | Widely available around the world. Proactively treat with a daily regimen of stool softeners plus periodic laxatives as needed. Some report generic oral dissolvable tablets do not dissolve as well. | Ondansetron in pregnancy and risk of adverse fetal outcomes in the United States. (2016) Ondansetron compared with doxylamine and pyridoxine (Diclegis/Diclectin) for treatment of nausea in pregnancy. (2014) Antiemetic medications in pregnancy: a prospective investigation of obstetric and neurobehavioral outcomes. (2014) Ondansetron in pregnancy and risk of adverse fetal outcomes. (2013) Secular Trends in the Treatment of Hyperemesis Gravidarum. (2007) Pharmacokinetics of Three Formulations of Ondansetron. (2000) More research articles on PubMed. |
| Kytril, Sancuso (Granisetron) | 1 mg every 12 hours (IV or orally) Twice a day dosing. Available in transdermal patch form as Sancuso. | Kytril is available as a generic. *** READ insert for for application of patch carefully. Avoid heat/sun on patch/application site during use then for 10 additional days. Apply to arm. May need additional single oral/IV dose of granisetron on days 1-2 until patch is full strength. Some side-effects may be less with transdermal. Patient Assistance info for patch Prescribing providers might be able to order a trial patch for free. | Observational Case Series Evaluation of the Granisetron Transdermal Patch System (Sancuso) for the Management of Nausea/Vomiting of Pregnancy. (2017) Comparison of Efficacy of Granisetron and Promethazine [Phenergan] in Control of Hyperemesis Gravidarum. (2016) Pharmacodynamics of transdermal granisetron in women with nausea and vomiting of pregnancy. (2016) Research articles on PubMed. |
| Mirtazapine (Remergil, Remeron) | Dose not established for HG. 15-45 mg/day in a single dose or 7.5-15 mg up to 3x per day used for other conditions. | May interact with sedatives, antihistamines, and tricyclic antidepressants. Do not use with other serotonin-antagonistic medications. Has both anti-vomiting and anti-depressant effects. | Is Mirtazapine an Effective Treatment for Nausea and Vomiting of Pregnancy? (2017) Treatment options for hyperemesis gravidarum. (2017) Mirtazapine use in resistant hyperemesis gravidarum: report of three cases and review of the literature. (2005) More research articles on PubMed. |
| EXPERIMENTAL: Aloxi (Palonosetron) | No trials for HG yet conducted. 0.25 mg IV given for chemo. | None for HG yet. Research on PubMed. | |
| Anzemet (Dolasetron) | Dose not established in HG. 50-150 mg orally daily is reported. | Research articles on PubMed. |
Antihistamines
Common side-effects: Drowsiness, dry mouth, blurred vision, constipation, urinary retention, restlessness, insomnia, sedation, upset stomach, nervousness, and headache.
Mostly Class A or B drugs
Effective for MILD cases of nausea and vomiting during pregnancy or as adjunctive therapy. 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) | Typical dose: 25-50 mg every 6 hours. | ||
| 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 | Component of Diclegis/Diclectin. Often taken with vitamin B6 (pyridoxine). | |
| Diclectin, Diclegis (doxylamine plus pyridoxine) | Average dose is 1 tablet in morning, one in afternoon and two at night. | Differs from Unisom/B6 combo because it is a delayed release formula. | Ondansetron compared with doxylamine and pyridoxine (Diclegis/Diclectin) for treatment of nausea in pregnancy. (2014) Fox & NPR Reports. (2017) More Research on PubMed. |
| Benadryl (Diphenhydramine or Gravol) | 25 mg IV/orally every 4–6 hours | ||
| Tigan (Trimethobenzamide) | 300 mg orally every 6-8 hours | IM (intramuscular injections not recommended during HG) | |
| Vistaril, Atarax (Hydroxyzine) | 25 mg orally every 6 hours Pill or syrup | Helpful for insomnia and reducing Rx side-effects such as restlessness and anxiety. |
Antidopaminergics: Phenothiazines
Common side-effects: Drowsiness, hypotension, dry mouth, constipation, urinary retention, rash, extrapyramidal symptoms (EPS)*, restlessness, confusion, fatigue. Phenothiazines lower seizure threshold.
*Call your doctor immediately for involuntary movements, tremors and rigidity, restlessness, muscle contractions and changes in breathing and heart rate.
Mostly Class C drugs.
May be helpful in mild and moderate cases or used in conjunction with other medications.
Co-administer antihistamines to minimize side-effects.
| Drug Name | Min/Max Dosage> | Notes | Research Studies |
|---|---|---|---|
| Compazine, Stemetil (Prochlorperazine) | 5–10 mg orally, IM, or IV every 6–8 hours 25 mg every 6–8 hours rectal | Risk of EPS increased with metoclopramide (Reglan). | Research articles on PubMed. |
| Phenergan (Promethazine) | 12.5–25 mg IV/orally, PR every 4-6 hours *IV dose contains sulfite *Do not inject or use subcutaneously & use cautiously IV. | Warning: IV or injected doses can cause tissue damage. (See FDA Warning) GIVE IV dose SLOWLY to avoid contractions. Side-effects of anxiety, sedation, and restlessness common and may limit use. | Promethazine compared with metoclopramide for hyperemesis gravidarum: a randomized controlled trial. (2010) Research articles on PubMed. |
| Thorazine (Chlorpromazine) | Oral/IM 12.5–25mg 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. | Research articles on PubMed. |
| Haldol (Haloperidol) | 1–2 mg orally/IM every 8 hours | Extrapyramidal symptoms (EPS) more common. May cause constipation. | Research articles on PubMed. |
Corticosteroids
Cortisone/Corticosteroids - Not recommended before 9 weeks of pregnancy.
Drug Classification:
Methylprednisolone: C Prednisone: B
(See below for FDA-Assigned Pregnancy Categories.)
| 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. Continued use in small doses is sometimes beneficial. See article for more on dosing. | Consider use with serotonin antagonists and/or during weaning from steroids to prevent relapse. | Management of hyperemesis gravidarum: the importance of weight loss as a criterion for steroid therapy. (2002) Termination is not the treatment of choice for severe hyperemesis gravidarum: Successful management using prednisolone. (2009) The efficacy low dose of prednisolone in the treatment of hyperemesis gravidarum. (2004) More Research on PubMed. |
Antireflux Medications
| Drug Name | Min/Max Dosage | Notes | Research Studies |
|---|---|---|---|
| H2 Histamine Blocker (Acid Reducers) Pepcid (Famotidine) | 20 mg IVP/orally every 12 hours | The safety of H(2)-blockers use during pregnancy. (2012) |
|
| Tagamet (Cimetidine) | Not recommended during pregnancy due to anti-androgenic effects in humans. | ||
| Proton Pump Inhibitors (PPI) Prevacid (Lansoprazole) Nexium (Esomeprazole) Prilosec (Omeprazole) | 30-60 mg/day Omeprazole ODT available 20-40 mg/day 20 mg/day | Turns off acid pump in stomach. Stronger than above H2 Blocking meds. | The safety of fetal exposure to proton-pump inhibitors during pregnancy. (2012) Are proton pump inhibitors safe during pregnancy and lactation? Evidence to date. (2012) |
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.
Common side-effects:
Drowsiness, dizziness, abdominal pain, diarrhea, restlessness, EPS*, depression
(*Report extrapyramidal symptoms immediately: 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; ODT available May be given orally, SQ pump, IV (SLOWLY) | FDA recommends this drug only be taken for up to 12 weeks. Risks of serious side-effects increase thereafter. Increased CNS side effects when used with phenothiazines. Side-effects common and may limit use. Use with antihistamines. Class B drug. | Ondansetron compared with metoclopramide for hyperemesis gravidarum: a randomized controlled trial. (2014) Ondansetrone or metoclopromide? Which is more effective in severe nausea and vomiting of pregnancy? (2013) Ondansetron compared with metoclopramide for hyperemesis gravidarum: a randomized controlled trial. (2010) 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.
| Drug Name | Min/Max Dosage | Notes | Research Studies |
|---|---|---|---|
| Scopolamine, Belladonna (Hyoscine Hydrobromide) | 0.3 to 0.65 mg administered IV, intramuscularly or subcutaneously every 6 to 8 hours as needed 1.5 mg transdermal disc behind the ear every 3 days | Effectiveness studies are lacking. Optimal management of nausea and vomiting of pregnancy. (2012) |
Miscellaneous & New Medications
| Drug Name | Min/Max Dosage | Notes | Research Studies |
|---|---|---|---|
| Catapres-TTS (Clonidine) | New medication being used for HG. | Transdermal clonidine in the treatment of severe hyperemesis. A pilot randomised control trial: CLONEMESI. (2014) Research articles on PubMed. |
|
| Gabapentin (Neurontin) | Dose not established for HG. | May be compounded into a suppository or cream. In trials for use in HG. Considered in patients who have not responded to other medication categories. May cause neonatal withdrawal. | Effect of gabapentin on hyperemesis gravidarum: a double-blind, randomized controlled trial. (2020) Potential maternal symptomatic benefit of gabapentin and review of its safety in pregnancy. (2014) A case of treatment refractory hyperemesis gravidarum in a patient with comorbid anxiety, treated successfully with adjunctive gabapentin. (2012) Research articles on PubMed. |
| Thiamine (Vitamin B1) | 5 mg/day minimum for normal diet. NON TOXIC. For HG: 100-500 mg BID IV. IM contraindicated due to volume and low muscle mass. All women with HG should be on at least 100 mg daily orally (ideally Lipothiamine or Benfotiamine.) If prolonged HG, continue taking during breastfeeding. Can be taken as a single supplement if prenatal vitamins are not tolerated. | Body's stores depleted in < 3 weeks. Infographic on thiamin deficiency in HG. Should be given orally before and during pregnancy as tolerated. Protective of mother's brain and heart, and baby's development. See www.hyperemesis.org/tools for Fact Sheets. | Iatrogenic wernicke encephalopathy in a patient with severe hyperemesis gravidarum. (2015) Mortality Secondary to Hyperemesis Gravidarum: A Case Report (2015) |
| Pyridoxine (Vitamin B6, Hexa-Betalin) Cobalamin, Cyanocobalamin, Hydroxocobalamin (Vitamin B12) | 20-75 mg/day Doses up to 150 mg are being used. 100 mcg/day | Paresthesias may occur if B6 is taken in high doses. Note: reactions to B vitamins are rare but possible. | |
| Reprivex Each tablet contains 25mg of Vitamin B6 (as Pyridoxine Hydrochloride) and 100mg of Ginger Root PE 5% Gingerois (Zingiber Officinalis) | 3 tablets daily | A prescription is NOT required for this medication. | |
| Ginger | 250 mg orally every 6 hours | May be helpful as adjunctive therapy. | |
| Emetrol (Fructose, Dextrose, and Phosphoric Acid) | One or two tablespoonfuls upon arising and every three hours as needed. | May be helpful as adjunctive therapy. | |
| Marijuana (Cannabis) or the pharmaceutical extract: Marinol (Dronabinol) | Dose not established for HG. | Use with caution. Potential fetal effects – see studies at right. | Cannabis and pregnancy: Maternal child health implications (2017) The effects of cannabis on embryological development. (2016) Prenatal Cannabis and Tobacco Exposure in Relation to Brain Morphology: A Prospective Neuroimaging Study in Young Children. (2016) Research on PubMed. |
| Benzodiazepine Derivatives: Valium (Diazepam) | Dose not established for HG. | Class D drug. | Use of diazepam for hyperemesis gravidarum. (2009) |
| Neuroleptic: Inapsine (Droperidol) | Gerald G. Briggs Briggs (LBMMC) Hyperemesis Protocol | Use with diphenhydramine to avoid side-effects. Category C drug. | Droperidol and diphenhydramine in the management of hyperemesis gravidarum (1996) |
** IM = Intramuscular (injection/shot)
** IV = Intravenous
** IVP = Intravenous push (injected into an IV)
** PR = Per rectum
** PR = Per vaginally
** SQ = subcutaneous (injected under the skin)
** TD = Transdermal
Substance P/Neurokinin 1 (NK1) Receptor Antagonist
This is a NEWER class of drugs that are effective for nausea and vomiting in non-pregnant patients.
NO safety data is available during pregnancy or HG.
We strongly caution the use of this medication class.
