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Antiemetics Drugs to Treat Nausea and Vomiting in Pregnancy

Nausea and vomiting are common complaints in the early trimester of pregnancy. However, when these complaints become burdensome (hyperemesis gravidarum), doctors need to determine which antiemetics are safe to use to overcome them.

Nausea and vomiting usually occur at 6-12 weeks' gestation. These complaints can last up to approximately the 20th week of pregnancy. Complaints of nausea and vomiting in pregnancy are classified as mild to moderate, in the form of nausea only (mild) or nausea accompanied by vomiting without dehydration (moderate). However, nausea and vomiting can be severe and accompanied by dehydration (hyperemesis gravidarum), even requires treatment in the hospital.

Antiemetics Drugs to Treat Nausea and Vomiting in Pregnancy



The initial management of patients with nausea and vomiting in pregnancy is modifying the diet and avoiding triggers. Small, frequent meals should be applied to reduce nausea in pregnancy.

Small, frequent meals are eating food every one or two hours in small portions to avoid a stomach that is too empty or too full, which can cause nausea. What foods should not contain lots of carbohydrates but contain lots of protein.

Avoid foods that can trigger nausea, such as foods that are too flavorful, too oily, and too spicy. Beverages containing mint or ginger can help relieve nausea but avoid coffee.

First-line antiemetics
Along with modifying the diet, avoiding triggers is also the key to reducing nausea and vomiting in pregnancy. If complaints of nausea in pregnancy do not subside by modifying the diet and or avoiding triggers, that is the right time when antiemetic drugs can be administrated.

The first-line antiemetics to treat nausea and vomiting in pregnancy are ginger and pyridoxine (vitamin B6) supplements or a combination of doxylamine-pyridoxine. In several other countries, the first-line antiemetics commonly used are the combination of doxylamine-pyridoxine. The recommended dose of oral pyridoxine is 10 to 25 mg every 6 to 8 hours with the maximum dose for pregnant women which is 200mg / day.

Second-line antiemetics
Second-line drugs to treat vomit in pregnant are antihistamines (H1 antagonists). Consider the safety reasons for the fetus; there are three recommended drugs, namely diphenhydramine, meclizine, and dimenhydrinate. All three of these drugs have the B safety category in pregnancy (based on the US FDA Pregnancy Category).

The oral diphenhydramine dose is 25 to 50 mg every 4 to 6 hours as needed. Difenhidramin can also be given IV at a dose of 10 to 50 mg every 4 to 6 hours as needed. The oral dimenhydrinate dosage is 25 to 50 mg every 4 to 6 hours as needed. Side effects of this class of drugs include sedation, dry mouth, and constipation.

Third-line antiemetics
Third-line antiemetics drugs are dopamine antagonists. The recommended drugs of this class are metoclopramide, phenothiazines (promethazine and prochlorperazine), and butyrophenone (droperidol).

The safety categories in pregnancy for metoclopramide, promethazine, and droperidol are B, C, and C. Consequently, based on safety in pregnancy, the most commonly used drug from this group is metoclopramide. The dose of metoclopramide used is 10 mg, can be given orally, IV, or IM (ideally given 30 minutes before eating and when going to sleep) every 6 to 8 hours per day.

Promethazine is given if there are no other alternative medicines and more benefits compared to the risk to the fetus. The dose of promethazine is 12.5 to 25 mg, can be given orally, rectally, or IM every 4 hours. Oral or rectal administration is recommended. Contraindications of promethazine administration are IV, intraarterial, and subcutaneous because it can cause gangrene in tissue extremities and necrosis.

Fourth-line antiemetics
The fourth-line antiemetic drug is the serotonin antagonist. These drugs that can be used to treat nausea and vomiting in pregnancy are ondansetron, granisetron, and dolasetron.

Ondansetron is the most commonly used drug in this group. Ondansetron has a safety category B in pregnancy. The dose of ondansetron used is 4 mg, can be given orally every 8 hours as needed, or can also be given IV by bolus injection every 8 hours as needed. The dose can be increased if required and is limited to 16 mg/dose (per one-time administration).

Headaches, fatigue, constipation, and drowsiness are the most common side effects. Ondansetron can also cause prolongation of QT intervals, especially in patients with risk factors for arrhythmias (history of prolongation of previous QT intervals, hypokalaemia or hypomagnesemia, heart failure, concomitant administration of drugs that cause prolongation of QT intervals, and use of multiple intravenous doses of ondansetron). ECG and electrolyte monitoring are recommended for these patients

Additional Therapy
An observational study showed that administration gastric acid reduction medications (eg, antacids, H2 blockers, and PPI) combined with antiemesis therapy significantly reduce symptoms within 3 to 4 days after the start of therapy.

However, among all groups, the safest and most recommended acid-reducing medication for pregnant women is the H2 blocker group, ranitidine, which has a safety category B in pregnancy, with an oral dose of 150 mg twice daily.


References
1. J.A. Smith, J.S. Refuerzo, dan S.M. Ramin, Treatment and Outcome of Nausea and Vomiting of Pregnancy,, 2017.
2. Royal College of Obstetricians and Gynaecologists. Green-top Guideline no.69: The Management of Nausea and Vomiting of Pregnancy and Hyperemesis Gravidarum. London: RCOG Press; 2016. https://www.rcog.org.uk/globalassets/documents/guidelines/green-top-guidelines/gtg69-hyperemesis.pdf
3. A. Grayson, Metoclopramide or Promethazine for Vomiting, Pregnant Women,, 2008.



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