Antiemetics and Breastfeeding

General Antinauseants

Phenothiazines are the conventional drugs used for nausea and vomiting. Two of the most commonly used phenothiazines, prochlorperazine and thiethylperazine, have no data on use during breastfeeding. Two others have a little published information. Chlorpromazine is detectable in the milk of some mothers during therapy, but milk levels appear not to correlate well with the maternal dose or serum level. Some breastfed infants have become drowsy during maternal chlorpromazine therapy. Limited information indicates that maternal doses of perphenazine up to 24 mg daily result in low levels in milk. Very limited long-term follow-up data from psychiatric usage of phenothiazines indicate no adverse developmental effects in breastfed infants when they are used alone. An advantage of the phenothiazines might be that they usually increase serum prolactin.

Antihistamines indicated for general use include dimenhydrinate, hydroxyzine, meclizine, and promethazine. Recall that dimenhydrinate is the 8-chlorotheophylline salt of diphenhydramine. Unfortunately, almost no information is available on the use of these drugs during breastfeeding. In a telephone survey of nursing mothers, irritability and colicky symptoms were reported in 10% of infants exposed to various antihistamines and drowsiness was reported in 1.6% of infants. In this study, 1 infant of 12 exposed to diphenhydramine in breast milk showed drowsiness and 1 of 7 infants whose mothers took dimenhydrinate showed irritability. In a second more focused study, infant reactions were observed by mothers in 53 of 234 infants exposed to an antihistamine in breast milk. Irritability, drowsiness, and decreased sleep were the most commonly observed reactions. Furthermore, in a report of adverse reactions in breastfed infants reported in France between January 1985 and June 2011, hydroxyzine was one of the drugs most often suspected in adverse reactions, primarily sedation.

The effect of antihistamines on nursing has not been fully elucidated, but several lines of evidence indicate they might interfere with lactation. Antihistamines in relatively high doses given by injection can decrease basal serum prolactin in early postpartum women, but suckling-induced prolactin secretion is not affected. Also, the first-generation antihistamines have anticholinergic properties. Anticholinergics can inhibit lactation in animals, apparently by inhibiting growth hormone and oxytocin secretion. Unlike most phenothiazines, promethazine usually causes a reduction in basal prolactin secretion in non-nursing women. In one small study, women given promethazine with meperidine and secobarbital during labor, had the time to lactogenesis II prolonged by 14 hours compared with unmedicated women. Women given meperidine or secobarbital without promethazine had lactogenesis II prolonged by 7 hours, but the difference between the two medicated groups was not statistically significant.

Two other products are used for general nausea and vomiting: phosphorated carbohydrate solution and trimethobenzamide. No specific information on their use in breastfeeding is available, but phosphorated carbohydrate solution is a mixture of sugar and phosphoric acid and very unlikely to cause problems in the breastfed infant or on lactation.

Motion Sickness

The drugs used for motion sickness are mostly older first-generation antihistamines as discussed under general antinauseants. Cyclizine is an additional antihistamine used for motion sickness.

The central anticholinergic scopolamine is also used for motion sickness, primarily as a long-acting patch. The main concern with its use is lactation suppression. A retrospective case–control study conducted in two hospitals in Iran compared breastfeeding behaviors in the first 2 hours postdelivery of the infants of primiparous women with healthy full-term singleton births who had vaginal deliveries. Three groups were those who received no medications during labor, those who received oxytocin plus scopolamine, and those who received oxytocin, scopolamine, and meperidine. The infants in the no medication group had better lactation performance than those in the scopolamine groups.

Postoperative Nausea and Vomiting

Antinauseants can be used for prophylaxis or treatment of postoperative nausea and vomiting (PONV), although several have FDA approval for both, including amisulpride, dolasetron, hydroxyzine, metoclopramide, promethazine, and trimethobenzamide. Drugs with FDA approval for prophylaxis only include droperidol, ondansetron, palonosetron, and scopolamine.

The serotonin receptor antagonists, dolasetron, granisetron, ondansetron, and palonosetron have not been studied well during breastfeeding, but ondansetron is frequently used for nausea in mothers having a cesarean section. Its use during and after cesarean section appears not to affect the onset of breastfeeding. No adverse infant effects have been reported in this setting in which low milk volume during the first day or two postpartum markedly limits the dose the infant receives. Dolasetron and granisetron have also been used during cesarean section, but fewer reports have been published.

Use of ondansetron in nursing mothers beyond the immediate postpartum setting has not been studied, but the drug is labeled for use in infants as young as 1 month of age in a dose of 4 mg. Amounts in milk are likely to be much less than this dose. Ondansetron appears to be the drug of choice among this class of drugs and perhaps the drug of choice in nursing mothers undergoing surgery.

Dopamine receptor antagonists such as amisulpride, droperidol, and metoclopramide antagonize the effects of dopamine at the D₂ receptors in the chemoreceptor trigger zone. Amisulpride is a relatively new drug in the United States, but has been studied and used extensively as a psychotherapeutic agent abroad. Excretion into milk is rather high, with relative infant doses ranging from 6% to 11% in two mothers. After a single dose for postoperative nausea and vomiting, the manufacturer suggests waiting 48 hours before resuming breastfeeding; however, with a half-life of 4–5 hours, a waiting period of 12–24 hours should be adequate. But, in the critical immediate postpartum period, withholding breastfeeding for even 12 hours can be disruptive to establish nursing, so amisulpride is not a desirable drug to use in mothers who are nursing or trying to establish lactation.

Droperidol and metoclopramide have been used successfully for intra- and postoperative nausea and vomiting during cesarean section, although ondansetron appears to be more effective than metoclopramide. Both of the drugs increase serum prolactin, but multiple doses of droperidol can cause infant sedation, especially in younger exclusively breastfed infants. A randomized study compared the breastfed infants born by cesarean section whose mothers received either morphine or morphine plus droperidol by patient-controlled analgesia postoperatively. On days 1 and 2 of life, the infants whose mothers received droperidol had a lower neonatal neurological and adaptive capacity score than those who received morphine only.

Hydroxyzine, promethazine, and scopolamine can potentially decrease milk supply, as discussed under general antinauseants, so are not desirable drugs in nursing mothers. Dexamethasone is sometimes used off-label for prophylaxis and treatment of PONV. In general, corticosteroids are acceptable during breastfeeding because very little appears in breast milk. Dexamethasone has not been specifically studied in breastfeeding, but it is not likely to be a problem with short-term use during breastfeeding.

Radiation- and Chemotherapy-Induced Nausea and Vomiting

Ondansetron and granisetron have indications for radiation therapy. Ondansetron is used in somewhat higher doses than for postoperative use and may be used for 1–2 days after radiation therapy. Because of the short-term nature of use, these drugs appear to be acceptable for nursing mothers receiving radiation therapy.

Generally, chemotherapy itself would be the overriding concern and the specific chemotherapy agent(s) used would determine breastfeeding acceptability. Older cytotoxic chemotherapy can cause nausea and vomiting that varies in severity depending on the drug(s) used. For chemotherapy, maximum doses of ondansetron may be used, as well as granisetron, dolasetron, and palonosetron, which are probably acceptable, although less well studied.

Neurokinin 1 (NK1) receptor antagonists such as aprepitant, fosaprepitant, netupitant, fosnetupitant, and rolapitant are indicated for chemotherapy-induced nausea and vomiting. No information is available on the NK1 receptor antagonists in nursing mothers, although they are not considered to be contraindicated. Dexamethasone is often combined with other antiemetic drugs for preventing and treating chemotherapy-induced nausea and vomiting.

Miscellaneous Drugs

Ginger is sometimes used for prevention and treatment of chemotherapy-induced and PONV, but more commonly it is used for motion sickness. There are no measurements of ginger compounds in milk, but the drug has been used as a galactogogue in some cultures and two reports did not find any adverse effects in breastfed infants.

Cannabis is often used (usually smoked) for chemotherapy-induced nausea and vomiting and two synthetic oral pharmaceuticals, dronabinol and nabilone, are available for oral use. Dronabinol is chemically identical to the psychoactive component of cannabis, delta-9-tetrahydrocannabinol (THC), and nabilone is similar in chemical structure. Concern has been expressed regarding the possible effects of cannabis on neurotransmitters, nervous system development, and endocannabinoid-related functions, but data are lacking in breastfed infants. THC has been detected in the milk of chronic cannabis users for periods of 6 days to >6 weeks, although in very small amounts. Labeling of dronabinol suggests that mothers not breastfeed for 9 days after use; nabilone labeling recommends that it must not be used in nursing mothers.

Summary

Although many classes of drugs have been used for nausea and vomiting, few of the individual drugs have been studied well. Most of these drugs are used only for short periods of time, limiting risk to the breastfed infant. However, some commonly used drugs such as antihistamines and scopolamine can potentially suppress lactation and cause minor symptoms, such as irritability or drowsiness, in breastfed infants. Care should be taken to select drugs that will not interfere with lactation. Ondansetron appears to be a good choice during lactation.