Metoclopramide

The Basics

What is Metoclopramide?

Used to relieve heartburn and speed the healing of ulcers and sores in the esophagus in people who have gastroesophageal reflux disease (GERD); also used to relieve symptoms caused by slow stomach emptying in people who have diabetes.

Brand names for Metoclopramide

Reglan

How Metoclopramide is classified

Antiemetics, Dopamine Antagonists, Galactogogues, Gastrointestinal Agents

Metoclopramide During Pregnancy

Metoclopramide pregnancy category

Category N/ANote that the FDA has deprecated the use of pregnancy categories, so for some medications, this information isn’t available. We still think it’s useful to list historical info, however, given what a common proxy this has been in the past.

What we know about taking Metoclopramide while pregnant

N/A

Taking Metoclopramide While Breastfeeding

What are recommendations for lactation if you're taking Metoclopramide?

Metoclopramide is excreted in variable amounts in breastmilk. Most infants would receive less than 10% of the maternal weight-adjusted dosage, but some receive doses that achieve pharmacologically active serum levels, elevated serum prolactin and possible gastrointestinal side effects. Although most studies have found no adverse effects in breastfed infants during maternal metoclopramide use, many did not adequately observe for side effects. Metoclopramide is used as a galactogogue.[1] Metoclopramide increases serum prolactin. A meta-analysis of 5 placebo-controlled studies concluded that 2 weeks of metoclopramide caused no increase of serum prolactin over placebo, but 3 weeks of treatment did.[2] The clinical value of metoclopramide in increasing milk supply is questionable. Galactogogues should never replace evaluation and counseling on modifiable factors that affect milk production.[3] In well-designed studies that evaluated the effectiveness of metoclopramide as a galactogogue in women who continue to have difficulty producing milk after nursing techniques have been optimized, it was of no additional benefit. Prophylactic use in the mothers of preterm infants has also shown little or no benefit.

Maternal / infant drug levels

Metoclopramide is excreted in variable amounts in breastmilk. Most infants would receive less than 10% of the maternal weight-adjusted dosage, but some receive doses that achieve pharmacologically active serum levels, elevated serum prolactin and possible gastrointestinal side effects. Although most studies have found no adverse effects in breastfed infants during maternal metoclopramide use, many did not adequately observe for side effects. Metoclopramide is used as a galactogogue.[1] Metoclopramide increases serum prolactin. A meta-analysis of 5 placebo-controlled studies concluded that 2 weeks of metoclopramide caused no increase of serum prolactin over placebo, but 3 weeks of treatment did.[2] The clinical value of metoclopramide in increasing milk supply is questionable. Galactogogues should never replace evaluation and counseling on modifiable factors that affect milk production.[3] In well-designed studies that evaluated the effectiveness of metoclopramide as a galactogogue in women who continue to have difficulty producing milk after nursing techniques have been optimized, it was of no additional benefit. Prophylactic use in the mothers of preterm infants has also shown little or no benefit.

Possible effects of Metoclopramide on milk supply

Metoclopramide increases serum prolactin in lactating and nonlactating women.[2][21][22] This effect is thought to be caused by the drug’s antidopaminergic effect. Galactorrhea has been reported after long-term use of metoclopramide for nausea associated with migraine. The patient was taking 10 to 40 mg 1 to 4 times weekly for about 4 months.[23] Another case of galactorrhea was reported in a woman after 5 days of treatment and having a slightly low serum prolactin level.[24]

Numerous papers have reported studies that used metoclopramide to increase milk production. All studies were small with 40 or fewer patients. Most of the studies have designs that would not be considered valid using today’s standards of evidence-based medicine. Many of the studies had no placebo control;[8][12][17][18][20][25][26][27] only 7 studies employed randomization;[7][11][14][19][28][29][30] and only 2 of the studies were clearly and adequately blinded.[14][28] Among all of the published studies, only 5 meet or come close to meeting current evidence-based medicine standards. These studies are described in more detail below.

In one early double-blind study, 20 women who had undergone delivery by emergency or elective cesarean section were randomized to take oral metoclopramide 10 mg 3 times daily (n=10) or placebo for 7 days (n=10) beginning on the first day after cesarean section.[11] All mothers expressed a desire to breastfeed their infants for at least 3 months and received daily visits by an investigator to discuss breastfeeding problems and were given advice and encouragement to breastfeed. The mothers in the 2 groups were closely matched except that 3 preterm infants in the metoclopramide group were separated from their mothers in the intensive care unit and were nursed there initially and fed expressed milk until discharge. At 10 days postpartum, there were no differences in the number of infants being breastfed in each group; at 6 weeks postpartum, 9 women were breastfeeding in the metoclopramide group and 8 in the placebo group; and 3 months postpartum 4 were breastfeeding in each group. Although this was a small study, it was well designed and executed. It provided preliminary evidence of the benefit of patient counseling and encouragement on breastfeeding success.

Thirteen primiparous nursing mothers without breastfeeding difficulties and normal infants were given either oral metoclopramide 10 mg 3 times daily (n=7) or placebo (n=6) for 8 days beginning on the first day postpartum in a randomized, double-blind study.[28] No attempt was made to improve nursing technique, but mothers nursed on a 3-hour schedule beginning at 6:30 am on the day following delivery. No mention was made of the type of feeding, or the number of feedings that the infants received between birth and the initiation of breastfeeding or any differences in the two groups of infants in this regard. All women completed the trial. No differences were found in serum prolactin of treated and control women throughout 28 days of observation. Milk intake as measured by infant weight change before and after the second daily feeding on days 3 through 8 was greater by an average of 24.3 mL (51.1 mL vs 75.4 mL) in the infants of treated mothers; however, statistically significant differences in milk production did not occur until day 5 postpartum. This paper has several serious flaws related to its analysis. A recent study showed that weighing infants is not an accurate method of estimating milk intake.[31] This problem is magnified by the fact that the paper does not state the number of feedings per day, so the fraction of the infant’s daily feedings that this one feeding represented is unknown. The study also failed to report serial infant weight gain during the study period. These serious problems invalidate the study results.

Fifty mothers who had complete or partial lactation failure received extensive instruction on how to increase their milk supply.[29] Their infants were hospitalized for various illnesses and ranged from 29 to 100 day of age. Maternal lactation history was comparable in the two groups. Mothers were randomized either to receive or not receive metoclopramide 10 mg 3 times daily for 10 days. Although no specific metoclopramide placebo was given to control mothers, all mothers received multivitamins, iron, and folic acid daily which the authors used to obscure to the mother whether she was receiving an active drug or not. No statistically significant differences were found between the groups in the time to initiation of milk secretion, to partial restoration of breastfeeding, or to complete breastfeeding or in the weight gain of the infants during the study period of 96 days. The authors concluded that successful relactation can be accomplished without galactogogues such as metoclopramide. This study lacked a true placebo control; however, it employed excellent breastfeeding instruction and infant evaluation techniques and had the best overall design of any of the studies on mothers who had older infants and well documented insufficient milk supplies at the start of the study.

In a well-controlled and analyzed, randomized, double-blinded study of the mothers of premature (23 to 34 weeks) infants, mothers received either metoclopramide 10 mg 3 times daily (n=31) or placebo (n=29) for 10 days beginning within 96 hours of delivery.[14] The groups were well matched and all mothers received standardized instructions from a lactation consultant and provided access to breastfeeding support. No selection was made for mothers who were having difficulties producing milk. Six subjects each in the drug and placebo groups dropped out for a relatively high dropout rate of 17.4%. Although by far the best designed and executed study to date on any galactogogue, the study enrolled all mothers of preterm infants without any evaluation of their ability to produce milk. This population may in general need lactation support, but the possible inclusion of women in both the active drug and placebo groups who would have had little difficulty in milk production may have minimized differences between the groups.

A study of 20 primiparous mothers whose infant were not gaining weight adequately compared metoclopramide (n = 10) to placebo (n = 10) for increasing milk supply. All mothers passed a brief training course on improving breastfeeding technique and the benefits of breastfeeding before entering the study. All infants gained weight over the next 2 weeks. The increase in weight in the metoclopramide group was not different from the placebo group.[30]

Two women whose infants were born via a surrogate pregnancy other women were given metoclopramide beginning at 28 weeks of the pregnancy. One woman stopped metoclopramide 1 week prior to the expected delivery date and the other continued meoclopramide postpartum. They also underwent postpartum nipple stimulation with an electric breast pump. Lactation was established and they were each able to partially breastfeed their infants for 3 months.[32][33]

A double-blind randomized study compared the effect on milk production of metoclopramide 10 mg to placebo 3 times daily for 10 days in the mothers of preterm infants born at 28 to 34 weeks of gestation. At the beginning of investigation, all participating women were taught a standard breastfeeding method. Mothers used a breast pump for 10 to 15 minutes every 2 hours and the volume of milk was measured and recorded at each pumping for 10 days. No difference in daily milk volumes between the two groups occurred until day 7 postpartum, when treated mothers pumped an average of 373 mL compared with 352 mL in the mothers receiving placebo. This difference of about 20 mL per day persisted until the end of the study on day 10 when the treated group pumped 446 mL and the placebo group pumped 422 mL.[34] The clinical importance of the extra 20 mL of milk per day is questionable.

A randomized, double-blind study of 26 mothers who delivered at 34 weeks of gestation or less, compared metoclopramide 10 mg 3 times daily to placebo. The drug or placebo was taken for 8 days beginning within 36 hours of delivery. All women were provided breast pumps and support from a lactation consultant. The total volume of milk pumped per day was recorded by the women, 19 of whom completed the entire protocol. Although milk production increased over the 8-day period, metoclopramide was no better than placebo and the standard care provided. No difference in reported side effects was found.[35]

Mothers who were expressing milk for their infants in a neonatal intensive care unit (mean gestational age 28 weeks) were given instructions on methods for increasing milk supply. If they were producing less than 160 mL of milk per kg of infant weight daily after several days, mothers were randomized to receive either domperidone or metoclopramide 10 mg by mouth 3 times daily for 10 days in a double-blinded fashion. Thirty-one mothers who received domperidone and 34 who received metoclopramide provided data on daily milk volumes during the 10 days. Milk volumes increased over the 10-day period by 96% with domperidone and 94% with metoclopramide, which was not statistically different between the groups. Some mothers continued to measure milk output after the end of the medication period. Results were similar between the 2 groups. Side effects in the domperidone group (3 women) included headache, diarrhea, mood swings and dizziness. Side effects in the metoclopramide group (7 women) included headache (3 women), diarrhea, mood swings, changed appetite, dry mouth and discomfort in the breasts. Of 29 women who took metoclopramide after the trial ended, 8 reported side effects including diarrhea, mood swings, depression (2 women), itchy skin, tiredness, restless legs and less effective milk stimulation.[5] The lack of a placebo group and the projection of milk volumes to impute missing data from some mothers detract from the findings of this study.

Possible alternatives to Metoclopramide

None listed