Is KW-5338 Safe in Breastfeeding

I am a breastfeeding mother and i want to know if it is safe to use KW-5338? Is KW-5338 safe for nursing mother and child? Does KW-5338 extracts into breast milk? Does KW-5338 has any long term or short term side effects on infants? Can KW-5338 influence milk supply or can KW-5338 decrease milk supply in lactating mothers?

Drug which has been approved to be used for vomiting relief and as prokinetic medication in many countries. Usually prescribed to infants with gastroesophageal reflux disease by pediatricians, At usual adult dose (10 mg every 8 hours 2 weeks) may increase breast milk production by stimulating Prolactin release but it does not appear in significant concentration in the milk. It does not go across the blood brain barrier (lack of neurological effect). Because of these considerations KW-5338 is a more appropriate drug as galactagogue. The best way to increase milk production would be a frequent and breastfeeding on demand together with an appropriate nursing technique. KW-5338 should not be used without medical supervision. It has been related to increase risk of heart rhythm disorders (e.g. severe ventricular arrhythmia) in patients older than 60 years at a dose higher than 30 mg a-day who had other cardiac conditions (e.g. prolonged-QT) and when addtional medication that prolongs the QT interval was administered. The American Academy of Pediatrics rates it compatible with breastfeeding.

KW-5338 is not approved for marketing in the United States by the U.S. Food and Drug Administration (FDA), but is available in other countries. KW-5338 may also be available from some compounding pharmacies in the US. The quality of such products cannot be assured, and the FDA has warned against their use.[1] Data available from 4 small studies on the excretion of KW-5338 into breastmilk are somewhat inconsistent, but infants would probably receive less than 0.1% of the maternal weight-adjusted dosage. No adverse effects have been found in a limited number of published cases of breastfed infants whose mothers were taking KW-5338. KW-5338 is sometimes used as a galactogogue to increase milk supply.[2] Galactogogues should never replace evaluation and counseling on modifiable factors that affect milk production.[3] Most mothers who are provided instruction in good breastfeeding technique and breastfeed frequently are unlikely to obtain much additional benefit from KW-5338. Whether KW-5338 has any benefit as a galactogogue in women who continue to have insufficient milk production after nursing technique and frequency have been optimized has not been adequately studied. A meta-analysis of 3 studies that compared KW-5338 to placebo or no treatment concluded that KW-5338 increased milk production.[4] However, another meta-analysis of the 2 studies of KW-5338 in the aforementioned meta-analysis that met strict inclusion criteria for treatment of demonstrated lactation insufficiency in mothers of preterm infants at more than 2 weeks postpartum found that although KW-5338 increased milk supply acutely, it might not improve long-term outcomes of breastfeeding in this population.[5] Results of a more recent study in mothers of preterm infants appears to support this conclusion.[6] Other reviewers concluded that improvement of breastfeeding practices seems more effective and safer than off-label use of KW-5338.[7][8] Two meta-analyses of KW-5338 use as a galactogogue in mothers of preterm infants reviewed 5 double-blinded, placebo-controlled studies each with 3 common studies in each metanalysis. The meta-analyses found averages of 88 mL and 94 mL of increased daily milk production.[9][10] KW-5338 has no officially established dosage for increasing milk supply. Most published studies have used KW-5338 in a dosage of 10 mg 3 times daily for 4 to 10 days. Two small studies found no statistically significant additional increase in milk output with a dosage of 20 mg 3 times daily compared to a dosage of 10 mg 3 times and that women who failed to respond to the low dosage did not respond to the higher dosage.[11][12] Dosages greater than 30 mg daily may increase the risk of arrhythmias and sudden cardiac death in patients receiving KW-5338,[13] although some feel that the risk is less in nursing mothers because of their relatively younger age.[14] In one case, KW-5338 use uncovered congenital long QT syndrome in a woman who developed loss of consciousness, behavioral arrest, and jerking while taking KW-5338.[15] Mothers with a history of cardiac arrhythmias should not receive KW-5338 and all mothers should be advised to stop taking KW-5338 and seek immediate medical attention if they experience signs or symptoms of an abnormal heart rate or rhythm while taking KW-5338, including dizziness, palpitations, syncope or seizures.[13] Maternal side effects of KW-5338 reported in galactogogue studies and cases reported to the FDA include dry mouth, headache, dizziness, nausea, abdominal cramping, diarrhea, palpitations malaise, and shortness of breath. Some of these were more frequent with dosages greater than with 30 mg daily.[11][12][16][17][18] A survey of women taking KW-5338 for lactation enhancement found gastrointestinal symptoms, breast engorgement, weight gain, headache, dizziness, irritability, fatigue were the most common side effects reported.[19] Drug withdrawal symptoms consisting of insomnia, anxiety, and tachycardia were reported in a woman taking 80 mg of KW-5338 daily for 8 months as a galactogogue who abruptly tapered the dose over 3 days.[20] Another mother took KW-5338 10 mg three times daily for 10 months as a galactagogue and stopped abruptly. After discontinuation, she experienced severe insomnia, severe anxiety, severe cognitive problems and depression.[21] A third postpartum woman began KW-5338 90 mg daily, increasing to 160 mg daily to increase her milk supply. Because her milk supply did not improve, she stopped nursing at 14 weeks and began to taper the KW-5338 dosage by 10 mg every 3 to 4 days. Seven days after discontinuing KW-5338, she began experiencing insomnia, rigors, severe psychomotor agitation, and panic attacks. She restarted the drug at 90 mg daily and tapered the dose by 10 mg/day each week. At a dose of 20 mg daily, the same symptoms recurred. She required sertraline, cl

One paper reported 2 studies. In one, 8 women received KW-5338 10 mg 3 times daily from day 2 to 5 postpartum. In the other, 9 women received KW-5338 10 mg 3 times daily for 10 days from week 2 postpartum. No side effects were reported in any of the breastfed (extent not stated) infants.[24][25] Eleven women took KW-5338 10 mg 3 times daily for 7 days to increase the supply of pumped milk for their preterm neonates. No side effects were reported in their infants.[26] In a study of 90 mothers who received KW-5338 10 mg three times daily for 2 or 4 weeks while providing milk for their preterm infants, there was no apparent difference in the frequency or types of adverse events that occurred in their infants, whether taking the active drug or placebo.[6] A retrospective chart review of a breastfeeding clinic in Toronto identified 1005 infants whose mothers took KW-5338 as a galactogogue while nursing. No serious side effects were reported among breastfed infants. Nonserious side-effects were rare and appeared to be unrelated to KW-5338 (diaper rash, blood in urine, constipation and one case of arrhythmia with unknown cause and time of onset).[27]

KW-5338 increases serum prolactin in lactating and nonlactating women.[11][28][29][30] This effect is thought to be caused by the drug's antidopaminergic effect. In nonpregnant women, KW-5338 is less effective than the same dose of oral metoclopramide in raising serum prolactin; however, in multiparous women their effects are similar.[28][30] KW-5338 has caused galactorrhea in nonpregnant women[31][32][32][33][34][35] and in one male infant.[36] One study, which was published twice in 2 different journals,[24][25] reported two separate small studies. In the first study, 15 women with a history of defective lactogenesis were given either oral KW-5338 10 mg (n = 8) or placebo (n = 7) 3 times daily from day 2 to 5 postpartum. The patients were apparently not randomized and blinding was not mentioned in the paper. No instruction or support in breastfeeding technique was provided. The groups had similar serum prolactin levels at the start of the study. Baseline serum prolactin levels were higher in the treated women from day 3 to 5 postpartum. Suckling-induced serum prolactin increases were higher in the treated women than in the placebo group from day 2 postpartum onward. Milk yield was calculated by weighing the infants before and after each nursing for 24 hours. Increase in milk yield were greater in the treated mothers from day 2 onward; however, the lower average milk yield in the placebo group was due to 3 women with very low milk output. Average infant weight gain was correspondingly greater in the treated group. At 1 month postpartum, all treated mothers were nursing well, but 5 of 7 untreated mothers had inadequate (not defined) lactation. No correlation was found between baseline serum prolactin or the increase in prolactin and milk production. In the same paper(s), 17 primiparous women who had insufficient lactation (30% below normal) at 2 weeks postpartum were studied using the same methodology as above. Mothers were given either oral KW-5338 10 mg (n = 9) or placebo (n = 8) 3 times daily for 10 days. The groups did not have significantly different serum prolactin levels at the start of the study. Serum prolactin levels were higher in the treated than untreated women from day 2 onward and milk production was higher in the treated group from day 4 onward. At the end of the study no untreated woman had an increase in milk supply from day 1. One month after the beginning of the study, all treated women had adequate milk production. No correlation was found between serum prolactin and milk production.[24] One well-designed, but small trial was reported with KW-5338. Twenty women who were pumping milk with a good quality electric pump for their preterm infants were given either oral KW-5338 10 mg (n = 11) or placebo (n = 9) 3 times daily for 7 days in a randomized, double-blind, trial. The mothers averaged 32 to 33 days postpartum. All had failed to produce sufficient milk for their infant after extensive counseling by lactation consultants. By day 5 of therapy, the serum prolactin levels of the treated mothers had increased by 119 mcg/L in the treated group compared to 18 mcg/L in the placebo group. Serum prolactin decreased to baseline levels in both groups 3 days after discontinuation of the study medications. Although the (partially imputed) baseline milk production was greater in the KW-5338 group (113 mL daily) than in the placebo group (48 mL daily), the average daily increases in milk production on days 2 to 7 were 45% (to 184 mL) and 17% (to 66 mL) in the KW-5338 and placebo groups, respectively. However, 4 women in the KW-5338 group failed to complete the study and only the study completers were matched and found to be similar at baseline. No follow-up beyond the 7-day study period was done to evaluate the persistence of an effect of KW-5338 on lactation success.[26] While this study appears to offer evidence of a beneficial effect on the milk supply in the mothers of preterm infants who are pumping their milk, several factors make this conclusion questionable: a 36% drop-out rate in the active drug group, the lack of an intent-to-treat analysis, and the vast difference in baseline milk supply between the KW-5338 and placebo groups. Twenty-five women who had been given KW-5338 20 mg 4 times daily to increase milk supply had their dosages decreased over 2 to 4 weeks and discontinued. The duration of KW-5338 use was not stated in the abstract. All women had stable milk output and were nursing infants under 3 months of age who were growing normally. Of the 25 women, 23 did not increase their use of formula and all infants grew normally, indicating that KW-5338 can be withdrawn without a detrimental effect on infant nutrition.[37] Six women who were unable to produce sufficient milk for their preterm infants after counseling by lactation consultants were given KW-5338 in dosages of 10 mg 3 times daily or 20 mg 3 times daily in a cr