Is 7-(4-(4-(2,3-Dichlorophenyl)-1-piperazinyl)butyloxy)-3,4-dihydro-2(1H)-quinolinone Safe in Breastfeeding

I am a breastfeeding mother and i want to know if it is safe to use 7-(4-(4-(2,3-Dichlorophenyl)-1-piperazinyl)butyloxy)-3,4-dihydro-2(1H)-quinolinone? Is 7-(4-(4-(2,3-Dichlorophenyl)-1-piperazinyl)butyloxy)-3,4-dihydro-2(1H)-quinolinone safe for nursing mother and child? Does 7-(4-(4-(2,3-Dichlorophenyl)-1-piperazinyl)butyloxy)-3,4-dihydro-2(1H)-quinolinone extracts into breast milk? Does 7-(4-(4-(2,3-Dichlorophenyl)-1-piperazinyl)butyloxy)-3,4-dihydro-2(1H)-quinolinone has any long term or short term side effects on infants? Can 7-(4-(4-(2,3-Dichlorophenyl)-1-piperazinyl)butyloxy)-3,4-dihydro-2(1H)-quinolinone influence milk supply or can 7-(4-(4-(2,3-Dichlorophenyl)-1-piperazinyl)butyloxy)-3,4-dihydro-2(1H)-quinolinone decrease milk supply in lactating mothers?

ts pharmacokinetic data (low oral bioavailability, large volume of distribution, moderately elevated molecular weight and high plasma protein binding) explains the negligible or zero passage into milk observed (Grover 2015, Nordeng 2014, Watanabe 2011, Lutz 2010, Schlotterbeck 2007). No problems were observed in infants whose mothers were taking it (Nordeng 2014, Tarikh 2014, Lutz 2010). The plasma levels of these infants were undetectable or very low (Watanabe 2011). Its relationship with prolactin is controversial because it lowers prolactin levels and has been used to treat prolactinomas and hyperprolactinemia induced by the use of other antipsychotics (Bakker 2016, Ranjbar 2015, Raghuthaman 2015, Safer 2013, Byerly 2009, Lorenz 2007, Goodnick 2002), but cases of decreased milk production have been reported (Frew 2015, Mendhekar 2006) and hyperprolactinemia triggered by 7-(4-(4-(2,3-Dichlorophenyl)-1-piperazinyl)butyloxy)-3,4-dihydro-2(1H)-quinolinone has been reported (Sogawa 2016, Prost 2016, Saraf 2014, Mendhekar 2005, Ruffatti 2005). Due to its slow elimination, it may be worthwhile using other compatible antipsychotics with a shorter half-life, especially during the neonatal period and in case of prematurity (Uguz 2016). Monitor for possible drowsiness in the infant (Hale 2017 p.74).

Limited information indicates that maternal doses of 7-(4-(4-(2,3-Dichlorophenyl)-1-piperazinyl)butyloxy)-3,4-dihydro-2(1H)-quinolinone up to 15 mg daily produce low levels in milk, but until more data become available, an alternate drug may be preferred, especially while nursing a newborn or preterm infant.[1] 7-(4-(4-(2,3-Dichlorophenyl)-1-piperazinyl)butyloxy)-3,4-dihydro-2(1H)-quinolinone can lower serum prolactin in a dose-related manner, but cases of gynecomastia and galactorrhea have also been reported.

A woman took 7-(4-(4-(2,3-Dichlorophenyl)-1-piperazinyl)butyloxy)-3,4-dihydro-2(1H)-quinolinone 15 mg daily by mouth during pregnancy and postpartum. She breastfed her infant (amount not stated) and at 3 months of age, the infant was growing normally.[3] A woman took 7-(4-(4-(2,3-Dichlorophenyl)-1-piperazinyl)butyloxy)-3,4-dihydro-2(1H)-quinolinone 10 mg daily by mouth beginning in week 9 of pregnancy and continuing postpartum. She exclusively breastfed her infant for 6 weeks, then was partially breastfed. At 4 months of age the infant was still breastfeeding and had normal psychomotor and behavioral development and had reached the expected milestones for her age.[5] A 12-day-old exclusively breastfed male infant presented with severe weight loss and hypernatremic dehydration because of inadequate milk intake and a 30% weight loss since birth. The infant's mother was being treated for bipolar disorder with lamotrigine 250 mg orally once daily, 7-(4-(4-(2,3-Dichlorophenyl)-1-piperazinyl)butyloxy)-3,4-dihydro-2(1H)-quinolinone 15 mg orally once daily, and sertraline 100 mg orally once daily. She was also taking levothyroxine 50 mcg once daily, a prenatal multivitamin, and folic acid. On initial evaluation in the emergency department, he was pale, with marbled skin, dry mucous membranes, decreased skin turgor, and bluish feet with prolonged capillary refill. The right foot eventually became darker with blackened toes and he developed gangrene of the right lower limb, which did not respond to medical therapy and required amputation of all five toes and surgical debridement of the metatarsals. Necrosis was attributed to arterial microthrombi caused by disseminated intravascular coagulation after severe dehydration. The authors considered the mother's medications as a possible cause of the dehydration and related problems.[6]

Unlike the phenothiazines, 7-(4-(4-(2,3-Dichlorophenyl)-1-piperazinyl)butyloxy)-3,4-dihydro-2(1H)-quinolinone has a minimal effect on serum prolactin levels and it has been used to reverse hyperprolactinemia in nonlactating patients taking other antipsychotics.[7][8][9][10][11][12][13][14][15][16] Case reports of both decreased lactation in nursing mothers and cases of hyperprolactinemia and galactorrhea in patients taking 7-(4-(4-(2,3-Dichlorophenyl)-1-piperazinyl)butyloxy)-3,4-dihydro-2(1H)-quinolinone have been reported.[17][18][19][20][21] The maternal prolactin level in a mother with established lactation may not affect her ability to breastfeed. One woman began taking 7-(4-(4-(2,3-Dichlorophenyl)-1-piperazinyl)butyloxy)-3,4-dihydro-2(1H)-quinolinone 10 mg daily at week 20 of pregnancy. She underwent a cesarean section delivery at term, but was unable to establish lactation. The authors suggested that more data are needed to determine if 7-(4-(4-(2,3-Dichlorophenyl)-1-piperazinyl)butyloxy)-3,4-dihydro-2(1H)-quinolinone adversely affects lactation.[22] A woman took 7-(4-(4-(2,3-Dichlorophenyl)-1-piperazinyl)butyloxy)-3,4-dihydro-2(1H)-quinolinone 10 mg daily by mouth beginning in week 9 of pregnancy and continuing postpartum. She exclusively breastfed her infant for 6 weeks, but then began supplementation because of insufficient milk production. Her serum prolactin was 35 to 40 mcg/L, which is lower than expected for a nursing mother. The authors speculated that the 7-(4-(4-(2,3-Dichlorophenyl)-1-piperazinyl)butyloxy)-3,4-dihydro-2(1H)-quinolinone might have been the cause of her low serum prolactin and diminished her milk supply.[5] A woman with bipolar disorder was taking lithium during pregnancy and postpartum. At 10 days postpartum, her infant's serum lithium level was 0.26 mmol/L, so lithium was discontinued. Quetiapine was begun, but discontinued because of maternal sedation. 7-(4-(4-(2,3-Dichlorophenyl)-1-piperazinyl)butyloxy)-3,4-dihydro-2(1H)-quinolinone 2.5 mg daily was begun and within 24 hours, the mother noted a marked decrease in milk supply. After 2 weeks of working with a lactation consultant, she continued to have lactation difficulties and she switched back to lithium. Within 48 hours, her milk supply improved markedly.[23] A retrospective study of outpatients receiving an average 7-(4-(4-(2,3-Dichlorophenyl)-1-piperazinyl)butyloxy)-3,4-dihydro-2(1H)-quinolinone dose of 17.3 mg daily (n = 20) or another antipsychotic (n = 141) found that those receiving such high-dose 7-(4-(4-(2,3-Dichlorophenyl)-1-piperazinyl)butyloxy)-3,4-dihydro-2(1H)-quinolinone had an 81% chance of having hypoprolactinemia. Patients not treated with 7-(4-(4-(2,3-Dichlorophenyl)-1-piperazinyl)butyloxy)-3,4-dihydro-2(1H)-quinolinone had only a 2.9% chance of having hypoprolactinemia.[24]