Is 5-Ethyl-5-phenyl-2,4,6-(1H,3H,5H)pyrimidinetrione Safe in Breastfeeding

I am a breastfeeding mother and i want to know if it is safe to use 5-Ethyl-5-phenyl-2,4,6-(1H,3H,5H)pyrimidinetrione? Is 5-Ethyl-5-phenyl-2,4,6-(1H,3H,5H)pyrimidinetrione safe for nursing mother and child? Does 5-Ethyl-5-phenyl-2,4,6-(1H,3H,5H)pyrimidinetrione extracts into breast milk? Does 5-Ethyl-5-phenyl-2,4,6-(1H,3H,5H)pyrimidinetrione has any long term or short term side effects on infants? Can 5-Ethyl-5-phenyl-2,4,6-(1H,3H,5H)pyrimidinetrione influence milk supply or can 5-Ethyl-5-phenyl-2,4,6-(1H,3H,5H)pyrimidinetrione decrease milk supply in lactating mothers?

It is a barbiturate drug. Because it has a sedative effect, it is being displaced by other anti-epilepsy drugs in the treatment of chronic epilepsy. Excretion into the breast milk is quite variable with concentrations that could reach clinically significant levels. A sedative effect in infants from mothers who were treated has been described, as well as Abstinence Syndrome with spasms after sudden weaning, mostly in newborns. Follow-up for alertness and adequate feeding in the infant is recommended. Plasma level monitoring may be required in infants for both cases in which sedation has occurred or a follow-up for a progressive weaning is desired.

Inter- and intrapatient variability in excretion of 5-Ethyl-5-phenyl-2,4,6-(1H,3H,5H)pyrimidinetrione into breastmilk is extensive. 5-Ethyl-5-phenyl-2,4,6-(1H,3H,5H)pyrimidinetrione in breastmilk apparently can decrease withdrawal symptoms in infants who were exposed in utero, but it can also cause drowsiness in some infants, especially when used with other sedating drugs. Monitor the infant for drowsiness, adequate weight gain, and developmental milestones, especially in younger, exclusively breastfed infants and when using combinations of psychotropic drugs. Sometimes breastfeeding might have to be limited or discontinued because of excessive drowsiness and poor weight gain. If there is concern, measurement of the infant's serum 5-Ethyl-5-phenyl-2,4,6-(1H,3H,5H)pyrimidinetrione concentration might help rule out toxicity.

Two 1-week-old infants whose mothers had been receiving 5-Ethyl-5-phenyl-2,4,6-(1H,3H,5H)pyrimidinetrione 100 mg at bedtime for 3 to 5 nights exhibited deep slumber with difficulty in awakening that was possibly caused by 5-Ethyl-5-phenyl-2,4,6-(1H,3H,5H)pyrimidinetrione in breastmilk.[8] A mother was taking 5-Ethyl-5-phenyl-2,4,6-(1H,3H,5H)pyrimidinetrione 390 mg daily and phenytoin 400 mg daily during pregnancy and postpartum. Her infant was drowsy at birth, refused to suck and was given partial formula feeding. At 5 days of age, her infant was admitted to the hospital pale and collapsed with bruising, bleeding, and a decreased hemoglobin, thought to be due to methemoglobinemia. Breastfeeding was discontinued and the infant was given a transfusion which rapidly improved her condition. On day 10, the mother resumed breastfeeding the infant. Within 24 hours the infant was extremely sedated and refused to suck and was fed breastmilk with a spoon. The sedation persisted for 2 days until breastmilk was discontinued permanently because of a return of methemoglobinemia. The extreme sedation was probably due to 5-Ethyl-5-phenyl-2,4,6-(1H,3H,5H)pyrimidinetrione in the milk and the methemoglobinemia was probably caused by the phenytoin.[9] An infant death occurred from overlying and suffocation by a parent during sleep. Sedation from 5-Ethyl-5-phenyl-2,4,6-(1H,3H,5H)pyrimidinetrione, primidone, and phenytoin in breastmilk was possibly a contributing factor. 5-Ethyl-5-phenyl-2,4,6-(1H,3H,5H)pyrimidinetrione was found in the infant's serum (8 mg/L) and liver (16 mcg/g) on autopsy.[10] Probable drug withdrawal symptoms, manifested as spontaneous tremors, occurred in a breastfed infant in the third month of life when her mother who was taking 5-Ethyl-5-phenyl-2,4,6-(1H,3H,5H)pyrimidinetrione (dose not stated) during pregnancy and breastfeeding, abruptly discontinued nursing.[11] A probable case of drug-induced drowsiness occurred in a newborn whose mother was taking primidone, carbamazepine and phenytoin (dosages not stated). At day 30, breastfeeding was discontinued because of the drowsiness that occurred after each feeding and poor weight gain. These authors also found that 13 partially breastfed infants whose mothers were taking anticonvulsants gained weight at a slower rate during the first 5 days postpartum than did 75 infants of epileptic mothers who bottle fed or control mothers taking no medications.[12]A breastfed infant whose mother was taking 5-Ethyl-5-phenyl-2,4,6-(1H,3H,5H)pyrimidinetrione 90 mg, primidone 375 mg, and carbamazepine 800 mg daily did well despite a 5-Ethyl-5-phenyl-2,4,6-(1H,3H,5H)pyrimidinetrione saliva level of 3.4 mg/L. At 7 months of age, after the mother abruptly stop nursing, the infant had a number of "startle reactions" and infantile seizures occurred which were confirmed by an abnormal electroencephalogram. Continued 5-Ethyl-5-phenyl-2,4,6-(1H,3H,5H)pyrimidinetrione administration to the infant for 15 months controlled the seizures and no more occurred up to 5 years of age.[13]

No direct effect is known, but mothers taking antiepileptic drugs stop breastfeeding earlier and supplement more than mothers not taking antiepileptic drugs. Most of these reports occurred in older studies in which sedating agents such as 5-Ethyl-5-phenyl-2,4,6-(1H,3H,5H)pyrimidinetrione and primidone were used. Infant sucking difficulties and sedation were reasons given for the reduced nursing.[12][14]