Is Primidone safe while breastfeeding?

Effects on the breastfed infant

An infant death occurred from overlying and suffocation by a parent during sleep. Sedation from primidone, phenobarbital and phenytoin in breastmilk was possibly a contributing factor. Phenobarbital was found in the infant's serum (8 mg/L) and liver (16 mcg/gram) on autopsy.[ 9 ] A mother with epilepsy was taking primidone 250 mg 3 times daily and valproic acid 2.4 g daily during pregnancy and postpartum. During the second week postpartum, her breastfed infant was sedated. Breastfeeding was stopped and the drowsiness cleared.[ 1 ] The sedation was possibly caused by primidone in breastmilk. A woman taking primidone 1 gram daily and carbamazepine 1 gram daily during pregnancy and postpartum breastfed her infant for 5 weeks and noted no difference in the infant's activity before and after nursing.[ 3 ] 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 15 partially breastfed infants whose mothers were taking anticonvulsants, including primidone, 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.[ 10 ] Possible drug-related drowsiness, pallor and feeding difficulties were reported in a 4-day-old whose mother was taking primidone 625 mg, phenobarbital 100 mg, phenytoin 200 mg and sulthiame 200 mg daily during pregnancy and postpartum. Nasogastric feeding was required for 5 weeks, during with time the infant continued to be partially breastfed.[ 6 ] In a cohort study of women who were taking primidone during pregnancy and their infants, 7 infants had withdrawal symptoms after birth. Of these infants, one was partially breastfed and the rest were not breastfed. In contrast, five infants who were breastfed did not

Effects on milk supply

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 phenobarbital and primidone were used. Infant sucking difficulties and sedation were reasons given for the reduced nursing.[ 10 , 14 ]

Levels in milk

Primidone is metabolized to phenobarbital and phenylethylmalonamide (PEMA) which have sedating and anticonvulsant properties. In published reports of anticonvulsant use during breastfeeding, most women were taking a combination of anticonvulsants. Some other anticonvulsants (e.g., phenytoin, carbamazepine) stimulate the metabolism of other drugs including anticonvulsants, whereas others (e.g., valproic acid) inhibit the metabolism of other drugs. Therefore, the relationship of the maternal dosage to the concentration in breastmilk can be quite variable, making calculation of the weight-adjusted percentage of maternal dosage less meaningful than for other drugs in this database. Maternal Levels. An epileptic mother was taking primidone 250 mg 3 times daily and valproic acid 2.4 grams daily during pregnancy and postpartum. During the second week postpartum, a breastmilk primidone level was 6 mg/L, which was 50% of her serum level. Primidone metabolites were not measured.[ 1 ] Twelve primidone breastmilk levels were measured between days 3 and 32 postpartum at unstated times after the dose in an unstated number of women who were taking primidone and other anticonvulsants in unstated dosages. Primidone levels averaged 2.3 mg/L (range 0.8 to 2.8 mg/L), while maternal serum levels averaged 2.8 mg/L.[ 2 ] An epileptic woman was taking primidone 1 gram daily and carbamazepine 1 gram daily during pregnancy and postpartum. At 5 weeks postpartum, a milk sample was measured. The milk fat contained 11 mg/L while the skimmed portion contained 9.1 mg/L of primidone. At the same time, phenobarbital levels in milk fat and skimmed milk were 11.2 and 11.4 mg/L, respectively.[ 3 ] Four mothers taking an average dosage of 7.3 mg/kg daily of primidone had breastmilk levels measured of primidone and its metabolites at various times during days 4 to 27 days postpartum. One of the mothers was also taking valproic acid. Average milk levels were as follows: primidone 4.2 mg/L, PEMA 2 mg/L, an

Alternatives LactMed lists

• Divalproex
• Gabapentin
• Lamotrigine
• Oxcarbazepine
• Phenytoin
• Valproic Acid