Hospital morphine preparation for abstinence syndrome in newborns exposed to buprenorphine or methadone.
OBJECTIVE
This study was undertaken to evaluate the adequacy of a hospital formulated oral morphine preparation for management of neonatal abstinence syndrome (NAS) and to compare clinical features in infants exposed to methadone or buprenorphine in utero.


METHODS
Between October 1998 and October 2004 all infants born to mothers treated with buprenorphine or methadone during pregnancy were enrolled into this prospective study. Morphine hydrochloride solution (0.2 mg/ml) was prepared without preservatives under a flow laminar air box (class 100).


METHODS
Morphine solution: quantitative and qualitative HPLC analysis and microbiological study at regular intervals during storage at 4 degrees C for 6 months. Maternal characteristics: age, opiate dose during pregnancy. Neonatal characteristics: gestational age at delivery, birth weight, Lipsitz scores. Morphine dose: daily morphine dose, maximum morphine dose, duration of NAS, and duration of treatment required to achieve stable Lipsitz scores below 4.


METHODS
Kruskal-Wallis test for comparison of median values.


RESULTS
Microbiological and HPLC analysis showed that the morphine preparation remained stable for 6 months at 4 degrees C. Nine methadone-exposed infants and 13 buprenorphine-exposed infants were included in the study. All infants presented NAS requiring treatment with the morphine solution. Lipsitz scores at birth were significantly different in the methadone and buprenorphine groups (P < 0.05). The methadone group required significantly higher doses of morphine preparation than the buprenorphine group during the first 38 days of treatment (P < 0.05): 0.435 +/- 0.150 mg/kg/day vs. 0.257 +/- 0.083 mg/kg/day.


CONCLUSIONS
This hospital morphine solution is adequate for management of NAS. Preparations showed good stability and doses could be adjusted with a margin of 0.02 mg. The onset of NAS occurred within 24 h after birth in methadone-exposed infants (range 6-24 h) and within 48 h after birth in buprenorphine-exposed infants (range 24-168 h). Due to the possibility of delayed onset of NAS up to 7 days, infants born to mothers treated with buprenorphine should be kept in the hospital for an appropriate surveillance period. Treatment time was significantly longer (45 vs. 28 days) and the mean morphine doses were higher (1.7 fold) in methadone-exposed than buprenorphine-exposed infants.
Colombini
Nathalie
N
Hospital Pharmacy, Marseilles University Hospital System, Hôpital Nord, Marseille, France. nathalie.colombini@aliceadsl.fr
Elias
Riad
R
Busuttil
Muriel
M
Dubuc
Myriam
M
Einaudi
Marie-Ange
MA
Bues-Charbit
Martine
M
D002047:Buprenorphine / Q000009:adverse effects*; D002851:Chromatography, High Pressure Liquid; D004340:Drug Contamination; D004355:Drug Stability; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D008691:Methadone / Q000009:adverse effects*; D009020:Morphine / Q000008:administration & dosage* / Q000627:therapeutic use*; D009292:Narcotic Antagonists / Q000009:adverse effects*; D009294:Narcotics / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use*; D009357:Neonatal Abstinence Syndrome / Q000188:drug therapy*; D019999:Pharmaceutical Solutions; D011247:Pregnancy; D011446:Prospective Studies
D009292:Narcotic Antagonists; D009294:Narcotics; D019999:Pharmaceutical Solutions; D002047:Buprenorphine; D009020:Morphine; D008691:Methadone