Version July 2025
| First-line therapy (opioids) | ||||
| Drug | Initial dose | Dose adjustment | Weaning | |
| Morphine | 0.03 to 0.05 mg/kg per dose orally every 3 to 4 hours. Higher initial doses occasionally may be required if the newborn has severe NAS signs and symptoms. | If symptoms are not controlled, may increase by 0.03 to 0.05 mg/kg per dose (maximum dose 0.2 mg/kg per dose orally). | Once NAS symptoms are controlled, wean dose by 10% to 20% every 24 to 48 hours. Discontinue morphine when the total daily dose is ≤0.04 mg/kg per day, provided that the newborn is stable without severe NAS signs or symptoms. | |
| Methadone | 0.05 to 0.1 mg/kg per dose orally every 6 hours. | If symptoms are not controlled, may increase by 0.05 mg/kg per dose. | Once NAS symptoms are controlled, wean dose by 10% to 20% every 24 to 48 hours. Discontinue methadone when the total daily dose is ≤0.05 mg/kg per day, provided that the newborn is stable without severe NAS signs or symptoms. | |
| Second-line add-on agents (for newborns with refractory NAS) | ||||
| Drug | Initial dose | Dose adjustment | Weaning | |
| Clonidine | 0.5 to 1 micrograms/kg per dose every 4 to 6 hours. | If symptoms are not controlled, may increase dose by 0.25 micrograms/kg per dose (maximum daily dose 12 micrograms/kg per day). | Clonidine should be weaned after fully tapering off the opioid agent (morphine or methadone). Decrease clonidine dose by 10% to 20% every 48 hours. Discontinue clonidine when the total daily dose is <1 microgram/kg per day. | |
| Phenobarbital | Loading dose (optional): 15 to 20 mg/kg given orally or intravenously. Maintenance dose (begin 12 hours after loading dose): 3 to 5 mg/kg per day divided every 12 hours orally or intravenously. | If symptoms are not controlled, may increase dose by 1 to 5 mg/kg per day. For newborns requiring dose escalation and/or ongoing treatment, plasma drug levels should be monitored and maintained <30 mg/dL (<130 micromoles/L). | Phenobarbital should be weaned after fully tapering off the opioid agent (morphine or methadone). Wean phenobarbital dose by 10% to 20% every other day. | |
This table summarizes the dosing of agents that are commonly used for treatment of NAS. The main goal of pharmacologic therapy is to reduce functional limitations caused by acute NAS manifestations. In general, pharmacologic therapy is warranted for infants whose withdrawal signs compromise their ability to feed, interact with caregivers, or regulate movements or autonomic function, despite adequate and individualized nonpharmacologic care. The threshold used for initiating treatment differs depending on the NAS assessment tool used. Refer to UpToDate topics on NAS for additional details.
The guidance in this table applies to term neonates. For dosing guidance for preterm neonates, refer to the drug monograph for the specific agent.