• Assess for considerations to use a lower (30 mg) starting dose and slower dose escalation:
  • Comorbid cardiac disease, severe pulmonary disease, ESRD, or cirrhosis.  
  • Lower opioid tolerance. Tolerance may be lower if the patient:
    • Does not need to use fentanyl multiple times daily to prevent/manage withdrawal.
    • Is using an opioid that is less potent than fentanyl (e.g., oxycodone).
  • Methadone-naïve. If the patient has never been on methadone, increased caution is warranted. 
  • Concurrent sedative use.
• Monitor for patient-reported opioid craving and withdrawal symptoms.
  • PRN methadone should be offered based on the patient's self-report of either withdrawal symptoms and/or cravings to use opioids.
  • A Clinical Opiate Withdrawal Scale (COWS) score is not recommended as a prerequisite for PRN methadone.
    • The COWS was designed to measure opioid withdrawal severity; it was not validated to determine when PRN methadone dosing is appropriate during methadone initiation.
    • The clinical goal during methadone titration is to treat the full spectrum of OUD symptoms, including cravings and subjective withdrawal, not only measurable withdrawal. 
    • Despite this, some clinicians have a strong preference for guiding assessment with an objective tool. In this case, a COWS of 4+ may be used to confirm appropriateness of a PRN methadone, but a low COWS score should not be used to withhold a PRN dose from a patient who reports cravings or subjective withdrawal.
• Monitoring for opioid safety
  • Monitor SpO2 and respiratory rate (RR). Interpret in conjunction with level of consciousness, work of breathing, and overall clinical status.
    • RR >12: generally safe to continue. 
    • RR 10-11: acceptable if overall clinical status is reassuring.
    • RR <10 or SpO2 <92%: hold doses until improved; consider resuming at a lower dose or extended interval.
    • RR <8: give naloxone 0.04 mg IV q4min until RR >10. 
    • If SpO2 <95% with normal RR, evaluate clinical status and comorbidities.
    • Chronically hypoxic patients require individualized pain management with close monitoring of oxygenation.
• Sedation  
  • Sedation alone should not determine opioid toxicity in opioid-tolerant patients; include the full assessment described above
  • Stimulant withdrawal, for example, can cause sedation and hypersomnia that mimics opioid over-sedation.
  • When the full assessment is reassuring, opioids should not be withheld from a patient in pain whose sedation may be attributable to stimulant withdrawal or other factors.
• ECG 12-lead for QTc monitoring
  • Patients with risk factors (e.g., heart disease, use of other QTc-prolongating medications, history of prolonged QTc) should receive an ECG. 
  • Consider a baseline ECG for any patient initiating methadone.
  • Do not delay treatment to obtain an ECG.
• Assess patient ability to connect with an opioid treatment program (OTP).
  • Ongoing dispensing of methadone for OUD can only be provided by an OTP.
  • Consider proximity, transportation, and OTP requirements (e.g., frequency of in person dosing).
  • If ongoing treatment with methadone is not feasible, offer buprenorphine instead.
  • If ongoing treatment plan is undecided, methadone or buprenorphine can be used to stabilize OUD while the patient is admitted. MOUD should be provided regardless of intent to continue it after discharge.
• Assess for and address other use disorders and withdrawal syndromes.
• Consider screening for sexually transmitted infections, including HIV, hepatitis C, syphilis, gonorrhea, and chlamydia. Consider linkage to PrEP as indicated.  

• Ensure pain and OUD symptoms are adequately controlled to prevent patient-directed discharge.
• Patients experience significant anxiety about pain.
  • A caring, supportive approach is essential.
  • Create a plan with the patient for what to do if their pain is not well controlled.
• Discussion of MOUD treatment options is more effective when pain and withdrawal are well-managed.
• Provide multimodal pain management and maximize non-opioid pain interventions. Consider acetaminophen, gabapentinoids, alpha-2 agonists, muscle relaxants, local anesthetics, regional anesthesia, and nonpharmacologic approaches. See Adjunct Medications.
• Treat acute pain with opioids, when indicated.
  • This does not worsen OUD.
  • Patients with opioid tolerance may require significantly higher than usual dose of opioid analgesics to adequately control pain. See Opioid Dosing for Acute Pain in Patients with OUD and High Opioid Tolerance.
  • There are no additional considerations for dose intervals between methadone and short acting opioids. Treat pain as indicated. There are no adjustments required related to methadone titration. 
  • Consider patient-controlled analgesia.
  • When providing high doses or multiple formulations of opioids, monitor SpO2 and respiratory rate (RR). Interpret in conjunction with level of consciousness, work of breathing, and overall clinical status. See Assessment.
• These pain considerations are not comprehensive for labor and delivery. Consult appropriate specialties.
• Discharge with a plan for ongoing pain management. Provide prescriptions, including short-acting opioids if needed, with appropriate counseling and a plan for discontinuation.

• Urine drug screening (UDS) is not needed to initiate treatment for OUD.    
  • UDS only indicates whether certain substances or their byproducts are present within a set detection window. It does not measure impairment, gauge severity of SUD, explain behavior, or rule out significant use when negative. It works best when it answers a specific clinical question and is part of a broader treatment plan.
  • False-positives and false-negatives are not uncommon.
  • If UDS is performed for clinical reasons, obtain informed consent. 
  • A positive UDS should not be conflated with child abuse or neglect. 
    • Support the dyad by providing evidence-based treatment and patient education.
    • In Washington state, substance use alone does not constitute a mandatory report to Child Protective Services. 

• Methadone is a long-acting opioid agonist that treats opioid withdrawal and lessens cravings to use extra-medical opioids.
• Methadone can be used for acute withdrawal management, even if buprenorphine is preferred for ongoing treatment. It peaks within ~2-4 hours of dosing. 
• Withdrawal management
  • Patients commonly experience withdrawal while methadone is titrated to a therapeutic dose.  
  • Manage symptoms with adjunct medications.
    • Early on, adjunct medications should be given scheduled. As patients stabilize, adjuncts can be given PRN.
    • Continue to provide PRN adjunct medications throughout the stabilization process, including prescriptions on discharge, if needed.
• For severe withdrawal
  • In addition to methadone, provide a short-acting opioid such as hydromorphone 4-8 mg PO every 3 hours PRN severe/breakthrough withdrawal. Hold for RR <12 and see Monitoring for opioid safety under Assessment, above.
  • Provide on Days 1- 2 only, as priority should be given to rapid methadone dose escalation.
• Adjust dosing as needed to adequately manage symptoms while ensuring safety.
  • Because methadone is long acting, doses accumulate by day 3 and 4 (known as “dose stacking”). If withdrawal is well managed without PRN doses on Day 3, do not increase the scheduled dose on Day 4, because of dose stacking and risk of over sedation.
  • Higher doses than recommended on days 3 and 4 increase the risk of over-sedation but may be necessary if withdrawal remains severe.
• Split (BID) methadone dosing is strongly recommended as the standard of care in pregnancy due to metabolic changes. Split dosing also allows for a faster up-titration of methadone to resolve withdrawal and reach a therapeutic dose.
• Example dosing:

Day 1: Give methadone 40 mg PO. Wait 4 hours after initial dose, then give 10 mg methadone every 4 hours PRN patient report of withdrawal/craving. Hold for RR <12.

Day 2: Give 40 mg BID, or total Day 1 dose spilt BID, whichever is less. Wait 4 hours after initial scheduled dose, then give 10 mg methadone every 4 hours PRN patient report of withdrawal/craving. Hold for RR <12.

If a patient continues to use extra-medical opioids while on methadone, a higher dose may be indicated to better manage OUD symptoms. Continued substance use is not a reason to stop treatment or consider it a failure. Methadone significantly reduces the risk of all-cause mortality for people with OUD, even with continued extra-medical opioid use.       

• For more information on methadone in pregnancy, see Medications for OUD in Pregnancy & Postpartum.
• Adolescents: 
  • Consent: In Washington State, youth age 13+ can consent to OUD treatment (including methadone) without parental consent (RCW 71.34.530).  
  • For ongoing OUD treatment after discharge: 
    • Consider whether buprenorphine or methadone is a better fit using shared decision making. 
    • Youth-specific methadone data is limited. 
    • Many OTPs are not well-equipped to provide care for youth. If considering methadone for ongoing OUD treatment, confirm there is an accessible OTP that serves youth and can accept the patient before discharge.

• Polysubstance use is not a contraindication to methadone for OUD. 
• Stimulant use
  • Stimulant withdrawal can cause sedation and hypersomnia that may be confused with over-sedation from methadone.  See Assessment.
  • Stimulant intoxication can mimic symptoms of opioid withdrawal, including dilated pupils, sweating, agitation, hypertension, tachycardia. Symptoms specific to opioid withdrawal include runny nose, yawning, and piloerection.
• Address withdrawal syndromes and other use disorders. 
  • Benzodiazepine and alcohol withdrawal must be monitored carefully and treated aggressively. 
  • Increase monitoring and consider splitting methadone dose BID if treating withdrawal syndromes with other CNS depressants. 
  • Methadone does not treat other withdrawal syndromes.

• This protocol rapidly escalates methadone to achieve a therapeutic dose. 
  • This approach is safe in observed settings with the included safety parameters, including split dosing, waiting 4 hours between PRN doses (methadone’s peak effect is typically within 2-4 hours of dosing), and holding for low respiratory rate.
  • Undertreated OUD symptoms are a well-recognized driver of patient-directed discharge and return to extra-medical opioid use, which carries greater risk to the patient and the pregnancy than medically managed, observed, rapid up titration of methadone.
• The risk of respiratory depression is lower in patients without cardiopulmonary co-morbidities, younger age, and/or high opioid tolerance (daily fentanyl use) compared to lower tolerance or opioid-naïve patients, but respiratory rate should be monitored. See Assessment.
• If withdrawal is well managed without PRN doses, do not increase the next day’s scheduled dose. 
  • Methadone is long acting; initial doses accumulate on days 3 and 4 (known as “dose stacking”). Increasing the dose when withdrawal symptoms are well managed the previous day risks over sedation.
• Use caution and increase monitoring when initiating or increasing doses of other sedating medications.  

• Dispensing methadone
  • If dispensed methadone doses are needed to bridge to care (e.g., OTP is closed or unable to accommodate patient at time of next dose), coordinate prior to discharge.
  • The facility must have a process must be in place prior to doing this. See Dispensing Methadone for Opioid Use Disorder Under the 72 Hour Rule for guidance.  
• Prescribe adjunct medications for withdrawal, if needed.
  • Patients commonly need adjunct medications to manage withdrawal symptoms until they stabilize on the medication. 
  • Prescription duration should be at least 7 days.
• Ensure the patient is discharged with naloxone in hand.

• Methadone is a safe and effective treatment for opioid withdrawal and OUD in pregnancy. It helps people with OUD have a healthier pregnancy.
• The baby may experience neonatal opioid withdrawal syndrome (NOWS) shortly after delivery. This is expected when taking methadone, is treatable, and does not cause long-term health issues. It is much riskier to leave OUD untreated.
• Patients should be strongly encouraged to discuss their MOUD treatment with their OB provider to help them plan for labor, delivery, and postpartum, including pain and NOWS management.
• Methadone can cause respiratory depression and overdose when taken at higher than prescribed doses or when combined with other sedatives. Patients should not start or increase the use of extra-medical CNS depressants, including alcohol, while starting methadone. 
• If discharging with dispensed methadone, ensure careful, comprehensive education on medication risks and appropriate dosing, including dosing at the same times each day and never combining doses. 
• Educate on overdose prevention strategies (see Discharge Instructions).
  • Emphasize that changes in opioid tolerance, particularly in the postpartum period, can increase the risk of overdose. 
  • Ensure the patient and their support system understand when and how to use naloxone.

• When possible, connect patients with social work, care navigation, and/or peer support to strengthen linkage to care.
• Discuss available OTP options for ongoing care.
• Help the patient schedule an appointment or inform them of walk-in availability for OTP intake.  
  • Hospitals enrolled in ScalaNW can call the 24/7 appointment scheduling line and receive a confirmed date, time, and location for MOUD follow up appointment during the 10-minute phone call.  
  • Hospitals not enrolled in ScalaNW may contact known sites directly or use the Washington Recovery Helpline to find available OTPs. 
  • Ensure the patient is aware of the date, time and location for follow up.  
• Prepare the patient for OTP follow up: 
  • Educate the patient on OTP expectations, which vary, but may initially include daily visits. 
  • The patient should tell the OTP that they were started on methadone in the hospital.
  • Provide the patient with documentation of methadone doses provided, including the date, time, and amount of last dose. The OTP will call the hospital pharmacy to confirm last dose, but providing this documentation can prevent delays.  
• If possible, obtain an ROI to coordinate with the receiving OTP. Send the discharge summary, including information on doses administered and bridge doses dispensed.   
• Refer to prenatal care. Encourage regular prenatal care for improved pregnancy/delivery outcomes.