“Methadone Use in Pregnancy and It's Effects on Baby”

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Methadone Use in Pregnancy and It's Effects on
Baby

• Evelyn Fulmore, Pharm.D.
• Supervisor, Pediatric Pharmacy Services
• McLeod Regional Medical Center
• Florence, SC

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Objectives

• Overview of Opiate Addiction in pregnancy
• Describe the use of methadone in opiate-dependent
  pregnant patient
• Discuss the effects of maternal methadone use on
  the newborn
• Review current treatment strategies for opiate
  abstinence syndrome in the newborn

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Statistics on Substance Abusein Pregnancy

• 4 percent of pregnant women use illicit drugs
  such as marijuana, cocaine, Ecstasy and other
  amphetamines, and heroin
• 50 of all babies of heroin users are born with
  low birth weight
• Babies exposed to heroin have increase risk of
  SIDS
• Stopping heroin abruptly during pregnancy may
  increase risk of death of the baby

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Statistics on Substance AbuseDemographics
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Overview of Addiction (Opioids)

• Naturally occurring opioids Endorphins
• Endorphins aka the morphine within
• Function identical to heroin or morphine
• Provide pain control, learning, regulating body
  temp, etc.
• Addiction assoc with use of opioids connected to
  chemical imbalance and damage

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Medications Used to Treat Opiate Addiction

• Methadone (Dolophine, Methadose, Methadose oral
  concentrate)
• Given orally
• Used throughout pregnancy
• Neonatal Abstinence Syndrome (NAS)
• Buprenorphine (Subutex, Suboxone)
• Given sublingually
• Limited studies in treatment of NAS

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Types of Opioid or Opiate Drugs

• Derived fully or partially from Opium
• Heroin
  Morphine
• Codeine Fentanyl
• Hydromorphone Meperidine
• Oxycodone Propoxyphene
• Hydrocodone Buprenorphine
• Methadone
• Pentazocine

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Structural CharacteristicsOpiates vs. Heroin
heroin
morphine
methadone
codeine
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Methadone

• C-II narcotic (opioid) µ receptor agonist
• a substitute for opiate drugs of abuse heroin
• produces similar effects and reduces withdrawal
  symptoms

methadone
heroin
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Methadone

• 40 mg dispersible tab - must be dissolved in
  water/juice
• 5 and 10 mg regular tablets
• 1 mg/ml or 10 mg/ml concentrate note
  concentrate must be mixed in water/juice

40 mg tab
5 and 10 mg tablets
10 mg/ml oral conc
1 mg/ml oral soln
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MethadoneTreatment of Opioid Abuse

• Goal of maintenance therapy
• Does not create euphoria, sedation, or analgesia
• Endpoint cravings stop
• Establish individualized dosing
• Usually require 60 to 120 mg/day

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MethadoneSide effects

• Long t-1/2 may result in overdose
• Potential for apnea, respiratory failure,
  seizures
• Be aware of multiple drugs that can potentiate
  effects
• Important Noncardiogenic pulmonary edema has
  resulted from therapeutic doses
• Other sweating, constipation, weight gain,
  urinary retention

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MethadoneDrug Interactions

• May increase or decrease effectiveness
• Rifampin, phenytoin, carbamazepine, HIV meds
• Amitriptyline, ketaconazole, fluvoxamine
• Drugs to avoid block effects of Methadone
• Pentazocine (Talwin)
• Naltrexone (Revia)
• Tramadol (Ultram)

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Methadone Effects on Pregnancy

• Widely studied
• Treatment of choice
• Not harmful to the developing fetus
• May prevent miscarriage, fetal distress, or
  premature labor

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Methadone Effects on Pregnancy

• Decrease dose in the 1st trimester increases
  risk for miscarriage
• Metabolism changes during pregnancy
• Once daily
• Split dosing

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MethadoneEffects on Baby

• Does not cause fetal abnormalities
• Not associated with premature and LBW
• Infant can be weaned (if needed)
• Breastfeeding is safe

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Methadone Maintenance tx in Pregnancy

• Do better if treated with methadone
• Longer gestational periods
• Higher birth weights
• Lower risk of exposure to HIV
• Neonates/premature infants born to women
  dependent to methadone at risk for neonatal
  abstinence syndrome (NAS)

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Buprenorphine(Suboxone/Subutex)

• FDA approved
• Treatment of opioid addiction
• Relieves withdrawal, reduces cravings, and blocks
  the effects of heroin and other opiates
• Maintenance doses 12 to 32 mg/day (sublingually)
• Doses must be individualized (like Methadone)
• Suboxone contains naloxone (hard to overdose)

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Buprenorphine(Suboxone/Subutex)

• Prescribers must be trained
• Internet or one day course
• A directory of prescribers can be found at
• http//buprenorphine.samhsa.gov/bwns_locator
• Doses must be individualized (like Methadone)

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Neonatal Abstinence Syndrome (NAS) - Definition

• NAS is a complex of signs and symptoms in the
  postnatal period associated with the sudden
  withdrawal of maternally transferred opioid

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Neonatal Abstinence Syndrome (NAS)

• 60-90 of infants born to substance abusing
  mothers will develop signs and symptoms of NAS
• 50-75 will require treatment
• The onset of withdrawal is 48 to 72 hours after
  delivery
• Larger doses of methadone in late pregnancy
  associated with greater risk for withdrawal
• Weaning of methadone in late pregnancy (?)

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Neonatal Abstinence Syndrome (NAS) - Assessment
Scales

• Lipsitz tool (1975)
• Finnegan method
• Ostrea system
• Modified Finnegan Scoring System

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Neonatal Abstinence Syndrome (NAS) - Diagnosis

• A maternal history of substance abuse during
  pregnancy often forms the basis for diagnosis of
  NAS
• AAP recommends the use of an objective abstinence
  scoring method to measure the severity of
  withdrawal
• APP favors the Lipsitz method for NAS scoring

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Neonatal Abstinence Syndrome (NAS) Clinical
Features

• Autonomic Signs
• Increased sweating
• Nasal stuffiness
• Fever
• Mottling
• Temp instability

• Gastrointestinal Dysfunction
• Poor feeding
• Uncoordinated and constant sucking
• Vomiting
• Diarrhea
• Dehydration
• Poor weight gain

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Neonatal Abstinence Syndrome (NAS) Clinical
Features

• Neurologic excitability
• Tremors
• Irritability
• Increased wakefulness
• High-pitched crying
• Increased muscle tone
• Hyperactive deep tendon reflexes

• Exaggerated Moro reflex
• Seizures
• Frequent yawning and sneezing

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NAS Treatment Strategies

• Tincture of Opium/Paregoric
• Morphine
• Methadone
• Other
• Buprenorphine
• Clonidine
• Phenobarbital
• Diazepam

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NAS Treatment StrategiesTO Dosing

• Tincture of Opium TO (10 mg/ml)
• Start at 0.1 ml/kg or 2 drops/kg with feedings
  every four hours
• Increased by 2 drops/kg every 2 hours as needed
• After symptoms stabilize over 3 to 5 days, begin
  taper
• 25 fold dilution of TO is the morphine
  equivalent to Paregoric 0.4 mg/ml

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NAS Treatment StrategiesMethadone Dosing

• Methadone
• 0.05 to 0.1 mg/kg every 6 hours with increase of
  0.05 mg/kg until signs controlled. After signs
  controlled give dose every 12 to 24 hours (AAP,
  1998)
• 0.05 to 0.2 mg/kg every 12 to 24 hours (Neofax)
• 0.5 mg/kg/day divided every 8 hours (Lexicomp)
• Tapering
• Decrease dose by 10 to 20 per week over 1 to
  1-1/2 months

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Conclusion

• Maternal use of methadone will continue to
  increase as prescription opioids and illicit
  drugs are used
• Larger maternal doses of methadone may result in
  delayed withdrawal in the infant
• Implementing a hospital specific NAS policy is
  recommended
• Evaluate the effectiveness of your NAS policy
• Training and education of all disciplines

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Questions ?