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

1. “Methadone Use in Pregnancy and It's Effects on Baby” Evelyn Fulmore, Pharm.D. Supervisor, Pediatric Pharmacy Services McLeod Regional Medical Center Florence, SC

2. 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

3. 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 March of Dimes 2009

4. Statistics on Substance AbuseDemographics

5. 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

6. 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

7. Types of Opioid or Opiate Drugs • Derived fully or partially from Opium • Heroin Morphine • Codeine Fentanyl • Hydromorphone Meperidine • Oxycodone Propoxyphene • Hydrocodone Buprenorphine • Methadone • Pentazocine

8. Structural CharacteristicsOpiates vs. Heroin heroin morphine methadone codeine

9. 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

10. 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

11. 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

12. 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 Anderson IB et.al. Use of Methadone; WJM 2000; 172: 43-46

13. 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)

14. Methadone Effects on Pregnancy • Widely studied • Treatment of choice • Not harmful to the developing fetus • May prevent miscarriage, fetal distress, or premature labor Anderson IB et.al. Use of Methadone. WJM, 2000; 172: 43

15. Methadone Effects on Pregnancy • Decrease dose in the 1st trimester – increases risk for miscarriage • Metabolism changes during pregnancy • Once daily • Split dosing Anderson IB. Use of Methadone. WJM, 2000; 172: 43

16. MethadoneEffects on Baby • Does not cause fetal abnormalities • Not associated with premature and LBW • Infant can be weaned (if needed) • Breastfeeding is safe Jansson LM et.al. Methadone Maintenance and Breastfeeding. Pediatrics, 2008; 121(1):106-114

17. 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) Anderson IB et al. Use of Methadone. WJM, 172; January 2000

18. 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)

19. 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) Reckitt and Benckiser Pharmaceuticals, Inc. Product Info, 2007

20. 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 AAP Neonatal Drug Withdrawal. Pediatrics, Vol.101(6), June 1998

21. 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 (?) APP Neonatal Drug Withdrawal. Pediatrics, 1998; 101 (6): 1079-1088

22. Neonatal Abstinence Syndrome (NAS) - Assessment Scales • Lipsitz tool (1975) • Finnegan method • Ostrea system • Modified Finnegan Scoring System

23. 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

24. Autonomic Signs Increased sweating Nasal stuffiness Fever Mottling Temp instability Neonatal Abstinence Syndrome (NAS) – Clinical Features • Gastrointestinal Dysfunction • Poor feeding • Uncoordinated and constant sucking • Vomiting • Diarrhea • Dehydration • Poor weight gain AAP Neonatal Drug Withdrawal. Pediatrics, Vol.101 (6), June 1998

25. Exaggerated Moro reflex Seizures Frequent yawning and sneezing Neonatal Abstinence Syndrome (NAS) – Clinical Features • Neurologic excitability • Tremors • Irritability • Increased wakefulness • High-pitched crying • Increased muscle tone • Hyperactive deep tendon reflexes AAP Neonatal Drug Withdrawal. Pediatrics, Vol.101 (6), June 1998

26. NAS Treatment Strategies • Tincture of Opium/Paregoric* • Morphine • Methadone* • Other • Buprenorphine • Clonidine • Phenobarbital • Diazepam

27. NAS Treatment Strategies“TO” 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

28. 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

29. 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

30. Questions ?