Consequences and Treatment of Opioid Abuse During Pregnancy. Katie Ellis, PharmD March 12, 2018

Transcription

1 Consequences and Treatment of Opioid Abuse During Pregnancy Katie Ellis, PharmD March 12, 2018

2 Disclosure I have nothing to disclose.

3 Objectives At the completion of this activity, the pharmacist will be able to: 1. Identify the short term and long term effects of opioid abuse in pregnancy. 2. Interpret data in relation to the opioid epidemic in South Carolina and nationwide. 3. Recommend potential treatment options for an opioid-dependent pregnant female to optimize maternal outcomes. 4. Develop a regimen for the treatment of neonatal abstinence syndrome. At the completion of this activity, the pharmacy technician will be able to: 1. Identify the short term and long term effects of opioid abuse in pregnancy. 2. Interpret data in relation to the opioid epidemic in South Carolina and nationwide. 3. Describe the treatment options for opioid abuse during pregnancy and for the neonate experiencing neonatal abstinence syndrome.

4 Poll Questions Text KATIEELLIS001 TO once to join Then A, B, C, or D

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6 Opioid Use Disorder Repeated occurrence within a 12 month period of 2 or more of 11 problems Craving Tolerance Withdrawal Use in physically hazardous situations Failure to fulfill major role obligations Great deal of time spent on activities necessary to obtain, use or recover from effects Taken in larger amounts or over longer period than was intended Giving up on important life events to use Unsuccessful efforts to cut down or control use Inability to cut down or control use Continued use despite recurrent social problems American Psychiatric Association, 2013

7 Opioid Use Disorder Pattern of opioid use characterized by tolerance, craving, inability to control use and continued use despite adverse consequences A chronic, treatable disease Behavior therapy Recovery support MEDICATIONS ACOG Committee Opinion Number 711, August 2017

8 Mechanism of Opioid Addiction Opioids bind to G-protein coupled receptors in the brain to produce a pleasurable sensation Mu, delta, kappa, nociceptin-orphanin FQ Depressed respiration could lead to respiratory arrest and death Drug seeking behavior, physical dependence, tolerance, and withdrawal Obstetrics & Gynecology. 2017; 130 (1): 10-28

9 Opioid Use in SC 135% increase in service utilization at statefunded substance use disorder treatment programs from % increase in the number of attempts to reverse opioid overdose by EMS personnel from : 594 opioid-related overdose deaths SC DAODAS Opioid Fact Sheet Available at:

10 Opioid Use Nationally Heroin use among women of childbearing age increased 31% from 2012 One third of reproductive-aged women on Medicaid fill a prescription for an opioid medication each year and one fourth with private insurance Every 3 minutes, a women seeks care in an emergency department related to prescription opioid misuse Obstetrics & Gynecology. 2017; 130 (1): 10-28

11 Substance Abuse Rates in Pregnancy 16% 14% 12% 10% 8% 6% 4% 2% 0% 18% 16% 14% 12% 10% 8% 6% 4% 2% 0% yo yo yo US Department of Health and Human Services Data; Available at:

12 Prenatal Care and Treatment Avoid for fear of legal consequences Prenatal care greatly reduces negative effects of substance abuse Decrease risk of low birth weight and prematurity Substance abuse treatment programs Decrease need for mechanical ventilation Reduce premature delivery and low birth weight J Perinatol 2003;23: J Perinatol 2003; 23:3-9. J Perinatol 2008; 28:

13 Screening and Resources Screening, Brief Intervention and Referral to Treatment (SBIRT) for pregnant Medicaid patients Screenings: WHO recommends healthcare professionals ask all pregnant women about their use of alcohol and other substances SC DAODAS SAMHSA s National Helpline: HELP

14 Substance Abuse Effects in Pregnancy Pregnancy complications Spontaneous abortion/fetal demise Premature delivery/prom Placental disorders Gestational diabetes, eclampsia, post-partum hemorrhage, infection Fetal/infant Congenital anomalies Gastroschisis, cardiac, cleft lip/palate Neurological/developmental deficits Decreased head circumference Cognitive deficits, behavioral/social problems Withdrawal ACOG Committee Opinion Number 711, August 2017

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16 Recommendations ACOG: Opioid agonist pharmacotherapy is the recommended therapy for pregnant women with opioid use disorder WHO: methadone or buprenorphine American Society of Addiction Medicine: methadone or buprenorphine No agreement on whether intrauterine exposure to buprenorphine or methadone results in longlasting developmental problems

17 Maintenance Therapy Options Methadone MOA: a synthetic opioid receptor agonist with pharmacological activity similar to that of morphine The higher the dose, the greater the effect Indication: for use in the treatment of opioid drug addictions, for use as an analgesic for moderate to severe pain Experience for narcotic abstinence since 1964 Buprenorphine MOA: Has both partial opioid agonist and opioid antagonist activity, providing a milder effect than full agonists After a certain dose, higher dose does not give more effect Indication: substitution treatment for opioid drug dependence Introduced in 2002

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20 Good Outcomes Adequate, individualized dosing Methadone: 100% risk of leaving treatment if dose <60 mg, 40% if mg, and 20% if 80+ mg Length of retention in treatment Consistent relationship with the same counselor Psychosocial services Med J Aust. 1993; 159(9): 640

21 Benefits of Methadone in Pregnancy Improve compliance with obstetric care for mother Decreased IV drug abuse, illicit drug use, and risk of HIV and hepatitis Improved fetal/neonatal outcomes Higher birth weights Lower rates of preterm birth, fetal mortality and neonatal death Greater chance of being discharged home with his or her parents Clin Perinatol. 1999;26(1): Obstetrics & Gynecology. 2017; 130 (1): 10-28

22 Methadone s Black Box per 1000 with methadone per 1000 with buprenorphine Drug Alcohol Depend 2009; 104: See next slide Heart 2007; 93: Adapted with permission from Sherry Luedtke, PharmD, FPPAG

23 QTc prolongation Methadone Buprenorphine Exposure effect Dose effect No Effect Heart 2007; 93: Adapted with permission from Sherry Luedtke, PharmD, FPPAG

24 Treatment Adherence Methadone (n=89) Buprenorphine (n=86) Treatment stopped by mother (%) NEJM 2010; 363:

25 Methadone vs. Buprenorphine Methadone group Buprenorphine group Treated for NAS (%) Duration of hospital stay (days) Duration of treatment for NAS (days) Total dose of morphine for NAS (mg) ± ± ± ± ± ± 0.7 NEJM 2010; 363:

26 Neonatal Outcomes Maternal methadone associated with a higher incidence of preterm labor and more respiratory distress in neonates at time of delivery Methadone exposed neonates Higher total NAS scores Required earlier treatment with morphine compared to buprenorphine-exposed neonates Tremors, hyperactive Moro reflex, irritability and failure to thrive all increased Obstetrics & Gynecology. 2017; 130 (1): 10-28

27 Neonatal Outcomes Buprenorphine-exposed neonates Higher mean gestational age Greater weight, length, and head circumference at birth Obstetrics & Gynecology. 2017; 130 (1): 10-28

28 Summary Characteristics Methadone Buprenorphine Dosing Directly observed therapy Outpatient prescription Convenience Retention rates Daily visit to federally certified clinic Higher in treatment settings (78.1%) Breastfeeding Safe Safe Ceiling effect? No Yes Drug interactions Yes-CNS depressants and CYP3A4 inhibitors/inducers Duration of NAS Longer Shorter Dispensed from office weekly or biweekly Lower in treatment settings (57.7%) Yes-CNS depressants and CYP3A4 inhibitors 1 st dose 20 mg (range mg) 2-4 mg (sublingual) Polysubstance abuse Preferred for long standing abuse May be more effective for Rx opioid use/new heroin use Cost ~$65/6 months ~$1500/6 months

29 Neonatal Abstinence Syndrome A drug withdrawal syndrome that occurs after in utero exposure to opioids (or other substances) Hyperactivity of central/autonomic nervous systems and GI tract SC: Incidence increased from 0.9 per 1000 births in 2000 to 3.9 in 2013 Curr Opin Pediatr. 2018; 30: 1-5 MMWR. 2016; 65:

30 NAS Incidence Rates per 1000 births MMWR. 2016; 65:

31 Timeline Withdrawal symptoms develop in 55-94% of infants exposed to opioids in utero Methadone: within 3-5 days of birth, can last days to weeks Buprenorphine: within 48 hours of birth, peaking at hours Obstetrics & Gynecology. 2017; 130 (1): 10-28

32 Abrupt Discontinuation of Opioid Increased receptor activity Adenyl Cylcase NT activity Corticotropin Stress Hyperphagia Seroto i Sleep disturbance Norepi ephri e Hyperthermia Hypertension Tremors Tachycardia Adapted with permission from Sherry Luedtke, PharmD, FPPAG Dopa i e Irritability Anxiety Acetylcholi e Diarrhea Vomiting Sneezing Yawning Diaphoresis

33 NAS Symptoms Symptom variations Maturity Severity Presentation Confounding variables Concomitant disease Infection Noise/overstimulation Underlying disease state Polydrug abuse symptoms overlap Difficult to discern causative agent Obstetrics & Gynecology. 2017; 130 (1): 10-28

34 Symptoms of Withdrawal CNS Irritability Agitation Anxiety Grimacing Increased muscle tension Sleep disturbance Inconsolable or high pitched crying Exaggerated Moro reflex Tremors Pupil dilatation Hallucinations Seizures Gastrointestinal Diarrhea Feeding intolerance Vomiting Sympathetic Hyperactivity Sweating Fever Tachypnea Tachycardia Hypertension Sneezing Mottling Yawning Obstetrics & Gynecology. 2017; 130 (1): 10-28

35 Scoring Tool Finnegan Neonatal Abstinence Scoring System is most widely used Start at 2 hours of life and assess every 3-4 hours, minutes after feeding Obstetrics & Gynecology. 2017; 130 (1): 10-28

36 Management of the Neonate Goals Improve severe symptoms Reduce weight loss Improve diarrhea and discomfort Prevent withdrawal which could lead to seizures Issues Detection of drug use Presentation (term vs pre-term) Monitoring Scoring system Decision to initiate therapy Obstetrics & Gynecology. 2017; 130 (1): 10-28

37 Non-Pharmacologic Interventions Encourage parental involvement Holding/rocking, skin to skin time Rooming in with mother prior to discharge Encourage breast feeding when appropriate Massage/range of motion exercise Avoid unnecessary sensory stimulation Obstetrics & Gynecology. 2017; 130 (1): HHS Publication No. (SMA) Rockville, MD: Substance Abuse and Mental Health Services Administration, 2018.

38 Pharmacologic Treatment The rule : consecutive scores average >8 or consecutive scores >12 First line: Morphine or methadone Score Initial morphine dosing mg/kg/dose mg/kg/dose mg/kg/dose > mg/kg/dose Add second medication if symptoms not controlled on total daily dose of morphine 1 mg/kg/day Obstetrics & Gynecology. 2017; 130 (1):

39 Additional Therapy Phenobarbital if polysubstance exposure is suspected or if scoring due to CNS disturbances Clonidine: when would we recommend? Autonomic over-stimulation Sweating, fever, yawning, sneezing Pediatrics. 2009; 123:e849-e856

40 Weaning Morphine When NAS scores are stable, decrease dose by 10% of the stabilizing dose once a day Allow hours between morphine weans Discontinue when infant has tolerated 0.02 mg/kg/dose for hours Pediatrics. 2012; 129 (2): e

41 Summary Incidence of NAS is increasing Morphine and methadone are considered first line agents for the treatment of NAS Important to have a scoring system in place Wean slowly to prevent withdrawal

42 Consequences and Treatment of Opioid Abuse During Pregnancy Katie Ellis, PharmD March 12, 2018