Opioid Use Disorder- Pregnancy Principles and Myths Brian Iriye MD - PowerPoint PPT Presentation

Opioid Use Disorder- Pregnancy Principles and Myths Brian Iriye MD and Farzad Kamyar MD High Risk Pregnancy Center

History of NAS / NOWS • Prior t o 1875 infant s not t hought t o be affect ed • Congenit al Morphinism • Normal at birth • Crying inconsolably day 3 of life • S ometimes developed seizures • Frequently fatal • 1901 • Result of withdrawal • Give babies small quantities of morphine to ease the symptom • S ympt oms occur in 60-80% of neonat es • Neonat al Opioid Wit hdrawal S yndrome (NOWS )

Again, this is data up to 2012

Cost of NAS • 2009 • $732 million hospital cost • 3.4/ 1000 births • 2012 • $1.5 billion • 5.8 / 1000 births • 81% of costs - Medicaid Patrick Am J Perinatol 2015

Increase in Opioid Rxs

Opioid Rx Map

Overdose Death Rates as a S ign of S UD

Maternal Mortality Rates- US A vs Developed Nations

Maternal Mortality Texas: 2012-2015 Total Maternal 382 Deaths Deaths from Drug OD 64 (16.7% ) Deaths from Opioid 37 OD Opioid 23 Heroin 18 Fentanyl 1

Pregnancy Associated Deaths and Drugs % of total deaths 25 20 15 10 5 0 Texas Maryland Alaska Georgia Virginia % of t ot al deat hs

Methadone Vs Buprenorphine in Pregnancy Jones NEJM 2010

Methadone Vs Buprenorphine in Pregnancy Jones NEJM 2010

Pros of Buprenorphine vs Methadone •Lower risk of overdose •Fewer drug interactions •Ability to be treated in a private office setting without the need for daily visits to a licensed treatment program •Dosing of buprenorphine is similar to that in nonpregnant women •Insurance in the United States may cover buprenorphine prescribed by a private physician in an office setting, while not covering methadone dispensed in a licensed opioid treatment program •Fewer side effects •Low risk of adverse cardiovascular side effects (in contrast, methadone is associated with small increase in risk of arrhythmia) •For the newborn, in utero exposure to buprenorphine rather than methadone may result in a lower risk of preterm birth, higher birth weight, larger head circumference, and, potentially, a lower rate and severity of neonatal withdrawal

Cons of Buprenorphine Vs Methadone •Only limited data are available on pregnancy outcomes after first trimester exposure •Lack of long-term neurodevelopmental outcome data •Clinically important patient dropout rate due to dissatisfaction with the drug •More difficult induction protocol with the potential risk of precipitated withdrawal •Increased risk of diversion -especially the buprenorphine monotherapy formulation •Less stringent structure of some office-based treatment programs •Reports of maternal hepatic dysfunction and elevated transaminases •Effects of buprenorphine are only partially reversible by naloxone •The maximum daily dose of buprenorphine is 32 mg, due to a ceiling effect, which may not be sufficient in all women (usually those requiring more than 140 mg per day of methadone) •More expensive than methadone •Treatment with methadone may result in greater reduction in illicit opioid use

Buprenorphine in Pregnancy • Drug dosing similar to non-pregnancy women with standard induction protocols • Initiation after obj ective observable signs of moderate opioid withdrawal • Greater than 6 hours after short acting opioid • 24-48 hours after longer acting opioids • Dose adj ustments may be needed with increasing gestational age • Blood volume increases from 5 to 8 L in pregnancy • Maximum blood volume and cardiac output at 28 weeks • Maintain dosing intrapartum and postpartum • Women should be encouraged to breastfeed • Less than 1% of maternal dose in breast milk

Buprenorphine Administration • Very important to discuss and educate patient on sublingual administration • Ingested buprenorphine gets extensively first pass metabolized with extremely poor bioavailability. What they swallow will not work. • Conservative recommendation to place under tongue and • Do not eat , drink, t alk or smoke for 30 minut es • Let complet ely dissolve

Buprenorphine Induction etting can vary [Inpatient  Office  Home] • S • Patient should be abstinent • From short acting opioid for > 6 hours (have them stop the day before) • From long acting opioids from 1-3 days (ie. Methadone) • Key here is to monitor for signs and symptoms of “ mild to moderate” withdrawal, not j ust time since last use • S core signs and symptoms using the Clinical Opiate Withdrawal S cale (aka COWS ). • Looking for COWS score of ~10-12 • This will lessen the likelihood of precipitated withdrawal

Buprenorphine Induction Cont. Day 1 • Administer test dose to patient of 2-4 mg sublingually • Monitor for ~2 hours • If still experiencing withdrawal symptoms can administer another 2-4 mg dose • This can be repeated later in the day when the patient is at home depending on previous dosing • Max on day one 8 mg

Buprenorphine Induction Cont. Day 2 • Administer total dose from day 1 sublingually • Monitor for ~2 hours • If still experiencing withdrawal symptoms can administer another 2-4 mg dose • This can be repeated later in the day when the patient is at home depending on previous dosing • Max on day two 12 mg

Buprenorphine Induction Cont. Day 3 • Administer total dose from day 2 sublingually • Monitor for ~2 hours • If still experiencing withdrawal symptoms can administer another 2-4 mg dose • This can be repeated later in the day when the patient is at home depending on previous dosing • Max on day three 16 mg • This will likely be the stabilization dose • Continue this dose for next several days to let it reach steady state

Buprenorphine S tabilization and Maintenance • Early on recommend more frequent visits (ie. Weekly) and can advance as patient becomes more stable with their sobriety (ie. Monthly) • Perform Urine Drug S creen testing – make sure to test for buprenorphine • If patient experiences cravings, withdrawal symptoms, return to substance use, etcetera. Assess needs, reasons, social situation, other stressors • Consider increasing frequency of visits • Consider increased intensity of treatment (including behavioral interventions) • Consider increasing dose or split dosing • Most will stabilize and maintain on 8-16 mg daily. • Consider capping maximum dose at 24 mg daily (per guideline recommendations)

S ubutex vs S uboxone • No reason for preferential starting of one over the other in pregnancy • Past concerns of naloxone in suboxone probably unwarranted • Do to risks of diversion, suboxone use will probably expand • No need to preferentially switch a patient already on either medication

Methadone Risks--Reprotox • Neonatal effects that were related to the gestational use of this agent included prematurity, low birth weight, microcephaly, j aundice, thrombocytosis, arrhythmias, abnormal flash visual evoked potentials, the neonatal abstinence syndrome, lower language and cognition scores, and poorer neurological development, particularly with respect to executive function, up to 57 months of age • Quick Take: Experimental animal studies show congenital anomalies to be increased in the offspring of some species after pregnancy exposure to high dose levels of methadone. The main concern in humans has been neonatal withdrawal after antepartum exposure to methadone.

S ubutex Risks (buprenorphine) • Placental transfer of buprenorphine might be limited in comparison with other opioids including methadone, thereby limiting fetal exposure and the development of dependency. • However, there are reports of neonatal abstinence syndrome of variable intensity that might occur less often or subside sooner than in methadone-exposed infants. S tudies indicated better outcome as evaluated by Apgar score, birth length, respiratory distress, or preterm labor with buprenorphine compared with methadone. • Quick t ake: Based on experiment al animal st udies, buprenorphine exposure during pregnancy is not expect ed t o increase t he risk of adverse out comes at birt h but might produce lat er behavioral changes. As wit h ot her opioids, a neonat al abst inence syndrome can occur.

S uboxone Risks- Buprenorphine/ naloxone • S ame as buprenorphine • For Naloxone Component: Quick take: Based on experimental animal studies, use of naloxone during pregnancy is not expected to increase the risk of congenital anomalies. • It is not known whether naloxone administration to pregnant women might increase the risk of preterm labor by blocking the endogenous opioid suppression of oxytocin release from the posterior pituitary, a phenomenon observed in rats- BUT THIS IS NOT S EEN IN LIMITED S TUDIES WITH S UBUXONE IN PREGNANCY IN HUMANS • There is a decrease in prolactin after naloxone administration (not oral dose)- Old Category C • Oral bioavailability of naloxone is 0.5-2.0%

NAS and Newborn HC Visconti, Towers 2015 AJP

These pregnancies require special ultrasound follow up during pregnancy- usually only available in MFM centers