Introduction: Sublingual buprenorphine is effective for opioid dependence treatment but associated with misuse, abuse, and diversion. The present Phase I/II study evaluated a novel buprenorphine subcutaneous depot formulation for once-weekly dosing (CAM2038 q1w) in patients receiving maintenance treatment for opioid use disorder with daily sublingual buprenorphine.
Results: Single doses of CAM2038 q1w indicated dose-proportional buprenorphine pharmacokinetics (Cmax and AUC0-7d), with time to Cmax 20h and an apparent terminal half-life of 3-5days, supporting once-weekly dosing. On average, patients showed a rapid and extended decrease in opiate-withdrawal symptoms from baseline, with zero or very low SOWS and COWS values measured at least up to 7days after dosing of CAM2038 q1w. The median time to first use of rescue buprenorphine was 10days. No dose dependence was seen in the pharmacodynamics, attributable to the selection of CAM2038 q1w doses based on patients' pre-study maintenance doses. CAM2038 q1w was safe and generally well tolerated.
The Rights of Patients with Opioid Use Disorder
Conclusions: Pharmacokinetics and pharmacodynamics of a novel buprenorphine subcutaneous depot formulation for once-weekly dosing was evaluated, suggesting utility in maintenance treatment of patients with opioid use disorder.
ABSTRACT: Opioid use in pregnancy has escalated dramatically in recent years, paralleling the epidemic observed in the general population. To combat the opioid epidemic, all health care providers need to take an active role. Pregnancy provides an important opportunity to identify and treat women with substance use disorders. Substance use disorders affect women across all racial and ethnic groups and all socioeconomic groups, and affect women in rural, urban, and suburban populations. Therefore, it is essential that screening be universal. Screening for substance use should be a part of comprehensive obstetric care and should be done at the first prenatal visit in partnership with the pregnant woman. Patients who use opioids during pregnancy represent a diverse group, and it is important to recognize and differentiate between opioid use in the context of medical care, opioid misuse, and untreated opioid use disorder. Multidisciplinary long-term follow-up should include medical, developmental, and social support. Infants born to women who used opioids during pregnancy should be monitored for neonatal abstinence syndrome by a pediatric care provider. Early universal screening, brief intervention (such as engaging a patient in a short conversation, providing feedback and advice), and referral for treatment of pregnant women with opioid use and opioid use disorder improve maternal and infant outcomes. In general, a coordinated multidisciplinary approach without criminal sanctions has the best chance of helping infants and families.
The American College of Obstetricians and Gynecologists (ACOG) makes the following recommendations and conclusions:Early universal screening, brief intervention (such as engaging the patient in a short conversation, providing feedback and advice), and referral for treatment of pregnant women with opioid use and opioid use disorder improve maternal and infant outcomes.
For pregnant women with an opioid use disorder, opioid agonist pharmacotherapy is the recommended therapy and is preferable to medically supervised withdrawal because withdrawal is associated with high relapse rates, which lead to worse outcomes. More research is needed to assess the safety (particularly regarding maternal relapse), efficacy, and long-term outcomes of medically supervised withdrawal.
Infants born to women who used opioids during pregnancy should be monitored by a pediatric care provider for neonatal abstinence syndrome, a drug withdrawal syndrome that opioid-exposed neonates may experience shortly after birth.
Opioid use in pregnancy has escalated dramatically in recent years, paralleling the epidemic observed in the general population. In 2012, U.S. health care providers wrote more than 259 million prescriptions for opioids, twice as many as in 1998 1. Rates of admission to substance use disorder treatment programs for misuse of prescription opioids more than quadrupled between 2002 and 2012 2 3, and rates of death associated with opioid analgesics rose nearly 400% between 2000 and 2014 4. Along with the increase in misuse of prescription opioids, there has been a sharp rise in rates of heroin use. Overdose deaths that involve heroin increased more than 300% in less than 5 years, from just above 3,000 in 2010 to more than 10,500 in 2014 5.
In 2007, 22.8% of women who were enrolled in Medicaid programs in 46 states filled an opioid prescription during pregnancy 6. In a study looking at hospital discharge diagnostic codes, antepartum maternal opioid use increased nearly fivefold from 2000 to 2009 7. The rising prevalence of opioid use in pregnancy has led to a sharp increase in neonatal abstinence syndrome from 1.5 cases per 1,000 hospital births in 1999 to 6.0 per 1,000 hospital births in 2013, with an associated $1.5 billion in related annual hospital charges. States with the highest rates of opioid prescribing also have the highest rates of neonatal abstinence syndrome 8. In addition, maternal mortality reviews in several states have identified substance use as a major risk factor for pregnancy-associated deaths 9 10.
A diagnosis is based on specific criteria such as unsuccessful efforts to cut down or control use, as well as use resulting in social problems and a failure to fulfill obligations at work, school, or home 12. The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), replaced the terms opioid abuse and opioid dependence with the term opioid use disorder. The DSM-5 outlines 11 main symptoms of opioid use disorder and defines the severity of the disorder based on the number of recurring symptoms experienced within a 12-month period. Severity is classified as mild (two to three symptoms), moderate (four to five symptoms), and severe (six or more symptoms) 13. The abuse and dependence terminology do not correlate precisely to the new categories of mild, moderate, and severe opioid use disorder. Although this diagnostic terminology has changed, much of the prior research, recommendations, and regulatory requirements in this field rely on the previous terminology, such as abuse and dependence; therefore, those terms are still used when referencing those sources.
Ensure that opioids are appropriately indicated. For women, including pregnant women, with an opioid use disorder, opioid agonist pharmacotherapy is the recommended therapy. For chronic pain, practice goals include strategies to avoid or minimize the use of opioids for pain management, highlighting alternative pain therapies such as nonpharmacologic (eg, exercise, physical therapy, behavioral approaches) and nonopioid pharmacologic treatments.
Discuss the risks and benefits of opioid use and review treatment goals with the patient at the outset. This discussion should include the risk of becoming physiologically dependent on opioids and, in the case of pregnant women, the possibility of an infant developing neonatal abstinence syndrome (NAS) Ref . However, health care providers should not hesitate to prescribe opioids based on a concern for neonatal abstinence syndrome alone.
Take a thorough history of substance use and review the Prescription Drug Monitoring Program, currently operational in 49 states and the District of Columbia. The Prescription Drug Monitoring Program is a valuable resource to determine whether patients have received prior opioid prescriptions or other high-risk medications such as benzodiazepines, and should be consulted when patients request opioid pain medication or when opioid misuse is suspected. This resource (available at www.pdmpassist.org/content/state-profiles can guide safe prescribing and help identify patients who suffer from opioid misuse or opioid use disorder and who would benefit from treatment. Several states now require that health care providers use Prescription Drug Monitoring Programs before prescribing certain controlled substances.
Finally, a cautious approach to prescribing opioids should be balanced with the need to address pain in the pregnant woman. Pregnancy should not be a reason to avoid treating acute pain because of concern for opioid misuse or NAS.
Obstetric care providers need to be knowledgeable about the medical, social, and legal consequences that can accompany opioid use by pregnant women. Pregnancy provides an important opportunity to identify and treat women with substance use disorders. Identifying patients with substance use disorders using validated screening tools, offering brief interventions (such as engaging a patient in a short conversation, providing feedback and advice), and referring for specialized care, as needed, are essential elements of care 14 Box 1. Additionally, it is important to advocate for this often-marginalized group of patients, particularly in terms of working to improve availability of treatment and to ensure that pregnant women with opioid use disorder who seek prenatal care are not criminalized. Finally, obstetric care providers have an ethical responsibility to their pregnant and parenting patients with substance use disorder to discourage the separation of parents from their children solely based on substance use disorder, either suspected or confirmed 15. In states that mandate reporting, policy makers, legislators, and physicians should work together to retract punitive legislation and identify and implement evidence-based strategies outside the legal system to address the needs of women with addictions 16.
Opioids diminish the intensity of pain signals and are generally prescribed for the treatment of pain, although cough and diarrhea are other indications for their use. Opioids have the additional effect of causing a sense of euphoria, which can lead to their misuse 17. Opioid use disorder may develop with repetitive use of any opioid, particularly in individuals with an underlying genetic vulnerability. Heroin is a rapidly acting opioid that may be injected, smoked, or nasally inhaled 18. Heroin has a short half-life, and to avoid opioid withdrawal symptoms, a physically dependent heroin user will need to take multiple doses daily. Prescribed opioids such as codeine, fentanyl, morphine, methadone, oxycodone, meperidine, hydromorphone, hydrocodone, propoxyphene, and buprenorphine all have the potential for misuse. These products may be swallowed, injected, nasally inhaled, smoked, chewed, or used as suppositories 19. The onset and intensity of effect will vary based on how the drug was taken and the formulation; however, all have the potential for causing respiratory depression, overdose, and death. The risk of respiratory depression, overdose, and death is greater for full opioid agonists (such as fentanyl) than for partial agonists (such as buprenorphine). Injection of opioids also carries the risk of cellulitis and abscess formation at the injection site, sepsis, endocarditis, osteomyelitis, hepatitis B, hepatitis C, and HIV infection. Sharing of snorting implements also has been identified as a risk factor for hepatitis C and other virus transmission in a group of pregnant women with hepatitis C 20. 2ff7e9595c
Comments