When switching to methadone from higher previous doses of another opioid, consider starting methadone at a dose that is 75% to 90% less than the calculated equianalgesic dose (no higher than 30 to 40 mg per day) with initial dose increases of no more than 10 mg per day every 5 to 7 days. 79 It is important to withhold methadone if there is evidence of sedation. 79 Bear in mind that pain relief from a methadone dose lasts only 4 to 8 hours, but methadone remains in the body much longer (8 to 59 hours). 78 Patients should be counseled never to exceed the prescribed dose, not to mix with alcohol or other unauthorized substances, and to take methadone doses only as scheduled, not as needed. HCPs without experience and knowledge of methadone should seek expert consultation before prescribing it. 76 Abuse-Deterrent Opioids The FDA defines abuse-deterrent properties as those that deter but do not prevent all abuse (i.e., misuse). 80 Common technologies incorporate physical barriers to deter crushing and chewing, chemical barriers to resist extraction in common solvents of the active ingredient for injection, or opioid antagonists to block euphoria when a pill is altered. These formulations have been suggested as a way to reduce harm from prescribed opioids. The FDA cautions that abuse may still occur by swallowing intact pills. Data on abuse-deterrent properties are included in the Drug Abuse and Dependence section of the drug’s prescribing information under 9.2 Abuse. If missing or located elsewhere, the FDA does not consider the product abuse deterrent. The label also contains information on the types of studies conducted and the routes of abuse the formulation is expected to deter (e.g., oral, intranasal, insufflation, intravenous). Thus far, 10 opioid formulations have received abuse-deterrent labeling from the FDA. Post-marketing studies for the approved formulations are in their infancy, and new deterrent formulations are continually in development. 81 Considerations with Opioids in Special Populations: 20 Women/Pregnant Women Several diseases with a high burden of pain are more common in women or are sex specific. These include endometriosis, musculoskeletal and orofacial pain, fibromyalgia, migraines, and abdominal and pelvic pain. 1 Sex differences extend to the pain response itself, and recent scientific literature suggests that, compared with men, women experience more pain, are more sensitive to painful stimuli, report more intense pain, and are more likely to misuse prescription opioids, though there remain many research gaps related to women’s health and pain. 1 During pregnancy, HCPs and patients together should carefully weigh risks and benefits when making decisions about whether to initiate opioid therapy. 61
All women should be informed of the risks of long- term opioid therapy to the developing fetus during current or potential future pregnancies, including a drug withdrawal syndrome in newborns called neonatal opioid withdrawal syndrome (NOWS). 61 An estimated 32,000 babies were born with NOWS in 2014, an five-fold increase from 2004. 82 Babies born to women who are taking opioids are at risk for birth defects (including neural tube defects, congenital heart defects, and gastroschisis), preterm delivery, poor fetal growth, and stillbirth. 61 Given the risks during pregnancy and postpartum, HCPs are encouraged to include obstetricians and gynecologists as part of the pain care management team. 1 When caring for pregnant women who are prescribed opioids, HCPs should arrange for delivery at a facility prepared to evaluate and treat NOWS. 61 Women with SUD should be offered evidence-based treatment. In pregnant women with OUD, the risk of opioid exposure from opioids used to treat OUD should be discussed and balanced against the risk of untreated OUD, which might lead to illicit opioid use associated with outcomes such as low birth weight, preterm birth, or fetal death. 83 Pain management guidelines in Tennessee recommend the following measures when treating women of child-bearing age: 84 • Every woman with reproductive capacity should discuss with the HCP a method to prevent unintended pregnancy when initiated on opioids • Agreement should be obtained to inform the HCP if the woman becomes or intends to become pregnant while prescribed opioids • Women who plan to become pregnant should be counseled on the risks of opioid exposure to the fetus and referred to an obstetrician • The obstetrician and HCP should work together to encourage compliance with chronic pain management and prenatal care • All newly pregnant women should have a urine drug test administered by the appropriate women’s health practitioner • If a urine result is positive for unprescribed controlled substances or illicit drugs during a prenatal visit, the woman should have another upon admission for delivery to help identify the infant at risk for NOWS Older adults People who are ≥65 years require cautious opioid dosing and management as they may have numerous co-occurring medical problems with treatments that increase the risk for polypharmacy and harmful drug interactions. 77 Their risk for falls and cognitive effects with sedating medications and their sensitivity to analgesic effects are increased. In addition, prescription drug or other substance use may be difficult to spot, mimicking symptoms of common conditions such as dementia, diabetes, and depression. Initial doses should be 25–50% lower than in those who are younger. 85 The VA/ DoD practice guideline suggests that tramadol has benefits in older patients because of its partial mu
agonist activity and demonstrated safety profile when combined with ACET, though drug-drug interactions should be evaluated when prescribing tramadol. 20 Children and adolescents Evaluating the origin of the pain condition is important in the pediatric age group. If pain is not controlled, children are at risk for persistent pain as they grow to adulthood. 1 Use of multidisciplinary treatments is advised as is treatment of psychological conditions to manage difficulty coping, anxiety, and depression. It has been suggested that opioid analgesia may be indicated for certain chronic pediatric conditions; however, current guidelines generally exclude this population from treatment recommendations, and scientific investigation is scant into the indications and safety concerns with opioids for the pediatric population. 86 Accidental exposure to and ingestion of opioids can result in death. People with renal and hepatic impairment Extra caution and increased monitoring is necessary when initiating and titrating opioid doses in people with renal and hepatic impairment. 61 In patients with renal compromise, accumulation resulting in toxicity has been observed in case studies; therefore, it is advised to monitor for opioid toxicity and to use non-opioids when possible. 87 People with sickle cell disease Sickle cell disease, which affects an estimated 90,000 people in the United States, is characterized by complex acute and chronic pain symptoms. 88 The disease is particularly prevalent among African Americans. According to the HHS Inter-Agency Task Force on best pain management practices, unpredictable, episodic exacerbations of acute pain pose a challenge to patients with sickle cell disease, and this pain generally has not responded to non- opioids prior to presentation. 1 Limited access to oral opioids at home for the treatment of unplanned acute pain can result in increased use of health care services that could have been avoided. Stigma, negative practitioner attitudes, and perceived racial bias may further complicate care. Effective models of pain treatment for patients with sickle cell disease include multidisciplinary teams of practitioners with experience treating the disease. Racial and ethnic disparities in pain care Evidence documents disparities in health care in racial and ethnic minority populations, often related to such factors as lack of insurance or primary care access, discrimination, environmental barriers to self-management, lower likelihood of being screened for or receiving pain treatment and more. 1,20 The disparities extend to mental health care and addiction treatment where access to care is very limited for Black individuals, Indigenous individuals, and other individuals of color. There is evidence that racial and ethnic minority populations prefer seeking treatment in primary care over specialty mental health settings. 89
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