Other adverse events In addition to risks of misuse, addiction, respiratory depression, and overdose death, there are many well-known side effects associated with chronic opioid use that can significantly compromise quality of life, including constipation, nausea or vomiting, sedation, pruritus, erectile dysfunction, menstrual changes, fracture, immunosuppression, hallucinations, and hyperalgesia. Gastrointestinal side effects Constipation is one of the most common opioid- related adverse events, affecting most patients to at least some degree, and which usually does not resolve with continued exposure. 28 To mitigate this side effect, patients should use a mild stimulant laxative such as senna or bisacodyl and increase the dosage in 48 hours if no bowel movement occurs. Physicians should perform a rectal examination if no bowel movement occurs in 72 hours. If there is no impaction, consider other therapies such as an enema, suppository, or magnesium citrate. 90 Medications for refractory, opioid-induced constipation include naloxone derivatives: naloxegol (Movantik), methylnaltrexone (Relistor), or naldemedine (Symproic). Naloxegol is an oral tablet that is used daily while methylnaltrexone is a subcutaneous injection or oral tablet used daily. Naldemedine is taken by mouth daily (0.2 mg) and may cause side effects such as abdominal pain or discomfort, diarrhea, and nausea. 88 In the COMPOSE-1 trial, patients on naldemedine had significantly more spontaneous bowel movements (defined as ≥3 per week) than those on placebo (47.6% vs. 34.6%, P=0.002). 91 For nausea or vomiting, physicians should consider a prophylactic antiemetic, add or increase non-opioid pain control agents (e.g., acetaminophen as an opioid- sparing drug), and decrease opioid dose by 25% if analgesic is satisfactory. Sedation Sedation is the first warning sign of a patient being at risk for opioid overdose. Take this symptom very seriously. If a patient complains of sedation, determine whether sedation is related to the opioid, eliminate nonessential depressants (such as benzodiazepines or alcohol), reduce dose by 10%-15% if analgesia is satisfactory, add or increase non-opioid or non- sedating adjuvant for additional pain to reduce opioid dose. There is insufficient evidence to recommend opioid rotation as a possible means of reducing sedation. 31 Patients should also be co-prescribed naloxone for opioid overdose reversal. Fracture A retrospective cohort study over seven years compared the risk of fracture associated with starting opioids vs. NSAIDs (2,436 older adults initiated on opioids and 4,874 older adults initiated on NSAIDs). Opioids significantly increased the risk of fracture in a dose-dependent fashion. The opioid formulation mattered with much of the risk in the first month after
drug initiation for short-acting opioids, though fracture increased for both long- and short-acting opioids over time. 92 Infection Opioids may increase risk of infection in older adults. A case-control study of 3,061 older community dwelling adults ages 64-95 years evaluated the association between pneumonia and opioid use. Current prescription opioid users had a 38% increased risk of pneumonia compared with nonusers. The risk was highest for opioid users categorized as being immunosuppressed, such as those with cancer, recent cancer treatment, or chronic kidney disease, or those receiving immunosuppressive medications or medications for HIV. 93 Myocardial Infarction (MI) A case-control study assessed the risk of MI among adults on opioids for chronic pain in the UK General Practice Research Database (11,693 cases with up to four matched controls). Current opioid use was associated with a 28% increased risk of MI compared to non-use. 94 Erectile Dysfunction (ED) In a cross-sectional analysis of 11,327 men with back pain, 909 (8%) were receiving ED medications or testosterone (documented between 6 months before and 6 months after the study index visit). Prescriptions for an ED drug or testosterone were 54% greater for men using doses ≥120 MMEDs compared with those using doses of 1 to <20 MMED. In addition, the proportion of men receiving either of types of medications was 95% greater for those with chronic opioid use compared with those with no opioid use. These findings suggest that dose and duration of opioid use are associated with ED. 95 Tamper-resistant/abuse-deterrent opioids One strategy to mitigate the risk of opioid abuse has been the development of “abuse-deterrent” formulations of opioids that make it more difficult to alter for non-oral consumption (e.g., injecting, snorting, or smoking). 96 However, these opioids are more aptly named as “tamper-resistant” formulations instead of “abuse-deterrent” since they are no less potentially addictive than regular opioids when taken by mouth. Tamper-resistant formulations often contain a higher opioid dose than immediate-release preparations. Furthermore, most are extended-release and also considerably more expensive than generic, off-patent opioids. 96 As of this writing, only one immediate- release opioid is available in an abuse deterrent formulation (oxycodone hydrochloride [RoxyBond]). 96 Patient education Before prescribing an opioid for pain, clinicians should discuss with patients the risks and benefits of such therapy. An important consideration in framing treatment, and a key message to communicate to patients, is that the goal is not “zero pain” but, rather, a level of analgesia that maximizes a patient’s physical
Book Code: MDAZ1124
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