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The following represent additions to UpToDate from the past six months that were considered by the editors and authors to be of particular interest. The most recent What's New entries are at the top of each subsection.
Opana ER withdrawn from the US market (July 2017)
A long-acting abuse-deterrent formulation of oxymorphone, Opana ER, is being voluntarily withdrawn from the United States (US) market at the request of the US Food and Drug Administration due to concerns related to injection abuse, including reports of thrombotic microangiopathy (TMA) when the oral formulation is injected intravenously (IV) [1-3]. The TMA is thought to be due to an inert component that was added to the formulation to make it crush-resistant and thus deter IV injection. Generic extended-release oxymorphone products remain on the US market. (See "Cancer pain management with opioids: Optimizing analgesia", section on 'Oxycodone, hydrocodone, hydromorphone, and oxymorphone' and "Drug-induced thrombotic microangiopathy", section on 'Drugs of abuse'.)
Safe storage of prescription opioids (May 2017)
Although safe storage of prescription opioid medications (eg, locked cabinet) is recommended, it infrequently occurs. In a United States nationally representative survey of over 1000 adults with prescription opioid use in the past 12 months, only 9 percent reported safe storage of their medications . In further analysis of those adults with children younger than 18 years of age in the household, safe storage was reported in less than one-third of households with young children and 12 percent of households with children older than six years of age . These results support the need for anticipatory guidance by health care providers, emphasizing opioid safe storage and how it may limit opioid misuse and overdose, especially in households with children and adolescents. Further research should focus on developing and implementing effective means of secure storage in households. (See "Opioid intoxication in children and adolescents", section on 'Safe storage'.)
Concurrent benzodiazepines in opioid-using patients and overdose risk (April 2017)
Benzodiazepines can potentiate the respiratory depressant effects of opioid medication, and concurrent use may be a factor in the rising rate of opioid overdose. In an analysis of a large sample of patients prescribed an opioid, the proportion who concurrently received a benzodiazepine nearly doubled over 12 years . Concurrent use of both medications was associated with an increased risk of opioid overdose compared with patients receiving only the opioid. Avoiding this medication combination may prevent some overdoses. (See "Prevention of lethal opioid overdose in the community", section on 'Risk factors'.)
Naldemedine for opioid-induced constipation (March 2017)
The benefit of naldemedine, an oral peripherally acting opioid receptor antagonist, for opioid-induced constipation (OIC) was shown in two identically designed 12-week phase III randomized trials conducted in patients with noncancer chronic pain and OIC . In a preliminary report, naldemedine, compared with placebo, decreased constipation and was well tolerated with no signs or symptoms of opioid withdrawal or decrease in opioid analgesic efficacy. Naldemedine has been approved in the United States for OIC in adult patients with chronic noncancer pain . However, efficacy has also been shown for treatment of OIC in cancer patients , and naldemedine can be used off label in this population. The European Medicines Agency has approved naldemedine for treatment of OIC without restriction to noncancer pain . (See "Prevention and management of side effects in patients receiving opioids for chronic pain".)
- http://endo.com/news-events/press-releases?c=123046&p=irol-newsArticle&ID=2284981 (Accessed on July 11, 2017).
- https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm562401.htm (Accessed on July 11, 2017).
- Hunt R, Yalamanoglu A, Tumlin J, et al. A mechanistic investigation of thrombotic microangiopathy associated with IV abuse of Opana ER. Blood 2017; 129:896.
- Kennedy-Hendricks A, Gielen A, McDonald E, et al. Medication Sharing, Storage, and Disposal Practices for Opioid Medications Among US Adults. JAMA Intern Med 2016; 176:1027.
- McDonald EM, Kennedy-Hendricks A, McGinty EE, et al. Safe Storage of Opioid Pain Relievers Among Adults Living in Households With Children. Pediatrics 2017; 139.
- Sun EC, Dixit A, Humphreys K, et al. Association between concurrent use of prescription opioids and benzodiazepines and overdose: retrospective analysis. BMJ 2017; 356:j760.
- Hale ME, Wild J, Reddy J, et al. Efficacy and Safety of Naldemedine for the treatment of opioid-induced constipation in subjects with chronic non-cancer pain receiving opioid therapy: results from two Phase 3 clinical trials (abstract 598). Data presented at the 2016 Digestive Disease Week, San Diego, CA, May 21, 2016. Abstract available online at http://www.gastrojournal.org/article/S0016-5085(16)30515-7/pdf (Accessed on March 30, 2017).
- https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2017/208854Orig1s000ltr.pdf (Accessed on March 30, 2017).
- Katakami N, Oda K, Tauchi K, et al. Phase IIb, Randomized, Double-Blind, Placebo-Controlled Study of Naldemedine for the Treatment of Opioid-Induced Constipation in Patients With Cancer. J Clin Oncol 2017; :JCO2016708453.
- http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/pips/EMEA-001893-PIP01-15/pip_001533.jsp&mid=WC0b01ac058001d129 (Accessed on March 30, 2017).