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Buprenorphine/naloxone/methadone/oxycodone Various toxicities: 2 case reports

In a case report, 2 male patients aged 17–19 years were described, who developed opioid withdrawal symptoms following oxycodone or methadone withdrawal. Additionally, they developed yawning, sweats or chills following buprenorphine-naloxone for pain [time to reaction onsets not stated; not all routes and outcomes stated]. Case 1: A 17-year-old boy, who had a history of haemoglobin sickle cell disease (SCD), presented to the emergency departments (ED) thirteen times for acute pain in 2016. He started receiving oxycodone immediate release (IR) formulation for pain along with hydroxycarbamide [hydroxyurea]. In 2017, he again presented to the ED several times, and was hospitalised for 36 days. He also had concurrent migraine headache. Subsequently, oxycodone extended release (ER) was added to his treatment regimen. Subsequently, his ED and hospital visits drastically decreased. He continued to do well, therefore, oxycodone IR and ER doses were tapered. However, following dose taper, his visits to the ED for pain increased. Thus, opioid withdrawal symptoms were suspected. He developed nausea, headaches, myalgias, sweating and anxiety as manifestations of opioid withdrawal symptoms. He was discharged with full agonist opioids. He was switched from oxycodone ER to methadone, and was treated with alternative medications. His ED visits continued and expanded to other hospital systems. He continued to present to outside ED for acute pain. Hence discontinuation of the opioids was required. In December 2019, his daily regimen was methadone 12.5mg and oxycodone IR 37.5mg i.e.approximately 106 morphine milligram equivalents (MME). He exhibited signs of opioid dependence and opioid tolerance. To wean off opioids, he started receiving SL buprenorphine-naloxone (0.5mg-0.125mg to 2mg-0.5mg) using the Bernese method of microdose induction. During 8-day induction, he did not experienced any opioid withdrawal symptoms, upto the maximum buprenorphine-naloxone dose of 6mg-1.5mg daily. He experienced two episodes of migraine during induction, which were managed by the standard migraine medications. He received maintenance dose of buprenorphine 1mg-0.25mg daily for 5 months. His pain was noted to be improved. Case 2: A 19-year-old man with a history of haemoglobin SCD had been receiving hydroxycarbamide [hydroxyurea] since childhood. He also had a history of avascular necrosis of bilateral hips diagnosed at the age of 7 years and in June 2018 he was treated with extracorporeal membrane oxygenation for multisystem organ failure due to a presumed fat embolus. At current presentation, He had been receiving 330 morphine milligram equivalents (MME) per day of oxycodone for acute and persistent pain. He occasionally received day-infusion of parenteral opioids, and was admitted six times (total 63 inpatient days). In January 2020, his oxycodone dose was tapered slowly, however, he experienced withdrawal symptoms manifested as body aches, worsening pains and sweats