Oral Morphine Overdose in a Cancer Patient Antagonized by Prolonged Naloxone Infusion

Abstract

An 80-year-old male was diagnosed with carcinoma in the lung with multiple bony metastases and had been prescribed pain medications as per World Health Organization analgesic ladder guidelines. However, he was not getting adequate pain relief and there were difficulties in titration of the morphine doses on an outpatient basis. Therefore, he was hospitalized for dose titration of oral morphine and was coprescribed amitriptyline and ranitidine. During the titration of the analgesic dose, he developed severe symptoms of morphine overdose. He was immediately treated with intravenous naloxone. After prolonged infusion of naloxone, he achieved his baseline vital parameters without any permanent sequel to the overdose event. This case report describes the possible causes of oral morphine overdose in the elderly and its successful treatment. To prevent such complications, one has to be very cautious of other factors such as drug interactions, particularly in the elderly.

Clinically significant drug–drug interactions involving opioid analgesics used for pain treatment in patients with cancer: a systematic review

“…Eleven papers reported DDIs resulting in sedation and respiratory depression. 18 , 19 , 22 , 24 , 30 , 32 , 36 – 40 Fifteen papers reported DDIs causing various other central nervous system (CNS) symptoms, including delirium, 10 , 20 , 23 – 25 , 29 , 31 , 34 – 36 serotonin syndrome, 25 , 26 , 35 myoclonus, 14 , 29 , 35 hyperalgesia, 14 extrapyramidal symptoms, 21 catatonia, 10 neuroleptic malignant syndrome, 34 or carbamazepine toxicity. 11 , 12 Seven papers reported DDIs causing impairment of pain control and/or opioid withdrawal.…”

“…The DDIs with increased opioid efficacy, resulting in sedation and respiratory depression, were caused by decreased opioid metabolism, 19 , 24 , 30 , 32 , 36 – 40 impaired renal excretion, 22 or an additional therapy that also relieves pain and possesses sedative and respiratory depressant effect (eg, amitriptyline or intrathecal bupivacaine added to morphine) 18 , 19 ( Tables 2 and 3 ). Most examples identified in the review refer to opioids metabolized by cytochrome P450 (CYP450), and cytochrome P450 izoenzyme CYP3A4 (CYP3A4) in particular, such as fentanyl, methadone, oxycodone, or buprenorphine, either by concomitant use of CYP3A4 substrates and inhibitors (voriconazole, fluconazole, clarithromycin, cimetidine, and sertraline) or by discontinuation of a CYP3A4 inducer (carbamazepine) ( Tables 2 and 4 ).…”

“… 24 , 30 , 32 , 36 – 40 , 44 Morphine pharmacokinetics were reported to be affected by a DDI leading to sedation and respiratory depression only in two case reports. 19 , 22 In one of these publications, morphine was coadministered with amitriptyline and ranitidine, 19 two drugs which can affect morphine glucuronidation 45 , 46 ( Table 2 ). Morphine may also indirectly be affected by renal failure caused by another drug.…”

Evaluation of Potential Drug Interaction of Analgesic in Cancer Patient Receiving Palliative Care in Dharmais Cancer Hospital

“…Based on the reports of the lung cancer patient with bone metastasis consuming both morphine and amitriptyline, amitriptyline was used not only to decrease incidental pain and contribute to cause a sedative effect but also to delay morphine clearance so that increase the serotonergic effect. The accumulated amitriptyline resulted from 24-hours half-life could increase the risk of drug interaction with morphine (Upadhyay, 2008). The administration of amitriptyline with morphine or the same type of analgesics is carried out by giving amitriptyline with a smaller dosage (The Christie NHS Foundation Trust, 2012).…”

Grenzen der Schmerztherapie

“…Dennoch werden immer wieder schwere Komplikatio nen, sogar Todesfälle berichtet [34,53,54,78]. Bei ausreichender und zeitlich adäquater Kontrolle lassen sich selbst schwere Atemdepressionen folgenlos behandeln [78].…”