Journal of Pain & Palliative Care Pharmacotherapy. 2014;28:170–171. ISSN: 1536-0288 print / 1536-0539 online DOI: 10.3109/15360288.2014.911798
EUROPEAN PERSPECTIVES ON PAIN AND PALLIATIVE CARE
J Pain Palliat Care Pharmacother Downloaded from informahealthcare.com by University of California San Francisco on 02/22/15 For personal use only.
Pain Management Discussion Forum: Serious Interaction Among Frequently Used Drugs for Chronic Pain Harald Breivik AB STRACT A query and response regarding a patient who was taking high-dose tramadol and duloxetine is presented. The patient developed serotonin syndrome. Risks for this clinically important drug interaction and management of the syndrome are discussed. This report is adapted from paineurope 2013; Issue 4, ©Haymarket Medical Publications Ltd., and is presented with permission. paineurope is provided as a service to pain management by Mundipharma International, Ltd., and is distributed free of charge to health care professionals in Europe. Archival issues can be accessed via the Web site: http://www.paineurope.com, at which European health professionals can register online to receive copies of the quarterly publication. KEYWORDS cyproheptadine, drug, interaction, duloxetine, pain, serotonin syndrome, tramadol
A 55-year-old woman with recently diagnosed type 2 diabetes had ongoing pain in her legs and feet. She was prescribed tramadol prolonged release tablets 100 mg, to take no more than three times daily. She gradually escalated her dosage and often took 600 mg to sometimes as much as 800 mg daily. The patient was also prescribed duloxetine 60 mg daily. Gradually, her burning leg pain diminished. She had a urinary tract infection treated with ciprofloxacin. About 10 days later, while still taking ciprofloxacin, she had high fever, profuse sweating, diarrhea, tachycardia, and high blood pressure (BP). She also had tremor of the hands, increased muscle tone, and very lively reflexes—almost clonus—when testing the patellar reflex. She was anxious and confused, complaining about more intense leg pain.
QUERY Pain now severely affects this confused and anxious patient and the new symptoms of fever, tachycardia, lively tendon reflexes, and diarrhea are worrisome. What is going on?
REPLY Your patient is taking a combination of drugs that is likely to cause serotonin syndrome1,2 (also known as serotoninergic or serotonergic syndrome). Tramadol and duloxetine can each, on their own, cause increasing amounts of serotonin in the central nervous system (CNS), a complication that is dose dependent. Your patient had a tendency to increase her tramadol intake above the maximum daily dosage of 400 mg. Duloxetine is a serotonergic and noradrenergic drug. In combination, the risk increases. Ciprofloxacin inhibits cytochrome P450 1A2, the enzyme that metabolizes duloxetine in the liver, causing an accumulation of duloxetine. Your patient is at high risk of serotonin syndrome. Serotonin syndrome is typically a triad of alteration of mental status with anxiety and confusion;
Harald Breivik, MD, DMSc, FRCA, is Emeritus Professor of Anesthesiology, University of Oslo, Oslo, Norway. This report is adapted from paineurope 2013; Issue 4, ©Haymarket Medical Publications Ltd., and is presented with permission. paineurope is provided as a service to pain management by Mundipharma International, Ltd., and is distributed free of charge to health care professionals in Europe. Archival issues can be accessed via the Web site: http://www.paineurope.com, at which European health professionals can register online to receive copies of the quarterly publication. Address correspondence to: Dr. Harald Brievik, Division of Anesthesiology and Intensive Care, Rikshospitalet University Hospital, 0027 Oslo, Norway. (E-mail: [email protected]).
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J Pain Palliat Care Pharmacother Downloaded from informahealthcare.com by University of California San Francisco on 02/22/15 For personal use only.
European Perspectives on Pain and Palliative Care
hyperactive autonomic systems with tachycardia, sometimes supraventricular tachyarrhythmias, increased BP, sweating, and increased bowel movements; and abnormalities of neuromuscular tone with muscle tremor and hyperactive tendon reflexes. The syndrome is often mild and hardly recognizable; I am sure many physicians and nurses are not aware of this possible complication with drugs used in the management of chronic pain. When the triad becomes more pronounced, increased temperature develops into hyperpyrexia and the patient becomes twitchy, nervous, and very confused and cannot take care of him/herself. This serious condition requires hospitalization in an intensive care unit. Treatment is to discontinue all drugs that may have serotonergic effects; for this patient all three drugs
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must immediately be stopped. A beta-blocker and a blood pressure–lowering drug may be needed, and if hyperpyrexia is present, the patient must be cooled with ice water and ice bags. Cyproheptadine is a serotonin antagonist and may be necessary. Chlorpromazine has antiserotonin effects as well. Declaration of interest: The author reports no conflicts of interest. The author alone is responsible for the content and writing of the paper.
REFERENCES [1] Rastogi R, Swarm RA, et al. Anesthesiology. 2011;115: 1291–1298. [2] Iqbal MM, Basil MJ, et al. Ann Clin Psychiatry. 2012;24: 310–318.
EUROPEAN PERSPECTIVES ON PAIN AND PALLIATIVE CARE
J Pain Palliat Care Pharmacother Downloaded from informahealthcare.com by University of California San Francisco on 02/22/15 For personal use only.
Pain Management Discussion Forum: Serious Interaction Among Frequently Used Drugs for Chronic Pain Harald Breivik AB STRACT A query and response regarding a patient who was taking high-dose tramadol and duloxetine is presented. The patient developed serotonin syndrome. Risks for this clinically important drug interaction and management of the syndrome are discussed. This report is adapted from paineurope 2013; Issue 4, ©Haymarket Medical Publications Ltd., and is presented with permission. paineurope is provided as a service to pain management by Mundipharma International, Ltd., and is distributed free of charge to health care professionals in Europe. Archival issues can be accessed via the Web site: http://www.paineurope.com, at which European health professionals can register online to receive copies of the quarterly publication. KEYWORDS cyproheptadine, drug, interaction, duloxetine, pain, serotonin syndrome, tramadol
A 55-year-old woman with recently diagnosed type 2 diabetes had ongoing pain in her legs and feet. She was prescribed tramadol prolonged release tablets 100 mg, to take no more than three times daily. She gradually escalated her dosage and often took 600 mg to sometimes as much as 800 mg daily. The patient was also prescribed duloxetine 60 mg daily. Gradually, her burning leg pain diminished. She had a urinary tract infection treated with ciprofloxacin. About 10 days later, while still taking ciprofloxacin, she had high fever, profuse sweating, diarrhea, tachycardia, and high blood pressure (BP). She also had tremor of the hands, increased muscle tone, and very lively reflexes—almost clonus—when testing the patellar reflex. She was anxious and confused, complaining about more intense leg pain.
QUERY Pain now severely affects this confused and anxious patient and the new symptoms of fever, tachycardia, lively tendon reflexes, and diarrhea are worrisome. What is going on?
REPLY Your patient is taking a combination of drugs that is likely to cause serotonin syndrome1,2 (also known as serotoninergic or serotonergic syndrome). Tramadol and duloxetine can each, on their own, cause increasing amounts of serotonin in the central nervous system (CNS), a complication that is dose dependent. Your patient had a tendency to increase her tramadol intake above the maximum daily dosage of 400 mg. Duloxetine is a serotonergic and noradrenergic drug. In combination, the risk increases. Ciprofloxacin inhibits cytochrome P450 1A2, the enzyme that metabolizes duloxetine in the liver, causing an accumulation of duloxetine. Your patient is at high risk of serotonin syndrome. Serotonin syndrome is typically a triad of alteration of mental status with anxiety and confusion;
Harald Breivik, MD, DMSc, FRCA, is Emeritus Professor of Anesthesiology, University of Oslo, Oslo, Norway. This report is adapted from paineurope 2013; Issue 4, ©Haymarket Medical Publications Ltd., and is presented with permission. paineurope is provided as a service to pain management by Mundipharma International, Ltd., and is distributed free of charge to health care professionals in Europe. Archival issues can be accessed via the Web site: http://www.paineurope.com, at which European health professionals can register online to receive copies of the quarterly publication. Address correspondence to: Dr. Harald Brievik, Division of Anesthesiology and Intensive Care, Rikshospitalet University Hospital, 0027 Oslo, Norway. (E-mail: [email protected]).
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J Pain Palliat Care Pharmacother Downloaded from informahealthcare.com by University of California San Francisco on 02/22/15 For personal use only.
European Perspectives on Pain and Palliative Care
hyperactive autonomic systems with tachycardia, sometimes supraventricular tachyarrhythmias, increased BP, sweating, and increased bowel movements; and abnormalities of neuromuscular tone with muscle tremor and hyperactive tendon reflexes. The syndrome is often mild and hardly recognizable; I am sure many physicians and nurses are not aware of this possible complication with drugs used in the management of chronic pain. When the triad becomes more pronounced, increased temperature develops into hyperpyrexia and the patient becomes twitchy, nervous, and very confused and cannot take care of him/herself. This serious condition requires hospitalization in an intensive care unit. Treatment is to discontinue all drugs that may have serotonergic effects; for this patient all three drugs
171
must immediately be stopped. A beta-blocker and a blood pressure–lowering drug may be needed, and if hyperpyrexia is present, the patient must be cooled with ice water and ice bags. Cyproheptadine is a serotonin antagonist and may be necessary. Chlorpromazine has antiserotonin effects as well. Declaration of interest: The author reports no conflicts of interest. The author alone is responsible for the content and writing of the paper.
REFERENCES [1] Rastogi R, Swarm RA, et al. Anesthesiology. 2011;115: 1291–1298. [2] Iqbal MM, Basil MJ, et al. Ann Clin Psychiatry. 2012;24: 310–318.
