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Opioid Pain Medicines: Drug Safety Communication - New Safety Warnings Added to Prescription Opioid Medications
AUDIENCE: Family Practice, Psychiatry, Pain Management, Nursing, Endocrinology
ISSUE: FDA is warning about several safety issues with the entire class of opioid pain medicines. See the FDA Drug Safety Communication for a complete listing. These safety risks are potentially harmful interactions with numerous other medications, problems with the adrenal glands, and decreased sex hormone levels. We are requiring changes to the labels of all opioid drugs to warn about these risks.
‧Opioids can interact with antidepressants and migraine medicines to cause a serious central nervous system reaction called serotonin syndrome, in which high levels of the chemical serotonin build up in the brain and cause toxicity.
Cases of serotonin syndrome in the FDA Adverse Event Reporting System (FAERS) database were reported more frequently with the opioids fentanyl and methadone used at the recommended doses. Therefore, FDA is requiring a new statement in the Warnings and Precautions section to be added to these drug labels. Some opioids, including tramadol, tapentadol, and meperidine, already have warnings about serotonin syndrome. Cases were also reported with other opioids, so the labels of all these drugs will be updated to include information about serotonin syndrome in the Drug Interactions and Adverse Reactions sections.
Patients taking an opioid along with a serotonergic medicine (see List of Serotonergic Medicines) should seek medical attention immediately if they develop symptoms such as agitation; hallucinations; rapid heart rate; fever; excessive sweating; shivering or shaking; muscle twitching or stiffness; trouble with coordination; and/or nausea, vomiting, or diarrhea. Symptoms generally start within several hours to a few days of taking an opioid with another medicine that increases the effects of serotonin in the brain, but symptoms may occur later, particularly after a dose increase.
‧Taking opioids may lead to a rare, but serious condition in which the adrenal glands do not produce adequate amounts of the hormone cortisol. Cortisol helps the body respond to stress. FDA is requiring a new statement about adrenal insufficiency to be added to the Warnings and Precautions section of all opioid labels.
Patients should seek medical attention if they experience symptoms of adrenal insufficiency such as nausea, vomiting, loss of appetite, fatigue, weakness, dizziness, or low blood pressure.
‧Long-term use of opioids may be associated with decreased sex hormone levels and symptoms such as reduced interest in sex, impotence, or infertility.
FDA reviewed published studies that assessed levels of sex hormones in patients taking opioids chronically; however, all had limitations that make it difficult to determine whether the symptoms were caused by the opioids or other factors. The labels of some opioids already describe this possible risk, and FDA is now adding consistent information to the Adverse Reactions section of all opioid labels.
Patients should inform their health care professionals if they experience symptoms of low libido, impotence, erectile dysfunction, lack of menstruation, or infertility.
BACKGROUND: Opioids are powerful prescription medicines that can help manage pain when other treatments and medicines are not able to provide enough pain relief (see List of Opioid Medicines in the FDA Drug Safety Communication). However, opioids also carry serious risks, including of misuse and abuse, addiction, overdose, and death.
Prescription opioids are divided into two main categories – immediate-release (IR) products, usually intended for use every 4 to 6 hours; and extended release/long acting (ER/LA) products, intended to be taken once or twice a day, depending on the individual product and patient.
RECOMMENDATIONS:
Serotonin syndrome:
Health care professionals should discontinue opioid treatment and/or use of the other medicine if serotonin syndrome is suspected.
Adrenal insufficiency:
Health care professionals should perform diagnostic testing if adrenal insufficiency is suspected. If diagnosed, treat with corticosteroids and wean the patient off of the opioid, if appropriate. If the opioid can be discontinued, follow-up assessment of adrenal function should be performed to determine if treatment with corticosteroids can be discontinued.
Decreased sex hormone levels:
Health care professionals should conduct laboratory evaluation in patients presenting with such signs or symptoms.
Read the MedWatch safety alert, including a link to the FDA Drug Safety Communication, at:
http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHuma...
美國FDA發布安全警訊，有關鴉片類止痛藥物與其他藥物併用可能發生嚴重交互作用之風險，美國FDA已要求所有鴉片類藥物應於仿單中加註相關警語。
鴉片類藥物為強效止痛處方藥，可用於緩解當其他處置或藥物無法止痛時之用藥。但使用此類藥物也可能伴隨嚴重風險，如不當使用、成癮、服用過量或嚴重導致死亡。此類藥物主要可分為兩大類：約4-6小時服用一次之立即釋放劑型及每日服用1-2次之緩釋/長效劑型。
鴉片類藥物與抗憂鬱劑及偏頭痛用藥併用可能導致腦部serotonin濃度增高，進而產生嚴重中樞神經系統反應-血清素症候群(serotonin syndrome)。美國FDA不良反應通報系統之serotonin syndrome通報案例常見為fentanyl和methadone，兩者皆使用一般建議劑量。部分鴉片類藥物如tramadol、tapentadol和meperidine已有加註與serotonin syndrome相關警語，美國FDA認為因其他鴉片類藥物也曾有接獲通報案例，故要求所有鴉片類藥物仿單皆應新增可能發生serotonin syndrome之警語。
病人併用鴉片類藥物與作用於血清素系統的藥物時，若出現燥動、幻覺、心跳加快、發燒、異常出汗、顫抖、肢體協調困難、且/或噁心嘔吐或腹瀉等症狀，建議應立即就醫。serotonin syndrome之症狀可能於服藥後幾小時甚至幾天後出現，尤其是給藥劑量增加後，症狀可能較晚發生。
鴉片類藥物可能發生腎上腺機能低下(adrenal insufficiency)，影響腎上腺分泌幫助身體適應壓力之腎上腺激素cortisol，使體內cortisol濃度不足。美國FDA要求應於仿單新增可能發生腎上腺機能低下之警語，並提醒病人若出現噁心嘔吐，食慾減少、疲勞、虛弱、頭暈或低血壓等腎上腺機能低下症狀，應立即就醫。
另長期服用鴉片類藥物可能會降低性荷爾蒙濃度而產生相關症狀如性慾減少、性功能障礙或不孕。雖經美國FDA回顧有關評估長期服用鴉片類藥物之病人之體內性荷爾蒙濃度之研究，尚無法確認此症狀是否為鴉片類藥物所造成，但目前已有部分鴉片類藥物將此風險標註於仿單中，美國FDA認為所有鴉片類藥物皆應於副作用欄位中新增此訊息。FDA提醒病人若出現性功能障礙、停經或不孕等症狀，應告知醫療人員。
美國FDA提供醫療人員以下建議：
Serotonin syndrome:
若病人出現疑似症狀時，應立即停止使用鴉片類藥物及/或改使用其他替代藥物。
Adrenal insufficiency:
若病人有腎上腺機能低下之疑慮，應進行診斷測試，若確為腎上腺機能低下，給予類固醇治療，如可應立即停用鴉片類藥物。停用鴉片類藥物後應依據病人腎上腺功能恢復情況評估是否可停用類固醇。
Decreased sex hormone levels:
若病人出現類似症狀，應進行相關檢驗數據之評估。
相關訊息與連結請參考FDA網址：
http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHuma...
[Posted 03/22/2016]
資料來源：美國FDA之藥物安全警訊
資料提供：台大醫院藥劑部
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資料來源：藥師週刊（第1963期）
