openFDA text is shown for search and cross-checking; DailyMed SPL is canonical.
Warnings sections page 1 of 1 · 1 matching rows.
warnings and cautions
5. WARNINGS AND PRECAUTIONS Risk of Injury during MRI : IONSYS contains metal parts and must be removed before an MRI. ( 5.6 ) Risk of Use During Other Procedures (cardioversion, defibrillation, X-ray, CT, diathermy ): Remove IONSYS before these procedures. ( 5.7 ) Life-Threatening Respiratory Depression in Patients with Chronic Pulmonary Disease or in Elderly, Cachectic, and Debilitated Patients : Monitor closely, particularly during initiation. ( 5.8 ) Serotonin Syndrome : Potentially life-threatening condition could result from concomitant serotonergic drug administration. Discontinue IONSYS if serotonin syndrome is suspected. ( 5.9 ) Adrenal Insufficiency : If diagnosed, treat with physiologic replacement of corticosteroids, and wean patient off of the opioid. ( 5.10 ) Severe Hypotension : Monitor during dosage initiation. Avoid use of IONSYS in patients with circulatory shock. ( 5.11 ) Risk of Use in Patients with Increased Intracranial Pressure, Brain Tumors, Head Injury, or Impaired Consciousness : Monitor for sedation and respiratory depression. Avoid use of IONSYS in patients with impaired consciousness or coma. ( 5.12 ) 5.1 Life-Threatening Respiratory Depression Serious, life-threatening, or fatal respiratory depression has been reported with the use of opioids, including fentanyl, even when used as recommended. Respiratory depression, if not immediately recognized and treated, may lead to respiratory arrest and death. Management of respiratory depression may include close observation, supportive measures, and use of opioid antagonists, depending on the patient’s clinical status [see Overdosage ( 10 )]. Carbon dioxide (CO 2 ) retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids. While serious, life-threatening, or fatal respiratory depression can occur at any time during the use of IONSYS, the risk is greatest during the initiation of therapy. Monitor patients closely for respiratory depression, especially within the first 24‑72 hours of initiating therapy with IONSYS. Accidental exposure to the hydrogel component of IONSYS, especially in children, can result in respiratory depression and death due to an overdose of fentanyl. Following accidental contact with IONSYS or its components, immediately rinse the affected area thoroughly with water. Do not use soap, alcohol, or other solvent because they may enhance the drug’s ability to penetrate the skin. The individual exposed should be monitored for signs of respiratory or central nervous system depression. If IONSYS is not handled correctly using gloves, healthcare professionals are at risk of accidental exposure to a fatal overdose of fentanyl. IONSYS is for hospital use only. Use of IONSYS outside of the hospital setting can lead to accidental exposure in others for whom it is not prescribed, causing fatal respiratory depression. Prior to the patient leaving the hospital, medical personnel must remove IONSYS and dispose of it properly. 5.2 IONSYS Risk Evaluation and Mitigation Strategy (REMS) Program IONSYS is available only through a restricted program under a REMS called the IONSYS REMS Program because of the risk of respiratory depression resulting from accidental exposure [see Warnings and Precautions ( 5.1 )]. Notable requirements of the IONSYS REMS Program include the following: Healthcare facilities that dispense and administer IONSYS must be certified in the IONSYS REMS program and comply with the REMS requirements. Hospitals must only dispense IONSYS for hospital use. Further information about the IONSYS REMS Program is available at www.ionsysrems.com , or by calling 1-877-488-6835. 5.3 Addiction, Abuse, and Misuse IONSYS contains fentanyl, a Schedule II controlled substance. As an opioid, IONSYS exposes users to the risks of addiction, abuse, and misuse [see Drug Abuse and Dependence ( 9 )]. Although the risk of addiction in any individual is unknown, it can occur in patients appropriately prescribed IONSYS. Addiction can occur at recommended dosages and if the drug is misused or abused. Assess each patient’s risk for opioid addiction, abuse, or misuse, prior to prescribing IONSYS, and monitor all patients receiving IONSYS for the development of these behaviors or conditions. Risks are increased in patients with a personal or family history of substance abuse (including drug or alcohol abuse or addiction) or mental illness (e.g., major depression). The potential for these risks should not, however, prevent the proper management of pain in any given patient. Patients at increased risk may be prescribed opioids, such as IONSYS, but use in such patients necessitates intensive counseling about the risks and proper use of IONSYS along with intensive monitoring for signs of addiction, abuse, and misuse. Opioids are sought by drug abusers and people with addiction disorders and are subject to criminal diversion. Consider these risks when prescribing or dispensing IONSYS. Contact local State Professional Licensing Board or State Controlled Substances Authority for information on how to prevent and detect abuse or diversion of this product. 5.4 Risks of Concomitant Use or Discontinuation of Cytochrome P450 3A4 Inhibitors and Inducers Concomitant use of IONSYS with a CYP3A4 inhibitor, such as macrolide antibiotics (e.g., erythromycin), azole-antifungal agents (e.g., ketoconazole), and protease inhibitors (e.g., ritonavir), may increase plasma concentrations of fentanyl, and prolong opioid adverse reactions, depression [see Warnings and Precautions ( 5.1 )] , particularly when an inhibitor is added after a stable dose of IONSYS is achieved. Similarly, discontinuation of a CYP3A4 inducer, such as rifampin, carbamazepine, and phenytoin, in IONSYS-treated patients may increase fentanyl plasma concentrations and prolong opioid adverse reactions. When using IONSYS with CYP3A4 inhibitors or discontinuing CYP3A4 inducers in IONSYS-treated patients, monitor patients closely at frequent intervals for respiratory depression and sedation [see Drug Interactions ( 7 )]. Concomitant use of IONSYS with CYP3A4 inducers or discontinuation of a CYP3A4 inhibitor could decrease fentanyl plasma concentrations, decrease opioid efficacy or, possibly lead to a withdrawal syndrome in a patient who had developed physical dependence to fentanyl. When using IONSYS with CYP3A4 inducers or discontinuing CYP3A4 inhibitors, monitor patients closely at frequent intervals and consider increasing the opioid dosage if needed to maintain adequate analgesia or if symptoms of opioid withdrawal occur [see Drug Interactions ( 7 )]. 5.5 Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants Profound sedation, respiratory depression, coma, and death may result from the concomitant use of IONSYS with benzodiazepines or other CNS depressants (e.g., non-benzodiazepine sedatives/hypnotics, anxiolytics, tranquilizers, muscle relaxants, general anesthetics, antipsychotics, other opioids, alcohol). Because of these risks, reserve concomitant prescribing of these drugs for use in patients for whom alternative treatment options are inadequate. Observational studies have demonstrated that concomitant use of opioid analgesics and benzodiazepines increases the risk of drug-related mortality compared to use of opioid analgesics alone. Because of similar pharmacological properties, it is reasonable to expect similar risk with the concomitant use of other CNS depressant drugs with opioid analgesics [see Drug Interactions ( 7 )]. If the decision is made to prescribe a benzodiazepine or other CNS depressant concomitantly with an opioid analgesic, prescribe the lowest effective dosages and minimum durations of concomitant use. In patients already receiving an opioid analgesic, prescribe a lower initial dose of the benzodiazepine or other CNS depressant than indicated in the absence of an opioid, and titrate based on clinical response. If an opioid analgesic is initiated in a patient already taking a benzodiazepine or other CNS depressant, prescribe a lower initial dose of the opioid analgesic, and titrate based on clinical response. Follow patients closely for signs and symptoms of respiratory depression and sedation. 5.6 Risk of Injury during Magnetic Resonance Imaging (MRI) Procedure The IONSYS device is considered MR Unsafe. IONSYS contains metal parts and must be removed and properly disposed of before an MRI procedure to avoid injury to the patient and damage to IONSYS. It is unknown if exposure to an MRI procedure increases release of fentanyl from IONSYS. Monitor any patients wearing IONSYS with inadvertent exposure to an MRI for signs of central nervous system and respiratory depression. 5.7 Risk of IONSYS Use during Other Procedures or Near Certain Equipment Cardioversion, Defibrillation, Radiographic Imaging Procedures other than MRI, or Diathermy Use of IONSYS during cardioversion, defibrillation, X-ray, CT, or diathermy can damage IONSYS from the strong electromagnetic fields set up by these procedures. IONSYS contains radio-opaque components and may interfere with an X-ray image or CT scan. Remove and properly dispose of IONSYS prior to cardioversion, defibrillation, X-ray, CT, or diathermy [see Dosage and Administration ( 2.3 , 2.4 )]. Synthetic Materials and Electronic Security Systems Avoid contact with synthetic materials (such as carpeted flooring) to reduce the possibility of electrostatic discharge and damage to IONSYS. Avoid exposing IONSYS to electronic security systems to reduce the possibility of damage to IONSYS. See IONSYS Important Device Instructions for additional details. Communications Equipment and Radio Frequency Identification Transmitters Use of IONSYS near communications equipment (e.g., base stations for radio telephones and land mobile radios, amateur radio, AM and FM radio broadcast and TV broadcast Radio) and Radio Frequency Identification (RFID) transmitters can damage IONSYS. Depending on the rated maximum output power and frequency of the transmitter, the recommended separation distance between IONSYS and communications equipment or the RFID transmitter ranges between 0.12 and 23 meters. See IONSYS Important Device Instructions for detailed instructions regarding recommended separation distances. Other Electromechanical Devices Including Pacemakers or Electrical Monitoring Equipment The low-level electrical current provided by IONSYS does not result in electromagnetic interference with other electromechanical devices like pacemakers or electrical monitoring equipment. If exposure to the procedures listed above, electronic security systems, electrostatic discharge, communications equipment, or RFID transmitters occurs, and if IONSYS does not appear to function normally [see Dosage and Administration ( 2.3 )] , remove IONSYS and replace with a new IONSYS. See IONSYS Important Device Instructions for additional details including information on troubleshooting device malfunction and electromagnetic compatibility. 5.8 Life-Threatening Respiratory Depression in Patients with Chronic Pulmonary Disease or in Elderly, Cachectic, or Debilitated Patients The use of IONSYS in patients with acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment is contraindicated. Patients with Chronic Pulmonary Disease : IONSYS-treated patients with significant chronic obstructive pulmonary disease or cor pulmonale, and those with a substantially decreased respiratory reserve, hypoxia, hypercapnia, or pre-existing respiratory depression are at increased risk of decreased respiratory drive including apnea, even at the recommended dosage of IONSYS [see Warnings and Precautions ( 5.1 )]. Elderly, Cachectic, or Debilitated Patients : Life - threatening respiratory depression is more likely to occur in elderly, cachectic, or debilitated patients as they may have altered pharmacokinetics or altered clearance compared to younger, healthier patients. Monitor such patients closely; particularly when initiating IONSYS and when IONSYS is used concomitantly with other drugs that depress respiration [see Warnings and Precautions ( 5.1 )] . Alternatively, consider the use of non-opioid analgesics in these patients. 5.9 Serotonin Syndrome with Concomitant Use of Serotonergic Drugs Cases of serotonin syndrome, a potentially life-threatening condition, have been reported during concomitant use of fentanyl, the active opioid ingredient of IONSYS, with serotonergic drugs. Serotonergic drugs include selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), triptans, 5-HT3 receptor antagonists, drugs that affect the serotonergic neurotransmitter system (e.g., mirtazapine, trazodone, tramadol), and drugs that impair metabolism of serotonin (including MAO inhibitors, both those intended to treat psychiatric disorders and also others, such as linezolid and intravenous methylene blue) [see Drug Interactions ( 7 )]. This may occur at the recommended dosage. Serotonin syndrome symptoms may include mental status changes (e.g., agitation, hallucinations, coma), autonomic instability (e.g., tachycardia, labile blood pressure, hyperthermia), neuromuscular aberrations (e.g., hyperreflexia, incoordination, rigidity), and/or gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea). The onset of symptoms generally occurs within several hours to a few days of concomitant use, but may occur later than that. Discontinue IONSYS if serotonin syndrome is suspected. 5.10 Adrenal Insufficiency Cases of adrenal insufficiency have been reported with opioid use, more often following greater than one month of use. Presentation of adrenal insufficiency may include non-specific symptoms and signs including nausea, vomiting, anorexia, fatigue, weakness, dizziness, and low blood pressure. If adrenal insufficiency is suspected, confirm the diagnosis with diagnostic testing as soon as possible. If adrenal insufficiency is diagnosed, treat with physiologic replacement doses of corticosteroids. Wean the patient off of the opioid to allow adrenal function to recover and continue corticosteroid treatment until adrenal function recovers. Other opioids may be tried as some cases reported use of a different opioid without recurrence of adrenal insufficiency. The information available does not identify any particular opioids as being more likely to be associated with adrenal insufficiency. 5.11 Severe Hypotension IONSYS may cause severe hypotension including orthostatic hypotension and syncope in ambulatory patients. There is increased risk in patients whose ability to maintain blood pressure has already been compromised by a reduced blood volume, or concurrent administration of certain CNS depressant drugs (e.g., phenothiazines or general anesthetics) [see Drug Interactions ( 7 )]. Monitor these patients for signs of hypotension after initiating IONSYS. In patients with circulatory shock, IONSYS may cause vasodilation that can further reduce cardiac output and blood pressure. Avoid the use of IONSYS in patients with circulatory shock. 5.12 Risks of Use in Patients with Increased Intracranial Pressure, Brain Tumors, Head Injury, or Impaired Consciousness In patients who may be susceptible to the intracranial effects of CO 2 retention (e.g., those with evidence of increased intracranial pressure or brain tumors). IONSYS may reduce respiratory drive, and the resultant CO 2 retention can further increase intracranial pressure. Monitor such patients for signs of sedation and respiratory depression, particularly when initiating therapy with IONSYS. Opioids may also obscure the clinical course in a patient with a head injury. Avoid the use of IONSYS in patients with impaired consciousness or coma. IONSYS is not suitable for use in patients who are not alert and able to follow directions. 5.13 Risks of Use in Patients with Gastrointestinal Conditions IONSYS is contraindicated in patients with known or suspected gastrointestinal obstruction, including paralytic ileus. The fentanyl in IONSYS may cause spasm of the sphincter of Oddi. Opioids may cause increases in serum amylase. Monitor patients with biliary tract disease, including acute pancreatitis for worsening symptoms. 5.14 Increased Risk of Seizures in Patients with Seizure Disorders The fentanyl in IONSYS may increase the frequency of seizures in patients with seizure disorders, and may increase the risk of seizures occurring in other clinical settings associated with seizures. Monitor patients with a history of seizure disorders for worsened seizure control during IONSYS therapy. 5.15 Topical Skin Reactions Topical skin reactions (erythema, sweating, vesicles, papules/pustules) may occur with use of IONSYS and are typically limited to the application site area. If a severe skin reaction is observed, remove IONSYS and discontinue further use. 5.16 Bradycardia IONSYS may produce bradycardia in some patients. Monitor patients with bradyarrhythmias closely for changes in heart rate, particularly when initiating therapy with IONSYS. 5.17 Withdrawal Avoid the use of mixed agonist/antagonist (e.g., pentazocine, nalbuphine, and butorphanol) or partial agonist (e.g., buprenorphine) analgesics in patients who are receiving a full opioid agonist analgesic, including IONSYS. In these patients, mixed agonist/antagonist and partial agonist analgesics may reduce the analgesic effect and/or precipitate withdrawal symptoms. Do not abruptly discontinue IONSYS [see Drug Abuse and Dependence ( 9.3 )]. 5.18 Hepatic Impairment Insufficient data are available on the use of IONSYS in patients with impaired hepatic function. Since fentanyl is eliminated by hepatic metabolism and fentanyl clearance may decrease in patients with hepatic disease, monitor patients with hepatic impairment for signs of sedation and respiratory depression [see Use in Specific Populations ( 8.6 ) and Clinical Pharmacology ( 12.3 )]. 5.19 Renal Impairment A clinical pharmacology study with intravenous fentanyl in patients undergoing kidney transplantation has shown that patients with high blood urea nitrogen level had low fentanyl clearance. Monitor for signs of sedation and respiratory depression in patients with renal impairment [see Use in Specific Populations ( 8.7 ) and Clinical Pharmacology ( 12.3 )]. 5.20 Neonatal Opioid Withdrawal Syndrome Prolonged use of IONSYS during pregnancy can result in withdrawal in the neonate. Neonatal opioid withdrawal syndrome, unlike opioid withdrawal syndrome in adults, may be life‑threatening if not recognized and treated, and requires management according to protocols developed by neonatology experts. Observe newborns for signs of neonatal opioid withdrawal syndrome and manage accordingly. Advise pregnant women using opioids for a prolonged period of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available [see Use in Specific Populations ( 8.1 ), Patient Counseling Information ( 17 )].