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| 4. WARNINGS ________________________ Physicians should inform patients about all potential risks and adverse events discussed in the VNS Therapy System physician’s manuals. Use (depression)— This device is a permanent implant. It is only to be used in patients with severe depression who are unresponsive to standard psychiatric management. It should only be prescribed and monitored by physicians who have specific training and expertise in the management of treatment-resistant depression and the use of this device. It should only be implanted by physicians who are trained in surgery of the carotid sheath and have received specific training in the implantation of this device. Use (epilepsy)—The VNS Therapy System should only be prescribed and monitored by physicians who have specific training and expertise in the management of seizures and the use of this device. It should only be implanted by physicians who are trained in surgery of the carotid sheath and have received specific training in the implantation of this device. Not curative (depression)—Physicians should warn patients that VNS Therapy has not been determined to be a cure for depression. Patients should be counseled to understand that individual results will likely vary. Beneficial results might not become evident for months. Most patients will continue to require antidepressant medications and/or electroconvulsive therapy (ECT) in addition to VNS Therapy. The VNS Therapy device is not curative (epilepsy)—Physicians should warn patients that VNS Therapy is not a cure for epilepsy and that since seizures may occur unexpectedly, patients should consult with a physician before engaging in unsupervised activities, such as driving, swimming, and bathing, and in strenuous sports that could harm them or others. Unapproved uses—The safety and efficacy of the VNS Therapy System have not been established for uses outside the “Intended Use / Indications” section of this multi-part physician’s manual, including (but not limited to) patients with: �� Acute suicidal thinking or behavior (depression) �� History of schizophrenia, schizoaffective disorder or delusional disorders (depression) �� History of rapid cycling bipolar disorder (depression) �� History of previous therapeutic brain surgery or CNS injury �� Progressive neurological diseases other than epilepsy or depression �� Cardiac arrhythmias or other abnormalities �� History of dysautonomias �� History of respiratory diseases or disorders, including dyspnea and asthma �� History of ulcers (gastric, duodenal, or other) �� History of vasovagal syncope �� Only one vagus nerve �� Other concurrent forms of brain stimulation �� Pre-existing hoarseness �� Under 12 years of age (epilepsy) �� Under 18 years of age (depression) �� Primary generalized seizures Worsening depression/suicidality (depression)—Patients being treated with adjunctive VNS Therapy should be observed closely for clinical worsening and suicidality, especially at the time of VNS Therapy stimulation parameter changes or drug or drug dose changes, including either increases or decreases in the stimulation parameters or concomitant treatments. Consideration should be given to changing the therapeutic regimen of VNS Therapy or concomitant treatments, including possibly discontinuing VNS Therapy or the concomitant therapy, in patients whose depression is persistently worse or whose emergent suicidality is severe, abrupt in onset, or was not part of the patient’s presenting symptoms. Dysfunctional cardiac conduction systems—The safety and effectiveness of the VNS Therapy System in patients with predisposed dysfunction of cardiac conduction systems (re-entry pathway) have not been established. Evaluation by a cardiologist is recommended if the family history, patient history, or electrocardiogram suggests an abnormal cardiac conduction pathway. Serum electrolytes, magnesium, and calcium should be documented before implantation. Additionally, postoperative bradycardia can occur among patients with certain underlying cardiac arrhythmias. Post-implant electrocardiograms and Holter monitoring are recommended if clinically indicated. It is important to follow recommended implantation procedures and intraoperative product testing described in the Implantation and Follow-up part of this multi-part physician’s manual. During the intraoperative System Diagnostics (Lead Test), infrequent incidents of bradycardia and/or asystole have occurred. If asystole, severe bradycardia (heart rate < 40 bpm), or a clinically significant change in heart rate is encountered during a System Diagnostics (Lead Test) or during initiation of stimulation, physicians should be prepared to follow guidelines consistent with Advanced Cardiac Life Support (ACLS). Additionally, postoperative bradycardia can occur among patients with certain underlying cardiac arrhythmias. If a patient has experienced asystole, severe bradycardia (heart rate < 40 bpm) or a clinically significant change in heart rate during a System Diagnostics (Lead Test) at the time of initial device implantation, the patient should be placed on a cardiac monitor during initiation of stimulation. The safety of this therapy has not been systematically established for patients experiencing bradycardia or asystole during VNS Therapy System implantation. Swallowing difficulties—Difficulty swallowing (dysphagia) may occur with active stimulation, and aspiration may result from the increased swallowing difficulties. Patients with pre-existing swallowing difficulties are at greater risk for aspiration. Appropriate aspiration precautions should be taken for such patients. Dyspnea or shortness of breath—Dyspnea (shortness of breath) may occur with active VNS Therapy. Any patient with underlying pulmonary disease or insufficiency such as chronic obstructive pulmonary disease or asthma may be at increased risk for dyspnea and should have their respiratory status evaluated prior to implantation and monitored following initiation of stimulation. Obstructive sleep apnea—Patients with obstructive sleep apnea (OSA) may have an increase in apneic events during stimulation. Lowering stimulus frequency or prolonging “OFF” time may prevent exacerbation of OSA. Vagus nerve stimulation may also cause new onset sleep apnea in patients who have not previously been diagnosed with this disorder. It is recommended that patients being considered for VNS Therapy who demonstrate signs or symptoms of OSA, or who are at increased risk for developing OSA, should undergo the appropriate evaluation(s) prior to implantation. Device malfunction—Device malfunction could cause painful stimulation or direct current stimulation. Either event could cause nerve damage and other associated problems. Patients should be instructed to use the Magnet to stop stimulation if they suspect a malfunction, and then to contact their physician immediately for further evaluation. Prompt surgical intervention may be required if a malfunction occurs. MRI—Patients with the VNS Therapy System or any part of the VNS Therapy System implanted should not have full body MRI. Additional surgery may be required to remove the VNS Therapy system if full body MRI is required. Excessive stimulation—Excessive stimulation at an excess duty cycle (that is, one that occurs when “ON” time is greater than “OFF” time) has resulted in degenerative nerve damage in laboratory animals. An excess duty cycle can be produced by continuous or frequent magnet activation (> 8 hours), as determined by animal studies. Do not stimulate at these combinations of ranges. Device manipulation—Patients who manipulate the Pulse Generator and Lead through the skin (Twiddler’s Syndrome) may damage or disconnect the Lead from the Pulse Generator and/or possibly cause damage to the vagus nerve. Patients should be warned against manipulating the Pulse Generator and Lead. Sudden unexplained death in epilepsy (SUDEP): Through August 1996, 10 sudden and unexplained deaths (definite, probable, and possible) were recorded among the 1,000 patients implanted and treated with the VNS Therapy device. During this period, these patients had accumulated 2,017 patient-years of exposure. Some of these deaths could represent seizure-related deaths in which the seizure was not observed, at night, for example. This number represents an incidence of 5.0 definite, probable, and possible SUDEP deaths per 1,000 patient-years. Although this rate exceeds that expected in a healthy (nonepileptic) population matched for age and sex, it is within the range of estimates for epilepsy patients not receiving vagus nerve stimulation, ranging from 1.3 SUDEP deaths for the general population of patients with epilepsy, to 3.5 (for definite and probable) for a recently studied antiepileptic drug (AED) clinical trial population similar to the VNS Therapy System clinical cohort, to 9.3 for patients with medically intractable epilepsy who were epilepsy surgery candidates. |