Onyx™ Liquid Embolic System Indications, Safety, and Warnings

INDICATIONS FOR USE

Embolization of lesions in the peripheral and neurovasculature, including arteriovenous malformations and hypervascular tumors.

CAUTION

• Federal (USA) law restricts this device to sale by or on the order of a physician.
• This device should be used only by physicians with a thorough understanding of angiography and percutaneous interventional procedures.

PRECAUTIONS

• Inspect product packaging prior to use. Do not use if sterile barrier is opened or damaged.
• Use prior to expiration date.
• Review both the catheter and interface adapter Instructions for Use prior to using Onyx™ LES.
• Verify that the catheters and accessories used in direct contact with the Onyx™ LES polymer are clean and compatible with the material and do not trigger precipitation or degrade with contact. Refer to the respective Warnings and Directions for Use sections.
• Failure to wait a few seconds to retrieve micro catheter after Onyx™ LES injection may result in fragmentation of Onyx™ LES into non-target vessels.
• Difficult catheter removal or catheter entrapment may be caused by one or more of the following factors:
      - Long catheterization time
      - Angio-architecture: very distal arteriovenous malformation fed by afferent, lengthened, small, or tortuous pedicles
      - Vasospasm
      - Reflux
      - Injection time
• To reduce the risk of catheter entrapment, carefully select catheter placement and manage reflux to minimize the factors listed above.

Onyx™ LES reflux along the distal tip of the micro catheter: Apart from the risk of ischemic complications due to unintended embolization, significant reflux may result in entrapment of the micro catheter causing difficult removal. The amount of reflux that can be accepted must always be compared to the angio-architecture of the malformation to minimize risk of unintended embolization or difficult catheter removal. In general, minimize the reflux to less than 1 cm along the distal tip of the micro catheter. All other factors may affect this limit.

• Should catheter removal become difficult, the following technique may assist in catheter retrieval:
      - Carefully pull the catheter to assess any resistance to removal.
      - If resistance is felt, remove any “slack” in the catheter.
      - Gently apply traction to the catheter (approximately 3-4 cm of stretch to the catheter).
      - Hold this traction for a few seconds and release. Assess traction on vasculature to minimize risk of hemorrhage.
      - This process can be repeated intermittently until catheter is retrieved.
      - When using micro catheters, do not apply more than 20 cm of traction to catheter, to minimize risk of catheter separation.
• For entrapped catheters:
      - Under some difficult clinical situations, it may be safer to leave a flowdirected catheter in the vascular system, rather than risk rupturing the malformation and, consequently a hemorrhage, by exercising too much traction on an entrapped catheter.
      - This is accomplished by stretching the catheter and cutting the shaft near the entry point of vascular access allowing the catheter to remain in the artery.
      - If catheter breaks during removal, distal migration or coiling of the catheter may occur.
      - Same day surgical resection should be considered to minimize risk of thrombosis.

CONTRAINDICATIONS

Onyx™ LES is not indicated for use with premature infants (<1,500 g) or individuals with significant liver function impairment.

POTENTIAL COMPLICATIONS

Potential complications include, but are not limited to, the following:

• Hematoma
• Arterial thrombosis
• Ischemic events due to embolic migration, vasospasm, thrombosis
• Catheter entrapment
• Catheter rupture
• Device migration and cast movement
• Hemorrhagic accidents: vascular rupture – perforation
• Hemodynamic changes induced by the embolization may result in hemorrhagic complications
• Hemorrhagic complications related to attempts to remove entrapped catheter
• These ischemic or hemorrhagic complications may result in various functional neurological deficits and possibly death

WARNINGS

Due to the possibility of electrical arcing with the tantalum metal in the Onyx™ LES material, use of monopolar electrocautery devices for surgical resection of bAVMs or arteriovenous fistula embolized with Onyx™ LES should be avoided. Bipolar devices should be used with caution.

This device is supplied STERILE for single use only. Do not reprocess or re-sterilize. Reprocessing and re-sterilization increase the risks of patient infection and compromised device performance.

• Use only the Onyx™ LES syringes to inject DMSO and Onyx™ LES. Other syringes may not be compatible with DMSO.
• Use only DMSO compatible micro catheters. Other micro catheters may not be compatible with DMSO and their use can result in thromboembolic events due to catheter degradation.
• Always consider the potential for Onyx™ LES to interact with other embolic agents, e.g., cyanoacrylates, coated coils, particles and/ or embolic spheres.
• Performing embolization to occlude blood vessels is a high-risk procedure. The procedure should be carried out by a specialist with the appropriate neuro or peripheral interventional training, and a thorough knowledge of the pathology to be treated, angiographic techniques, and super-selective embolization.
• The patient’s anigoanatomy must be amenable to microcatheter tip placement at a location that is distal to arterial branches that potentially may feed a cranial nerve.
• Adjunctive coil use should be considered if angiography shows that venous drainage of the AVM appears almost simultaneously with arterial opacification.
• Premature solidification of Onyx™ LES may occur if micro catheter luer contacts saline, blood or contrast of any amount.
• Failure to continuously mix Onyx™ LES for the required time may result in inadequate suspension of the tantalum, resulting in inadequate fluoroscopic visualization during delivery. Inject Onyx™ LES immediately after mixing. If Onyx™ LES injection is delayed, tantalum settling can occur within the syringe resulting in poor visualization of Onyx™ LES during injection.
• Using the Onyx™ LES Syringe-Catheter Interface Adapter will reduce labelled dead space of the micro catheter. Failure to make the appropriate allowances may result in unintended embolization.
• Reference the Onyx Syringe-Catheter Interface Adapter Instructions for Use for a list of compatible micro catheters and dead space information.

When injecting Onyx™ LES, fluoroscopic visualization should reveal Onyx™ LES traveling through the catheter lumen. It is recommended to obtain fluoroscopic imaging prior to reaching the minimum catheter + adapter deadspace in order to visualize the embolic material before it exits the tip of the catheter.

• Only use thumb pressure to inject Onyx™ LES. Using palm of hand to advance plunger may result in catheter rupture due to overpressurization in the event of catheter occlusion.
• Inject Onyx™ LES and DMSO at a slow, steady rate, not to exceed 0.3 ml/minute. Animal studies have shown that a rapid injection of DMSO into the vasculature may lead to vasospasm and/or angionecrosis.
• Do not allow more than 1 cm of Onyx™ LES to reflux back over catheter tip. Angioarchitecture, vasospasm, excessive Onyx reflux, or prolonged injection time may result in difficult catheter removal and catheter entrapment. Excessive force to remove an entrapped catheter may cause serious intracranial hemorrhage. The long term effects of an entrapped catheter that is left in a patient is unknown, but could potentially include clot formation, infection or catheter migration.
• DO NOT interrupt Onyx™ LES injection for longer than two minutes prior to re-injection. Solidification of Onyx™ LES may occur at the catheter tip resulting in catheter occlusion, and use of excessive pressure to clear the catheter may result in catheter rupture.
• Adequate fluoroscopic visualization must be maintained during Onyx™ LES delivery or non-target vessel embolization may result. If visualization is lost at any time during the embolization procedure, HALT Onyx™ LES delivery until adequate visualization is re-established. Testing has shown that overpressurization and rupture can occur if 0.05 ml of Onyx™ LES is injected and is not visualized exiting the catheter tip.
• Increased resistance to Onyx™ LES injection – Stop Injection. Do not attempt to clear or overcome resistance by applying increased injection pressure. If this occurs, determine the cause of resistance (for example, Onyx™ LES occlusion in catheter lumen), and replace catheter. Use of excessive pressure may result in catheter rupture and embolization of unintended areas.
• After using a micro catheter with Onyx™ LES, do not attempt to clear the micro catheter or to inject any material through it. Attempts to clear catheter may lead to embolus or embolization of unintended area.
• If Onyx™ LES escapes outside the vascular space, as might occur if the vessel wall is compromised, a subacute inflammatory response to the material may occur.