XenMatrix™ AB Surgical Graft

1 IMS Data, Q2 2014, 51 OK search, fda.gov.

2 Preclincal data 011 file: results may not correlate to clinical performance.

3 Literature search and analysis of Rifampin and Minocycline coated medical devices. Data on file. 2014.

Indications:

Intended for implantation to reinforce soft tissue where weakness exists and for surgical repair of damaged or ruptured soft tissue, including: abdominal plastic and reconstructive surgery: muscle flap reinforcement; hernia repair including abdominal, inguinal, femoral. diaphragmatic, scrotal, umbilical, and incisional hernias. The Rifampin and Minocycline coating has been shown in preclinical in vitro and in vivo testing to reduce or inhibit microbial colonization on the device. The claim of reduction of bacterial colonization of the device has not been established with human clinical data, nor has a clinical impact associated with this claim been demonstrated.

Contraindications:

1. XenMatrix'" AB Surgical Graft should not be used on patients with known sensitivity to porcine products.

2. Do not use in patients with allergy, history of allergy or hypersensitivity to tetracyclines or rifamycins or other components in the device.

3. Do not use in pregnant or nursing women.

4. The contraindications, warnings and precautions regarding the use of the antimicrobial agents Rifampin (a derivative of rifamycinB) and Minocycline (a derivative of tetracycline) apply and should be considered when using this device. See FDA’s drug labeling database for Rifampin and Minocycline labeling. For reference the contraindications for Minocycline and Rifampin are as follows:

Contraindications for Oral Cpasule (1mg/kg) of Minocycline: This drug is contraindicated in persons who have shown hypersensitivity to any of the tetracyclines.

Contraindications for both IV (600mg) and Oral Capsule (150mg-300mg) of Rifampin: Rifampin in contraindicated in patients with a history of hypersensitivity to Rifampin or any of the components, or to any of the rifamycins.

The use of this product in patients with compromised hepatic function should be carefully considered since Rifampin can cause additional stress to hepatic metabolism. Implantation of this device would not result in detectable systemic concentrations of Rifampin or Minocycline.

Patients implanted with the largest product size (30 cm x 45 cm) are calculated to receive a one time total dose of approximately 327 mg each of Rifampin and Minocycline. This is in contrast to typical systemic treatment doses, which are 600 mg for Rifampin and 200 mg for Minocycline administered multiple times per day, over several days to several months.

5. Not for reconstruction of cardiovascular defects.

6. Not for reconstruction of central nervous system or peripheral nervous system defects.

7. Use of this product in applications other than those indicated has the potential for serious complications.

Warnings:

1. This device is not indicated for the treatment of infection. If an infection develops, treat the infection aggressively.

2. To minimize recurrences when repairing hernias, the graft should be large enough to provide sufficient overlap beyond the margins of the defect on all sides.

3. Prior to use, carefully examine package and product to verify neither is damaged and that all seals are intact. Do not use if the package is damaged or open.

4. Postoperative signs of toxicity, as possibly evidenced by worsening renal or hepatic function, or an allergic reaction that is unrelated to other therapy is an indication to consider removal of XenMatrix'" AB Surgical Graft.

5. Do not use this product in patients with allergy, history of allergy or hypersensitivity to tetracyclines or rifamycins or other components of the device.

6. The safety and performance of XenMatrix'" AB Surgical Graft in pediatric patients has not been evaluated.

7. After use, any unused product and packaging should be treated as a potential biohazard. Handle and dispose of in accordance with accepted medical practice and applicable local, state, and federal laws and regulations.

8. Do not resterilize. This device has been designed for single use only. Reuse, reprocessing, resterilization, or repackaging may compromise the structural integrity and/or essential material and design characteristics that are critical to the overall performance of the device and may lead to device failure which may result in injury to the patient. Reuse, reprocessing, resterilization, or repackaging may also create a risk of contamination of the device and/or cause patient infection or cross infection, including, but not limited to, the transmission of infectious diseases from one patient to another. Contamination of the device may lead to injury, illness or death of the patient or end user.

Precautions:

1. Please read all instructions prior to use.

2. Strict aseptic technique should be followed.

3. The use of this product in patients with compromised hepatic function should be carefully considered since Rifampin can cause additional stress to hepatic metabolism.

Rifampin given at systemic therapeutic doses over multiple days, has been shown to produce liver dysfunction. Fatalities associated with jaundice have occurred in patients with liver disease and in patients taking Rifampin with other hepatotoxic agents systemically. Patients with impaired liver function should be given Rifampin systemically only in cases of necessity and then with caution and under strict medical supervision. In these patients, careful monitoring of liver function, especially SGPT/ALT and SGOT/AST should be performed prior to therapy.

4. The risk of anti-anabolic effects (azotemia, hypophosphatemia, and acidosis) can be observed when using tetracyclines post-surgery. In patients with significantly impaired renal function, monitoring of Creatinine and BUN for 24 hours is recommended.

5. Do not alter practice of pre-, peri-, or postoperative administration of local or systemic antibiotics.

6. U. S. federal law restricts this device to sale by or on the order of a physician.

7. Only physicians qualified in the appropriate surgical techniques should use this surgical graft.

8. The surgeon should thoroughly understand the surgical procedure and the performance characteristics of the surgical graft.

9. Place device in maximum possible contact with healthy, well-vascularized tissue to promote cell ingrowth and tissue remodeling.

10. When unable to close skin over the XenMatrix™ AB Surgical Graft, ensure that the implant remains moist. Avoid drying of the implant through “continued suction devices” as this may negatively impact the performance of the implant.

11. Due to the orange color in the coating, hydration solution and fluid from surgical drains may be tinted orange.

Adverse Reactions:

Potential complications with the use of any prosthesis may include, but are not limited to, allergic reaction or hypersensitivity to device materials or antimicrobial coating, seroma, infection, inflammation, adhesion, fistula formation, erosion, hematoma, and recurrence of tissue defect.

WARNING: This product can expose you to Rifarnpin and Minocycline HCL, which are known to the State of California to cause birth defects or other reproductive harm. For more information go to www.P65Warnings.ca.gov.

BD-14768