LIMITED POPULATION: DEFENCATH® is indicated to reduce the incidence of catheter-related bloodstream infections (CRBSI) in adult patients with kidney failure receiving chronic hemodialysis (HD) through a central venous catheter (CVC). This drug is indicated for use in a limited and specific population of patients [see Clinical Studies (14)].

Limitations of Use

The safety and effectiveness of DEFENCATH have not been established for use in populations other than adult patients with kidney failure receiving chronic HD through a CVC.

DEFENCATH is for instillation into CVCs only [see Indications and Usage (1)]. DEFENCATH is not intended for systemic administration. Do not use DEFENCATH as a catheter lock flush product.

Withdraw a sufficient volume of DEFENCATH catheter lock solution (CLS) from the vial using a sterile needle and syringe to fill the catheter lumen. Use 3 mL or 5 mL single-dose vial (depending on the volume of the catheter lumen) to instill DEFENCATH into each catheter lumen at the conclusion of each HD session for patients with kidney failure requiring chronic HD. Prior to initiation of the next HD session, DEFENCATH must be aspirated from the catheter and discarded.

Each DEFENCATH single-dose vial is designed for use with a single patient as a single instillation in the CVC. Discard any unused portion of DEFENCATH remaining in the vial.

DEFENCATH CLS is available as a sterile, preservative-free, clear, aqueous-based solution in the following strengths:

• 3 mL of catheter lock solution in a single-dose vial containing taurolidine 40.5 mg/3 mL (13.5 mg/mL), and heparin 3,000 USP Units/3 mL (1,000 USP Units/mL)
• 5 mL of catheter lock solution in a single-dose vial containing taurolidine 67.5 mg/5 mL (13.5 mg/mL), and heparin 5,000 USP Units/5 mL (1,000 USP Units/mL)

DEFENCATH is contraindicated in patients with:

• Known heparin-induced thrombocytopenia (HIT) [see Warnings and Precautions (5.1)].
• Known hypersensitivity to taurolidine, heparin or the citrate excipient (components of DEFENCATH) or pork products [see Warnings and Precautions (5.2)].

The following clinically significant adverse reactions are described elsewhere in the labeling:

• Heparin-Induced Thrombocytopenia [see Warnings and Precautions (5.1)]
• Drug Hypersensitivity [see Warnings and Precautions (5.2)]

DEFENCATH (taurolidine and heparin) CLS contains taurolidine, a thiadiazinane antimicrobial, and heparin sodium, an anti-coagulant.

Taurolidine
Taurolidine is an antimicrobial agent derived from the naturally occurring amino acid taurine. The chemical name is 4,4’-methylenebis(1,2,4-thiadiazinane)-1,1,1’,1’-tetraoxide. The molecular weight is 284.36, and the molecular formula is C7H16N4O4S2.

The structural formula of taurolidine is:

Heparin Sodium
Heparin is an anticoagulant consisting of heterogeneous group of straight-chain anionic mucopolysaccharides, called glycosaminoglycans. It is composed of polymers of alternating derivatives of α-D-glucosamido (N-sulfated, O-sulfated, or N-acetylated) and O-sulfated uronic acid (α-L-iduronic acid or β-D-glucuronic acid). Heparin is derived from porcine intestinal mucosa.

The structure of heparin sodium (representative subunits) is:

DEFENCATH is for central venous catheter instillation use. DEFENCATH CLS is available as a sterile, non-pyrogenic, preservative-free, clear, aqueous-based solution of taurolidine and heparin with a pH of 5.5-6.5 in the following strengths:

• 3 mL of catheter lock solution in a single-dose vial containing taurolidine 40.5 mg/3 mL (13.5 mg/mL), and heparin 3,000 USP Units/3 mL (1,000 USP Units/mL)
• 5 mL of catheter lock solution in a single-dose vial containing taurolidine 67.5 mg/5 mL (13.5 mg/mL), and heparin 5,000 USP Units/5 mL (1,000 USP Units/mL)

The heparin potency is determined by a biological assay using a USP reference standard based on units of heparin activity per milligram. The inactive ingredients are 26.1 mg/mL of citric acid, anhydrous (which is added to control pH and maintain the solubility of taurolidine),and may include hydrochloric acid and/or sodium hydroxide for pH adjustment.

The efficacy and safety of DEFENCATH for reducing the incidence of CRBSI in patients with kidney failure receiving chronic HD was evaluated in LOCK-IT-100 (referred to as Trial 1, NCT02651428), a randomized, double-blind, active-controlled, multicenter trial.

A total of 806 patients were randomized in a 1:1 ratio to receive either DEFENCATH or heparin (heparin sodium USP 1,000 units/mL, benzyl alcohol 9.45 mg/mL and sodium chloride 9.0 mg/mL) as a CLS. Enrollment in Trial 1 was not limited to patients with specific types of HD catheters. DEFENCATH or heparin was instilled into central venous HD catheters at the end of all dialysis sessions and was withdrawn prior to the initiation of the next dialysis session. The median age of the study population was 63 years (range 21-94 years); 58% identified as males and 63% identified as white. The majority of patients (98%) had HD treatment three times per week, and 48% had their catheter implanted within three months prior to randomization.

A clinical adjudication committee (CAC) assessed the cases of CRBSI. The CAC definition for CRBSI included one positive blood culture (other than for coagulase-negative staphylococci, which required a confirmatory culture) from a peripheral site or either the arterial or venous catheter hub or the arterial or venous dialysis blood line and the patient had to have signs and symptoms of infection and no other apparent source of bloodstream infection.

Results of analyses of CAC-adjudicated CRBSI among the DEFENCATH and heparin groups in all randomized patients who received at least one dose of allocated study CLS are presented in Table 3. Patients in the DEFENCATH group had a lower incidence of CRBSI events compared to patients in the control group.

In total, 5% [18/397] of subjects in the DEFENCATH arm and 5% [21/398] of subjects in the heparin arm died during the trial (difference [DEFENCATH – Heparin]: -0.7% with a 95% CI[-3.7%, 2.3%]).

Among the 9 patients in the DEFENCATH arm with a CAC-adjudicated CRBSI, 1 had a gram-negative organism isolated and 8 had a gram-positive organism isolated; among the 32 patients in the heparin arm with a CAC-adjudicated CRBSI, 14 had a gram-negative organism isolated and 18 had a gram-positive organism isolated.

1. Torres-Viera, C, Thauvin-Eliopoulos C., Souli M, DeGirolamin P, Farris MG, Wennerstein CB, Sofia RD and Eliopoulos GM. 2000. Antimicrobial Agents and Chemotherapy 44(6):1720 - 1724.

DEFENCATH cathether lock solution is available in:

• 3 mL of catheter lock solution in a single-dose vial containing taurolidine 40.5 mg/3 mL (13.5 mg/mL), and heparin 3,000 USP Units/3 mL (1,000 USP Units/mL) (NDC 72990-103-03)
• 5 mL of catheter lock solution in a single-dose vial containing taurolidine 67.5 mg/5 mL (13.5 mg/mL), and heparin 5,000 USP Units/5 mL (1,000 USP Units/mL) (NDC 72990-105-05)

Each vial contains a sterile, preservative-free, clear aqueous-based solution for instillation in central venous catheters. Each carton contains 10 single-dose vials.

DEFENCATH vials must be stored at a controlled room temperature of 20°C to 25°C (68°F to 77°F); excursions are permitted from 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature]. Do not freeze. DEFENCATH vials must be stored in the commercial carton, prior to the instillation in central venous catheters.

Manufactured for:
CorMedix Inc.
300 Connell Drive, Suite 4200
Berkeley Heights, NJ 07922

NDC 72990-103-10

Rx Only

DEFENCATH®

Taurolidine and Heparin Catheter Lock Solution

Limited
Population*

Taurolidine 40.5 mg/3 mL (13.5 mg/mL) and
Heparin 3,000 USP Units/3 mL (1,000 USP Units/mL)

Derived from Porcine Intestinal Mucosa

3 mL

For Instillation in Central Venous Catheters
Not for systemic administration
Do not use as a catheter lock flush

*See prescribing information for
DEFENCATH for information about
the limited population.

Contains 10 Single-dose vials.
Discard unused portion.

CorMedix Inc.TM

NDC 72990-103-03

Rx Only

DEFENCATH®

Taurolidine and Heparin Catheter Lock Solution

Limited
Population*

Taurolidine 40.5 mg/3 mL (13.5 mg/mL)
and Heparin 3,000 USP Units/3 mL
(1,000 USP Units/mL)

Derived from Porcine Intestinal Mucosa

For Instillation in Central Venous
Catheters
Not for systemic administration
Do not use as a catheter lock flush

Store at 20°C to 25°C
(68°F to 77°F)

3 mL Fill Single-Dose Vial
Discard Unused Portion

NDC 72990-105-10

Rx Only

DEFENCATHTM

Taurolidine and Heparin Catheter Lock Solution

Limited
Population*

Taurolidine 67.5 mg/5mL (13.5 mg/mL) and
Heparin 5,000 USP Units/5 mL (1,000 USP Units/mL)

Derived from Porcine Intestinal Mucosa

5 mL

For Instillation in Central Venous Catheters
Not for systemic administration
Do not use as a catheter lock flush

*See prescribing information for
Defencath for information about
the limited population.

Contains 10 Single-dose vials.
Discard unused portion.

CorMedix Inc.TM

NDC 72990-105-05

Rx Only

DEFENCATHTM

Taurolidine and Heparin Catheter Lock Solution

Limited
Population*

Taurolidine 67.5 mg/5mL (13.5 mg/mL)
and Heparin 5,000 USP Units/5 mL
(1,000 USP Units/mL)

Derived from Porcine Intestinal Mucosa

For Instillation in Central Venous
Catheters
Not for systemic administration
Do not use as a catheter lock flush

Store at 20°C to 25°C
(68°F to 77°F)

5 mL Fill Single-Dose Vial -
Discard Unused Portion