BRIEF SUMMARY

TAURLIDE,HEPARIN -(Nov 2023)

Indn-      to treat the incidence of blood related infections in adults with   kidney failure receiving chronic hemodialysis thru a central venous catherter                                                                  

Comp-   DEFENCATH is a sterile catheter lock solution available in singledose vials in the following strengths: o 3 mL containing taurolidine 40.5 mg/3 mL (13.5 mg/mL), and heparin 3,000 USP Units/3 mL (1,000 USP Units/mL) (3) o 5 mL containing taurolidine 67.5 mg/5 mL (13.5 mg/mL), and heparin 5,000 USP Units/5 mL (1,000 USP Units/mL)

 Withdraw a sufficient volume of DEFENCATH catheter lock solution (CLS) from the vial using a sterile needle and syringe to fill the catheter lumens.

 Use 3 mL or 5 mL single dose vial (depending on the volume of the catheter lumens) to instill DEFENCATH into each catheter lumen at the conclusion of each HD session.

ADR-    The most frequently reported adverse reactions occurring in greater than or equal to 2% of patients in Trial 1 using DEFENCATH as a CLS were hemodialysis catheter malfunction, hemorrhage/bleeding, nausea, vomiting, dizziness, musculoskeletal chest pain, and thrombocytopenia.

CI-   Known hypersensitivity to taurolidine, heparin or the citrate excipient (components of DEFENCATH), or pork products. 

WARNINGS-                                                                                                                         • Heparin-Induced Thrombocytopenia (HIT): HIT was reported in Trial 1 at an incidence rate of 0.3% in patients using heparin, a component of DEFENCATH as a CLS. If HIT occurs, discontinue DEFENCATH and institute appropriate supportive measures.

Pat Inform-                                                                                                            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.

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U.S.  APPROVED DRUGS DURING 2023                                        

Serial No 48

Name-          DEFENCATH

Active ingedient-       Taurolide, Heparin              

Indication              to treat the incidence of blood related infections in adults with                                     kidney failure receiving chronic hemodialysis thru a central                                       venous catherter

Date  of approval       11/15/2023 

HIGHLIGHTS OF PRESCRIBING INFORMATION-

These highlights do not include all the information needed to use                      DEFENCATH safely and effectively.

See full prescribing information for DEFENCATH. DEFENCATH® (taurolidine and heparin) catheter lock solution, for central venous catheter instillation use

Initial U.S. Approval: 2023

INDICATIONS AND USAGE--

 LIMITED POPULATION:                                                                                           DEFENCATH is a combination of taurolidine, a thiadiazinane antimicrobial, and heparin, an anti-coagulant, 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. 

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.

ADVERSE REACTIONS-

 The most frequently reported adverse reactions occurring in greater than or equal to 2% of patients in Trial 1 using DEFENCATH as a CLS were hemodialysis catheter malfunction, hemorrhage/bleeding, nausea, vomiting, dizziness, musculoskeletal chest pain, and thrombocytopenia.

CONTRAINDICATIONS-

Known heparin-induced thrombocytopenia.

Known hypersensitivity to taurolidine, heparin or the citrate excipient (components of DEFENCATH), or pork products. 

WARNINGS AND PRECAUTIONS-

 • Heparin-Induced Thrombocytopenia (HIT): HIT was reported in Trial 1 at an incidence rate of 0.3% in patients using heparin, a component of DEFENCATH as a CLS. If HIT occurs, discontinue DEFENCATH and institute appropriate supportive measures.

 • Drug Hypersensitivity Reactions: Drug hypersensitivity reactions were reported in Trial 1 at an incidence rate of 0.5% in patients using heparin, a component of DEFENCATH, as a CLS. If a hypersensitivity reaction occurs, discontinue DEFENCATH and institute appropriate supportive measures.

DOSAGE AND ADMINISTRATION-

DEFENCATH is for instillation into CVCs only.

 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 lumens.

 Use 3 mL or 5 mL single dose vial (depending on the volume of the catheter lumens) to instill DEFENCATH into each catheter lumen at the conclusion of each HD session.

 DEFENCATH must be aspirated from the catheter and discarded prior to the initiation of the next HD session.

 Discard any unused portion of DEFENCATH remaining in the vial. 

DOSAGE FORMS AND STRENGTHS-

 DEFENCATH is a sterile catheter lock solution available in singledose vials in the following strengths: o 3 mL containing taurolidine 40.5 mg/3 mL (13.5 mg/mL), and heparin 3,000 USP Units/3 mL (1,000 USP Units/mL) (3) o 5 mL containing taurolidine 67.5 mg/5 mL (13.5 mg/mL), and heparin 5,000 USP Units/5 mL (1,000 USP Units/mL)

STORAGE AND HANDLING-

 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 0792

CLINICAL PHARMACOLOGY

1. Mechanism of Action-

 Heparin Heparin interacts with the naturally occurring plasma protein, Antithrombin III, to induce a conformational change, which markedly enhances the serine protease activity of Antithrombin III, thereby inhibiting the activated coagulation factors involved in the clotting sequence, particularly Xa Reference ID: 5276483 and IIa.

Small amounts of heparin inhibit Factor Xa, and larger amounts inhibit thrombin (Factor IIa). Heparin also prevents the formation of a stable fibrin clot by inhibiting the activation of the fibrin stabilizing factor

Heparin does not have fibrinolytic activity; therefore, it will not lyse existing clots. Taurolidine Taurolidine is an antimicrobial drug [see Microbiology (12.4)].

2. Pharmacodynamics-                                                                                                 The pharmacodynamics of DEFENCATH are unknown.

3. Pharmacokinetics-                                                                                                      No pharmacokinetic studies were conducted because DEFENCATH is intended to be instilled into the catheter lumens at the conclusion of each HD session for patients with kidney failure requiring chronic HD.

DEFENCATH is not intended for systemic administration 

4. Microbiology- Mechanism of Action-                                                                         The mechanism of action of taurolidine and its metabolites is non-specific, causing damage to microbial cell walls and inhibiting adherence of microorganisms to biological surfaces.

Resistance Time kill studies showed that taurolidine is bactericidal (>3 log10 CFU reduction) at 1x to 4x minimum inhibitory concentration (MIC). The frequency of resistant mutants was <10-9 at 2x and 4x MIC for two strains each of Escherichia coli, Staphylococcus aureus, Enterococcus faecalis, Enterococcus faecium and Pseudomonas aeruginosa.

 Antimicrobial Activity- The following in vitro data are available but their clinical significance is unknown.

Taurolidine has been shown to be active against most isolates of the following microorganisms: Gram-positive Staphylococcus aureus (including methicillin-sensitive Staphylococcus aureus (MSSA) and methicillin-resistant Staphylococcus aureus (MRSA)) Staphylococcus epidermidis Enterococcus faecalis Gram-negative Escherichia coli Klebsiella pneumoniae Pseudomonas aeruginosa Serratia marc

USE IN SPECIFIC POPULATIONS

1. Pregnancy Risk Summary-                                                                                  DEFENCATH is not intended for systemic administration. It is intended for use as a CLS in patients with kidney failure requiring chronic HD; therefore, maternal use is not expected to result in fetal exposure to the drug .

No animal reproduction study was conducted with DEFENCATH.

2 Lactation Risk Summary-                                                                                     DEFENCATH is not intended for systemic administration. It is intended for use as a CLS in patients with kidney failure requiring chronic HD; therefore, breastfeeding is not expected to result in exposure of the infant to DEFENCATH .

3. Pediatric Use-                                                                                                            The safety and effectiveness of DEFENCATH have not been established in pediatric patients. There are no available data on DEFENCATH use in pediatric patients.

4. Geriatric Use-                                                                                                          There were 327 patients 65 years of age and older in Trial 1 [see Clinical Studies (14)].

Of the total number of patients using DEFENCATH in this study, 162 (41%) were 65 years of age and older, while 64 (16%) were 75 years of age and older.

No overall differences in safety or effectiveness were observed between patients 65 years of age and older and younger adult patients.