COLISTIMETHATE

Colistimethate for Injection, USP is a sterile parenteral antibiotic product which, when reconstituted (see Reconstitution ), is suitable for intramuscular or intravenous administration. The color of the reconstituted solution is colorless to light yellow. Each vial contains colistimethate sodium or pentasodium colistinmethanesulfonate (150 mg colistin base activity) as a white to slightly yellow lyophilized cake. The sodium content is approximately 0.07 mg (0.003 mEq) of sodium per milligram of Colistin. Colistimethate sodium is a polypeptide antibiotic with an approximate molecular weight of 1,750. The molecular formula is C 58 H 105 N 16 Na 5 O 28 S 5 and the structural formula is represented below: pentasodium colistinmethanesulfonate (colistimethate sodium) Dbu is 2, 4-diaminobutanoic acid, R is 5-methylheptyl in colistin A and 5-methylhexyl in colistin B micro

Colistimethate for Injection, USP is indicated for the treatment of acute or chronic infections due to sensitive strains of certain gram-negative bacilli. It is particularly indicated when the infection is caused by sensitive strains of Pseudomonas aeruginosa . This antibiotic is not indicated for infections due to Proteus or Neisseria . Colistimethate for Injection, USP has proven clinically effective in treatment of infections due to the following gram-negative organisms: Enterobacter aerogenes, Escherichia coli, Klebsiella pneumoniae and Pseudomonas aeruginosa . Colistimethate for Injection, USP may be used to initiate therapy in serious infections that are suspected to be due to gram-negative organisms and in the treatment of infections due to susceptible gram-negative pathogenic bacilli. To reduce the development of drug-resistant bacteria and maintain the effectiveness of Colistimethate for Injection, USP and other antibacterial drugs, Colistimethate for Injection, USP should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.

Important Colistimethate for Injection, USP is supplied in vials containing colistimethate sodium equivalent to 150 mg colistin base activity per vial. Reconstitution for Intravenous or Intramuscular Administration The 150 mg vial should be reconstituted with 2 mL Sterile Water for Injection, USP. The reconstituted solution provides colistimethate sodium at a concentration equivalent to 75 mg/mL colistin base activity. During reconstitution swirl gently to avoid frothing. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. If these conditions are observed, the product should not be used. Dosage Adults and Pediatric Patients — Intravenous or Intramuscular Administration The dose of Colistimethate for Injection, USP should be 2.5 to 5 mg/kg per day of colistin base in 2 to 4 divided doses for patients with normal renal function, depending on the severity of the infection. In obese individuals, dosage should be based on ideal body weight. The daily dose and frequency should be reduced for the patients with renal impairment. Suggested modifications of dosage schedule for patients with renal impairment are presented in Table 1. TABLE 1. Suggested Modification of Dosage Schedules of Colistimethate for Injection, USP for Adults with Impaired Renal Function Degree of Renal Impairment Normal Mild Moderate Severe Creatinine Clearance (mL/min) ≥ 80 50 to 79 30 to 49 10 to 29 Dosage Schedule 2.5 to 5 mg/kg, divided into 2 to 4 doses per day 2.5 to 3.8 mg/kg, divided into 2 doses per day 2.5 mg/kg, once daily or divided into 2 doses per day 1.5 mg/kg, every 36 hours Note: The suggested total daily dose is calculated from colistin base activity. Important Colistimethate for Injection, USP is supplied in vials containing colistimethate sodium equivalent to 150 mg colistin base activity per vial. Reconstitution for Intravenous or Intramuscular Administration The 150 mg vial should be reconstituted with 2 mL Sterile Water for Injection, USP. The reconstituted solution provides colistimethate sodium at a concentration equivalent to 75 mg/mL colistin base activity. During reconstitution swirl gently to avoid frothing. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. If these conditions are observed, the product should not be used. Dosage Adults and Pediatric Patients — Intravenous or Intramuscular Administration The dose of Colistimethate for Injection, USP should be 2.5 to 5 mg/kg per day of colistin base in 2 to 4 divided doses for patients with normal renal function, depending on the severity of the infection. In obese individuals, dosage should be based on ideal body weight. The daily dose and frequency should be reduced for the patients with renal impairment. Suggested modifications of dosage schedule for patients with renal impairment are presented in Table 1. TABLE 1. Suggested Modification of Dosage Schedules of Colistimethate for Injection, USP for Adults with Impaired Renal Function Degree of Renal Impairment Normal Mild Moderate Severe Creatinine Clearance (mL/min) ≥ 80 50 to 79 30 to 49 10 to 29 Dosage Schedule 2.5 to 5 mg/kg, divided into 2 to 4 doses per day 2.5 to 3.8 mg/kg, divided into 2 doses per day 2.5 mg/kg, once daily or divided into 2 doses per day 1.5 mg/kg, every 36 hours Note: The suggested total daily dose is calculated from colistin base activity.

The use of Colistimethate for Injection, USP is contraindicated for patients with a history of sensitivity to the drug or any of its components.

The following adverse reactions have been reported: Gastrointestinal - gastrointestinal upset Nervous System - tingling of extremities and tongue, slurred speech, dizziness, vertigo, paresthesia, and seizures Integumentary - generalized itching, urticaria and rash Body as a Whole - fever and anaphylaxis Laboratory Deviations - increased blood urea nitrogen (BUN), elevated creatinine and decreased creatinine clearance Respiratory System - respiratory distress and apnea Renal System - nephrotoxicity and decreased urine output For medical advice about adverse reactions contact your medical professional. To report SUSPECTED ADVERSE REACTIONS, contact Fresenius Kabi USA, LLC, at 1-800-551-7176 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.