Colistimethate

Clinical summary

Indications and usage INDICATIONS AND USAGE 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. Dosage and administration DOSAGE AND ADMINISTRATION 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 50-79 30-49 10-29 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. INTRAVENOUS ADMINISTRATION Direct Intermittent Administration - Slowly inject one-half of the total daily dose over a period of 3 to 5 minutes every 12 hours. Continuous Infusion - Slowly inject one-half of the total daily dose over 3 to 5 minutes. Add the remaining half of the total daily dose of Colistimethate for Injection, USP to one of the following: 0.9% NaCI 5% dextrose in 0.9% NaCI 5% dextrose in water 5% dextrose in 0.45% NaCI 5% dextrose in 0.225% NaCI lactated Ringer's solution 10% invert sugar solution There are not sufficient data to recommend usage of colistimethate for injection with other drugs or other than the above listed infusion solutions. Administer the second half of the total daily dose by slow intravenous infusion, starting 1 to 2 hours after the initial dose, over the next 22 to 23 hours. In the presence of impaired renal function, reduce the infusion rate depending on the degree of renal impairment. The choice of intravenous solution and the volume to be employed are dictated by the requirements of fluid and electrolyte management. Any final intravenous infusion solution containing colistimethate sodium should be freshly prepared and used for no longer than 24 hours. INTRAMUSCULAR ADMINISTRATION 1. For Intramuscular Injection, administer by deep intramuscular injection into a large muscle mass (such as the gluteal muscles or lateral part of the thigh). Store reconstituted solution for intramuscular injection in a refrigerator 2° to 8°C (36° to 46°F) or between 20° to 25°C (68° to 77°F), and use within 7 days. Warnings and cautions WARNINGS Maximum daily dose calculated from colistin base activity should not exceed 5 mg/kg/day with normal renal function. Transient neurological disturbances may occur. These inclu