Colistimethate Sodium

Description

DESCRIPTION Colistimethate for Injection, USP is a sterile parenteral antibiotic product which, when reconstituted (see Reconstitution ), is suitable for intramuscular or intravenous administration. Each vial contains colistimethate sodium or pentasodium colistinmethanesulfonate (150 mg colistin base activity). Colistimethate sodium is a polypeptide antibiotic with an approximate molecular weight of 1750. The empirical formula is C 58 H 105 N 16 Na 5 O 28 S 5 and the structural formula is represented below: Dbu is 2,4-diaminobutanoic acid; R is 5-methylheptyl in colistin A and 5-methylhexyl in colistin B Chemical Structure

What Is Colistimethate Sodium Used For?

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 Note: The suggested total daily dose is calculated from colistin base activity. 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 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....

Side Effects (Adverse Reactions)

ADVERSE REACTIONS 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 Xellia Pharmaceuticals USA, LLC at 1-833-295-6953, or FDA at 1-800-FDA-1088 or http://www.fda.gov/medwatch/.

Drug Interactions

Drug Interactions Certain other antibiotics (aminoglycosides and polymyxin) have also been reported to interfere with the nerve transmission at the neuromuscular junction. Based on this reported activity, they should not be given concomitantly with Colistimethate for Injection, USP except with the greatest caution. Curariform muscle relaxants (e.g., tubocurarine) and other drugs, including ether, succinylcholine, gallamine, decamethonium and sodium citrate, potentiate the neuromuscular blocking effect and should be used with extreme caution in patients being treated with Colistimethate for Injection, USP. Sodium cephalothin may enhance the nephrotoxicity of Colistimethate for Injection, USP. The concomitant use of sodium cephalothin and Colistimethate for Injection, USP should be avoided.

Contraindications

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

Pregnancy and Breastfeeding

Pregnancy Teratogenic Effects Pregnancy Category C Colistimethate sodium given intramuscularly during organogenesis to rabbits at 4.15 and 9.3 mg/kg resulted in talipes varus in 2.6% and 2.9% of fetuses, respectively. These doses are 0.25 and 0.55 times the maximum daily human dose based on mg/m 2 . In addition, increased resorption occurred at 9.3 mg/kg. Colistimethate sodium was not teratogenic in rats at 4.15 or 9.3 mg/kg. These doses are 0.13 and 0.30 times the maximum daily human dose based on mg/m 2 . There are no adequate and well-controlled studies in pregnant women. Since colistimethate sodium is transferred across the placental barrier in humans, it should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Nursing Mothers It is not known whether colistimethate sodium is excreted in human breast milk. However, colistin sulphate is excreted in human breast milk. Therefore, caution should be exercised when colistimethate sodium is administered to nursing women.

Overdosage

OVERDOSAGE Overdosage with colistimethate sodium can cause neuromuscular blockade characterized by paresthesia, lethargy, confusion, dizziness, ataxia, nystagmus, disorders of speech and apnea. Respiratory muscle paralysis may lead to apnea, respiratory arrest and death. Overdosage with the drug can also cause acute renal failure, manifested as decreased urine output and increases in serum concentrations of BUN and creatinine. As in any case of overdose, colistimethate sodium therapy should be discontinued and general supportive measures should be utilized. It is unknown whether colistimethate sodium can be removed by hemodialysis or peritoneal dialysis in overdose cases.

How Supplied

HOW SUPPLIED Colistimethate for Injection, USP is supplied in vials containing colistimethate sodium (equivalent to 150 mg colistin base activity per vial) as a white to slightly yellow Iyophilized cake. NDC-70594-023-09: one individual vial. Store between 20° to 25°C (68° to 77°F). (See USP controlled room temperature). Store reconstituted solution in refrigerator 2° to 8°C (36° to 46°F) or between 20° to 25°C (68° to 77°F), and use within 7 days.