Label: COLISTIMETHATE- colistimethate sodium injection, powder, lyophilized, for solution

Rx only

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 bacteria.

FOR INTRAMUSCULAR AND INTRAVENOUS USE

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 C58H105N16Na5O28S5 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

Typical serum and urine levels following a single 150 mg dose of colistimethate IM or IV in normal adult subjects are shown in Figure 1. 

Higher serum levels were obtained at 10 minutes following IV administration.  Serum concentration declined with a half-life of 2 to 3 hours following either intravenous or intramuscular administration in adults and in the pediatric population, including premature infants.

Average urine levels ranged from about 270 mcg/mL at 2 hours to about 15 mcg/mL at 8 hours after intravenous administration and from 200 to about 25 mcg/mL during a similar period following intramuscular administration.

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.

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

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 include circumoral paresthesia or numbness, tingling or formication of the extremities, generalized pruritus, vertigo, dizziness, and slurring of speech.  For these reasons, patients should be warned not to drive vehicles or use hazardous machinery while on therapy. Reduction of dosage may alleviate symptoms. Therapy need not be discontinued, but such patients should be observed with particular care.

Nephrotoxicity can occur and is probably a dose-dependent effect of colistimethate sodium. These manifestations of nephrotoxicity are reversible following discontinuation of the antibiotic. 

Overdosage can result in renal insufficiency, muscle weakness, and apnea (see OVERDOSAGE section).  See PRECAUTIONS, Drug Interactions subsection for use concomitantly with other antibiotics and curariform drugs. 

Respiratory arrest has been reported following intramuscular administration of colistimethate sodium.  Impaired renal function increases the possibility of apnea and neuromuscular blockade following administration of colistimethate sodium.  Therefore, it is important to follow recommended dosing guidelines. See DOSAGE AND ADMINISTRATION section for use in renal impairment. 

Clostridium difficile associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including Colistimethate for Injection, USP, and may range in severity from mild diarrhea to fatal colitis.  Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile.

C. difficile produces toxins A and B which contribute to the development of CDAD.  Hypertoxin producing strains of C. difficile cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy.  CDAD must be considered in all patients who present with diarrhea following antibiotic use.  Careful medical history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial agents.

If CDAD is suspected or confirmed, ongoing antibiotic use not directed against C. difficile may need to be discontinued.  Appropriate fluid and electrolyte management, protein supplementation, antibiotic treatment of C. difficile, and surgical evaluation should be instituted as clinically indicated.

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.

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.

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 lyophilized cake, packaged individually.

The container closure is not made with natural rubber latex.

Store unreconstituted product between 20º to 25ºC (68º to 77ºF) (see  USP Controlled Room Temperature).

Store reconstituted solution in refrigerator 2º to 8ºC (36º to 46ºF) or between 20º to 25ºC (68º to 77ºF) and use within 7 days.

www.fresenius-kabi.com/us
 

451075D

Revised: January 2020

PACKAGE LABEL - PRINCIPAL DISPLAY - Colistimethate 150 mg Vial Label

Colistimethate
for Injection, USP
150 mg* per vial
Colistin base activity
For intramuscular
and intravenous use
One Sterile Vial
Rx only

PACKAGE LABEL - PRINCIPAL DISPLAY - Colistimethate 150 mg Vial Carton Panel

Colistimethate
for Injection, USP
150 mg* per vial
Colistin base activity
For intramuscular and intravenous use
Rx only
One Sterile Vial