NDC 42023-131 Colistimethate

Colistimethate Sodium

NDC Product Code 42023-131

NDC Product Information

Colistimethate with NDC 42023-131 is a a human prescription drug product labeled by Par Pharmaceutical, Inc.. The generic name of Colistimethate is colistimethate sodium. The product's dosage form is injection and is administered via intramuscular; intravenous form. The RxNorm Crosswalk for this NDC code indicates a single RxCUI concept is associated to this product: 1117522.

Dosage Form: Injection - A sterile preparation intended for parenteral use; five distinct classes of injections exist as defined by the USP.

Product Type: Human Prescription Drug What kind of product is this?
Indicates the type of product, such as Human Prescription Drug or Human Over the Counter Drug. This data element matches the “Document Type” field of the Structured Product Listing.

Colistimethate Active Ingredient(s)

What is the Active Ingredient(s) List?
This is the active ingredient list. Each ingredient name is the preferred term of the UNII code submitted.


Administration Route(s)

What are the Administration Route(s)?
The translation of the route code submitted by the firm, indicating route of administration.

  • Intramuscular - Administration within a muscle.
  • Intravenous - Administration within or into a vein or veins.

Pharmacological Class(es)

What is a Pharmacological Class?
These are the reported pharmacological class categories corresponding to the SubstanceNames listed above.

  • Polymyxin-class Antibacterial - [EPC] (Established Pharmacologic Class)
  • Polymyxins - [CS]

Product Labeler Information

What is the Labeler Name?
Name of Company corresponding to the labeler code segment of the Product NDC.

Labeler Name: Par Pharmaceutical, Inc.
Labeler Code: 42023
FDA Application Number: NDA050108 What is the FDA Application Number?
This corresponds to the NDA, ANDA, or BLA number reported by the labeler for products which have the corresponding Marketing Category designated. If the designated Marketing Category is OTC Monograph Final or OTC Monograph Not Final, then the Application number will be the CFR citation corresponding to the appropriate Monograph (e.g. “part 341”). For unapproved drugs, this field will be null.

Marketing Category: NDA AUTHORIZED GENERIC - A product marketed as a “generic” drug under an approved New Drug Application (NDA), rather than an Abbreviated New Drug Application (ANDA),. What is the Marketing Category?
Product types are broken down into several potential Marketing Categories, such as NDA/ANDA/BLA, OTC Monograph, or Unapproved Drug. One and only one Marketing Category may be chosen for a product, not all marketing categories are available to all product types. Currently, only final marketed product categories are included. The complete list of codes and translations can be found at www.fda.gov/edrls under Structured Product Labeling Resources.

Start Marketing Date: 06-01-2012 What is the Start Marketing Date?
This is the date that the labeler indicates was the start of its marketing of the drug product.

Listing Expiration Date: 12-31-2021 What is the Listing Expiration Date?
This is the date when the listing record will expire if not updated or certified by the product labeler.

Exclude Flag: N - NO What is the NDC Exclude Flag?
This field indicates whether the product has been removed/excluded from the NDC Directory for failure to respond to FDA"s requests for correction to deficient or non-compliant submissions ("Y"), or because the listing certification is expired ("E"), or because the listing data was inactivated by FDA ("I"). Values = "Y", "N", "E", or "I".

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Information for Patients

Colistimethate Injection

Colistimethate Injection is pronounced as (koe lis" ti meth' ate)

Why is colistimethate injection medication prescribed?
Colistimethate injection is used to treat certain infections caused by bacteria. Colistimethate injection is in a class of medications called antibiotics. It works by kil...
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Colistimethate Product Labeling Information

The product labeling information includes all published material associated to a drug. Product labeling documents include information like generic names, active ingredients, ingredient strength dosage, routes of administration, appearance, usage, warnings, inactive ingredients, etc.

Product Labeling Index

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 C58H105N16Na5O28S5 and the structural formula is represented below:

Clinical Pharmacology

Typical serum and urine levels following a single 150 mg dose of colistimethate for injection 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 2–3 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.

Microbiology:

Colistimethate sodium is a surface active agent which penetrates into and disrupts the bacterial cell membrane. It has been shown to have bactericidal activity against most strains of the following microorganisms, both in vitro and in clinical infections as described in the INDICATIONS AND USAGE section:Aerobic gram-negative microorganisms: Enterobacter aerogenes, Escherichia coli, Klebsiella pneumoniae and Pseudomonas aeruginosa.Susceptibility Tests: Colistimethate sodium is no longer listed as an antimicrobial for routine testing and reporting by clinical microbiology laboratories.

Indications And Usage

Colistimethate for injection 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 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 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 and other antibacterial drugs, colistimethate 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.

Contraindications

The use of colistimethate for injection is contraindicated for patients with a history of sensitivity to the drug or any of its components.

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 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, 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.

General

Since colistimethate is eliminated mainly by renal excretion, it should be used with caution when the possibility of impaired renal function exists. The decline in renal function with advanced age should be considered.When actual renal impairment is present, colistimethate for injection may be used, but the greatest caution should be exercised and the dosage should be reduced in proportion to the extent of the impairment. Administration of amounts of colistimethate for injection in excess of renal excretory capacity will lead to high serum levels and can result in further impairment of renal function, initiating a cycle which, if not recognized, can lead to acute renal insufficiency, renal shutdown, and further concentration of the antibiotic to toxic levels in the body. At this point, interference of nerve transmission at neuromuscular junctions may occur and result in muscle weakness and apnea (see OVERDOSAGE section).Signs indicating the development of impaired renal function include: diminishing urine output, rising BUN and serum creatinine and decreased creatinine clearance. Therapy with colistimethate for injection should be discontinued immediately if signs of impaired renal function occur. However, if it is necessary to reinstate the drug, dosing should be adjusted accordingly after drug plasma levels have fallen (see DOSAGE AND ADMINISTRATION section).Prescribing colistimethate in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria.

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 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.Sodium cephalothin may enhance the nephrotoxicity of colistimethate for injection. The concomitant use of sodium cephalothin and colistimethate for injection should be avoided.

Carcinogenesis, Mutagenesis, Impairment Of Fertility

Long-term animal carcinogenicity studies and genetic toxicology studies have not been performed with colistimethate sodium. There were no adverse effects on fertility or reproduction in rats at doses of 9.3 mg/kg/day (0.30 times the maximum daily human dose when based on mg/m2).

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.

Geriatric Use

Clinical studies of colistimethate sodium did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.

Pediatric Use

In clinical studies, colistimethate sodium was administered to the pediatric population (neonates, infants, children and adolescents). Although adverse reactions appear to be similar in the adult and pediatric populations, subjective symptoms of toxicity may not be reported by pediatric patients. Close clinical monitoring of pediatric patients is recommended.

Information For Patients

Patients should be counseled that antibacterial drugs including colistimethate should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When colistimethate is prescribed to treat a bacterial infection, patients should be told that although it is common to feel better early in the course of therapy, the medication should be taken exactly as directed. Skipping doses or not completing the full course of therapy may (1) decrease the effectiveness of the immediate treatment and (2) increase the likelihood that bacteria will develop resistance and will not be treatable by colistimethate or other antibacterial drugs in the future.Diarrhea is a common problem caused by antibiotics which usually ends when the antibiotic is discontinued. Sometimes after starting treatment with antibiotics, patients can develop watery and bloody stools (with or without stomach cramps and fever) even as late as two or more months after having taken the last dose of the antibiotic. If this occurs, patients should contact their physician as soon as possible.

Adverse Reactions

The following adverse reactions have been reported:Gastrointestinal: gastrointestinal upsetNervous System: tingling of extremities and tongue, slurred speech, dizziness, vertigo, paresthesia, and seizuresIntegumentary: generalized itching, urticaria and rashBody as a Whole: fever and anaphylaxisLaboratory Deviations: increased blood urea nitrogen (BUN), elevated creatinine and decreased creatinine clearance Respiratory System: respiratory distress and apnea Renal System: nephrotoxicity and decreased urine outputFor medical adviceabout adverse reactions contact your medical professional. To report SUSPECTED ADVERSE REACTIONS, contact Par Pharmaceutical at 1-800-828-9393 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

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.

Dosage And Administration

Important: Colistimethate for injection 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.

How Supplied

Colistimethate for injection 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 42023-131-01: one individual vial.NDC 42023-131-06: six vials per carton.

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