Colistimethate

Follow all directions on your prescription label. Do not use this medicine in larger or smaller amounts or for longer than recommended.

Colistimethate is injected into a muscle, or into a vein through an IV. You may be shown how to use injections at home. Do not give yourself this medicine if you do not understand how to use the injection and properly dispose of needles, IV tubing, and other items used.

Colistimethate is a powder medicine that must be mixed with a liquid (diluent) before using it. If you are using the injections at home, be sure you understand how to properly mix and store the medicine.

After mixing colistimethate for injection into a vein (IV infusion), you must use the medicine right away. Do not store for later use.

After mixing colistimethate for injection into a muscle, you may store the mixture in a refrigerator or at cool room temperature. Do not freeze. Use within 7 days.

Colistimethate must be given slowly. Your IV infusion may take 3 to 5 minutes to complete. In some cases, colistimethate is given over a period of up to 23 hours. Follow your doctor's dosing instructions very carefully.

Use this medicine for the full prescribed length of time. Your symptoms may improve before the infection is completely cleared. Skipping doses may also increase your risk of further infection that is resistant to antibiotics. Colistimethate will not treat a viral infection such as the flu or a common cold.

If you need surgery, tell the surgeon ahead of time that you are using colistimethate. You may need to stop using the medicine for a short time.

Store unmixed colistimethate powder at cool room temperature, away from moisture and heat.

Use a disposable needle only once. Follow any state or local laws about throwing away used needles and syringes. Use a puncture-proof "sharps" disposal container (ask your pharmacist where to get one and how to throw it away). Keep this container out of the reach of children and pets.

Tell your doctor about all your current medicines and any you start or stop using, especially:

• any injected or IV antibiotics--amikacin, gentamicin, neomycin, polymyxin, streptomycin, tobramycin.

This list is not complete. Other drugs may interact with colistimethate, including prescription and over-the-counter medicines, vitamins, and herbal products. Not all possible interactions are listed in this medication guide.

Use colistimethate as ordered by your doctor. Read all information given to you. Follow all instructions closely.

• It is given as a shot into a muscle or as an infusion into a vein over a period of time.
• It may be given as a shot into a vein.

What do I do if I miss a dose?

• Call your doctor to find out what to do.

Rx only

Colistimethate for Injection USP is supplied in vials (NDC 39822-0615-1) containing Colistimethate sodium (equivalent to 150 mg colistin base per vial) as a white to slightly yellow lyophilized cake and is available as twelve vial per carton (NDC 39822-0615-2).

Storage and Handling

Store between 20˚ to 25˚C (68˚ to 77˚F). Excursions permitted to 15° to 30°C (59° to 86°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.

Manufactured for:
X-GEN Pharmaceuticals, Inc.
Big Flats, NY 14814

Manufactured in the USA

COLI-PI12-00

Revised April 2013

• Colistimethate Sodium
• Colistin Methanesulfonate
• Colistin Methanesulphonate
• Colistin Sulfomethate
• Pentasodium Colistin Methanesulfonate
• Polymyxin E

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution Reconstituted, Injection [strength expressed as base, preservative free]:

Coly-Mycin M: 150 mg (1 ea)

Generic: 150 mg (1 ea)

Treatment of acute or chronic infections due to sensitive strains of certain gram-negative bacilli (particularly Pseudomonas aeruginosa) which are resistant to other antibacterials or in patients allergic to other antibacterials

Hypersensitivity to colistimethate, colistin, or any component of the formulation

IV or IM use: Reconstitute each vial containing 150 mg of colistin base activity with 2 mL of SWFI resulting in a concentration of 75 mg colistin base activity/mL; swirl gently to avoid frothing. May further dilute in D5W or NS for IV infusion.

Intrathecal/intraventricular use (off-label route): Reconstitute with preservative-free diluent (SWFI or NS) only; use promptly after preparation; discard unused portion of vial (Quinn 2005).

Inhalation (via nebulizer; off-label route): Reconstitute vial containing 150 mg of colistin base activity with NS; further dilute dose with NS to a final concentration between 3 to 30 mg colistin base activity/mL (Maskin 2015; Yapa 2014). Optimal dosing regimens have not been determined and final concentrations used in studies vary widely; the nebulizer reservoir volume may also determine the final concentration (Berlana 2005). Storing for >24 hours may increase the risk for potential lung toxicity; preparation immediately prior to administration is recommended (FDA 2007; Le 2010, Wallace 2008); see Warnings/Precautions, Appropriate Use and Safety.

Mechanically ventilated patients: Dilute 150 mg colistin base activity with SWFI; further dilute dose with 10 mL SWFI to a final concentration of 15 mg colistin base activity/mL (Lu 2012).

Frequency not always defined.

Central nervous system: Neurotoxicity (7%; higher incidence with high-dose IV use in cystic fibrosis [Boss 1991; Koch-Weser 1970]), dizziness, headache, oral paresthesia, peripheral paresthesia, slurred speech, vertigo

Dermatologic: Pruritus, skin rash, urticaria

Gastrointestinal: Gastric distress

Genitourinary: Decreased urine output, nephrotoxicity (18% to 26% [Dalfino 2012; Oliveira 2009]), proteinuria

Neuromuscular & skeletal: Lower extremity weakness

Renal: Acute renal failure (33% to 60% [Akajagbor 2013; Deryke 2010]), increased blood urea nitrogen, increased serum creatinine

Respiratory: Apnea, respiratory distress

Miscellaneous: Fever

<1% (Limited to important or life-threatening): Pulmonary toxicity (acute respiratory tract failure following inhalation, bronchoconstriction, bronchospasm, chest tightness, respiratory distress)

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience diarrhea or nausea. Have patient report immediately to prescriber signs of kidney problems (urinary retention, hematuria, change in amount of urine passed, or weight gain), burning or numbness feeling, slurred speech, dizziness, passing out, seizures, muscle weakness, difficulty breathing, slow breathing, shallow breathing, or signs of Clostridium difficile (C. diff)-associated diarrhea (abdominal pain or cramps, severe diarrhea or watery stools, or bloody stools) (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.

Applies to colistimethate: compounding powder, injectable powder for injection

Nervous system

Nervous system side effects have included tingling of the tongue and extremities, slurred speech, dizziness, vertigo, paresthesia, confusion, psychosis, and seizures. Neuromuscular blockade may occur with overdoses.[Ref]

Respiratory

Respiratory side effects have included respiratory distress and apnea. Inhalation treatment has been associated with cough and bronchospasm. At least one case of fatal acute respiratory distress syndrome with nebulized colistimethate has been reported.[Ref]

Dermatologic

Dermatologic side effects have included generalized itching, urticaria, and rash.[Ref]

Gastrointestinal

Gastrointestinal side effects have included gastrointestinal upset, nausea, and vomiting.[Ref]

Hypersensitivity

Hypersensitivity side effects have included rash, drug fever, and eosinophilia.[Ref]

Local

Local side effects have included pain at the injection site.[Ref]

Musculoskeletal

Musculoskeletal side effects have included muscular weakness.[Ref]

Other

Other side effects have included fever.[Ref]

Renal

Renal side effects have included increases in blood urea nitrogen and serum creatinine, nephrotoxicity, decreased urine output, acute tubular necrosis, and hematuria.[Ref]

Some side effects of colistimethate may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.

Colistimethate should be used with extreme caution in the presence of renal dysfunction.

Suggested modification for adults:
Normal renal function (CrCl 80 mL/min or greater): 2.5 to 5 mg/kg/day IM or IV in 2 to 4 divided doses
Mild renal dysfunction (CrCl 50 to 79 mL/min): 2.5 to 3.8 mg/kg/day IM or IV in 2 divided doses
Moderate renal dysfunction (CrCl 30 to 49 mL/min): 2.5 mg/kg/day IM or IV in 1 to 2 divided doses
Severe renal dysfunction (CrCl 10 to 29 mL/min): 1.5 mg/kg IM or IV every 36 hours

If signs of impaired renal function occur (including decreased urine output, rising serum creatinine and BUN, and decreased CrCl): Colistimethate should be discontinued at once.