COLY-MYCIN M

1 Dosing Considerations • Maximum daily dose of COLY-MYCIN M should not exceed 5 mg/kg/day with normal renal function. • Since sodium 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, sodium colistimethate may be used, but the greatest caution should be exercised and the dosage should be reduced in proportion to the extent of the impairment (see 7 WARNINGS AND PRECAUTIONS, Renal).

5 mg/kg/day given in 2 to 4 divided doses. • In the presence of bacteremia, septicemia or other serious infections, greater than average doses may be required. • Maximal dose of 5 mg/kg/day should not be exceeded in patients with normal renal function.

) Page 5 of 14 • Overdosage can result in renal insufficiency, muscle weakness and apnea. • Reduction of dosage may alleviate symptoms. Therapy need not be discontinued, but such patients should be observed with particular care. 3 Reconstitution Table 1 - Reconstitution Vial size Volume of diluent to be Added to Vial Approx.

Available Volume Concentration per mL 10 mL vial 2 mL of Sterile Water for Injection 2 mL 75 mg / mL After reconstitution, COLY-MYCIN M solution should be stored refrigerated 2 to 8°C and used within 3 days (or within 24 hours, when stored at controlled room temperature 15 to 30°C).

Any infusion solution containing colistimethate sodium should be freshly prepared and used for no longer than 24 hours (see 11 STORAGE, STABILITY AND DISPOSAL). 4 Administration Intravenous or intramuscular administration.

5 Post-Market Adverse Reactions Respiratory, thoracic and mediastinal disorders: Respiratory arrest has been reported following IM administration of sodium colistimethate. Impaired renal function increases the possibility of apnea and neuromuscular blockade following administration of sodium cholistimethate.

This has generally been due to failure to follow recommended guidelines, usually overdosage, failure to reduce dose commensurate with degree of renal impairment, and/or concomitant use of other antibiotics or drugs with neuromuscular blocking potential.

Renal and urinary disorders:

A decrease in urine output or increase in BUN or serum creatinine can be interpreted as signs of nephrotoxicity, which is probably a dose dependent effect of sodium colistimethate. These manifestations of nephrotoxicity are reversible following discontinuation of the antibiotic.

6 to 5 mg/kg/day. The BUN values returned to normal following cessation of sodium colistimethate administration.

Metabolic and Nutrition Disorders:

Cases of pseudo-Bartter syndrome have been reported (see 7 WARNINGS AND PRECAUTIONS, Endocrine and Metabolism).

Others:

Paresthesia, tingling of the extremities or tingling of the tongue and generalized itching or urticaria have been reported by patients who received sodium colistimethate by IM or IV injection. In addition, the following adverse reactions have been reported for sodium colistimethate: drug fever and gastrointestinal upset, vertigo, and slurring of speech.

The subjective symptoms reported by the adult may not be manifest in infants or young children, thus requiring close attention to renal function.

, Endocrine and Metabolism 10/2024 TABLE OF CONTENTS Sections or subsections that are not applicable at the time of authorization are not listed. RECENT MAJOR LABEL CHANGES ......................................................................................................

2 TABLE OF CONTENTS ........................................................................................................................ 2 PART I: HEALTH PROFESSIONAL INFORMATION ................................................................................

4 1 INDICATIONS ....................................................................................................................... 4 2 CONTRAINDICATIONS ..........................................................................................................

4 4 DOSAGE AND ADMINISTRATION .......................................................................................... 5 5 OVERDOSAGE ......................................................................................................................

5 6 DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING ............................................ 5 7 WARNINGS AND PRECAUTIONS ............................................................................................ 7 8 ADVERSE REACTIONS ...........................................................................................................

7 9 DRUG INTERACTIONS ........................................................................................................... 8 10 CLINICAL PHARMACOLOGY ..................................................................................................

8 11 STORAGE, STABILITY AND DISPOSAL ..................................................................................... 9 12 SPECIAL HANDLING INSTRUCTIONS ......................................................................................

• COLY-MYCIN M is contraindicated in patients who are hypersensitive to this drug or to any ingredient in the formulation, including any non-medicinal ingredient, or component of the container. For a complete listing, see 6 DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING.