Coly-Mycin M

Polymyxin Antibiotics

NOTE: To avoid errors in dosing and administration, colistimethate sodium should only be prescribed as colistin in terms of colistin base activity.
NOTE: Approximately 33 mg colistin base activity corresponds to approximately 80 mg of colistimethate sodium and 1 million International Units (IU) of colistimethate sodium.
 
Visually inspect parenteral drug products for particulate matter and discoloration prior to administration, whenever solution and container permit. Do not administer if particulate matter or discoloration is present.

Intravenous (IV) Infusion
Powder Vials for Injection
Reconstitution
Reconstitute vial with 2 mL of Sterile Water for Injection; final concentration provides 75 mg/mL colistin base activity.
Gently swirl to avoid frothing.
Storage: The reconstituted solution can be stored in the refrigerator (2 to 8 degrees C or 36 to 46 degrees F) or at room temperature (20 to 25 degrees C or 68 to 77 degrees F) for up to 7 days.
 
Dilution
Dilute half of the daily dose to a compatible IV solution.
Compatible IV solutions include 0.9% Sodium Chloride Injection, 5% Dextrose Injection, 5% Dextrose and 0.9% Sodium Chloride Injection, 5% Dextrose and 0.45% Sodium Chloride Injection, 5% Dextrose and 0.225% Sodium Chloride Injection, Lactated Ringer's Injection, and 10% Invert Sugar Solution.
The volume and type of solution should be dictated by the patient's fluid and electrolyte requirements.
Storage: Use the diluted solution immediately and infuse completely within 24 hours of preparation.
 
Continuous IV Infusion
Administer one-half of the total daily dose IV over 3 to 5 minutes and follow 1 to 2 hours later with the remaining one-half of the total daily dose by continuous IV infusion over 22 to 23 hours.
 
Intermittent IV Infusion†
NOTE: Colistin is not FDA-approved for intermittent IV infusion.
Administer over 30 minutes to 1 hour.
 
Intravenous (IV) Push
Powder Vials for Injection
Reconstitution
Reconstitute vial with 2 mL of Sterile Water for Injection; final concentration provides 75 mg/mL colistin base activity.
Gently swirl to avoid frothing.
Storage: The reconstituted solution can be stored in the refrigerator (2 to 8 degrees C or 36 to 46 degrees F) or at room temperature (20 to 25 degrees C or 68 to 77 degrees F) for up to 7 days.
 
Intermittent IV Push
Slowly inject IV over 3 to 5 minutes.

Powder Vials for Injection
Reconstitution
Reconstitute vial with 2 mL of Sterile Water for Injection; final concentration provides 75 mg/mL colistin base activity.
Gently swirl to avoid frothing.
Storage: The reconstituted solution can be stored in the refrigerator (2 to 8 degrees C or 36 to 46 degrees F) or at room temperature (20 to 25 degrees C or 68 to 77 degrees F) for up to 7 days.[47035]
 
Intramuscular Injection
Inject IM deeply into a large muscle mass such as the gluteal muscles or lateral part of the thigh.[47035]

NOTE: Colistin is not FDA-approved for intrathecal administration.
Reconstitution
Use preservative-free product.
Concentrations of 4.1 mg of colistin base activity in 2, 3, and 5 mL of diluent (i.e. 0.9% Sodium Chloride Injection) and 8.25 mg of colistin base activity in 2 to 3 mL of diluent have been described.
 
Intrathecal Administration†
Administer via lumbar puncture.

Intraventricular Administration†
NOTE: Colistin is not FDA-approved for intraventricular administration.
Reconstitution
Use preservative-free product.
Concentrations of 4.1 mg of colistin base activity in 2, 3, and 4 mL of diluent (i.e. 0.9% Sodium Chloride Injection) and 8.25 mg of colistin base activity in 2 mL of diluent have been described.
 
Intraventricular Administration
Reports describe varying amounts of CSF aspirated prior to administration.
When administered through a ventricular drain, the drain should be clamped for 15 to 60 minutes to allow the antimicrobial solution to equilibrate in the CSF before opening the drain.

NOTE: To avoid errors in dosing and administration, colistimethate sodium should only be prescribed as colistin in terms of colistin base activity.
NOTE: Approximately 33 mg colistin base activity corresponds to approximately 80 mg of colistimethate sodium and 1 million International Units (IU) of colistimethate sodium.
NOTE: Nebulized use of colistin has been possibly associated with the death of a cystic fibrosis (CF) patient. To avoid this toxicity, administer promptly after mixing.
NOTE: Colistin is not FDA-approved for inhalation administration.
 
Reconstitution
0.9% Sodium Chloride Injection has been used as a diluent.
For adults, 75 mg of colistin base activity in 4 mL of diluent has been described.
For pediatric patients, 75 mg of colistin base activity in 3 mL of diluent has been described. 4 to 5 mg/kg/dose colistin base activity in 3 mL of diluent has also been described. Another study reconstituted 150 mg colistin base activity with 2 mL 0.9% Sodium Chloride Injection and then further diluted a 4 mg/kg/dose with 3 mL of 0.9% Sodium Chloride Injection. A dose of approximately 33 mg colistin base activity was diluted in 3 mL of diluent in a single study.
 
Nebulization†
Consider pretreating with a bronchodilator.
Various nebulizers have been utilized.
The dose should be nebulized and inhaled over 10 to 15 minutes.

anuria / Delayed / Incidence not known
renal failure (unspecified) / Delayed / Incidence not known
renal tubular necrosis / Delayed / Incidence not known
oliguria / Early / Incidence not known
seizures / Delayed / Incidence not known
hearing loss / Delayed / Incidence not known
respiratory arrest / Rapid / Incidence not known
bronchospasm / Rapid / Incidence not known
apnea / Delayed / Incidence not known
anaphylactoid reactions / Rapid / Incidence not known
C. difficile-associated diarrhea / Delayed / Incidence not known

hematuria / Delayed / Incidence not known
proteinuria / Delayed / Incidence not known
dysarthria / Delayed / Incidence not known
confusion / Early / Incidence not known
ataxia / Delayed / Incidence not known
psychosis / Early / Incidence not known
myopathy / Delayed / Incidence not known
hallucinations / Early / Incidence not known
candidiasis / Delayed / Incidence not known
pseudomembranous colitis / Delayed / Incidence not known
superinfection / Delayed / Incidence not known

cylindruria / Delayed / Incidence not known
dizziness / Early / Incidence not known
paresthesias / Delayed / Incidence not known
vertigo / Early / Incidence not known
weakness / Early / Incidence not known
throat irritation / Early / Incidence not known
cough / Delayed / Incidence not known
pruritus / Rapid / Incidence not known
rash / Early / Incidence not known
urticaria / Rapid / Incidence not known
fever / Early / Incidence not known
dyspepsia / Early / Incidence not known

Coly-Mycin M

Rx

Parenteral polymyxin antibiotic
Used for the treatment of acute or chronic infections due to gram-negative bacilli
Only prescribe as colistin in terms of colistin base activity to avoid errors

300 mg colistin base activity IV loading dose, followed by 150 to 180 mg colistin base activity IV every 12 hours. The FDA-approved dose is 2.5 to 5 mg/kg/day colistin base activity IV or IM in 2 to 4 divided doses. In obese patients, base the dose on ideal body weight.

2.5 to 5 mg/kg/day colistin base activity IV or IM in 2 to 4 divided doses; up to 7 mg/kg/day colistin base activity may be required. In obese patients, base the dose on ideal body weight.

2.5 to 5 mg/kg/day colistin base activity IV or IM in 2 to 4 divided doses.

2.5 to 5 mg/kg/day colistin base activity continuous IV infusion. Give one-half of the total daily dose IV over 3 to 5 minutes and follow 1 to 2 hours later with the remaining one-half of the total daily dose by continuous IV infusion over 22 to 23 hours. In obese patients, base the dose on ideal body weight.

2.5 to 5 mg/kg/day colistin base activity continuous IV infusion. Give one-half of the total daily dose IV over 3 to 5 minutes and follow 1 to 2 hours later with the remaining one-half of the total daily dose by continuous IV infusion over 22 to 23 hours. In obese patients, base the dose on ideal body weight.

2.5 to 5 mg/kg/day colistin base activity continuous IV infusion. Give one-half of the total daily dose IV over 3 to 5 minutes and follow 1 to 2 hours later with the remaining one-half of the total daily dose by continuous IV infusion over 22 to 23 hours. In obese patients, base the dose on ideal body weight.

300 mg colistin base activity IV loading dose, followed by 150 to 180 mg colistin base activity IV every 12 hours. The FDA-approved dose is 2.5 to 5 mg/kg/day colistin base activity IV or IM in 2 to 4 divided doses. In obese patients, base the dose on ideal body weight.

2.5 to 5 mg/kg/day colistin base activity IV or IM in 2 to 4 divided doses; up to 7 mg/kg/day colistin base activity may be required. In obese patients, base the dose on ideal body weight. 

2.5 to 5 mg/kg/day colistin base activity IV or IM in 2 to 4 divided doses.

2.5 to 5 mg/kg/day colistin base activity continuous IV infusion. Give one-half of the total daily dose IV over 3 to 5 minutes and follow 1 to 2 hours later with the remaining one-half of the total daily dose by continuous IV infusion over 22 to 23 hours. In obese patients, base the dose on ideal body weight.

2.5 to 5 mg/kg/day colistin base activity continuous IV infusion. Give one-half of the total daily dose IV over 3 to 5 minutes and follow 1 to 2 hours later with the remaining one-half of the total daily dose by continuous IV infusion over 22 to 23 hours. In obese patients, base the dose on ideal body weight.

2.5 to 5 mg/kg/day colistin base activity continuous IV infusion. Give one-half of the total daily dose IV over 3 to 5 minutes and follow 1 to 2 hours later with the remaining one-half of the total daily dose by continuous IV infusion over 22 to 23 hours. In obese patients, base the dose on ideal body weight.

4.1 mg colistin base activity intrathecally or intraventricularly once daily as part of combination therapy. Up to 8.25 mg/day colistin base activity has been used.

4.1 mg colistin base activity intrathecally or intraventricularly once daily as part of combination therapy.

Up to 1.64 mg colistin base activity intrathecally or intraventricularly once daily as part of combination therapy. Due to a lower CSF volume in infants, the dose reflects a 60% or more reduction from the adult dose.

300 mg colistin base activity IV loading dose, followed by 150 to 180 mg colistin base activity IV every 12 hours for 7 days as part of combination therapy. The FDA-labeled dose is 2.5 to 5 mg/kg/day colistin base activity IV or IM in 2 to 4 divided doses. In obese patients, base the dose on ideal body weight.

2.5 to 5 mg/kg/day colistin base activity IV or IM in 2 to 4 divided doses; up to 7 mg/kg/day colistin base activity may be required. In obese patients, base the dose on ideal body weight.

2.5 to 5 mg/kg/day colistin base activity IV or IM in 2 to 4 divided doses.

2.5 to 5 mg/kg/day colistin base activity continuous IV infusion. Give one-half of the total daily dose IV over 3 to 5 minutes and follow 1 to 2 hours later with the remaining one-half of the total daily dose by continuous IV infusion over 22 to 23 hours. In obese patients, base the dose on ideal body weight.

2.5 to 5 mg/kg/day colistin base activity continuous IV infusion. Give one-half of the total daily dose IV over 3 to 5 minutes and follow 1 to 2 hours later with the remaining one-half of the total daily dose by continuous IV infusion over 22 to 23 hours. In obese patients, base the dose on ideal body weight.

2.5 to 5 mg/kg/day colistin base activity continuous IV infusion. Give one-half of the total daily dose IV over 3 to 5 minutes and follow 1 to 2 hours later with the remaining one-half of the total daily dose by continuous IV infusion over 22 to 23 hours. In obese patients, base the dose on ideal body weight.

NOTE: Consider pretreating with bronchodilators. 

75 to 150 mg colistin base activity inhaled by nebulizer every 12 hours as part of combination therapy.

75 mg colistin base activity or 2.5 mg/kg/dose colistin base activity inhaled by nebulizer every 12 hours as part of combination therapy.

2.5 to 4 mg/kg/dose colistin base activity inhaled by nebulizer every 12 hours as part of combination therapy.

4 to 5 mg/kg/dose colistin base activity inhaled by nebulizer every 12 hours as part of combination therapy. 33 mg colistin base activity inhaled by nebulizer every 12 hours has also been used.

300 mg colistin base activity IV loading dose, followed by 150 to 180 mg colistin base activity IV every 12 hours.

2.5 to 5 mg/kg/day colistin base activity IV or IM in 2 to 4 divided doses; up to 7 mg/kg/day colistin base activity may be required. In persons with obesity, base the dose on ideal body weight.

300 mg colistin base activity IV loading dose, followed by 150 to 180 mg colistin base activity IV every 12 hours for 7 to 14 days. The FDA-approved dose is 2.5 to 5 mg/kg/day colistin base activity IV or IM in 2 to 4 divided doses. In persons with obesity, base the dose on ideal body weight.

2.5 to 5 mg/kg/day colistin base activity IV or IM in 2 to 4 divided doses; up to 7 mg/kg/day colistin base activity may be required. In persons with obesity, base the dose on ideal body weight. Treat for 24 to 48 hours or until patient is clinically stable and afebrile, followed by oral antibiotics for a total duration of 7 to 14 days.

2.5 to 5 mg/kg/day colistin base activity IV or IM in 2 to 4 divided doses; up to 7 mg/kg/day colistin base activity may be required. In persons with obesity, base the dose on ideal body weight. Infants younger than 2 to 3 months are at risk for systemic infection and rapid change in their clinical condition. Treat UTIs as presumed pyelonephritis in these patients.

2.5 to 5 mg/kg/day colistin base activity IV or IM in 2 to 4 divided doses. Neonates are at risk for systemic infection and rapid change in their clinical condition. Treat UTIs as presumed pyelonephritis in these patients.

2.5 to 5 mg/kg/day colistin base activity continuous IV infusion. Give one-half of the total daily dose IV over 3 to 5 minutes and follow 1 to 2 hours later with the remaining one-half of the total daily dose by continuous IV infusion over 22 to 23 hours. In persons with obesity, base the dose on ideal body weight.

2.5 to 5 mg/kg/day colistin base activity continuous IV infusion. Give one-half of the total daily dose IV over 3 to 5 minutes and follow 1 to 2 hours later with the remaining one-half of the total daily dose by continuous IV infusion over 22 to 23 hours. In persons with obesity, base the dose on ideal body weight.

2.5 to 5 mg/kg/day colistin base activity continuous IV infusion. Give one-half of the total daily dose IV over 3 to 5 minutes and follow 1 to 2 hours later with the remaining one-half of the total daily dose by continuous IV infusion over 22 to 23 hours.

300 mg colistin base activity IV loading dose, followed by 150 to 180 mg colistin base activity IV every 12 hours for 7 to 14 days for moderate or severe infections in patients with risk factors for resistant gram negative rods. Continue treatment for up to 28 days if infection is improving but is extensive and resolving slower than expected or if patient has severe peripheral artery disease.   The FDA-approved dosage is 2.5 to 5 mg/kg/day colistin base activity IV or IM in 2 to 4 divided doses. In obese patients, base the dose on ideal body weight.

2.5 to 5 mg/kg/day colistin base activity continuous IV infusion. Give one-half of the total daily dose IV over 3 to 5 minutes and follow 1 to 2 hours later with the remaining one-half of the total daily dose by continuous IV infusion over 22 to 23 hours. In obese patients, base the dose on ideal body weight.

300 mg colistin base activity IV loading dose, followed by 150 to 180 mg colistin base activity IV every 12 hours. The FDA-approved dose is 2.5 to 5 mg/kg/day colistin base activity IV or IM in 2 to 4 divided doses. In obese patients, base the dose on ideal body weight.

2.5 to 5 mg/kg/day colistin base activity IV or IM in 2 to 4 divided doses; up to 7 mg/kg/day colistin base activity may be required. In obese patients, base the dose on ideal body weight.

2.5 to 5 mg/kg/day colistin base activity IV or IM in 2 to 4 divided doses.

2.5 to 5 mg/kg/day colistin base activity continuous IV infusion. Give one-half of the total daily dose IV over 3 to 5 minutes and follow 1 to 2 hours later with the remaining one-half of the total daily dose by continuous IV infusion over 22 to 23 hours. In obese patients, base the dose on ideal body weight.

2.5 to 5 mg/kg/day colistin base activity continuous IV infusion. Give one-half of the total daily dose IV over 3 to 5 minutes and follow 1 to 2 hours later with the remaining one-half of the total daily dose by continuous IV infusion over 22 to 23 hours. In obese patients, base the dose on ideal body weight.

2.5 to 5 mg/kg/day colistin base activity continuous IV infusion. Give one-half of the total daily dose IV over 3 to 5 minutes and follow 1 to 2 hours later with the remaining one-half of the total daily dose by continuous IV infusion over 22 to 23 hours. In obese patients, base the dose on ideal body weight.

NOTE: Consider pretreating with bronchodilators.

75 to 150 mg colistin base activity inhaled by nebulizer every 12 hours as part of combination therapy for up to 3 months.

75 mg colistin base activity or 2.5 mg/kg/dose colistin base activity inhaled by nebulizer every 12 hours as part of combination therapy for up to 3 months.

2.5 to 4 mg/kg/dose colistin base activity inhaled by nebulizer every 12 hours as part of combination therapy for up to 3 months.

NOTE: Consider pretreating with bronchodilators.

75 to 150 mg colistin base activity inhaled by nebulizer every 12 hours.

75 mg colistin base activity inhaled by nebulizer every 12 hours.

2.5 to 4 mg/kg/dose colistin base activity inhaled by nebulizer every 12 hours.

300 mg colistin base activity IV loading dose, followed by 150 to 180 mg colistin base activity IV every 12 hours as part of combination therapy for 3 to 7 days. Complicated infections include peritonitis and appendicitis complicated by rupture, and intraabdominal abscess. The FDA-approved dose is 2.5 to 5 mg/kg/day colistin base activity IV or IM in 2 to 4 divided doses. In obese patients, base the dose on ideal body weight.

2.5 to 5 mg/kg/day colistin base activity IV or IM in 2 to 4 divided doses as part of combination therapy for 3 to 7 days; up to 7 mg/kg/day colistin base activity may be required. In obese patients, base the dose on ideal body weight. Complicated infections include peritonitis and appendicitis complicated by rupture, and intraabdominal abscess.

2.5 to 5 mg/kg/day colistin base activity IV or IM in 2 to 4 divided doses.

2.5 to 5 mg/kg/day colistin base activity continuous IV infusion. Give one-half of the total daily dose IV over 3 to 5 minutes and follow 1 to 2 hours later with the remaining one-half of the total daily dose by continuous IV infusion over 22 to 23 hours. In obese patients, base the dose on ideal body weight.

2.5 to 5 mg/kg/day colistin base activity continuous IV infusion. Give one-half of the total daily dose IV over 3 to 5 minutes and follow 1 to 2 hours later with the remaining one-half of the total daily dose by continuous IV infusion over 22 to 23 hours. In obese patients, base the dose on ideal body weight.

2.5 to 5 mg/kg/day colistin base activity continuous IV infusion. Give one-half of the total daily dose IV over 3 to 5 minutes and follow 1 to 2 hours later with the remaining one-half of the total daily dose by continuous IV infusion over 22 to 23 hours. In obese patients, base the dose on ideal body weight.

300 mg colistin base activity IV loading dose, followed by 150 to 200 mg colistin base activity IV once daily for 21 to 28 days.

NOTE: Consider pretreating with bronchodilators.

75 to 150 mg colistin base activity inhaled by nebulizer every 12 hours; may be used in combination with initial systemic therapy for 14 days; treat for 4 to 12 weeks following systemic therapy.

75 mg colistin base activity or 2.5 mg/kg/dose colistin base activity inhaled by nebulizer every 12 hours; may be used in combination with initial systemic therapy for 14 days; treat for 4 to 12 weeks following systemic therapy.

2.5 to 4 mg/kg/dose colistin base activity inhaled by nebulizer every 12 hours; may be used in combination with initial systemic therapy for 14 days; treat for 4 to 12 weeks following systemic therapy.

NOTE: Consider pretreating with bronchodilators.

75 to 150 mg colistin base activity inhaled by nebulizer every 12 hours based on limited data.

75 mg colistin base activity or 2.5 mg/kg/dose colistin base activity inhaled by nebulizer every 12 hours based on limited data.

2.5 to 4 mg/kg/dose colistin base activity inhaled by nebulizer every 12 hours based on limited data.

†Indicates off-label use

Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.

NOTE: To avoid errors in dosing and administration, colistimethate sodium should only be prescribed as colistin in terms of colistin base activity.
NOTE: Approximately 33 mg colistin base activity corresponds to approximately 80 mg of colistimethate sodium and 1 million International Units (IU) of colistimethate sodium.
 
Adults (FDA-approved)
CrCl 80 mL/minute or more: No dosage adjustment needed.
CrCl 50 to 79 mL/minute: 2.5 to 3.8 mg/kg/day colistin base activity IV or IM divided in 2 doses.
CrCl 30 to 49 mL/minute: 2.5 mg/kg/day colistin base activity IV or IM once daily or divided in 2 doses.
CrCl 10 to 29 mL/minute: 1.5 mg/kg colistin base activity IV or IM every 36 hours.
 
Adults (alternative)†
NOTE: Use adjusted body weight to estimate creatinine clearance.
CrCl 90 mL/minute or more: 300 mg colistin base activity IV loading dose, followed by 180 mg colistin base activity IV every 12 hours.
CrCl 80 to 89 mL/minute: 300 mg colistin base activity IV loading dose, followed by 170 mg colistin base activity IV every 12 hours.
CrCl 70 to 79 mL/minute: 300 mg colistin base activity IV loading dose, followed by 150 mg colistin base activity IV every 12 hours.
CrCl 60 to 69 mL/minute: 300 mg colistin base activity IV loading dose, followed by 137.5 mg colistin base activity IV every 12 hours.
CrCl 50 to 59 mL/minute: 300 mg colistin base activity IV loading dose, followed by 122.5 mg colistin base activity IV every 12 hours.
CrCl 40 to 49 mL/minute: 300 mg colistin base activity IV loading dose, followed by 110 mg colistin base activity IV every 12 hours.
CrCl 30 to 39 mL/minute: 300 mg colistin base activity IV loading dose, followed by 97.5 mg colistin base activity IV every 12 hours.
CrCl 20 to 29 mL/minute: 300 mg colistin base activity IV loading dose, followed by 87.5 mg colistin base activity IV every 12 hours.
CrCl 10 to 19 mL/minute: 300 mg colistin base activity IV loading dose, followed by 80 mg colistin base activity IV every 12 hours.
CrCl 5 to 9 mL/minute: 300 mg colistin base activity IV loading dose, followed by 72.5 mg colistin base activity IV every 12 hours.
CrCl less than 5 mL/minute: 300 mg colistin base activity IV loading dose, followed by 65 mg colistin base activity IV every 12 hours.
 
Intermittent hemodialysis†
Adults
300 mg colistin base activity IV loading dose, followed by 65 mg colistin base activity IV every 12 hours on nondialysis days with a supplemental dose of 40 or 50 mg colistin base activity IV on dialysis days for a 3- or 4-hour intermittent hemodialysis session, respectively. If possible, administer the supplement to the baseline (nondialysis) daily dose with the next regular dose, after the dialysis session has ended. Conduct the dialysis session as late as possible within the dosage interval.
 
Continuous renal replacement therapy (CRRT)†
NOTE: Various CRRT modalities include continuous venovenous hemofiltration (CVVH), continuous venovenous hemodialysis (CVVHD), continuous venovenous hemodiafiltration (CVVHDF), continuous venovenous high-flux hemodialysis (CVVHFD), continuous arteriovenous hemofiltration (CAVH), continuous arteriovenous hemodialysis (CAVHD), and continuous arteriovenous hemodiafiltration (CAVHDF). Dosing should take into consideration patient-specific factors (e.g., intrinsic renal function), type of infection, the duration of renal replacement therapy, the effluent flow rate, and the replacement solution administered.[42303]
 
Adults
300 mg colistin base activity IV loading dose, followed by 220 mg colistin base activity IV every 12 hours.
 
Hybrid hemodialysis†
NOTE: Hybrid treatments include prolonged intermittent renal replacement therapy (PIRRT), sustained low-efficiency dialysis (SLED), slow extended daily dialysis/diafiltration (SLEDD-f), and extended daily dialysis (EDD). Dosing should take into consideration patient-specific factors (e.g., intrinsic renal function), the type of infection, the duration of renal replacement therapy, the ultrafiltration rate, the dialysis flow rate, and how often dialysis sessions occur.[65397]
 
Adults
300 mg colistin base activity IV loading dose, followed by a maintenance daily dose calculated as 10% of the dose added to the baseline daily dose per hour of SLED. For a patient with a CrCl of less than 5 mL/minute receiving a 10-hour SLED session, the total dose would be the sum of the baseline dose (130 mg/day colistin base activity) plus an additional 130 mg/day colistin base activity, for a total daily dose of 260 mg colistin base activity administered as 130 mg colistin base activity IV every 12 hours.
 
Peritoneal dialysis†
Adults
In a study of 8 continuous ambulatory peritoneal dialysis (CAPD) patients who received a single dose of 150 mg colistin base activity IV, population pharmacokinetic modeling and Monte Carlo simulations were conducted. Clearance by CAPD was low for both colistimethate sodium and formed colistin. Monte Carlo simulations suggest a 300 mg colistin base activity IV loading dose, followed by 150 to 200 mg colistin base activity IV once daily.

AbobotulinumtoxinA: (Moderate) The effects of botulinum toxin type A or botulinum toxin type B can be potentiated by drugs that interfere with neuromuscular transmission, such as colistimethate sodium. If these drugs are used in combination, monitor patients for increased adverse effects. Neuromuscular blockade may be associated with colistimethate sodium, and is more likely to occur in patients with renal dysfunction.
Acyclovir: (Moderate) Since colistimethate sodium is eliminated by the kidney, coadministration with other potentially nephrotoxic drugs, including acyclovir, may increase serum concentrations of either drug. Theoretically, the chronic coadministration of these drugs may increase the risk of developing nephrotoxicity, even in patients who have normal renal function. Monitor patients for changes in renal function if these drugs are coadministered.
Amikacin: (Major) The concomitant use of colistimethate sodium with systemic aminoglycosides may increase the risk of nephrotoxicity, ototoxicity, and neurotoxicity. Since polymyxins and aminoglycosides are both eliminated by the kidney, coadministration may increase serum concentrations of either drug class. If these drugs are used in combination, monitor renal function and patients for increased adverse effects. Additionally, neuromuscular blockade has been associated with both polymyxins and aminoglycosides, and is more likely to occur in patients with renal dysfunction.
Aminoglycosides: (Major) The concomitant use of colistimethate sodium with systemic aminoglycosides may increase the risk of nephrotoxicity, ototoxicity, and neurotoxicity. Since polymyxins and aminoglycosides are both eliminated by the kidney, coadministration may increase serum concentrations of either drug class. If these drugs are used in combination, monitor renal function and patients for increased adverse effects. Additionally, neuromuscular blockade has been associated with both polymyxins and aminoglycosides, and is more likely to occur in patients with renal dysfunction.
Amphotericin B lipid complex (ABLC): (Major) Since colistimethate sodium is eliminated by the kidney, coadministration with other potentially nephrotoxic drugs, including amphotericin B and the amphotericin B lipid formulations, may increase serum concentrations of either drug. Chronic coadministration of these drugs may increase the risk of developing nephrotoxicity, even in patients who have normal renal function. Monitor patients for changes in renal function if these drugs are coadministered.
Amphotericin B liposomal (LAmB): (Major) Since colistimethate sodium is eliminated by the kidney, coadministration with other potentially nephrotoxic drugs, including amphotericin B and the amphotericin B lipid formulations, may increase serum concentrations of either drug. Chronic coadministration of these drugs may increase the risk of developing nephrotoxicity, even in patients who have normal renal function. Monitor patients for changes in renal function if these drugs are coadministered.
Amphotericin B: (Major) Since colistimethate sodium is eliminated by the kidney, coadministration with other potentially nephrotoxic drugs, including amphotericin B and the amphotericin B lipid formulations, may increase serum concentrations of either drug. Chronic coadministration of these drugs may increase the risk of developing nephrotoxicity, even in patients who have normal renal function. Monitor patients for changes in renal function if these drugs are coadministered.
Bacitracin: (Major) Coadministration of these drugs may increase the risk of developing nephrotoxicity, even in patients who have normal renal function. Monitor patients for changes in renal function if these drugs are coadministered. Since colistimethate sodium is eliminated by the kidney, coadministration with other potentially nephrotoxic drugs, including bacitracin, may increase serum concentrations of either drug.
Bictegravir; Emtricitabine; Tenofovir Alafenamide: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with a nephrotoxic agent, such as colistimethate sodium. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs; thus, increasing the risk of developing renal-related adverse reactions.
Botulinum Toxins: (Moderate) The effects of botulinum toxin type A or botulinum toxin type B can be potentiated by drugs that interfere with neuromuscular transmission, such as colistimethate sodium. If these drugs are used in combination, monitor patients for increased adverse effects. Neuromuscular blockade may be associated with colistimethate sodium, and is more likely to occur in patients with renal dysfunction.
Bupivacaine; Lidocaine: (Moderate) Lidocaine can potentiate the neuromuscular blocking effect of colistimethate sodium by impairing transmission of impulses at the motor nerve terminals. If these drugs are used in combination, monitor patients for increased adverse effects. Neuromuscular blockade may be associated with colistimethate sodium, and is more likely to occur in patients with renal dysfunction.
Capreomycin: (Major) Avoid concomitant administration of capreomycin with colistimethate sodium if possible; however, if they must be coadministered, use extreme caution. Concurrent use of capreomycin and colistimethate sodium may increase the risk of nephrotoxicity and neurotoxicity. Since capreomycin is eliminated by the kidney, coadministration with other potentially nephrotoxic drugs like colistimethate sodium may increase serum concentrations of either capreomycin or colistimethate sodium. Theoretically, coadministration may increase the risk of developing nephrotoxicity, even in patients who have normal renal function. Monitor patients for changes in renal function if these drugs are coadministered. Additionally, neuromuscular blockade has been associated with capreomycin resulting from administration of large doses or rapid intravenous infusion. Colistimethate sodium has also been reported to interfere with nerve impulse transmission at the neuromuscular junction.
Carboplatin: (Major) Both colistimethate sodium and carboplatin can cause nephrotoxicity. The coadministration of these drugs may increase the risk of developing nephrotoxicity, even in patients who have normal renal function. Monitor patients for changes in renal function if these drugs are coadministered.
Cidofovir: (Major) Theoretically, the chronic coadministration of these drugs may increase the risk of developing nephrotoxicity, even in patients who have normal renal function. Monitor patients for changes in renal function if these drugs are coadministered. Since colistimethate sodium is eliminated by the kidney, coadministration with other potentially nephrotoxic drugs, including cidofovir, may increase serum concentrations of either drug.
Cisplatin: (Major) Colistimethate sodium should be used cautiously in patients receiving cisplatin. Other nephrotoxic drugs can aggravate the nephrotoxicity and electrolyte loss seen with cisplatin if given concurrently or shortly after cisplatin therapy. Assessment of serum creatinine, blood urea nitrogen, creatinine clearance, magnesium, sodium, potassium, and calcium concentrations before the initial and each subsequent treatment course is recommended.
Clindamycin: (Moderate) Clindamycin can potentiate the neuromuscular blocking effect of colistimethate sodium by impairing transmission of impulses at the motor nerve terminals. If these drugs are used in combination, monitor patients for increased adverse effects. Neuromuscular blockade may be associated with colistimethate sodium, and is more likely to occur in patients with renal dysfunction.
Cyclosporine: (Major) Theoretically, chronic coadministration may increase the risk of developing nephrotoxicity, even in patients who have normal renal function. Monitor patients for changes in renal function during concurrent use. Since colistimethate sodium is eliminated by the kidney, coadministration with other potentially nephrotoxic drugs, including cyclosporine, may increase serum concentrations of either drug.
Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with a nephrotoxic agent, such as colistimethate sodium. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs; thus, increasing the risk of developing renal-related adverse reactions.
DaxibotulinumtoxinA: (Moderate) The effects of botulinum toxin type A or botulinum toxin type B can be potentiated by drugs that interfere with neuromuscular transmission, such as colistimethate sodium. If these drugs are used in combination, monitor patients for increased adverse effects. Neuromuscular blockade may be associated with colistimethate sodium, and is more likely to occur in patients with renal dysfunction.
Dextromethorphan; Quinidine: (Moderate) Quinidine can potentiate the neuromuscular blocking effect of colistimethate sodium by impairing transmission of impulses at the motor nerve terminals. If these drugs are used in combination, monitor patients for increased adverse effects. Neuromuscular blockade may be associated with colistimethate sodium, and is more likely to occur in patients with renal dysfunction.
Doravirine; Lamivudine; Tenofovir disoproxil fumarate: (Moderate) Tenofovir-containing products should be avoided with concurrent or recent use of a nephrotoxic agent, such as colistimethate sodium. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir with drugs that are eliminated by active tubular secretion may increase concentrations of tenofovir and/or the co-administered drug. Drugs that decrease renal function may also increase concentrations of tenofovir. Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir with a majority of the cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Monitor patients receiving concomitant nephrotoxic agents for changes in serum creatinine and phosphorus, and urine glucose and protein.
Efavirenz; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Tenofovir-containing products should be avoided with concurrent or recent use of a nephrotoxic agent, such as colistimethate sodium. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir with drugs that are eliminated by active tubular secretion may increase concentrations of tenofovir and/or the co-administered drug. Drugs that decrease renal function may also increase concentrations of tenofovir. Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir with a majority of the cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Monitor patients receiving concomitant nephrotoxic agents for changes in serum creatinine and phosphorus, and urine glucose and protein.
Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Moderate) Tenofovir-containing products should be avoided with concurrent or recent use of a nephrotoxic agent, such as colistimethate sodium. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir with drugs that are eliminated by active tubular secretion may increase concentrations of tenofovir and/or the co-administered drug. Drugs that decrease renal function may also increase concentrations of tenofovir. Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir with a majority of the cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Monitor patients receiving concomitant nephrotoxic agents for changes in serum creatinine and phosphorus, and urine glucose and protein.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with a nephrotoxic agent, such as colistimethate sodium. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs; thus, increasing the risk of developing renal-related adverse reactions.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Tenofovir-containing products should be avoided with concurrent or recent use of a nephrotoxic agent, such as colistimethate sodium. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir with drugs that are eliminated by active tubular secretion may increase concentrations of tenofovir and/or the co-administered drug. Drugs that decrease renal function may also increase concentrations of tenofovir. Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir with a majority of the cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Monitor patients receiving concomitant nephrotoxic agents for changes in serum creatinine and phosphorus, and urine glucose and protein.
Emtricitabine; Rilpivirine; Tenofovir alafenamide: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with a nephrotoxic agent, such as colistimethate sodium. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs; thus, increasing the risk of developing renal-related adverse reactions.
Emtricitabine; Rilpivirine; Tenofovir Disoproxil Fumarate: (Moderate) Tenofovir-containing products should be avoided with concurrent or recent use of a nephrotoxic agent, such as colistimethate sodium. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir with drugs that are eliminated by active tubular secretion may increase concentrations of tenofovir and/or the co-administered drug. Drugs that decrease renal function may also increase concentrations of tenofovir. Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir with a majority of the cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Monitor patients receiving concomitant nephrotoxic agents for changes in serum creatinine and phosphorus, and urine glucose and protein.
Emtricitabine; Tenofovir alafenamide: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with a nephrotoxic agent, such as colistimethate sodium. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs; thus, increasing the risk of developing renal-related adverse reactions.
Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Tenofovir-containing products should be avoided with concurrent or recent use of a nephrotoxic agent, such as colistimethate sodium. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir with drugs that are eliminated by active tubular secretion may increase concentrations of tenofovir and/or the co-administered drug. Drugs that decrease renal function may also increase concentrations of tenofovir. Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir with a majority of the cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Monitor patients receiving concomitant nephrotoxic agents for changes in serum creatinine and phosphorus, and urine glucose and protein.
Entecavir: (Major) The manufacturer of entecavir recommends monitoring for adverse effects when administered with potentially nephrotoxic agents, such as colistimethate sodium. Because entecavir is primarily eliminated by the kidneys and colistimethate sodium can affect renal function, concurrent administration may increase entecavir serum concentrations and the risk of adverse events.
Etomidate: (Moderate) General anesthetics can potentiate the neuromuscular blocking effect of colistimethate sodium by impairing transmission of impulses at the motor nerve terminals. If these drugs are used in combination, monitor patients for increased adverse effects. Neuromuscular blockade may be associated with colistimethate sodium, and is more likely to occur in patients with renal dysfunction.
Foscarnet: (Major) Theoretically, chronic coadministration may increase the risk of developing nephrotoxicity, even in patients who have normal renal function. Monitor patients for changes in renal function during concurrent use. Since colistimethate sodium is eliminated by the kidney, coadministration with other potentially nephrotoxic drugs, including foscarnet, may increase serum concentrations of either drug.
Ganciclovir: (Major) Theoretically, chronic coadministration may increase the risk of developing nephrotoxicity, even in patients who have normal renal function. Monitor patients for changes in renal function during concurrent use. Since colistimethate sodium is eliminated by the kidney, coadministration with other potentially nephrotoxic drugs, including ganciclovir, may increase serum concentrations of either drug.
General anesthetics: (Moderate) General anesthetics can potentiate the neuromuscular blocking effect of colistimethate sodium by impairing transmission of impulses at the motor nerve terminals. If these drugs are used in combination, monitor patients for increased adverse effects. Neuromuscular blockade may be associated with colistimethate sodium, and is more likely to occur in patients with renal dysfunction.
Gentamicin: (Major) The concomitant use of colistimethate sodium with systemic aminoglycosides may increase the risk of nephrotoxicity, ototoxicity, and neurotoxicity. Since polymyxins and aminoglycosides are both eliminated by the kidney, coadministration may increase serum concentrations of either drug class. If these drugs are used in combination, monitor renal function and patients for increased adverse effects. Additionally, neuromuscular blockade has been associated with both polymyxins and aminoglycosides, and is more likely to occur in patients with renal dysfunction.
Hyaluronidase, Recombinant; Immune Globulin: (Moderate) Use caution with concomitant Immune Globulin (IG) products and colistimethate sodium. IG products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Closely monitor renal function.
Immune Globulin IV, IVIG, IGIV: (Moderate) Use caution with concomitant Immune Globulin (IG) products and colistimethate sodium. IG products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Closely monitor renal function.
IncobotulinumtoxinA: (Moderate) The effects of botulinum toxin type A or botulinum toxin type B can be potentiated by drugs that interfere with neuromuscular transmission, such as colistimethate sodium. If these drugs are used in combination, monitor patients for increased adverse effects. Neuromuscular blockade may be associated with colistimethate sodium, and is more likely to occur in patients with renal dysfunction.
Isoflurane: (Moderate) General anesthetics can potentiate the neuromuscular blocking effect of colistimethate sodium by impairing transmission of impulses at the motor nerve terminals. If these drugs are used in combination, monitor patients for increased adverse effects. Neuromuscular blockade may be associated with colistimethate sodium, and is more likely to occur in patients with renal dysfunction.
Ketamine: (Moderate) General anesthetics can potentiate the neuromuscular blocking effect of colistimethate sodium by impairing transmission of impulses at the motor nerve terminals. If these drugs are used in combination, monitor patients for increased adverse effects. Neuromuscular blockade may be associated with colistimethate sodium, and is more likely to occur in patients with renal dysfunction.
Lamivudine; Tenofovir Disoproxil Fumarate: (Moderate) Tenofovir-containing products should be avoided with concurrent or recent use of a nephrotoxic agent, such as colistimethate sodium. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir with drugs that are eliminated by active tubular secretion may increase concentrations of tenofovir and/or the co-administered drug. Drugs that decrease renal function may also increase concentrations of tenofovir. Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir with a majority of the cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Monitor patients receiving concomitant nephrotoxic agents for changes in serum creatinine and phosphorus, and urine glucose and protein.
Lidocaine: (Moderate) Lidocaine can potentiate the neuromuscular blocking effect of colistimethate sodium by impairing transmission of impulses at the motor nerve terminals. If these drugs are used in combination, monitor patients for increased adverse effects. Neuromuscular blockade may be associated with colistimethate sodium, and is more likely to occur in patients with renal dysfunction.
Lidocaine; Epinephrine: (Moderate) Lidocaine can potentiate the neuromuscular blocking effect of colistimethate sodium by impairing transmission of impulses at the motor nerve terminals. If these drugs are used in combination, monitor patients for increased adverse effects. Neuromuscular blockade may be associated with colistimethate sodium, and is more likely to occur in patients with renal dysfunction.
Lidocaine; Prilocaine: (Moderate) Lidocaine can potentiate the neuromuscular blocking effect of colistimethate sodium by impairing transmission of impulses at the motor nerve terminals. If these drugs are used in combination, monitor patients for increased adverse effects. Neuromuscular blockade may be associated with colistimethate sodium, and is more likely to occur in patients with renal dysfunction.
Lithium: (Moderate) Lithium can potentiate the neuromuscular blocking effect of colistimethate sodium by impairing transmission of impulses at the motor nerve terminals. If these drugs are used in combination, monitor patients for increased adverse effects. Neuromuscular blockade may be associated with colistimethate sodium, and is more likely to occur in patients with renal dysfunction.
Methohexital: (Moderate) General anesthetics can potentiate the neuromuscular blocking effect of colistimethate sodium by impairing transmission of impulses at the motor nerve terminals. If these drugs are used in combination, monitor patients for increased adverse effects. Neuromuscular blockade may be associated with colistimethate sodium, and is more likely to occur in patients with renal dysfunction.
Neuromuscular blockers: (Moderate) Use neuromuscular blockers and polymyxins with extreme caution. Concomitant use of neuromuscular blockers and polymyxins may prolong neuromuscular blockade. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration.
Non-Ionic Contrast Media: (Major) Because the use of other nephrotoxic drugs, including colistimethate sodium, is an additive risk factor for nephrotoxicity in patients receiving radiopaque contrast agents, concomitant use should be avoided when possible. Monitor patients for changes in renal function if these drugs are coadministered.
Nonsteroidal antiinflammatory drugs: (Major) The administration of colistimethate sodium may increase the risk of developing nephrotoxicity, even in patients who have normal renal function. Nonsteroidal antiinflammatory drugs (NSAIDs) may increase the risk for nephrotoxicity when used concurrently. Monitor patients for changes in renal function if these drugs are coadministered. Since colistimethate sodium is eliminated by the kidney, coadministration with other potentially nephrotoxic drugs, including nonsteroidal antiinflammatory drugs (NSAIDs), may theoretically increase serum concentrations of either drug.
OnabotulinumtoxinA: (Moderate) The effects of botulinum toxin type A or botulinum toxin type B can be potentiated by drugs that interfere with neuromuscular transmission, such as colistimethate sodium. If these drugs are used in combination, monitor patients for increased adverse effects. Neuromuscular blockade may be associated with colistimethate sodium, and is more likely to occur in patients with renal dysfunction.
Oral Contraceptives: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Pamidronate: (Major) Theoretically, chronic coadministration may increase the risk of developing nephrotoxicity, even in patients who have normal renal function. Monitor patients for changes in renal function if these drugs are coadministered. Since colistimethate sodium is eliminated by the kidney, coadministration with other potentially nephrotoxic drugs, including pamidronate, may increase serum concentrations of either drug.
Paromomycin: (Major) The concomitant use of colistimethate sodium with systemic aminoglycosides may increase the risk of nephrotoxicity, ototoxicity, and neurotoxicity. Since polymyxins and aminoglycosides are both eliminated by the kidney, coadministration may increase serum concentrations of either drug class. If these drugs are used in combination, monitor renal function and patients for increased adverse effects. Additionally, neuromuscular blockade has been associated with both polymyxins and aminoglycosides, and is more likely to occur in patients with renal dysfunction.
Plazomicin: (Major) The concomitant use of colistimethate sodium with systemic aminoglycosides may increase the risk of nephrotoxicity, ototoxicity, and neurotoxicity. Since polymyxins and aminoglycosides are both eliminated by the kidney, coadministration may increase serum concentrations of either drug class. If these drugs are used in combination, monitor renal function and patients for increased adverse effects. Additionally, neuromuscular blockade has been associated with both polymyxins and aminoglycosides, and is more likely to occur in patients with renal dysfunction.
Polymyxin B: (Major) The concomitant use of colistimethate sodium (also known as colistin or Polymyxin E) and Polymyxin B may increase the risk of nephrotoxicity and neurotoxicity. Since colistimethate sodium is eliminated by the kidney, coadministration of colistimethate sodium with other potentially nephrotoxic drugs, including polymyxin B, may increase serum concentrations of either colistimethate sodium or polymyxin B. Theoretically, coadministration may increase the risk of developing nephrotoxicity, even in patients who have normal renal function. Monitor patients for changes in renal function if these drugs are coadministered. Additionally, neuromuscular blockade has been associated with colistimethate sodium, and is more likely to occur in patients with renal dysfunction.
Procainamide: (Moderate) Procainamide can potentiate the neuromuscular blocking effect of colistimethate sodium by impairing transmission of impulses at the motor nerve terminals. If these drugs are used in combination, monitor patients for increased adverse effects. Neuromuscular blockade may be associated with colistimethate sodium, and is more likely to occur in patients with renal dysfunction.
Propofol: (Moderate) General anesthetics can potentiate the neuromuscular blocking effect of colistimethate sodium by impairing transmission of impulses at the motor nerve terminals. If these drugs are used in combination, monitor patients for increased adverse effects. Neuromuscular blockade may be associated with colistimethate sodium, and is more likely to occur in patients with renal dysfunction.
Pyridostigmine: (Moderate) Parenteral administration of high doses of certain antibiotics such as colistimethate sodium may intensify or produce neuromuscular blockade through their own pharmacologic actions. If unexpected prolongation of neuromuscular blockade or resistance to its reversal with pyridostigmine occurs, consider the possibility of an antibiotic effect. Neuromuscular blockade may be associated with colistimethate sodium, and is more likely to occur in patients with renal dysfunction.
Quinidine: (Moderate) Quinidine can potentiate the neuromuscular blocking effect of colistimethate sodium by impairing transmission of impulses at the motor nerve terminals. If these drugs are used in combination, monitor patients for increased adverse effects. Neuromuscular blockade may be associated with colistimethate sodium, and is more likely to occur in patients with renal dysfunction.
RimabotulinumtoxinB: (Moderate) The effects of botulinum toxin type A or botulinum toxin type B can be potentiated by drugs that interfere with neuromuscular transmission, such as colistimethate sodium. If these drugs are used in combination, monitor patients for increased adverse effects. Neuromuscular blockade may be associated with colistimethate sodium, and is more likely to occur in patients with renal dysfunction.
Salicylates: (Major) Theoretically, the chronic coadministration of these drugs may increase the risk of developing nephrotoxicity, even in patients who have normal renal function. Monitor patients for changes in renal function if these drugs are coadministered. Since colistimethate sodium is eliminated by the kidney, coadministration with other potentially nephrotoxic drugs, including salicylates, may increase serum concentrations of either drug.
Sevoflurane: (Moderate) General anesthetics can potentiate the neuromuscular blocking effect of colistimethate sodium by impairing transmission of impulses at the motor nerve terminals. If these drugs are used in combination, monitor patients for increased adverse effects. Neuromuscular blockade may be associated with colistimethate sodium, and is more likely to occur in patients with renal dysfunction.
Streptomycin: (Major) The concomitant use of colistimethate sodium with systemic aminoglycosides may increase the risk of nephrotoxicity, ototoxicity, and neurotoxicity. Since polymyxins and aminoglycosides are both eliminated by the kidney, coadministration may increase serum concentrations of either drug class. If these drugs are used in combination, monitor renal function and patients for increased adverse effects. Additionally, neuromuscular blockade has been associated with both polymyxins and aminoglycosides, and is more likely to occur in patients with renal dysfunction.
Tacrolimus: (Major) Theoretically, the chronic coadministration of these drugs may increase the risk of developing nephrotoxicity, even in patients who have normal renal function. Monitor patients for changes in renal function if these drugs are coadministered. Since colistimethate sodium is eliminated by the kidney, coadministration with other potentially nephrotoxic drugs, including tacrolimus, may increase serum concentrations of either drug.
Telavancin: (Major) Concurrent or sequential use of telavancin with other potentially nephrotoxic drugs, such as colistimethate sodium, may lead to additive nephrotoxicity. Closely monitor renal function and adjust telavancin doses based on calculated creatinine clearance.
Tenofovir Alafenamide: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with a nephrotoxic agent, such as colistimethate sodium. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs; thus, increasing the risk of developing renal-related adverse reactions.
Tenofovir Alafenamide: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with a nephrotoxic agent, such as colistimethate sodium. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs; thus, increasing the risk of developing renal-related adverse reactions.
Tenofovir Disoproxil Fumarate: (Moderate) Tenofovir-containing products should be avoided with concurrent or recent use of a nephrotoxic agent, such as colistimethate sodium. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir with drugs that are eliminated by active tubular secretion may increase concentrations of tenofovir and/or the co-administered drug. Drugs that decrease renal function may also increase concentrations of tenofovir. Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir with a majority of the cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Monitor patients receiving concomitant nephrotoxic agents for changes in serum creatinine and phosphorus, and urine glucose and protein.
Tobramycin: (Major) The concomitant use of colistimethate sodium with systemic aminoglycosides may increase the risk of nephrotoxicity, ototoxicity, and neurotoxicity. Since polymyxins and aminoglycosides are both eliminated by the kidney, coadministration may increase serum concentrations of either drug class. If these drugs are used in combination, monitor renal function and patients for increased adverse effects. Additionally, neuromuscular blockade has been associated with both polymyxins and aminoglycosides, and is more likely to occur in patients with renal dysfunction.
Valacyclovir: (Moderate) Since colistimethate sodium is eliminated by the kidney, coadministration with other potentially nephrotoxic drugs, including valacyclovir, may increase serum concentrations of either drug. Theoretically, the chronic coadministration of these drugs may increase the risk of developing nephrotoxicity, even in patients who have normal renal function. Monitor patients for changes in renal function if these drugs are coadministered.
Vancomycin: (Major) Since colistimethate sodium is eliminated by the kidney, coadministration with other potentially nephrotoxic drugs, including vancomycin, may increase serum concentrations of either drug. The chronic coadministration of these drugs may increase the risk of developing nephrotoxicity, even in patients who have normal renal function. Monitor patients for changes in renal function if these drugs must be coadministered.
Warfarin: (Moderate) The concomitant use of warfarin with many antibiotics, including colistimethate sodium, may result in an increased INR thereby potentiating the risk for bleeding. Inhibition of vitamin K synthesis due to alterations in the intestinal flora may be a mechanism; however, concurrent infection is also a potential risk factor for elevated INR. Monitor patients for signs and symptoms of bleeding. Additionally, increased monitoring of the INR, especially during initiation and upon discontinuation of the antibiotic, may be necessary.
Zoledronic Acid: (Major) Coadministration of these drugs systemically may increase the risk of developing nephrotoxicity, even in patients who have normal renal function. Monitor patients for changes in renal function if these drugs are coadministered. Since colistimethate sodium is eliminated by the kidney, coadministration with other potentially nephrotoxic drugs, including zoledronic acid, may theoretically increase serum concentrations of either drug.

Colistimethate Sodium/Coly-Mycin M Intramuscular Inj Pwd F/Sol: 150mg
Colistimethate Sodium/Coly-Mycin M Intravenous Inj Pwd F/Sol: 150mg

NOTE: To avoid errors in dosing and administration, colistimethate sodium should only be prescribed as colistin in terms of colistin base activity.
NOTE: Approximately 33 mg colistin base activity corresponds to approximately 80 mg of colistimethate sodium and 1 million International Units (IU) of colistimethate sodium.

5 mg/kg/day colistin base activity IV/IM is FDA-approved with 360 mg/day colistin base activity IV used off-label; 8.25 mg colistin base activity intrathecally or intraventricularly used off-label; 300 mg/day colistin base activity via inhalation used off-label.

5 mg/kg/day colistin base activity IV/IM is FDA-approved with 360 mg/day colistin base activity IV used off-label; 8.25 mg colistin base activity intrathecally or intraventricularly used off-label; 300 mg/day colistin base activity via inhalation used off-label.

5 mg/kg/day colistin base activity IV/IM is FDA-approved with 7 mg/kg/day colistin base activity IV/IM used off-label; 4.1 mg colistin base activity intrathecally or intraventricularly used off-label; 150 mg/day or 5 mg/kg/day colistin base activity via inhalation used off-label.

5 mg/kg/day colistin base activity IV/IM is FDA-approved with 7 mg/kg/day colistin base activity IV/IM used off-label; 4.1 mg colistin base activity intrathecally or intraventricularly used off-label; 150 mg/day or 5 mg/kg/day colistin base activity via inhalation used off-label.

5 mg/kg/day colistin base activity IV/IM is FDA-approved with 7 mg/kg/day colistin base activity IV/IM used off-label; 1.64 mg colistin base activity intrathecally or intraventricularly used off-label; 8 mg/kg/day colistin base activity via inhalation used off-label.

5 mg/kg/day colistin base activity IV/IM; 10 mg/kg/day colistin base activity via inhalation used off-label.

NOTE: The term colistin can describe 2 distinct products, colistin sulfate (colistin base) or colistimethate sodium. There are differences in the basic chemistry, pharmacology, pharmacokinetics, and clinical applications of these 2 formulations. If the term colistin is used, then the information described applies to both products. However, the terms colistin sulfate or colistimethate sodium will be used whenever there are specific differences between the drugs.
 
Colistin is a cationic agent that binds to the anionic bacterial outer membrane, leading to a detergent effect that disrupts membrane integrity. It can preferentially bind to the lipid A of lipopolysaccharide and displace magnesium and calcium from cationic binding sites. This binding can have neutralizing effects on the biological properties of endotoxins. Due to this disruptive effect, increased susceptibility to hydrophobic antimicrobials may occur after exposure.[65111] [65113]
 
Colistimethate sodium, which is the parenteral formulation, is an inactive prodrug of the bioactive form colistin base. In aqueous solution, colistimethate sodium undergoes spontaneous hydrolysis to form colistin base, which is a complex bioactive antimicrobial mixture with two active components, colistin A (polymyxin E1) and colistin B (polymyxin E2).[61557]
 
Polymyxins exhibit concentration-dependent pharmacodynamics where the free-drug area under the concentration-time curve to minimal inhibitory concentration ratio (AUC/MIC) appears to best correlate with antibacterial activity. Concentrations above the MIC result in extremely rapid initial killing with large decreases in colony-forming units per milliliter occurring as early as 5 minutes after exposure. An AUC over 24 hours at steady-steady of approximately 50 mg x hour/L is required and equates to a target average steady-state plasma concentration of approximately 2 mg/L for total drug. This should be considered as maximum tolerable exposure. There is a modest postantibiotic effect for high concentrations of colistin.[65112] [65114]
 
The susceptibility interpretive criteria for colistin are delineated by pathogen. The Clinical and Laboratory Standards Institute (CLSI) defines MICs for Enterobacterales, P. aeruginosa, and A. baumannii as intermediate at 2 mcg/mL or less and resistant at 4 mcg/mL or more. The CLSI recommends that colistin should generally be given with a loading dose and at maximum recommended doses in combination with other agents and that systemic use is not likely to be effective for pneumonia. The FDA does not support these breakpoints.
 
Resistance to polymyxins include alterations in lipid A that reduce binding and a decrease in anionic surface charges that may correlate with decreased binding sites for the cationic polymyxins.[65111]

NOTE: The term colistin can describe 2 distinct products, colistin sulfate (colistin base) or colistimethate sodium. There are differences in the basic chemistry, pharmacology, pharmacokinetics, and clinical applications of these 2 formulations. If the term colistin is used, then the information described applies to both products. However, the terms colistin sulfate or colistimethate sodium will be used whenever there are specific differences between the drugs.
 
Colistimethate sodium is administered intravenously, intramuscularly, intrathecally, intraventricularly, or via nebulization.
 
It is difficult to compare peak serum concentrations when assessing different studies analyzing colistin. Part of this is due to the different dosage regimens used internationally. In one study in patients with cystic fibrosis receiving colistin as 7.5 mg/kg/day in divided doses given as 30 minute infusions, steady state Cmax was determined to be 23 +/- 6 mg/L and Cmin at 8 h was 4.5 +/- 4 mg/L. In another study in similar patients given 2 million units every 8 hours for 12 days, the Cmax was 12.9 mg/L (5.7 to 29.6 mg/L) and the Cmin was 2.76 mg/L (1 to 6.2 mg/L). In healthy volunteers given a bolus injection of 150 mg (approximately 2 million units), peak serum concentrations of 18 mg/L were observed 10 minutes after injection. Adding to the difficulty in assessing these data, early studies to determine the pharmacokinetic properties after parenteral colistimethate sodium were based on microbiological assays for measuring drug concentrations. However, these methods are inaccurate as they lack the ability to differentiate colistimethate sodium from colistin base. Also, different manufacturer preparations may have contained different proportions of colistin A and B. More contemporary high-performance liquid chromatographic (HPLC) methods have been employed in animal studies and in studies of patients with cystic fibrosis for the separate determination of colistimethate sodium and colistin base pharmacokinetics. In an interim study of 105 critically-ill patients with 851 plasma samples, the AUC for colistin ranged from 11.5 to 225 mg x hour/L with an average steady-state concentration range of 0.48 to 9.38 mg/L (median 2.36 mg/L). There was a strong inverse trend between the colistin steady-state average and CrCl.
 
Overall, protein binding is low. In animal studies, colistin base is tightly bound to cell membranes in the liver, lung, kidney, brain, heart, and muscles. Drug is slowly released from these tissues and can persist up to five days after the drug has been discontinued. In contrast, colistimethate sodium is poorly bound to tissues. Generally, colistin does not penetrate well into the pleural cavity, lung parenchyma, bones, and CSF based on older studies. However, in 2002, a case report of meningitis due to resistant Acinetobacter baumannii showed sufficient CSF penetration to cure the infection and demonstrated that the colistin concentration in the CSF was 25% of the serum concentration.
 
The half-life of colistin is reported to be 2 to 3 hours; however, older studies determining the pharmacokinetic properties of colistin were based on microbiological assays for measuring drug concentrations; therefore, this may represent the composite values representing the summed half-lives of colistimethate sodium and colistin sulfate. A study using HPLC assays in 12 cystic fibrosis patients showed that for colistimethate sodium, the total body clearance was 2.01 +/- 0.46 mL/minute, with a half-life of 124 +/- 52 minutes. The volume of distribution in these patients was 340 +/- 95 mL/kg. Colistin base had a longer half-life of 251 +/- 79 minutes. In an interim study of critically-ill patients, 19 patients with a CrCl > 70 mL/minute/1.73 m2 had a median colistin half-life of 9.1 hours (6.3 to 12 hours). Colistimethate sodium is hydrolyzed in vitro to colistin base and is extensively cleared renally via filtration and net renal tubular secretion. Approximately 60% of colistimethate sodium is excreted as unchanged drug in the urine within the first 24 hours. Animal studies that directly administered colistin base IV showed that the majority was non-renally cleared with a minor route of elimination via the kidney involving extensive net tubular reabsorption. Although colistin base is not extensively eliminated renally, impaired renal function will still likely result in increased colistin base concentrations. This results from decreased colistimethate sodium elimination, which would result in a higher proportion of colistimethate sodium being available for hydrolysis to colistin base.

After IV administration, colistimethate sodium, a prodrug, undergoes spontaneous hydrolysis to form colistin base, which is a complex bioactive antimicrobial mixture with two active components, colistin A (polymyxin E1) and colistin B (polymyxin E2). An in vitro study showed that 31.2% of colistimethate sodium in human plasma was hydrolyzed to colistin base in 4 hours at 37 degrees.

After IM administration, colistimethate sodium, a prodrug, undergoes spontaneous hydrolysis to form colistin base, which is a complex bioactive antimicrobial mixture with two active components, colistin A (polymyxin E1) and colistin B (polymyxin E2). An in vitro study showed that 31.2% of colistimethate sodium in human plasma was hydrolyzed to colistin base in 4 hours at 37 degrees.

When colistimethate sodium is given by nebulization, variable absorption has been reported that may depend on the aerosol particle size, nebulizer system, and lung status; studies in healthy volunteers and patients with various infections have reported serum concentrations from undetectable to >= 4mg/L. Therefore, the possibility of systemic absorption should always be borne in mind when treating patients by inhalation. However, a study in cystic fibrosis patients showed that colistimethate sodium was undetectable in the urine after 3 months of daily use indicating minimal absorption (renal elimination is the main route of excretion). Since GI absorption of colistimethate sodium is negligible, swallowing colistimethate sodium deposited in the nasopharynx after nebulization is unlikely to add to the systemic exposure.

Intraperitoneal Route
Initial case reports state that colistimethate sodium given intraperitoneally is absorbed, but not at concentrations consistent with therapeutic use. They also imply that there is limited drug removal with peritoneal dialysis, although it is unclear how this data would translate to current peritoneal dialysis practices.

Colistimethate sodium is classified as FDA pregnancy category C. There are no adequate and well controlled studies in pregnant women. Animal reproduction studies have demonstrated adverse fetal effects. Single dose studies in human pregnancy show that colistimethate sodium crosses the placental barrier and there may be a risk of fetal toxicity if repeated doses are given to pregnant patients. Therefore, use colistimethate sodium during pregnancy only if the potential benefit justifies the potential risk to the fetus.

It is not known whether colistimethate sodium is excreted in human milk. However, colistimethate sodium in converted to colistin sulfate in vivo and colistin sulfate is excreted in human breast milk. Use caution when administering colistin to a breast-feeding woman. In a single-dose study of 29 women, 9 women received colistimethate sodium 1 million international units IM and 20 women received 2 million international units IM. In the patients who received the 1 million international units dose, breast milk concentrations of colistin sulfate were 740 mcg/L at 1 hour in a patient, 760 mcg/L at 2 hours in 3 patients, and 140 mcg/L at 3 hours in 5 patients. In the patients who received the 2 million international units IM dose, breast milk concentrations averaged 500 mcg/L at 1 hour after the dose and 789 mcg/L at 2 hours after the dose. In another study, colistimethate sodium 2 million international units IM was administered to 15 women on day 5 postpartum. Peak breast milk concentrations occurred 5 hours post-dose. After 2 doses, the average peak breast milk concentration was 165 mcg/L and the trough was 50 mcg/L. Additionally, 5 women received a dose of 4 million international units IM on day 5 postpartum. After 2 doses, the average peak breast milk concentration was 215 mcg/L and trough was 50 mcg/L. Studies in adults have demonstrated no systemic absorption of colistin sulfate following oral administration; however, caution should be used when administering to breast-feeding mothers as absorption in neonates and infants is erratic.