Colistimethate Information
Colistimethate ()
Colistimethate () Description
Colistimethate () for injection (Colistimethate () sodium) is a sterile parenteral antibiotic product which, when reconstituted (see ), is suitable for intramuscular or intravenous administration.
Each vial contains Colistimethate () sodium or pentasodium colistinmethanesulfonate (equivalent to 150 mg colistin base). Colistimethate () sodium appears as a white to slightly yellow lyophilized cake. The sodium content is approximately 0.099 mg (0.0043 mEq) of sodium per milligram of Colistin. Colistimethate () sodium is a polypeptide antibiotic with an approximate molecular weight of 1750. The molecular formula is C H N NaO S and the structural formula is represented below:
Colistimethate () Clinical Pharmacology
Typical serum and urine levels following a single 150 mg dose of Colistimethate () for injection IM or IV in normal adult subjects are shown in Figure 1.
Higher serum levels were obtained at 10 minutes following IV administration. Serum concentration declined with a half-life of 2-3 hours following either intravenous or intramuscular administration in adults and in the pediatric population, including premature infants.
Average urine levels ranged from about 270 mcg/mL at 2 hours to about 15 mcg/mL at 8 hours after intravenous administration and from 200 to about 25 mcg/mL during a similar period following intramuscular administration.
Colistimethate () Indications And Usage
Colistimethate () for injection is indicated for the treatment of acute or chronic infections due to sensitive strains of certain gram-negative bacilli. It is particularly indicated when the infection is caused by sensitive strains of . This antibiotic is not indicated for infections due to or . Colistimethate () for injection has proven clinically effective in treatment of infections due to the following gram-negative organisms: and .
Colistimethate () for injection may be used to initiate therapy in serious infections that are suspected to be due to gram-negative organisms and in the treatment of infections due to susceptible gram-negative pathogenic bacilli.
To reduce the development of drug-resistant bacteria and maintain the effectiveness of Colistimethate () for injection and other antibacterial drugs, Colistimethate () for injection should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.
Colistimethate () Contraindications
The use of Colistimethate () for injection is contraindicated for patients with a history of sensitivity to the drug or any of its components.
Colistimethate () Warnings
Maximum daily dose should not exceed 5 mg/kg/day (2.3 mg/lb) with normal renal function.
Transient neurological disturbances may occur. These include circumoral paresthesia or numbness, tingling or formication of the extremities, generalized pruritus, vertigo, dizziness, and slurring of speech. For these reasons, patients should be warned not to drive vehicles or use hazardous machinery while on therapy. Reduction of dosage may alleviate symptoms. Therapy need not be discontinued, but such patients should be observed with particular care.
Nephrotoxicity can occur and is probably a dose-dependent effect of Colistimethate () sodium. These manifestations of nephrotoxicity are reversible following discontinuation of the antibiotic.
Overdosage can result in renal insufficiency, muscle weakness, and apnea (see section). See subsection for use concomitantly with other antibiotics and curariform drugs.
Respiratory arrest has been reported following intramuscular administration of Colistimethate () sodium. Impaired renal function increases the possibility of apnea and neuromuscular blockade following administration of Colistimethate () sodium. Therefore, it is important to follow recommended dosing guidelines. See section for use in renal impairment.
Treatment with antibacterial agents alters the normal flora of the colon and may permit overgrowth of clostridia. Studies indicate that a toxin produced by is a primary cause of "antibiotic-associated colitis."
After the diagnosis of pseudomembranous colitis has been established, appropriate therapeutic measures should be initiated. Mild cases of pseudomembranous colitis usually respond to drug discontinuation alone. In moderate-to-severe cases, consideration should be given to management with fluids and electrolytes, protein supplementation, and treatment with an antibacterial drug clinically effective against colitis.
Colistimethate () Precautions
Since Colistimethate () for injection is eliminated mainly by renal excretion, it should be used with caution when the possibility of impaired renal function exists. The decline in renal function with advanced age should be considered.
When actual renal impairment is present, Colistimethate () for injection may be used, but the greatest caution should be exercised and the dosage should be reduced in proportion to the extent of the impairment. Administration of amounts of Colistimethate () for injection in excess of renal excretory capacity will lead to high serum levels and can result in further impairment of renal function, initiating a cycle which, if not recognized, can lead to acute renal insufficiency, renal shutdown, and further concentration of the antibiotic to toxic levels in the body. At this point, interference of nerve transmission at neuromuscular junctions may occur and result in muscle weakness and apnea (see section).
Signs indicating the development of impaired renal function include: diminishing urine output, rising BUN and serum creatinine and decreased creatinine clearance. Therapy with Colistimethate () for injection should be discontinued immediately if signs of impaired renal function occur. However, if it is necessary to reinstate the drug, dosing should be adjusted accordingly after drug plasma levels have fallen (see section).
Prescribing Colistimethate () for injection in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria.
Certain other antibiotics (aminoglycosides and polymyxin) have also been reported to interfere with the nerve transmission at the neuromuscular junction. Based on this reported activity, they should not be given concomitantly with Colistimethate () for injection except with the greatest caution.
Curariform muscle relaxants (e.g., tubocurarine) and other drugs, including ether, succinylcholine, gallamine, decamethonium and sodium citrate, potentiate the neuromuscular blocking effect and should be used with extreme caution in patients being treated with Colistimethate () for injection.
Sodium cephalothin may enhance the nephrotoxicity of Colistimethate () for injection. The concomitant use of sodium cephalothin and Colistimethate () for injection should be avoided.
Colistimethate () Adverse Reactions
The following adverse reactions have been reported:
Colistimethate () Overdosage
Overdosage with Colistimethate () sodium can cause neuromuscular blockade characterized by paresthesia, lethargy, confusion, dizziness, ataxia, nystagmus, disorders of speech and apnea. Respiratory muscle paralysis may lead to apnea, respiratory arrest and death. Overdosage with the drug can also cause acute renal failure, manifested as decreased urine output and increases in serum concentrations of BUN and creatinine.
As in any case of overdose, Colistimethate () sodium therapy should be discontinued and general supportive measures should be utilized.
It is unknown whether Colistimethate () sodium can be removed by hemodialysis or peritoneal dialysis in overdose cases.
Colistimethate () Dosage And Administration
The vial should be reconstituted with Sterile Water for Injection, USP. The reconstituted solution provides Colistimethate () sodium at a concentration equivalent to 75 mg/mL colistin base activity.
During reconstitution swirl to avoid frothing.
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. If these conditions are observed, the product should not be used.
1. Direct Intermittent Administration—Slowly inject one-half of the total daily dose over a period of 3 to 5 minutes every 12 hours.
2. Continuous Infusion—Slowly inject one-half of the total daily dose over 3 to 5 minutes. Add the remaining half of the total daily dose of Colistimethate () for injection to one of the following:
There are not sufficient data to recommend usage of Colistimethate () for injection with other drugs or other than the above listed infusion solutions.
Administer the second half of the total daily dose by slow intravenous infusion, starting 1 to 2 hours after the initial dose, over the next 22 to 23 hours. In the presence of impaired renal function, reduce the infusion rate depending on the degree of renal impairment.
The choice of intravenous solution and the volume to be employed are dictated by the requirements of fluid and electrolyte management.
Any infusion solution containing Colistimethate () sodium should be freshly prepared and used for no longer than 24 hours.
Colistimethate () How Supplied
Colistimethate () for injection is supplied in vials containing Colistimethate () sodium (equivalent to 150 mg colistin base per vial). Colistimethate () sodium appears as a white to slightly yellow lyophilized cake and is available as one vial per carton.
NDC 0574-0858-01
Colistimethate ()
