Source: Health Products and Food Branch (CA) Revision Year: 2011
Polymyxin B for Injection USP (polymyxin B sulphate) is indicated for the treatment of patients with the following infections, when caused by susceptible strains of the designated aerobic gramnegative bacteria:
Polymyxin B for Injection should be used where sensitivity suggests more commonly used systemic antibacterial agents may be contraindicated or ineffective because of bacterial resistance.
Polymyxin B for Injection, if prescribed for intravenous, intramuscular or intrathecal administration, should be used only in hospitalized patients under close monitoring for kidney function and neurological signs and symptoms.
To reduce the development of drug-resistant bacteria and maintain the effectiveness of polymyxin B sulphate and other antibacterial drugs, polymyxin B sulphate 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.
Polymyxin B for Injection USP may be administered intravenously, intramuscularly or intrathecally only to hospitalized patients under constant supervision by a physician. Dosage should not exceed 2.5 mg/kg/day or 200 mg/day. Larger doses may produce nephrotoxicity. Transient neurotoxic symptoms may be seen with therapeutic doses.
Estimation of renal function prior to and regularly during therapy is recommended. Monitoring of renal function is strongly recommended in the elderly and in patients with renal impaired function.
Subconjunctival injection of polymyxin B sulphate is painful.
Polymyxin B for Injection USP should not be administered by inhalation.
In medical literature, dosages have been given in terms of equivalent weights of pure polymyxin B base. Each milligram of pure polymyxin B is equivalent to 10,000 units of polymyxin B.
Safety and efficacy of polymyxin B sulphate in children greater than 2 years is limited. Renal function should be frequently monitored in this population.
Safety and efficacy of intravenous and intramuscular polymyxin B sulphate administration in infants less than 2 years of age is limited. A possibility of higher serum levels and prolonged half-life has been reported in infants and neonates, therefore dosage recommendations are not available for this population (See PART II: SCIENTIFIC INFORMATION, DETAILED PHARMACOLOGY).
Adults and Children (Older than 2 years): A total of 1.5 to 2.5 mg/kg/day in individuals with normal kidney function. The total daily dose must not exceed 2.5 mg/kg/day or in any case, 200 mg/day.
Elderly (≥65 years): Renal status of elderly patients may be impaired, therefore renal function assessment prior to and regularly during treatment is suggested to provide guidance for dosing in such patients.
Patients with Renal Impairment: Polymyxin B sulphate is eliminated primarily by the kidney and therefore the dosage should be reduced from 1.5 mg/kg for individuals with kidney impairment. No dosing recommendations in patients on peritoneal dialysis- or hemodialysis are available (See ACTION AND CLINICAL PHARMACOLOGY, Pharmacokinetics; DETAILED PHARMACOLOGY, Pharmacokinetics, Factors Influencing Pharmacokinetics, Special Populations, Renal Insufficiency).
Dissolve 50 mg polymyxin B sulphate powder in 200 to 500 mL of Dextrose Injection 5 percent, for continuous IV drip. Reconstituted solution should be stored under refrigeration (2-8°C) and the unused portion should be discarded after 24 hours.
Infusions may be given every 12 or 8 hours over a period of approximately 60 to 90 minutes.
Adults and Children (older than 2 years): 1.5 to 2.5 mg/kg/day in individuals with normal kidney function. Dosage may be divided and given at either 4 or 6 hour intervals.
Elderly (≥65 years): Renal status of elderly patients may be impaired, therefore renal function assessment prior to and regularly during treatment is suggested to provide guidance for dosing in such patients.
Patients with Renal Impairment: The dosage should be reduced in individuals with kidney impairment. No dosing recommendations in patients on peritoneal dialysis or hemodialysis are available (See ACTION AND CLINICAL PHARMACOLOGY, Pharmacokinetics; DETAILED PHARMACOLOGY, Pharmacokinetics, Factors Influencing Pharmacokinetics, Special Populations, Renal Insufficiency).
Polymyxin B for Injection USP is compatible with the following reconstitution diluents for intramuscular administration:
Sterile Water for Injection
Sodium Chloride Injection 0.9 percent
Procaine hydrochloride Injection 1 percent or 2 percent.
To the vial containing Polymyxin B for Injection USP 50 mg, add diluent volume as shown in Table 1. Shake well to dissolve the powder.
Table 1. Reconstitution of Polymyxin B for Injection USP for 4 Hour Intramuscular Administration in Adults and Children (older than 2 years):
| Patient Population | Total Average Daily Dose | Polymyxin B sulphate per vial | Volume of Diluent to be Added | Nominal Concentration Per mL | Dose Volume per 4 Hours | |
|---|---|---|---|---|---|---|
| 80 kg or more | Up to | 200 mg | 50 mg | 3 mL | 16 mg/mL | 2 mL |
| 60 to 80 kg | 150 mg | 50 mg | 4 mL | 12.5 mg/mL | 2 mL | |
| 40 to 60 kg | 100 mg | 50 mg | 6 mL | 8 mg/mL | 2 mL | |
| 20 to 40 kg | 50 mg | 50 mg | 6 mL | 8 mg/mL | 1 mL | |
| Less than 20 kg | 1.5-2.5 mg/kg/day | 50 mg | 6 mL | 8 mg/mL | As calculated |
Reconstituted solutions should be stored under refrigeration (2-8°C) and the unused portion should be discarded after 24 hours.
Note: Dibucaine hydrochloride can potentiate the neurotoxic effects of polymyxins and should not be used as a diluent for IM injection.
Intramuscular administration is not recommended routinely because of severe pain at injection sites, particularly in children. Pain may be immediate or delayed. The immediate type may be prevented by the presence of a local anaesthetic in the drug solution. The delayed type tends to develop about 1 hour after injection and is not prevented by the presence of a local anaesthetic.
Polymyxin B for Injection USP should be injected well within the body of a relatively large muscle such as in the upper outer quadrant of the buttock or the lateral thigh. To avoid the possibility of radial nerve injury, injections should not be made into the lower and middle thirds of the upper arm. Aspiration and proper anatomical selection of injection site should be observed as a precaution against inadvertent injection into a blood vessel or a major nerve.
Adults and Children (older than 2 years): Dosage is 5 mg once daily intrathecally for 3 or 4 days, then 5 mg once every other day for at least 2 weeks after cultures of the cerebrospinal fluid are negative and sugar content has returned to normal.
Infants (less than 2 years): 2 mg once daily intrathecally for 3 to 4 days or 2.5 mg once every other day. Continue with a dose of 2.5 mg once every other day for at least 2 weeks after cultures of the cerebrospinal fluid are negative and sugar content has returned to normal.
Dissolve 50 mg Polymyxin B for Injection USP in 10 mL Sodium Chloride Injection 0.9 percent to obtain a concentration of 5 mg/mL polymyxin B sulphate. Shake well. Reconstituted solutions should be stored under refrigeration (2-8°C) and the unused portion should be discarded after 24 hours.
Adults and Children (older than 2 years): Inject 1 mL (5 mg) of reconstituted polymyxin B sulphate solution intrathecally.
Infants (less than 2 years): Inject 0.4 mL (2 mg) of reconstituted polymyxin B sulphate solution intrathecally for 3 to 4 days or 0.5 mL (2.5 mg) once every other day.
1 to 2.5 mg/mL (0.1 to 0.25 percent w/v) solution as 1 to 3 drops every hour, increasing the interval as response indicates.
Deep seated or walled off Pseudomonas aeruginosa infections cannot be expected to respond to topical polymyxin B treatment.
Reconstitution for Topical Administration:
Dissolve 50 mg Polymyxin B for Injection USP powder in 20 to 50 mL of Sterile Water for Injection USP or Sodium Chloride Injection USP 0.9 percent, for 1 to 2.5 mg/mL concentration. Reconstituted solutions should be stored under refrigeration (2-8°C) and the unused portion should be discarded after 72 hours.
Administration:
Instill 1 to 3 drops in the affected eye every hour, increasing the interval as response indicates.
Subconjunctival injection of up to 1 mg/day is administered for the treatment of Pseudomonas aeruginosa infections of the cornea and conjunctiva.
Reconstitution for Subconjectival Administration:
Dissolve 50 mg polymyxin B sulfate lyophilized powder in 50 mL of Sterile Water for Injection USP or Sodium Chloride Injection USP for a 1 mg/mL concentration. Reconstituted solutions should be stored under refrigeration (2-8°C) and the unused portion should be discarded after 24 hours.
Administration:
1 mL of reconstituted polymyxin B sulphate solution.
Avoid total systemic and ophthalmic instillation over 2.5 mg/kg/day.
This information is not available.
For management of a suspected drug overdose, contact your regional Poison Control Centre.
Polymyxin-induced toxicity associated with overdose has been reported. Overdose of polymyxin can result in neuromuscular blockade, which can lead to apnea, muscular weakness, vertigo, transient facial paresthesia, slurred speech, vasomotor instability, visual disturbance, confusion, psychosis and possible respiratory arrest. Overdose can also cause renal failure characterized by decreased urine output and increased serum concentrations of BUN and creatinine.
There is no specific antidote for polymyxin B sulphate overdose. In case of polymyxin B sulphate overdose, the drug should be stopped and symptomatic treatment instituted.
Quick diuresis by IV administered mannitol may help to enhance renal clearance of the drug and thus to reduce serum drug levels. Hemodialysis or peritoneal dialysis may help in order to manage renal complications.
Before reconstitution: Store at room temperature (15-30°C). Protect from light. Retain in carton until time of use.
After reconstitution for Intravenous, Intramuscular, Intrathecal and Ophthalmic (Subconjunctival): Reconstituted solutions should be stored under refrigeration (2-8°C) and the unused portion should be discarded after 24 hours.
After reconstitution for Ophthalmic (Topical): Reconstituted solutions should be stored under refrigeration (2-8°C). Any unused portion should be discarded after 72 hours.
Polymyxin B sulphate should not be stored in alkaline solutions since they are less stable.
© All content on this website, including data entry, data processing, decision support tools, "RxReasoner" logo and graphics, is the intellectual property of RxReasoner and is protected by copyright laws. Unauthorized reproduction or distribution of any part of this content without explicit written permission from RxReasoner is strictly prohibited. Any third-party content used on this site is acknowledged and utilized under fair use principles.
