POLYMYXIN B

Polymyxin B for Injection, USP is one of a group of basic polypeptide antibiotics derived from B polymyxa (B aerosporous) . Polymyxin B sulfate is the sulfate salt of Polymyxins B 1 and B 2 , which are produced by the growth of Bacillus polymyxa (Prazmowski) Migula (Fam. Bacillacea). It has a potency of not less than 6000 polymyxin B units per mg, calculated on the anhydrous basis. The structural formulae are: Each vial contains 500,000 polymyxin B units for parenteral or ophthalmic administration. Polymyxin B for Injection, USP is in powder form suitable for preparation of sterile solutions for intramuscular, intravenous drip, intrathecal, or ophthalmic use. In the medical literature, dosages have frequently been given in terms of equivalent weights of pure polymyxin B base. Each milligram of pure polymyxin B base is equivalent to 10,000 units of polymyxin B and each microgram of pure polymyxin B base is equivalent to 10 units of polymyxin B. Aqueous solutions of polymyxin B sulfate may be stored up to 12 months without significant loss of potency if kept under refrigeration. In the interest of safety, solutions for parenteral use should be stored under refrigeration and any unused portion should be discarded after 72 hours. Polymyxin B sulfate should not be stored in alkaline solutions since they are less stable. Structural Formulae

Acute Infections Caused by Susceptible Strains of Pseudomonas aeruginosa . Polymyxin B sulfate is a drug of choice in the treatment of infections of the urinary tract, meninges, and blood-stream caused by susceptible strains of P. aeruginosa . It may also be used topically and subconjunctivally in the treatment of infections of the eye caused by susceptible strains of P. aeruginosa . It may be indicated in serious infections caused by susceptible strains of the following organisms, when less potentially toxic drugs are ineffective or contraindicated: H influenzae, specifically meningeal infections. Escherichia coli, specifically urinary tract infections. Aerobacter aerogenes, specifically bacteremia. Klebsiella pneumoniae, specifically bacteremia. NOTE: IN MENINGEAL INFECTIONS, POLYMYXIN B SULFATE SHOULD BE ADMINISTERED ONLY BY THE INTRATHECAL ROUTE. To reduce the development of drug-resistant bacteria and maintain the effectiveness of polymyxin B and other antibacterial drugs, polymyxin B 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.

PARENTERAL: Intravenous . Dissolve 500,000 polymyxin B units in 300 to 500 mL solutions for parenteral 5% Dextrose Injection for continuous drip. Adults and children. 15,000 to 25,000 units/kg body weight/day in individuals with normal kidney function. This amount should be reduced from 15,000 units/kg downward for individuals with kidney impairment. Infusions may be given every 12 hours; however, the total daily dose must not exceed 25,000 units/kg/day. Infants. Infants with normal kidney function may receive up to 40,000 units/kg/day without adverse effects. Intramuscular . Not recommended routinely because of severe pain at injection sites, particularly in infants and children. Dissolve 500,000 Polymyxin B units in 2 mL sterile water for injection or sodium chloride injection or procaine hydrochloride injection 1%. Adults and children. 25,000 to 30,000 units/kg/day. This should be reduced in the presence of renal impairment. The dosage may be divided and given at either 4 or 6 hour intervals. Infants . Infants with normal kidney function may receive up to 40,000 units/kg/day without adverse effects. Note : Doses as high as 45,000 units/kg/day have been used in limited clinical studies in treating prematures and newborn infants for sepsis caused by P. aeruginosa. Intrathecal . A treatment of choice for P. aeruginosa meningitis. Dissolve 500,000 polymyxin B units in 10 mL sodium chloride injection, USP for 50,000 units per mL dosage unit. Adults and children over 2 years of age. Dosage is 50,000 units once daily intrathecally for 3 to 4 days, then 50,000 units once every other day for at least 2 weeks after cultures of the cerebrospinal fluid are negative and sugar content has returned to normal. Children under 2 years of age. 20,000 units once daily, intrathecally for 3 to 4 days or 25,000 units once every other day. Continue with a dose of 25,000 units once every other day for at least 2 weeks after cultures of the cerebrospinal fluid are negative and sugar content has returned to normal. IN THE INTEREST OF SAFETY, SOLUTIONS OF PARENTERAL USE SHOULD BE STORED UNDER REFRIGERATION, AND ANY UNUSED PORTIONS SHOULD BE DISCARDED AFTER 72 HOURS.

This drug is contraindicated in persons with a prior history of hypersensitivity reactions to polymyxins.

See WARNING box. Nephrotoxic reactions: Albuminuria, cylinduria, azotemia, and rising blood levels without any increase in dosage. Neurotoxic reactions: Facial flushing, dizziness progressing to ataxia, drowsiness, peripheral paresthesias (circumoral and stocking glove), apnea due to concurrent use of curariform muscle relaxants, other neurotoxic drugs or inadvertent overdosage, and signs of meningeal irritation with intrathecal administration, e.g., fever, headache, stiff neck and increased cell count and protein cerebrospinal fluid. Other reactions occasionally reported: Drug fever, urticarial rash, pain (severe) at intramuscular injection sites, and thrombophlebitis at intravenous injection sites. To report SUSPECTED ADVERSE REACTIONS, contact Fresenius Kabi USA, LLC at 1-800-551-7176 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Storage recommendations: Before reconstitution: Store at 20° to 25° C (68° to 77° F) (See USP controlled Room Temperature) Protect from light. Retain in carton until time of use. After reconstitution: Product must be stored under refrigeration, between 2° to 8°C (36° to 46°F) and any unused portion should be discarded after 72 hours. This container closure is not made with natural rubber latex. PREMIERProRx ® is a registered trademark of Premier Healthcare Alliance, L.P., used under license. Manufactured by: Fresenius Kabi Lake Zurich, IL 60047 www.fresenius-kabi.com/us 451688 Issued: February 2021 Fresenius Kabi Logo