POLYMYXIN B

INDICATIONS AND USAGE 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 bloodstream caused by susceptible strains of Ps. aeruginosa. It may also be used topically and subconjunctivally in the treatment of infections of the eye caused by susceptible strains of Ps. 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.

DOSAGE AND ADMINISTRATION 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 0.9 % 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 Ps aeruginosa. Intrathecal . A treatment of choice for Ps aeruginosa meningitis. Dissolve 500,000 polymyxin B units in 10 mL 0.9 % 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. TOPICAL: Ophthalmic . Dissolve 500,000 polymyxin B units in 20 to 50 mL sterile water for injection or sodium chloride injection USP for a 10,000 to 25,000 units per mL concentration. For the treatment of Ps aeruginosa infections of the eye, a concentration of 0.1 percent to 0.25 percent (10,000 units to 25,000 units per mL) is administered 1 to 3 drops every hour, increasing the intervals as response indicates. Subconjunctival injection of up to 100,000 units/day may be used for the treatment of Ps aeruginosa infections of the cornea and conjunctiva. Note: Avoid total systemic and ophthalmic instillation over 25,000 units/kg/day.

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

ADVERSE REACTIONS See WARNING box. Nephrotoxic reactions: Albuminuria, cylinduria, azotemia, and rising blood levels without any increase in dosage. Renal system reactions: Electrolyte and acid/base abnormalities (i.e., Pseudo-Bartter syndrome). 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 Fosun Pharma USA Inc. at 1-866-611-3762 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .

DESCRIPTION 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). Polymyxin B sulfate, USP is a white or off-white powder. It has a potency of not less than 6,000 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 a sterile, white lyophilized cake or powder, 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. Polymyxin B Sulfate Chemical Structure

HOW SUPPLIED Each vial of Polymyxin B for Injection contains polymyxin B sulfate equivalent to 500,000 polymyxin B units. It is supplied in rubber-stoppered glass vial with flip off cap, carton of 10. Product Code Unit of Sale Strength Each PRX306711 NDC 63323-367-44 Unit of 10 500,000 units per vial NDC 63323-367-41 10 mL glass vial. 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. PREMIERProRx ® is a registered trademark of Premier Healthcare Alliance, L.P., used under license. Manufactured for: Fresenius Kabi USA, LLC Lake Zurich, IL 60047 Made in India 451606 Issued: March 2019 LEA-020172-00 Code No: AP/DRUGS/103/97 PREMIER ProRx ®