Rx only units of polymyxin B. toxic drugs are ineffective or contraindicated: WARNING (continued) Aqueous solutions of polymyxin B sulfate may be H influenzae, specifically meningeal infections. MYCIN, AMIKACIN, CEPHALORIDINE, PAROMO- stored up to 12 months without significant loss of Escherichia coli, specifically urinary tract infections. MYCIN, VIOMYCIN, AND COLISTIN SHOULD BE Polymyxin B for Injection, USP potency if kept under refrigeration. In the interest of Aerobacter aerogenes, specifically bacteremia. AVOIDED. safety, solutions for parenteral use should be stored 500,000 Units/vial Klebsiella pneumoniae, specifically bacteremia. THE NEUROTOXICITY OF POLYMYXIN B SUL- under refrigeration and any unused portion should be NOTE: IN MENINGEAL INFECTIONS, POLYMYXIN To reduce the development of drug-resistant bacteria FATE CAN RESULT IN RESPIRATORY PARA- discarded after 72 hours. Polymyxin B sulfate should B SULFATE SHOULD BE ADMINISTERED ONLY BY and maintain the effectiveness of polymyxin B and LYSIS FROM NEUROMUSCULAR BLOCKADE, not be stored in alkaline solutions since they are less THE INTRATHECAL ROUTE. other antibacterial drugs, polymyxin B should be used ESPECIALLY WHEN THE DRUG IS GIVEN stable. only to treat or prevent infections that are proven or SOON AFTER ANESTHESIA AND/OR MUSCLE To reduce the development of drug-resistant bacteria strongly suspected to be caused by bacteria RELAXANTS. CLINICAL PHARMACOLOGY and maintain the effectiveness of polymyxin B and other USAGE IN PREGNANCY: THE SAFETY OF THIS Polymyxin B sulfate has a bactericidal action against antibacterial drugs, polymyxin B should be used only to DRUG IN HUMAN PREGNANCY HAS NOT BEEN treat or prevent infections that are proven or strongly WARNING almost all gram-negative bacilli except the Proteus ESTABLISHED. group. Polymyxins increase the permeability of suspected to be caused by susceptible bacteria. When CAUTION: WHEN THIS DRUG IS GIVEN INTRA- bacterial cell membrane leading to death of the cell. All culture and susceptibility information are available, MUSCULARLY AND/OR INTRATHECALLY, IT gram positive bacteria, fungi, and gram-negative cocci they should be considered in selecting or modifying SHOULD BE GIVEN ONLY TO HOSPITALIZED DESCRIPTION are resistant to polymyxin B. antibacterial therapy. In the absence of such data, local PATIENTS, SO AS TO PROVIDE CONSTANT Polymyxin B for Injection is one of a group of basic For specific information regarding susceptibility test epidemiology and susceptibility patterns may contribute SUPERVISION BY A PHYSICIAN. polypeptide antibiotics derived from B polymyxa (B criteria and associated test methods and quality control to the empiric selection of therapy. RENAL FUNCTION SHOULD BE CARFULLY aerosporous). Polymyxin B sulfate is the sulfate salt standards recognized by FDA for this drug, please see: of Polymyxins B and B , which are produced by the CONTRAINDICATIONS DETERMINED AND PATIENTS WITH RENAL 1 2 www.fda.gov/STIC. growth of Bacillus polymyxa (Prazmowski) Migula This drug is contraindicated in persons with a prior DAMAGE AND NITROGEN RETENTION Polymyxin B sulfate is not absorbed from the normal (Fam. Bacillacea). It has a potency of not less than history of hypersensitivity reactions to polymyxins. SHOULD HAVE REDUCED DOSAGE. PATIENTS alimentary tract. Since the drug loses 50 percent of its WITH NEPHROTOXICITY DUE TO POLYMYXIN 6000 polymyxin B units per mg, calculated on the anhydrous basis. The structural formulae are: activity in the presence of serum, active blood levels WARNINGS B SULFATE USUALLY SHOW ALBUMINURIA, are low. Repeated injections may give a cumulative Clostridium difficile associated diarrhea (CDAD) has CELLULAR CASTS, AND AZOTEMIA. g-NH2 effect. Levels tend to be higher in infants and children. been reported with use of nearly all antibacterial agents, DIMINISHING URINE OUTPUT AND A RISING CH3 Dab-D-Phe-Leu The drug is excreted slowly by the kidneys. Tissue BUN ARE INDICATIONS FOR DISCONTINUING diffusion is poor and the drug does not pass the including Polymyxin B for Injection, and may range in RCH CH (CH ) CO-Dab-Thr-Dab-Dab • xH2 SO4 THERAPY WITH THIS DRUG. 2 2 4 severity from mild diarrhea to fatal colitis. Treatment g g g blood brain barrier into the cerebrospinal fluid. In -NH2 -NH2 -Thr-Dab-Dab with antibacterial agents alters the normal flora of the NEUROTOXIC REACTIONS MAY BE MANIFE- therapeutic dosage, polymyxin B sulfate causes some g-NH2 g-NH2 colon leading to overgrowth of C. difficile. STED BY IRRITABILITY, WEAKNESS, DROW- nephrotoxicity with tubule damage to a slight degree. Polymyxin B (R=CH ) Polymyxin B (R=H) SINESS, ATAXIA, PERIORAL PARESTHESIA, 1 3 2 C. difficile produces toxins A and B which contribute NUMBNESS OF THE EXTREMITIES, AND INDICATIONS AND USAGE to the development of CDAD. Hypertoxin producing Each vial contains 500,000 polymyxin B units for BLUR-RING OF VISION. THESE ARE USUALLY Acute Infections Caused by Susceptible Strains of strains of C. difficile cause increased morbidity and parenteral or ophthalmic administration. ASSOCIATED WITH HIGH SERUM LEVELS Pseudomonas aeruginosa. mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy. FOUND IN PATIENTS WITH IMPAIRED RE- Polymyxin B for Injection is in powder form suitable Polymyxin B sulfate is a drug of choice in the treatment CDAD must be considered in all patients who present NALFUNCTION AND/OR NEPHROTOXICITY. for preparation of sterile solutions for intramuscular, of infections of the urinary tract, meninges, and blood- with diarrhea following antibiotic use. Careful medical intravenous drip, intrathecal, or ophthalmic use. stream caused by susceptible strains of Ps. aeruginosa. THE CONCURRENT OR SEQUENTIAL USE history is necessary since CDAD has been reported In the medical literature, dosages have frequently been It may also be used topically and subconjunctivally OF OTHER NEUROTOXIC AND/OR NEPHRO- to occur over two months after the administration of given in terms of equivalent weights of pure polymyxin in the treatment of infections of the eye caused by TOXIC DRUGS WITH POLYMYXIN B SULFATE, antibacterial agents. PARTICULARLY BACITRACIN, STREPTOMYCIN, B base. Each milligram of pure polymyxin B base is susceptible strains of Ps. aeruginosa. It may be equivalent to 10,000 units of polymyxin B and each If CDAD is suspected or confirmed, ongoing antibiotic NEOMYCIN, KANAMYCIN, GENTAMICIN, TOBRA- indicated in serious infections caused by susceptible microgram of pure polymyxin B base is equivalent to 10 strains of the following organisms, when less potentially use not directed against C. difficile may need to be discontinued. Appropriate fluid and electrolyte patients can develop watery and bloody stools (with or Intramuscular. Not recommended routinely because (10,000 units to 25,000 units per mL) is administered management, protein supplementation, antibiotic treat- without stomach cramps and fever) even as late as two of severe pain at injection sites, particularly in infants 1 to 3 drops every hour, increasing the intervals as ment of C. difficile, and surgical evaluation should be or more months after having taken the last dose of the and children. Dissolve 500,000 Polymyxin B units in 2 response indicates. instituted as clinically indicated. antibiotic. If this occurs, patients should contact their mL Sterile Water for Injection or 0.9 % Sodium Chloride Subconjunctival injection of up to 100,000 units/ physician as soon as possible. Injection or Procaine Hydrochloride Injection 1%. day may be used for the treatment of Ps aeruginosa PRECAUTIONS Adults and children. 25,000 to 30,000 units/kg/ infections of the cornea and conjunctiva. ADVERSE REACTIONS General. Prescribing polymyxin B in the absence of a day. This should be reduced in the presence of renal Note: Avoid total systemic and ophthalmic instillation proven or strongly suspected bacterial infection or a See WARNING box. impairment. The dosage may be divided and given at over 25,000 units/kg/day. prophylactic indication is unlikely to provide benefit to Nephrotoxic reactions: Albuminuria, cylinduria, either 4 or 6 hour intervals. the patient and increases the risk of the development of azotemia, and rising blood levels without any increase Infants. Infants with normal kidney function may receive HOW SUPPLIED drug-resistant bacteria. in dosage. up to 40,000 units/kg/day without adverse effects. Each vial of Polymyxin B for Injection contains See WARNING box. Neurotoxic reactions: Facial flushing, dizziness Note: Doses as high as 45,000 units/kg/day have been polymyxin B sulfate equivalent to 500,000 polymyxin B Baseline renal function should be done prior to therapy, progressing to ataxia, drowsiness, peripheral used in limited clinical studies in treating prematures and units. It is supplied in rubber-stoppered glass vial with with frequent monitoring of renal function and blood paresthesias (circumoral and stocking glove), apnea newborn infants for sepsis caused by Ps aeruginosa. flip off cap, as a single-vial carton (NDC 70594-049- 01) and ten vials per carton (NDC 70594-049-02). levels of the drug during parenteral therapy. due to concurrent use of curariform muscle relaxants, Intrathecal. A treatment of choice for Ps aeruginosa Avoid concurrent use of a curariform muscle relaxant and other neurotoxic drugs or inadvertent overdosage, meningitis. and signs of meningeal irritation with intrathecal Storage recommendations: other neurotoxic drugs (ether, tubocurarine, succinyl- Dissolve 500,000 polymyxin B units in 10 mL 0.9 % choline, gallamine, decamethonium and sodium citrate) administration, e.g., fever, headache, stiff neck and Before reconstitution: Store at 20° to 25° C (68° to increased cell count and protein cerebrospinal fluid. Sodium Chloride Injection USP for 50,000 units per mL 77° F) (See USP controlled Room Temperature) which may precipitate respiratory depression. If signs dosage unit. of respiratory paralysis appear, respiration should be Other reactions occasionally reported: Drug fever, Protect from light. Retain in carton until time of use. Adults and children over 2 years of age. assisted as required, and the drug discontinued. urticarial rash, pain (severe) at intramuscular injection Dosage is 50,000 units once daily intrathecally for 3 to After reconstitution: Product must be stored under As with other antibiotics, use of this drug may result sites, and thrombophlebitis at intravenous injection refrigeration, between 2° to 8°C (36° to 46°F) and any sites. 4 days, then 50,000 units once every other day for at in overgrowth of nonsusceptible organisms, including least 2 weeks after cultures of the cerebrospinal fluid unused portion should be discarded after 72 hours. fungi. To report SUSPECTED ADVERSE REACTIONS, are negative and sugar content has returned to normal. Manufactured for: If superinfection occurs, appropriate therapy should be contact Xellia Pharmaceuticals USA, LLC at safety@ Children under 2 years of age. 20,000 units once Xellia Pharmaceuticals USA, LLC instituted xellia.com or 1-855-642-2594, or FDA at 1-800-FDA- 1088 or www.fda.gov/medwatch. daily, intrathecally for 3 to 4 days or 25,000 units once Raleigh, NC 27616 Information for Patients. Patients should be counseled every other day. Continue with a dose of 25,000 units that antibacterial drugs including polymyxin B should DOSAGE AND ADMINISTRATION once every other day for at least 2 weeks after cultures Made in India only be used to treat bacterial infections. They do not of the cerebrospinal fluid are negative and sugar treat viral infections (e.g., the common cold). When PARENTERAL: content has returned to normal. Revised: June 2018 Intravenous. Dissolve 500,000 polymyxin B units in LEA-019454-00 polymyxin B is prescribed to treat a bacterial infection, IN THE INTEREST OF SAFETY, SOLUTIONS OF 300 to 500 mL solutions for parenteral 5% Dextrose patients should be told that although it is common to PARENTERAL USE SHOULD BE STORED UNDER Code No: AP/DRUGS/103/97 Injection for continuous drip. feel better early in the course of therapy, the medication REFRIGERATION, AND ANY UNUSED PORTIONS should be taken exactly as directed. Adults and children. 15,000 to 25,000 units/kg body SHOULD BE DISCARDED AFTER 72 HOURS. Skipping doses or not completing the full course of weight/day in individuals with normal kidney function. TOPICAL: therapy may (1) decrease the effectiveness of the This amount should be reduced from 15,000 units/ immediate treatment and (2) increase the likelihood that kg downward for individuals with kidney impairment. Ophthalmic. Dissolve 500,000 polymyxin B units in 20 bacteria will develop resistance and will not be treatable Infusions may be given every 12 hours; however, the to 50 mL sterile water for injection or sodium chloride by polymyxin B or other antibacterial drugs in the future. total daily dose must not exceed 25,000 units/kg/day. injection USP for a 10,000 to 25,000 units per mL concentration. Diarrhea is a common problem caused by antibiotics Infants. Infants with normal kidney function may receive which usually ends when the antibiotic is discontinued. up to 40,000 units/kg/day without adverse effects. For the treatment of Ps aeruginosa infections of the Sometimes after starting treatment with antibiotics, eye, a concentration of 0.1 percent to 0.25 percent