Polymyxin B for Injection is one of a group of basic polypeptide antibiotics derived from B polymyxa (B aerosporous). Polymyxin B sulfate is the sulfate salt of Polymyxins B₁ and B₂, 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 forInjection 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.

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, POLYMYX-IN 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 dextrose injection 5% 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 Ps aeruginosa.

Intrathecal: A treatment of choice for Ps aeruginosameningitis. 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.

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.

Polymyxin B for Injection, 500,000 polymyxin B units per vial is supplied in rubber-stoppered glass vial with flip off cap, carton of 10, NDC 55390-139-10.

Storage recommendations

Before reconstitution: Store at controlled room temperature 15° to 30°C (59° to 86°F).

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.

Manufactured for: Bedford Laboratories™, Bedford, OH 44146. Manufactured by: Ben Venue Laboratories, Inc., Bedford, OH 44146. February 2004. FDA Rev date: 5/15/2002

See WARNING box.

Nephrotoxic reactions: Albuminuria, cylin-duria, 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.

No information provided.

No information provided.

General. Prescribing polymyxin B 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.

See WARNING box.

Baseline renal function should be done prior to therapy, with frequent monitoring of renal function and blood levels of the drug during parenteral therapy.

Avoid concurrent use of a curariform muscle relaxant and other neurotoxic drugs (ether, tubocurarine, succinylcholine, gallamine, decamethonium and sodium citrate) which may precipitate respiratory depression. If signs of respiratory paralysis appear, respiration should be assisted as required, and the drug discontinued.

As with other antibiotics, use of this drug may result in overgrowth of nonsusceptible organisms, including fungi.

If superinfection occurs, appropriate therapy should be instituted.

No information provided.

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

Polymyxin B sulfate has a bactericidal action against almost all gram-negative bacilli except the Proteus group. Polymyxins increase the permeability of bacterial cell wall membranes. All gram-positive bacteria, fungi, and the gram-negative cocci, N gonorrhoeae and N meningitidis, are resistant.

Susceptibility plate testing: If the Kirby-Bauer method of disc susceptibility testing is used, a 300-unit polymyxin B disc should give a zone of over 11 mm when tested against a polymyxin B susceptible bacterial strain.

Polymyxin B sulfate is not absorbed from the normal alimentary tract.Since the drug loses 50 percent of its activity in the presence of serum, active blood levels are low. Repeated injections may give a cumulative effect. Levels tend to be higher in infants and children.The drug is excreted slowly by the kidneys.Tissue diffusion is poor and the drug does not pass the blood brain barrier into the cerebrospinal fluid. In therapeutic dosage, polymyxin B sulfate causes some nephrotoxicity with tubule damage to a slight degree.

Patients should be counseled that antibacterial drugs including polymyxin B should only be used to treat bacterial infections.They do not treat viral infections (e.g., the common cold).When polymyxin B is prescribed to treat a bacterial infection, patients should be told that although it is common to feel better early in the course of therapy, the medication should be taken exactly as directed.Skipping doses or not completing the full course of therapy may (1) decrease the effectiveness of the immediate treatment and (2) increase the likelihood that bacteria will develop resistance and will not be treatable by polymyxin B or other antibacterial drugs in the future.

IMPORTANT NOTE: This is a summary and does not contain all possible information about this product. For complete information about this product or your specific health needs, ask your health care professional. Always seek the advice of your health care professional if you have any questions about this product or your medical condition. This information is not intended as individual medical advice and does not substitute for the knowledge and judgment of your health care professional. This information does not contain any assurances that this product is safe, effective, or appropriate for you.

POLYMYXIN B SULFATE - INJECTION

(paw-lee-MIX-in B SUL-fate)

COMMON BRAND NAME(S): Polymyxin B Sulfate

WARNING: This medication can cause serious kidney problems and nerve damage. It is usually given only in the hospital where you can be monitored closely for problems. The risk is increased if you already have kidney disease or are receiving other drugs that can harm the kidneys or nerves (e.g., cisplatin, colistin, high-dose aspirin, aminoglycosides such as amikacin, gentamicin, tobramycin, nonsteroidal anti-inflammatory drugs-NSAIDs such as ibuprofen or naproxen). Before starting polymyxin, tell your doctor if you already have kidney problems.

Tell your doctor immediately if you notice an unusual decrease in the amount of urine, mental/mood changes (such as confusion, drowsiness, or irritability), numbness/tingling (especially around the lips), difficulty walking, unsteadiness, blurred vision, or weakness. To reduce the risk of these side effects, your doctor will monitor your progress and may test your kidneys.

USES: Polymyxin B is an antibiotic used to treat certain bacterial infections (e.g., urinary tract infections, meningitis, blood infections, eye infections). It works by killing the bacteria that cause the infection.

This antibiotic treats only bacterial infections. It will not work for viral infections (e.g., common cold, flu). Unnecessary use or misuse of any antibiotic can lead to its decreased effectiveness.

HOW TO USE: This medication is given by a health care professional. It may be injected into a vein, muscle, or the spinal fluid or into the area around the eye (subconjunctival sac). It can also be prepared as eye drops. Injection into the muscle is not recommended because doing so can cause severe pain at the injection site. Health care professionals must follow all the manufacturer's instructions for properly mixing and giving this drug. Before using, check this product visually for particles or discoloration. If either is present, do not use the liquid. If you have any questions about using this medication properly, consult your doctor or pharmacist.

The dosage, how the drug is given, and length of treatment depends on your medical condition and response to treatment.

Continue to use this medication until you have received the full amount prescribed, even if symptoms disappear after a few days. Stopping the medication too early may allow bacteria to continue to grow, which may result in a return of the infection.

Tell your doctor if your condition persists or worsens.

SIDE EFFECTS: See also Warning section.

Pain, redness, and swelling at the injection site may occur. If any of these effects persist or worsen, tell your doctor or pharmacist promptly.

Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

Tell your doctor immediately if any of these rare but very serious side effects occur: slow/shallow breathing, facial flushing, dizziness, unexplained fever, muscle weakness, severe headache, stiff neck, seizures, vision changes, change in the amount of urine, red/pink urine.

Use of this medication for prolonged or repeated periods may result in a new bacterial or fungal infection (opportunistic infection). Tell your doctor if you notice any symptoms of a new infection (e.g., white patches in your mouth, a change in vaginal discharge).

A very serious allergic reaction to this drug is rare. However, seek immediate medical attention if you notice any symptoms of a serious allergic reaction, including: rash, itching, swelling, severe dizziness, trouble breathing.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

Contact your doctor for medical advice about side effects. The following numbers do not provide medical advice, but in the US you may report side effects to the Food and Drug Administration (FDA) at 1-800-FDA-1088. In Canada, you may call Health Canada at 1-866-234-2345.

PRECAUTIONS: Before using polymyxin B, tell your doctor or pharmacist if you are allergic to it; or to similar drugs such as colistin; or if you have any other allergies.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: disease of the nerves/muscles (e.g., myasthenia gravis), kidney disease.

Before having surgery, tell your doctor or dentist that you are using this medication.

During pregnancy, this medication should be used only when clearly needed. Discuss the risks and benefits with your doctor.

It is not known if this drug passes into breast milk. Consult your doctor before breast-feeding.

DRUG INTERACTIONS: Your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor or pharmacist first.

Before using this medication, tell your doctor or pharmacist of all prescription and nonprescription/herbal products you may use, especially of: aminoglycoside antibiotics (e.g., gentamicin, tobramycin, paromomycin), anesthesia drugs or muscle relaxants (e.g., tubocurarine, succinylcholine, gallamine, decamethonium), live vaccines (e.g., flu vaccine inhaled through the nose, polio vaccine taken by mouth), sodium citrate, quinine/quinidine, colistin, bacitracin.

This document does not contain all possible interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you, and share the list with your doctor and pharmacist.

OVERDOSE: If overdose is suspected, contact your local poison control center or emergency room immediately. US residents can call the US National Poison Hotline at 1-800-222-1222. Canada residents can call a provincial poison control center. Symptoms of overdose may include: extreme drowsiness, slow/shallow breathing, seizures.

NOTES: Laboratory and/or medical tests (e.g., kidney function tests, drug levels) should be performed periodically to monitor your progress or check for side effects. Consult your doctor for more details.

MISSED DOSE: If you miss a dose or your dose is interrupted, contact your doctor or pharmacist promptly to establish a new dosing schedule.

STORAGE: Store unmixed vials in original packaging at room temperature between 59-86 degrees F (15-30 degrees C) away from light and moisture. Do not store in the bathroom. Keep all medicines away from children and pets.

After mixing, store the medication in the refrigerator between 36-46 degrees F (2-8 degrees C). Discard any unused liquid after 72 hours.

Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company for more details about how to safely discard this product.

Information last revised July 2008 Copyright(c) 2008 First DataBank, Inc.