Polymyxin B Sulfate

(rINNM)
Polymyxin B Sulfate Chemical formula
Synonyms: Polimiksin B Sülfat; Polimiksino B sulfatas; Polimixin-B-szulfát; Polimyksyny B siarczan; Polimyxini b sulfas; Polymyksiini-B-sulfaatti; Polymyxin B sulfat; Polymyxin B Sulphate sulfát; Polymyxine B, sulfate de; Polymyxini B sulfas; Polymyxinum B Sulfas; Sulfato de polimixina B.
Cyrillic synonym: Полимиксина B Сульфат.

💊 Chemical information

CAS — 1404-26-8 (polymyxin B); 1405-20-5 (polymyxin B sulfate); 4135-11-9 (polymyxin B1); 34503-87-2 (polymyxin B2); 71140-58-4 (polymyxin B3).
ATC — A07AA05; J01XB02; S01AA18; S02AA11; S03AA03.
ATC Vet — QA07AA05; QJ01XB02; QS01AA18; QS02AA11; QS03AA03.

Pharmacopoeias.

In Chin., Eur., Jpn, and US.

Ph. Eur. 6.2

(Polymyxin B Sulphate). A mixture of the sulfates of polypeptides produced by the growth of certain strains of Bacillus polymyxa or obtained by any other means. A white or almost white, hygroscopic powder. Soluble in water; slightly soluble in alcohol. A 2% solution in water has a pH of 5.0 to 7.0. Store in airtight containers. Protect from light.

USP 31

(Polymyxin B Sulfate). The sulfate salt of a kind of polymyxin, a substance produced by the growth of Bacillus polymyxa (Bacillaceae), or a mixture of two or more such salts. A white to buff-coloured, powder, odourless or has a faint odour. It has a potency of not less than 6000 Polymyxin B units/mg, calculated on the dried substance. Freely soluble in water; slightly soluble in alcohol. pH of a 0.5% solution in water is between 5.0 and 7.5. Store in airtight containers. Protect from light.

Incompatibility.

Incompatibility has been reported with many other drugs including antibacterials. Polymyxin B sulfate is rapidly inactivated by strong acids and alkalis.

💊 Units

The second International Standard Preparation (1969) of polymyxin B sulfate contains 8403 units/mg. NOTE. The available forms of polymyxin B sulfate are generally less pure than the International Standard Preparation. Doses have sometimes been stated in terms of pure polymyxin base; 100 mg of pure polymyxin B is considered to be equivalent to 1 million units (1 mega unit).

💊 Adverse Effects, Treatment, and Precautions

When given parenterally, the major adverse effects of the polymyxins are dose-related neurotoxicity and nephrotoxicity. Hypersensitivity reactions are rare, although rashes and fever have been reported, and polymyxins cause histamine release, which may lead to bronchoconstriction and other anaphylactoid symptoms. Polymyxins should be avoided in patients with a history of hypersensitivity to any of the group. Neurotoxic reactions can occur in up to 7% of patients with normal renal function and include peripheral effects such as circumoral and ‘stocking-glove’ pattern paraesthesias, visual disturbances, and dizziness, ataxia, confusion, drowsiness, and other CNS effects. The polymyxins are potent neuromuscular blockers, and respiratory paralysis and apnoea may result, especially in overdosage and in patients with renal impairment or pre-existing disorders of neuromuscular transmission such as myasthenia gravis, in whom particular care is needed; certain medications may also increase the risk (see Interactions, below). Neostigmine or calcium salts are usually of little value in reversing neuromuscular blockade and artificial ventilation may be required if it develops. Nephrotoxicity may occur in up to 20% of patients after parenteral use and may be marked by nitrogen retention, haematuria, proteinuria, and tubular necrosis. Electrolyte disturbances are common. Baseline renal function levels should be established before starting parenteral polymyxin B therapy and renal function and blood concentrations of polymyxins should be monitored frequently during therapy. Patients with pre-existing renal impairment and nitrogen retention are at particular risk and require dosage reduction. Signs of decreasing urine output and increasing nitrogen retention are an indication for stopping the drug in all patients. Although polymyxin B is said to be more nephrotoxic than colistin on a weight-for-weight basis, their effects on the kidney seem to be similar at therapeutically equivalent doses. Polymyxin B is irritant; pain after intramuscular injection may be severe and thrombophlebitis can occur after intravenous injection. Meningeal irritation, manifest as fever, headache, stiff neck, and increased cell count and protein levels in the CSF, may follow intrathecal doses. Ear drops containing polymyxins should not be used in patients with perforated ear drums, due to the increased risk of ototoxicity. Topical application to large areas of skin should be avoided because of the risk of systemic absorption resulting in neurotoxicity and nephrotoxicity, particularly in children, the elderly, and patients with renal impairment.

💊 Interactions

Polymyxins may enhance the action of neuromuscular blockers possibly resulting in respiratory depression and apnoea, and concurrent use should be avoided. Additive neurotoxicity and/or nephrotoxicity may occur if polymyxins are given with other potentially neurotoxic and/or nephrotoxic drugs including aminoglycosides and cefaloridine; concurrent use should also be avoided.

💊 Antimicrobial Action

Polymyxin B and the other polymyxin antibacterials act primarily by binding to membrane phospholipids and disrupting the bacterial cytoplasmic membrane. Polymyxin B has a bactericidal action on most Gramnegative bacilli except Proteus spp. It is particularly effective against Pseudomonas aeruginosa. Of the other Gram-negative organisms, Acinetobacter spp., Escherichia coli, Enterobacter and Klebsiella spp., Haemophilus influenzae, Bordetella pertussis, Salmonella, and Shigella spp. are sensitive. Classical Vibrio cholerae 01 is sensitive but the El Tor and O139 biotypes are resistant. Serratia, Burkholderia, and Providencia spp., and Bacteroides fragilis are usually resistant. It is not active against Neisseria spp., obligate anaerobes, and Gram-positive bacteria. Some fungi such as Coccidioides immitis are susceptible but most are resistant. Antimicrobial synergy has been reported with other drugs, including chloramphenicol, tetracyclines, and the sulfonamides and trimethoprim. The action of polymyxin B is reduced by divalent cations such as calcium and magnesium, and so activity in vivo is less marked than in vitro. Acquired resistance to polymyxin B is uncommon, although adaptive resistance may develop in enterobacteria exposed to sublethal concentrations. There is complete cross-resistance between polymyxin B and colistin.

💊 Pharmacokinetics

Polymyxin B sulfate is not absorbed from the gastrointestinal tract, except in infants who may absorb up to 10% of a dose. It is not absorbed through mucous membranes, or intact or denuded skin. Peak plasma concentrations after intramuscular injection usually occur within 2 hours, but are variable and polymyxin B sulfate is partially inactivated by serum. It is widely distributed and extensively bound to cell membranes in the tissues; it does not appear to be highly bound to serum proteins. Accumulation may occur after repeated doses. There is no diffusion into the CSF and it does not cross the placenta. Polymyxin B is reported to have a serum half-life of about 6 hours but this is prolonged in renal impairment; values of 2 to 3 days have been reported in patients with a creatinine clearance of less than 10 mL/minute. Polymyxin B sulfate is excreted mainly by the kidneys by glomerular filtration, about 60% of a dose being recovered unchanged in the urine, but there is a time lag of 12 to 24 hours before polymyxin B is recovered in the urine. Polymyxin B is not removed to an appreciable extent by peritoneal dialysis or haemodialysis.

💊 Uses and Administration

Polymyxin B sulfate is used topically, often with other drugs, in the treatment of skin, ear, and eye infections due to susceptible organisms. Eye drops containing polymyxin B with neomycin and gramicidin have been used for the prophylaxis of infection in patients undergoing ocular surgery and, with propamidine isetionate, for the treatment of acanthamoeba keratitis. Polymyxin B has been given orally with other drugs in regimens for selective digestive-tract decontamination (SDD) in patients at high risk of endogenous infections. Polymyxin B has also been used parenterally for the treatment of infections due to susceptible Gram-negative bacteria, especially Pseudomonas aeruginosa, but other drugs are generally preferred. Polymyxin B has been given intrathecally in meningeal infection, and by subconjunctival injection for eye infections. For topical application polymyxin B is usually available as a 0.1% solution or ointment (10 000 units per mL or per g respectively) combined with other drugs. Intravenous doses range from 15 000 to 25 000 units/kg daily, by infusion and may be given every 12 hours. The intramuscular route has also been used despite the severe pain which may be associated with it; doses range from 25 000 to 30 000 units/kg daily, and may be given every 4 or 6 hours. Doses should be reduced in patients with renal impairment (see below). Intrathecal doses of 50 000 units may be given once daily for 3 to 4 days, then on alternate days for at least 2 weeks after the CSF cultures become negative. For details of doses in children, including infants, see below. For subconjunctival injection, doses of up to 100 000 units daily may be used for infections of the cornea and conjunctiva.
1. Evans ME, et al. Polymyxin B sulfate and colistin: old antibiotics for emerging multiresistant Gram-negative bacteria. Ann Pharmacother 1999; 33: 960–7
2. Falagas ME, et al. The use of intravenous and aerosolized polymyxins for the treatment of infections in critically ill patients: a review of the recent literature. Clin Med Res 2006; 4: 138–46
3. Arnold TM, et al. Polymyxin antibiotics for gram-negative infections. Am J Health-Syst Pharm 2007; 64: 819–26
4. Zavascki AP, et al. Polymyxin B for the treatment of multidrugresistant pathogens: a critical review. J Antimicrob Chemother 2007; 60: 1206–15.

Administration in children.

Up to 40 000 units/kg daily of polymyxin sulfate may be given to infants with normal renal function by intravenous infusion or by intramuscular injection, although the latter is not recommended routinely because of severe pain at injection sites. Doses as high as 45 000 units/kg daily have been tried in premature and full-term neonates. For suggested doses in children with renal impairment see below. In children under 2 years of age, intrathecal doses of 20 000 units once daily for 3 to 4 days or 25 000 units on alternate days may be given, followed by the latter dose for at least 2 weeks after the CSF cultures become negative. Older children may be given the usual adult dose (see above).

Administration in renal impairment.

Parenteral doses of polymyxin sulfate should be reduced in adults and children with renal impairment; a maximum intravenous dose of 15 000 units/kg daily has been suggested.

💊 Preparations

BP 2008: Polymyxin and Bacitracin Eye Ointment; USP 31: Bacitracin and Polymyxin B Sulfate Topical Aerosol; Bacitracin Zinc and Polymyxin B Sulfate Ointment; Bacitracin Zinc and Polymyxin B Sulfate Ophthalmic Ointment; Chloramphenicol and Polymyxin B Sulfate Ophthalmic Ointment; Chloramphenicol, Polymyxin B Sulfate, and Hydrocortisone Acetate Ophthalmic Ointment; Neomycin and Polymyxin B Sulfates and Bacitracin Ointment; Neomycin and Polymyxin B Sulfates and Bacitracin Ophthalmic Ointment; Neomycin and Polymyxin B Sulfates and Bacitracin Zinc Ointment; Neomycin and Polymyxin B Sulfates and Bacitracin Zinc Ophthalmic Ointment; Neomycin and Polymyxin B Sulfates and Dexamethasone Ophthalmic Ointment; Neomycin and Polymyxin B Sulfates and Dexamethasone Ophthalmic Suspension; Neomycin and Polymyxin B Sulfates and Gramicidin Cream; Neomycin and Polymyxin B Sulfates and Gramicidin Ophthalmic Solution; Neomycin and Polymyxin B Sulfates and Hydrocortisone Acetate Cream; Neomycin and Polymyxin B Sulfates and Hydrocortisone Acetate Ophthalmic Suspension; Neomycin and Polymyxin B Sulfates and Hydrocortisone Ophthalmic Suspension; Neomycin and Polymyxin B Sulfates and Hydrocortisone Otic Solution; Neomycin and Polymyxin B Sulfates and Hydrocortisone Otic Suspension; Neomycin and Polymyxin B Sulfates and Lidocaine Cream; Neomycin and Polymyxin B Sulfates and Pramoxine Hydrochloride Cream; Neomycin and Polymyxin B Sulfates and Prednisolone Acetate Ophthalmic Suspension; Neomycin and Polymyxin B Sulfates Cream; Neomycin and Polymyxin B Sulfates Ophthalmic Ointment; Neomycin and Polymyxin B Sulfates Ophthalmic Solution; Neomycin and Polymyxin B Sulfates Solution for Irrigation; Neomycin and Polymyxin B Sulfates, Bacitracin Zinc, and Hydrocortisone Acetate Ophthalmic Ointment; Neomycin and Polymyxin B Sulfates, Bacitracin Zinc, and Hydrocortisone Ointment; Neomycin and Polymyxin B Sulfates, Bacitracin Zinc, and Hydrocortisone Ophthalmic Ointment; Neomycin and Polymyxin B Sulfates, Bacitracin Zinc, and Lidocaine Ointment; Neomycin and Polymyxin B Sulfates, Bacitracin, and Hydrocortisone Acetate Ointment; Neomycin and Polymyxin B Sulfates, Bacitracin, and Hydrocortisone Acetate Ophthalmic Ointment; Neomycin and Polymyxin B Sulfates, Bacitracin, and Lidocaine Ointment; Neomycin and Polymyxin B Sulfates, Gramicidin, and Hydrocortisone Acetate Cream; Oxytetracycline Hydrochloride and Polymyxin B Sulfate Ointment; Oxytetracycline Hydrochloride and Polymyxin B Sulfate Ophthalmic Ointment; Oxytetracycline Hydrochloride and Polymyxin B Sulfate Topical Powder; Oxytetracycline Hydrochloride and Polymyxin B Sulfate Vaginal Tablets; Polymyxin B for Injection; Polymyxin B Sulfate and Bacitracin Zinc Topical Aerosol; Polymyxin B Sulfate and Bacitracin Zinc Topical Powder; Polymyxin B Sulfate and Hydrocortisone Otic Solution; Polymyxin B Sulfate and Trimethoprim Ophthalmic Solution.

Proprietary Preparations

Braz.: Polixil B†; Philipp.: Aerosporin; Port.: Oto-Synalar N. Multi-ingredient: Arg.: Belbar; Ginal Cent; Ginkan; Irix Biotic; Isoptomax; Linfol Cicatrizante; Mailen; Min O; Nebapol B†; Neoftalm; Neoftalm Dexa; Neolag; O-Biol P; Otosporin; Otosporin L; Ovumix; Pantometil; Pentol; Poenbioptal NF; Polygynax; Polyplex; Septigyn; Sincerum Biotic L; Terramicina con Polimixina B†; Trimepol; Trimepol D; Vagicural Plus; Austral.: Neosporin; Austria: Neocones; Otosporin; Polytrim; Belg.: De Icin†; DexaPolyspectran New; Maxitrol; Ophtalmotrim†; Otosporin†; Panotile; Polydexa; Polygynax†; Polyspectran Gramicidine; Polytrim; Predmycin P; Statrol; Synalar Bi-Otic; Terra-Cortril + Polymyxine B; Terramycine + Polymyxine B; Braz.: Anaseptil; Colpolase; Elotin; Ginec†; Lidosporin; Maxitrol; Nepodex; Otauril†; Otocort†; Otomixyn; Otosporin; Otosynalar; Panotil; Poliginax; Polipred; Polysporin; Predmicin; Terramicina c/Polimixina; Canad.: Antibiotic Cold Sore Ointment; Antibiotic Cream†; Antibiotique Onguent; Bacimyxin; Band-Aid Antibiotic; Bioderm; Cortimyxin; Cortisporin; Dioptrol†; Johnson & Johnson First Aid Ointment†; Lidomyxin; Lidosporin; Maxitrol; Neosporin; Neotopic†; Optimyxin; Optimyxin Plus; Ozonol Antibiotic Plus; PMS-Polytrimethoprim; Polycidin†; Polyderm; Polysporin; Polysporin Complete Antibiotic; Polysporin For Kids; Polysporin Plus Pain Relief; Polysporin Triple Antibiotic; Polytopic; Polytrim; Chile: Dermabiotico; Gotalgic; Grifoftal-D; Grifoftal†; Maxitrol; Oftabiotico; Otazol†; Oticum; Otolisan; Otoseptil; Unguento Dermico Antibiotico†; Cz.: Maxitrol; Otosporin; Polygynax; Pulpomixine; Statrol†; Denm.: Hydrocortison med Terramycin og Polymyxin-B; Terramycin Polymyxin B; Fin.: Maxitrol; Polysporin; Terra-Cortril P; Fr.: Antibio-Synalar; Antibiotulle Lumiere; Atebemyxine; Auricularum; Cebemyxine; Corticotulle Lumiere†; Framyxone; Maxidrol; Novomyxine†; Panotile; Polydexa; Polyfra; Polygynax; Polygynax Virgo; Primyxine†; Sterimycine†; Ger.: Antibiotulle Lumiere†; Corticotulle Lumiere†; Dexa Polyspectran; Farco-Tril†; Isopto Max; Kombi-Stulln N; Panotile N†; Polygynax†; Polyspectran; Polyspectran HC; Terracortril†; Terramycin†; Gr.: Fotocollyre; Isopto Maxitrol; Oxacycle-P; Paroticin; Statrol†; Terramycin; Hong Kong: Aplosyn-Otic; Cebemyxine; Maxitrol; Neosporin; Otosporin; Otozambon; PMS-Baximycin†; Polydex-N; Polydexa; Polyfax†; Polygynax; Polyoph; Terramycin with Polymyxin B; Hung.: Oftalmotrim†; Otosporin; Polyspor; India: Chlormixin; Dexosyn Plus; Neosporin; Neosporin-H; Ocupol; Ocupol-D; Indon.: Inmatrol; Isotic Enpigi; Isotic Neolyson; Isotic Nepafrin; Kenetrol; Kloramixin; Kloramixin D; Maxitrol; Nelicort; Neocortic; Neofen; Neosyd; Oregan; Osatrol; Otolin; Otopain; Otopraf; Otozambon; Polidemisin; Polifrisin; Terramycin Poly; Ximex Optixitrol; Irl.: Maxitrol; Neosporin†; Otosporin; Polyfax; Israel: Auricularum; Bamyxin; Desoren; Dex-Otic; Maxitrol; Phenimixin; Tarocidin; Tarocidin D; Terramycin; Ital.: Anauran; Cicatrene; Mixotone; Otosporin†; Rinojet SF†; Malaysia: Bacitracin-N; Maxitrol; Oftalmotrim; Pocin G; Pocin H; Terramycin; Mex.: Alosol; Biodexan; Biofrin; Biotriamin; Cortisporin; Dexsul; Hidropolicin; Maxitrol; Neobacigrin; Neosporin; Nicobio†; Polixin; Poly-Micron; Rinadex Compuesto; Septilisin; Sulned; Synalar N; Synalar O; Synalar Oftalmico; Terramicina; Tribiot; Neth.: Maxitrol; Otosporin; Panotile; Polyspectran G†; Polytrim; Synalar Bi-Otic†; Terra-Cortril Gel Steraject met polymyxine-B†; Terra-Cortril met polymyxine-B; Norw.: Maxitrol; Terra-Cortril Polymyxin B; Terramycin Polymyxin B; NZ: Maxitrol; Philipp.: Aplosyn-Otic; BNP Ointment; Cortisporin; Hydrospor; Isonep; Isonep H; Maxirap; Maxitrol; Maxoptic; Neosporin; Novasorin; Postop; Postotic; Predmycin-P; Statrol; Synalar Otic; Syntemax; Terramycin; Terramycin Plus; Trimycin; Trimyci n-H; Pol.: Atecortin; Dexadent; Maxitrol; Multibiotic; Neotopic; Tribiotic; Port.: Conjunctilone; Conjunctilone-S; Oftalmotrim; Otosporin; Polisulfade; Polydexa; Rus.: Anauran (Анауран); Maxitrol (Макситрол); Polydexa (Полидекса); Polydexa with Phenylephrine (Полидекса С Фенилефрином); Polygynax (Полижинакс); S.Afr.: Maxitrol; Neosporin†; Otosporin; Polysporin; Polytrim†; Terra-Cortril; Terramycin; Singapore: Maxitrol; Polybamycin; Polydexa; Polygynax; Predmycin-P†; Terramycin; Spain: Bacisporin; Blastoestimulina; Creanolona; Dermisone Tri Antibiotic; Liquipom Dexa Antib; Maxitrol; Neocones; Oftalmotrim; Oftalmotrim Dexa†; Oftalmowell; Otix; Otosporin; Panotile; Phonal; Poly Pred; Pomada Antibiotica; Synalar Nasal; Synalar Otico; Terra-Cortril; Terramicina; Tivitis; Tulgrasum Antibiotico; Vinciseptil Otico; Swed.: Isopto Biotic†; Terracortril med polymyxin B; Terramycin Polymyxin B; Switz.: Baneopol; Maxitrol; Mycinopred; Neosporin; Otosporin; Panotile; Polydexa; Spersapolymyxin; Terracortril†; Thai.: Banocin; Maxitrol; My-B; Neosporin†; Opsacin†; Otosamthong; Otosporin†; Polyoph; Predmycin†; Primoptic†; Spersapolymyxin; Terramycin; Terrasil†; Xanalin; Turk.: Cebemyxine; Geotril; Heksa; Neosporin; Oftalmotrim; Polimisin; Polycilline; Polytrim; Sekamisin; Terramycin; UK: Gregoderm†; Maxitrol; Neosporin; Otosporin; Polyfax; Polytrim†; USA: Ak-Poly-Bac; Ak-Spore; Ak-Trol†; Betadine First Aid Antibiotics + Moisturizer; Betadine Plus First Aid Antibiotics & Pain Reliever; Cortatrigen; Cortimycin; Cortisporin; Dexacidin†; Dexacine†; Dexasporin; Ear-Eze; Lanabiotic†; LazerSporin-C; Maxitrol; Mycitracin†; Neocin; Neopolydex; Neosporin; Neosporin + Pain Relief; Neosporin GU; Neosporin†; Neotricin HC; Octicair†; Ocu-Spor-B; Ocu-Spor-G; Ocu-Trol; Ocutricin; OticCare; OtiTricin; Otobiotic; Otocort; Otomycin-HPN; Otosporin; Pediotic; Poly-Dex; Poly-Pred; Polycin-B; Polymycin; Polysporin†; Polytracin; Polytrim; Spectrocin Plus†; Terak; Terramycin with Polymyxin B; Tri-Biozene; UADOtic; Venez.: Dermabiotic; Maxicort; Maxitrol; Neo-Synalar†; Ofterra; Otocort; Poli-Otico; Terramicina con Polimixina B.
Published May 08, 2019.