Poliz-B Special Precautions

General: The intravenous administration of polymyxin B for injection should be restricted to hospitalized patients so as to provide constant clinical supervision. The dose greater than the recommendation (see Dosage & Administration) should be avoided in the absence of therapeutic drug monitoring (TDM).
Polymyxin B for injection should be used with extreme caution in patients with porphyria.
Polymyxin B for injection is not active and therefore should not be used for the treatment of bacterial infections caused by gram negative bacteria (Proteus spp., Providencia spp., Morganella spp., Serratia marcescens, Burkholderia spp , Neisseria spp.), all gram-positive bacteria and anaerobes. It is critical that adjunct therapy be initiated immediately if a concomitant bacterial pathogen is documented or suspected (see Indications/Uses and Pharmacology: Pharmacodynamics under Actions).
Cardiovascular: QT Interval Prolongation: The effect of polymyxin B for injection on prolonged cardiac repolarization, QT interval, and increased risk of developing cardiac arrhythmia and torsades de pointes is not known.
Gastrointestinal: Clostridium difficile-associated disease: Clostridium difficile-associated disease CDAD has been reported with the use of many antibacterial agents, including polymyxin B sulphate. CDAD may range in severity from mild diarrhea to fatal colitis. It is important to consider this diagnosis in patients who present with diarrhea, symptoms of colitis, pseudomembranous colitis, toxic megacolon, or perforation of colon subsequent to the administration of any antibacterial agent CDAD has been reported to occur over 2 months after the administration of antibacterial agents.
Treatment with antibacterial agents may alter the normal flora of the colon and may permit overgrowth of Clostridium difficile. C. difficile produces toxins A and B, which contribute to the development of CDAD. CDAD may cause significant morbidity and mortality. CDAD can be refractory to antimicrobial therapy. If the diagnosis of CDAD is suspected or confirmed, appropriate therapeutic measures should be initiated. Mild cases of CDAD usually respond to discontinuation of antibacterial agents not directed against C. difficile. In moderate to severe cases, consideration should be given to management with fluids and electrolytes, protein supplementation, and treatment with an antibacterial agent clinically effective against C. difficile. Surgical evaluation should be instituted as clinically indicated; as surgical intervention may be required in certain severe cases (see Adverse Reactions).
Immune: Hypersensitivity reactions: Serious hypersensitivity reactions including apnea and bronchoconstriction have been reported in patients receiving polymyxin B sulphate by inhalation administration. Anaphylactoid reactions have been reported with parenteral administration of polymyxin B for injection. Patients with a known allergy to bacitracin are at higher risk of developing hypersensitivity reactions with the use of polymyxins as cross-reactivity between bacitracin and polymyxins exists.
Before therapy with polymyxin B for injection is instituted, careful inquiry should be made to determine whether the patient has had a previous hypersensitivity reaction to polymyxins or bacitracin. Polymyxin B for injection should not be administered by inhalation. If an allergic reaction occurs, discontinue the drug. Serious acute hypersensitivity (anaphylaxis or air way constriction) requires emergency treatment as clinically indicated (see Neurologic as follows and Adverse Reactions).
Neurologic: Neurological disturbances including neuromuscular blockade (generalized muscle weakness, respiratory depression or arrest), seizure, circumoral paresthesia or numbness, vertigo, blurred vision, facial flushing, and slurring of speech, have been reported with polymyxin B for injection at therapeutic doses. These usually occur with high serum drug concentrations found in patients with renal impairment, drug nephrotoxicity or with inhalation of polymyxin B sulphate.
Mild neurological manifestations of polymyxins usually subside after prompt cessation of polymyxin B for injection therapy. If signs of respiratory paralysis appear, discontinue use of polymyxin B for injection and other neurotoxic agents immediately. Apnea should be treated with assisted respiration. Avoid concurrent use of nephrotoxic and/or neuromuscular blocking curariform muscle relaxants and other potential neurotoxic drugs, which may precipitate respiratory depression (see Renal as follows, Adverse Reactions, and Interactions).
Renal: Polymyxins induce nephrotoxicity by increasing membrane permeability. Rising blood concentrations of polymyxin B, albuminuria, cellular casts, diminishing urine output and rising blood urea nitrogen (BUN) have been reported with the use of polymyxin B for injection at therapeutic doses. Acute renal failure has been reported in patients on polymyxin B for injection therapy. Nephrotoxicity is dose dependent.
Baseline renal function should be assessed prior to and regularly during therapy. In case acute kidney injury (AKI) develops, therapy with polymyxin B for injection should be discontinued immediately if infection diagnosis is uncertain or when an alternative less nephrotoxic drug is available. If AKI develops when polymyxin B is being administered for life-threatening infection or when the infecting pathogen has an MIC higher than 1 mg/L, the polymyxin B dose should not be decreased outside the recommended dose. The nephrotoxic effect is usually reversible upon discontinuation of therapy.
The concurrent use of other nephrotoxic drugs including antimicrobials (particularly bacitracin, aminoglycosides, cephaloridine, cephalothin, amphotericin B, paromomycin, polymyxin E (colistin) and vancomycin) should be avoided (see Interactions).
Respiratory: Significant deterioration of lung function including apnea, bronchospasm, decreases in vital capacity, forced expiratory volume over one second and maximum voluntary ventilation have been reported following aerosol administration of polymyxin B sulphate. Polymyxin B for injection should not be administered by inhalation (see Adverse Reactions).
Monitoring and Laboratory Tests: Renal: Consideration should be given to monitoring renal function (albuminuria, cellular casts, BUN, serum creatinine or creatinine clearance) prior to and regularly during polymyxin B for injection treatment.
Neurologic: Patients should be monitored for neurologic signs and symptoms (e.g., apnea, numbness, vertigo, blurred vision, facial flushing and slurring of speech) during polymyxin B for injection therapy.
Drug-Lab Interactions: Consideration should be given to monitoring electrolyte abnormalities such as hypokalemia, hyponatremia, hypochloremia.
Effects on ability to drive and use machines: No studies on the effects on ability to drive and use machines have been performed.
Use in Pregnancy & Lactation: See Use in Pregnancy & Lactation section for further information.
Use in the Elderly (≥65 years of age): Limited data is available on the safety and efficacy of polymyxin B sulphate in the elderly. The renal function should be assessed prior to and regularly during therapy.