Drug reference
The polymyxin antibiotic, colistimethate sodium (colistin sulfomethate sodium), is active against Gram-negative organisms including Pseudomonas aeruginosa, Acinetobacter baumanii, and Klebsiella pneumoniae. It is not absorbed by mouth and thus needs to be given by injection for a systemic effect.
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Serious infections due to selected aerobic Gram-negative bacteria in patients with limited treatment options ▶BY INTRAVENOUS INFUSION ▶Adult: 9 million units daily in 2–3 divided doses, an initial loading dose of 9 million units should be used in those who are critically ill, loading and maintenance doses of up to 12 million units may be required in some cases, however clinical experience is limited and safety has not been established—consult product literature for details Management of chronic pulmonary infections due to Pseudomonas aeruginosa in patients with cystic fibrosis ▶BY INHALATION OF NEBULISED SOLUTION ▶Child 2–17 years: 1–2 million units 2–3 times a day, for specific advice on administration using nebulisers— consult product literature; maximum 6 million units per day ▶Adult: 1–2 million units 2–3 times a day, for specific advice on administration using nebulisers—consult product literature; maximum 6 million units per day ▶BY INHALATION OF POWDER ▶Adult: 1.66 million units twice daily
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Myasthenia gravis History of tendon disorders related to quinolone use
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▶When used by inhalation Severe haemoptysis—risk of further haemorrhage Can prolong the QT interval. children or adolescents (arthropathy has developed in weight-bearing joints in young animals). conditions that predispose to seizures. diabetes (may affect blood glucose). exposure to excessive sunlight and UV radiation should be avoided during treatment and for 48 hours after stopping treatment. G6PD deficiency. history of epilepsy. myasthenia gravis (risk of exacerbation). psychiatric disorders CAUTIONS, FURTHER INFORMATION ▶Use in children Quinolones cause arthropathy in the weight-bearing joints of immature animals and are therefore generally not recommended in children and growing adolescents. However, the significance of this effect in humans is uncertain and in some specific circumstances use of ciprofloxacin may be justified in children.
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Colistimethate sodium is included in some preparations for topical application.
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NICE decisions ▶Colistimethate sodium and tobramycin dry powders for inhalation for treating pseudomonas lung infection in cystic fibrosis (March 2013) NICE TA276 Colistimethate sodium dry powder for inhalation is recommended for chronic pulmonary infection caused by Pseudomonas aeruginosa in patients with cystic fibrosis who would benefit from continued treatment, but do not tolerate the drug in its nebulised form. The manufacturer must provide colistimethate sodium dry powder for inhalation at the discount agreed as part of the patient access scheme to primary, secondary and tertiary care in the NHS. Patients currently receiving colistimethate sodium dry powder for inhalation can continue treatment until they and their NHS clinician consider it appropriate to stop. www.nice.org.uk/guidance/ta276
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Use of quinolones contra-indicated in quinolone hypersensitivity.
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→Appendix 1: colistimethate
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▶Common or very common ▶When used by inhalation Arthralgia. asthenia. asthma. balance impaired. chest discomfort. cough. dysphonia. dyspnoea. fever. haemorrhage. headache. lower respiratory tract infection. nausea. respiratory disorders. taste altered. throat complaints. tinnitus. vomiting ▶Uncommon ▶When used by inhalation Anxiety. appetite decreased. diarrhoea. drowsiness. ear congestion. flatulence. oral disorders. proteinuria. seizure. sputum purulent. thirst. weight change ▶Rare or very rare ▶With parenteral use Confusion. nephrotoxicity. presyncope . psychosis. speech slurred. visual impairment ▶Frequency not known ▶With parenteral use Apnoea. neurological effects. neurotoxicity. renal disorder. sensory disorder SIDE-EFFECTS, FURTHER INFORMATION Neurotoxicity and nephrotoxicity are dose-related. ▶Common or very common Appetite decreased. arthralgia. asthenia. constipation (in adults). diarrhoea. dizziness. dyspnoea. eye discomfort. eye disorders. fever. gastrointestinal discomfort. headache. muscle complaints . nausea. QT interval prolongation. skin reactions. sleep disorders. taste altered. tinnitus. vision disorders. vomiting ▶Uncommon Anaemia. antibiotic associated colitis. anxiety . arrhythmias. asthma. chest pain. confusion. cough (in adults). depression. drowsiness. dry eye. eosinophilia. eye inflammation. flatulence. hallucination. hearing impairment. hepatic disorders. hyperhidrosis. hypersensitivity. hypotension. increased risk of infection. leucopenia. movement disorders. neutropenia. oedema. pain. palpitations. renal impairment. respiratory disorders. seizure. sensation abnormal. smell altered (in adults). tendon disorders. thrombocytopenia. thrombocytosis. tremor. vasodilation. vertigo ▶Rare or very rare Agranulocytosis. angioedema. arthritis. cardiac arrest (in adults). gait abnormal. haemolytic anaemia. hyperglycaemia. hypoglycaemia. idiopathic intracranial hypertension. muscle weakness. myasthenia gravis aggravated. nephritis tubulointerstitial. pancreatitis. pancytopenia. peripheral neuropathy (sometimes irreversible). photosensitivity reaction. polyneuropathy. psychotic disorder. self-injurious behaviour. severe cutaneous adverse reactions (SCARs). stomatitis (in adults). suicidal tendencies. syncope. vasculitis ▶Frequency not known Corneal deposits (reversible after completion of treatment). hypoglycaemic coma. increased risk of aortic aneurysm (more common in elderly). increased risk of aortic dissection (more common in elderly). ligament rupture. rhabdomyolysis (in adults) SIDE-EFFECTS, FURTHER INFORMATION The drug should be discontinued if neurological, psychiatric, tendon disorders or hypersensitivity reactions (including severe rash) occur. For more information regarding the safety of fluoroquinolones, please see Important Safety Information.
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▶When used by inhalation Clinical use suggests probably safe. ▶With intravenous use Manufacturer advises use only if potential benefit outweighs risk. Avoid in pregnancy—shown to cause arthropathy in animal studies; safer alternatives are available.
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Present in milk but poorly absorbed from gut; manufacturers advise avoid (or use only if potential benefit outweighs risk).
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▶With intravenous use Manufacturer advises caution (no information available).
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▶When used by inhalation Manufacturer advises caution. Dose adjustments ▶With intravenous use in adults Manufacturer advises reduce maintenance dose if creatinine clearance less than 50 mL/minute—consult product literature. Monitoring ▶With intravenous use In renal impairment, monitor plasma colistimethate sodium concentration during parenteral treatment—consult product literature. Recommended ‘peak’ plasma colistimethate sodium concentration (approx. 1 hour after intravenous injection or infusion) 5–15 mg/litre; pre-dose (‘trough’) concentration 2–6 mg/litre.
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▶With intravenous use Monitor renal function. ▶When used by inhalation Measure lung function before and after initial dose of colistimethate sodium and monitor for bronchospasm; if bronchospasm occurs in a patient not using a bronchodilator, repeat test using a bronchodilator before the dose of colistimethate sodium.
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The CSM has warned that quinolones may induce convulsions in patients with or without a history of convulsions; taking NSAIDs at the same time may also induce them. TENDON DAMAGE Tendon damage (including rupture) has been reported rarely in patients receiving quinolones. Tendon rupture may occur within 48 hours of starting treatment; cases have also been reported several months after stopping a quinolone. Healthcare professionals are reminded that: . quinolones are contra-indicated in patients with a history of tendon disorders related to quinolone use; . patients over 60 years of age are more prone to tendon damage; . the risk of tendon damage is increased by the concomitant use of corticosteroids; . if tendinitis is suspected, the quinolone should be discontinued immediately. MHRA/CHM ADVICE: SYSTEMIC AND INHALED FLUOROQUINOLONES: SMALL INCREASED RISK OF AORTIC ANEURYSM AND DISSECTION; ADVICE FOR PRESCRIBING IN HIGH- RISK PATIENTS (NOVEMBER 2018) The MHRA advises that benefit-risk should be assessed and other therapeutic options considered before using fluoroquinolones in patients at risk of aortic aneurysm and dissection. Patients (particularly the elderly and those at risk) and their carers should be informed about Infection rare events of aortic aneurysm and dissection, and advised to seek immediate medical attention if sudden- onset severe abdominal, chest, or back pain develops. MHRA/CHM ADVICE: FLUOROQUINOLONE ANTIBIOTICS: NEW RESTRICTIONS AND PRECAUTIONS FOR USE DUE TO VERY RARE REPORTS OF DISABLING AND POTENTIALLY LONG-LASTING OR IRREVERSIBLE SIDE EFFECTS (MARCH 2019) Disabling, long-lasting or potentially irreversible adverse reactions affecting musculoskeletal and nervous systems have been reported very rarely with fluoroquinolone antibiotics. Healthcare professionals are advised to inform patients to stop treatment at the first signs of a serious adverse reaction, such as tendinitis or tendon rupture, muscle pain, muscle weakness, joint pain, joint swelling, peripheral neuropathy, and CNS effects, and to contact their doctor immediately. Fluoroquinolones should not be prescribed for non-severe or self-limiting infections, or non-bacterial conditions. Unless other commonly recommended antibiotics are inappropriate, fluoroquinolones should not be prescribed for some mild to moderate infections, such as acute exacerbation of chronic bronchitis and chronic obstructive pulmonary disease, and ciprofloxacin or levofloxacin should not be prescribed for uncomplicated cystitis. Fluoroquinolones should be avoided in patients who have previously had serious adverse reactions. Use of fluoroquinolones with corticosteroids should also be avoided as it may exacerbate fluoroquinolone-induced tendinitis and tendon rupture. Fluoroquinolones should be prescribed with caution in patients older than 60 years and in patients with renal impairment or solid-organ transplants as they are at a higher risk of tendon injury.
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▶When used by inhalation Manufacturer advises if other treatments are being administered, they should be taken in the order recommended by the physician. For nebulisation, consult product literature for information on reconstitution and dilution. ▶With intravenous use in adults For intravenous infusion, manufacturer advises following reconstitution, dilute requisite dose, usually with 50 mL Sodium Chloride 0.9%; give over 30–60 minutes. Patients fitted with a totally implantable venous access device may tolerate an injection. For slow intravenous injection into a totally implantable venous access device, dilute to a concentration of 200 000 units/mL with Sodium Chloride 0.9%; give over at least 5 minutes.
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There can be variation in the licensing of different medicines containing the same drug. Powder for solution for injection ELECTROLYTES: May contain Sodium ▶Colistimethate sodium (Non-proprietary) Colistimethate sodium 1000000 unit Colistimethate 1million unit powder for solution for injection vials | 10 vial P £30.00 DT = £18.00 (Hospital only) ▶Colomycin (Teva UK Ltd) Colistimethate sodium 1000000 unit Colomycin 1million unit powder for solution for injection vials | 10 vial P £18.00 DT = £18.00 Colistimethate sodium 2000000 unit Colomycin 2million unit powder for solution for injection vials | 10 vial P £32.40 DT = £32.40 ▶Promixin (Profile Pharma Ltd) Colistimethate sodium 1000000 unit Promixin 1million unit powder for solution for injection vials | 10 vial P £37.50 DT = £18.00 (Hospital only) Inhalation powder ▶Colobreathe (Teva UK Ltd) Colistimethate sodium 1662500 unit Colobreathe 1,662,500unit inhalation powder capsules | 56 capsule P £968.80 DT = £968.80 Powder for nebuliser solution ▶Promixin (Profile Pharma Ltd) Colistimethate sodium 1000000 unit Promixin 1million unit powder for nebuliser solution unit dose vials | 30 unit dose P £204.00 DT = £204.00 ANTIBACTERIALS › QUINOLONES Quinolones MHRA/CHM advice: Systemic and inhaled fluoroquinolones (November 2018, and March 2019) The MHRA and CHM have released important safety Infection information regarding the use of systemic and inhaled fluoroquinolones. For restrictions and precautions, see Important safety information for all quinolones: ciprofloxacin p. 590, levofloxacin p. 592, moxifloxacin p. 593, and ofloxacin p. 593. Overview In the UK, only fluoroquinolones are available; the recommendations below therefore refer to the use of fluoroquinolones. Ciprofloxacin is active against both Gram-positive and Gram-negative bacteria. It is particularly active against Gram-negative bacteria, including Salmonella, Shigella, Campylobacter, Neisseria, and Pseudomonas. Ciprofloxacin has only moderate activity against Gram-positive bacteria such as Streptococcus pneumoniae and Enterococcus faecalis; it should not be used for pneumococcal pneumonia. It is active against Chlamydia and some mycobacteria. Most anaerobic organisms are not susceptible. Ciprofloxacin can be used for respiratory tract infections (but not for pneumococcal pneumonia), infections of the gastro- intestinal system (including typhoid fever), bone and joint infections, gonorrhoea and septicaemia caused by sensitive organisms. Ofloxacin is licensed for urinary-tract infections, lower respiratory-tract infections, gonorrhoea, and non- gonococcal urethritis and cervicitis. Levofloxacin is active against Gram-positive and Gram- negative organisms. It has greater activity against Pneumococci than ciprofloxacin. Many Staphylococci are resistant to quinolones and their use should be avoided in MRSA infections. Moxifloxacin is active against Gram-positive and Gram- negative organisms. It has greater activity against Gram- positive organisms, including Pneumococci, than ciprofloxacin. Moxifloxacin is not active against Pseudomonas aeruginosa or meticillin-resistant Staphylococcus aureus (MRSA). Quinolones f
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▶When used by inhalation Patient should be advised to rinse mouth with water after each dose of dry powder inhalation. Patients or carers should be given advice on how to administer colistimethate sodium; first dose should be given under medical supervision. Driving and skilled tasks Manufacturer advises patients and carers should be counselled on the effects on driving and performance of skilled tasks—increased risk of dizziness, confusion and visual disturbances. The MHRA has produced an advice sheet on serious adverse reactions affecting musculoskeletal and nervous systems associated with fluoroquinolone use, which should be provided to patients and their carers. eiiii F 589
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9 million units daily in 2–3 divided doses, an
First-line fragment. Read the complete Indications and Dose section above.
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1–2 million units 2–3 times a day, for specific
First-line fragment. Read the complete Indications and Dose section above.
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1.66 million units twice daily
First-line fragment. Read the complete Indications and Dose section above.
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