Chemical formula: C₅₉H₁₁₄N₁₆O₃₀S₆ Molecular mass: 1,634.87 g/mol PubChem compound: 70789202
Colistimethate interacts in the following cases:
Co-treatment with colistimethate sodium and macrolides such as azithromycin and clarithromycin, or fluoroquinolones such as norfloxacin and ciprofloxacin should be undertaken with caution in patients with myasthenia gravis.
Co-treatment with colistimethate sodium and macrolides such as azithromycin and clarithromycin, or fluoroquinolones such as norfloxacin and ciprofloxacin should be undertaken with caution in patients with myasthenia gravis.
Dose adjustments in renal impairment are necessary, but pharmacokinetic data available for patients with impaired renal function is very limited.
The following dose adjustments are suggested as guidance.
Dose reductions are recommended for patients with creatinine clearance <50 ml/min: Twice daily dosing is recommended.
| Creatinine clearance (ml/min) | Daily dose |
|---|---|
| <50-30 | 5.5-7.5 MIU |
| <30-10 | 4.5-5.5 MIU |
| <10 | 3.5 MIU |
MIU = million IU
Concomitant use of inhaled colistimethate sodium with other medicinal products that are potentially nephrotoxic or neurotoxic, such as aminoglycosides, or neuromuscular blocking products, such as curariform agents should be undertaken with caution.
Due to the effects of colistin on the release of acetylcholine, non-depolarising muscle relaxants should be used with caution in patients receiving colistimethate sodium as their effects could be prolonged
Concomitant use of intravenous colistimethate sodium with other medications that are potentially nephrotoxic or neurotoxic should be undertaken with great caution.
Colistin appears to be dialyzable through conventional haemodialysis and continuous venovenous haemo(dia)filtration (CVVHF, CVVHDF). There are extremely limited data from population PK studies from very small numbers of patients on renal replacement therapy. Firm dose recommendations cannot be made. The following regimes could be considered.
No-HD days: 2.25 MIU/day (2.2-2.3 MIU/day).
HD days: 3 MIU/day on haemodialysis days, to be given after the HD session. Twice daily dosing is recommended.
As in patients with normal renal function. Three times daily dosing is recommended. Hepatic impairment.
Antibiotic-associated colitis and pseudomembranous colitis have been reported with nearly all antibacterial agents and may occur with colistimethate sodium. They may range from mild to lifethreatening in severity. It is important to consider this diagnosis in patients who develop diarrhoea during or after the use of colistimethate sodium. Discontinuation of therapy and the administration of specific treatment for Clostridium difficile should be considered. Medicinal products that inhibit peristalsis should not be given.
Colistimethate sodium should be used with extreme caution in patients with porphyria.
Haemoptysis is a complication in cystic fibrosis and is more frequent in adults. The use of colistimethate sodium in patients with clinically significant haemoptysis should be undertaken or continued only if the benefits of treatment are considered to outweigh the risks of inducing further haemorrhage.
Bronchospasm or coughing may occur on inhalation. These reactions usually disappear or significantly diminish with continued use and may be ameliorated by appropriate treatment with beta2-agonists prior to or following dry powder colistimethate sodium inhalation. If bronchospasm or coughing remain problematic, withdrawal of treatment should be considered.
Colistimethate sodium is known to reduce the presynaptic release of acetyl-choline at the neuromuscular junction and should be used in patients with myasthenia gravis with the greatest caution and only if clearly needed.
Colistimethate sodium should be used with extreme caution in patients with myasthenia gravis because of potential for drug induced neuromuscular blockade.
There are no adequate data from the use of colistimethate sodium in pregnant women. Animal studies in rats and mice do not indicate teratogenic properties. However, single dose studies in human pregnancy show that colistimethate crosses the placental barrier and there may be a risk of foetal toxicity if repeated doses are given to pregnant patients.
Colistimethate should be used in pregnancy only if the benefit to the mother outweighs the potential risk to the foetus.
Physico-chemical data suggest excretion of colistimethate sodium in human milk. A risk to the newborns/infants cannot be excluded. A decision must be made whether to discontinue breastfeeding or to discontinue/abstain from colistimethate sodium therapy taking into account the benefit of breastfeeding for the child and the benefit of therapy for the woman.
Colistimethate sodium has no notable effects on fertility in male or female rats or mice.
Based on the safety profile of colistimethate sodium, neurotoxity may occur with the possibility of dizziness, confusion or visual disturbances. Patients should be warned not to drive or operate machines if this occurs.
The likelihood of adverse events may be related to the age, renal function and condition of the patient.
In cystic fibrosis patients neurological events have been reported in up to 27% of patients. These are generally mild and resolve during or shortly after treatment.
Adverse effects on renal function have been reported, usually following use of higher than recommended doses in patients with normal renal function, or failure to reduce the dose in patients with renal impairment or during concomitant use of other nephrotoxic antibiotics. The effects are usually reversible on discontinuation of therapy.
In cystic fibrosis patients treated within the recommended dosage limits, nephrotoxicity appears to be rare (less than 1%). In seriously ill hospitalised non-CF patients, signs of nephrotoxicity have been reported in approximately 20% of patients.
Neurotoxicity has been reported often in association with overdose, failure to reduce dose in patients with renal insufficiency and concomitant use of either neuromuscular blocking drugs or other drugs with similar neurological effects. Reducing the dose may alleviate symptoms.
Effects may include apnoea, transient sensory disturbances (such as facial paraesthesia and vertigo) and, rarely, vasomotor instability, slurred speech, visual disturbances, confusion or psychosis.
Hypersensitivity reactions including skin rash have been reported. If these occur treatment should be withdrawn.
Local irritation at the site of injection may occur.
No significant systemic absorption has been found to occur in older children and adults following oral administration nor have any systemic side effects been reported.
However, since the use of colistin may be associated with unpredictable, albeit limited, absorption in infants under 6 months the potential adverse effects of systemic administration should be noted for this patient population. These adverse effects may include transient sensory disturbances such as perioral parasthesia and vertigo.
Neuro-toxicity and adverse effects on renal function have been reported in association with systemic over-dosage, failure to reduce dosage in patients with renal insufficiency and the concomitant use of either curariform agents or antibiotics with similar neurotoxic effects. Therapy need not be discontinued and reduction of dosage may alleviate symptoms. Permanent nerve damage such as deafness or vestibular damage has not been reported.
The safety of colistimethate sodium has been assessed in a total of 237 subjects (225 cystic fibrosis patients and 12 healthy volunteers). Of these, 187 patients aged 6 years and above were exposed to Colistimethate sodium one capsule twice daily in a 24-week, phase 3 comparative study. There were 32 patients aged 6-12 years, 41 patients aged 13-17 years and 114 patients aged 18 years and older. The most commonly reported adverse reactions as a percent of all Colistimethate sodium treated patients were: unpleasant taste (62%), cough (59.4%), throat irritation (43.9%), dyspnoea (16.6%) and dysphonia (10.7%). Inhalation may induce coughing or bronchospasm which may be controlled by pre-treatment with inhaled beta2 agonists.
Sore throat or mouth has been reported with nebulised colistimethate sodium and may occur. This may be related to Candida albicans infection or hypersensitivity. Skin rash may also indicate hypersensitivity and if this occurs treatment should be withdrawn.
In the 24 week clinical study, the following adverse reactions were observed across all ages. Frequencies are defined as: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1,000 to <1/100), rare (≥1/10,000 to <1/1,000), very rare <1/10,000), not known (cannot be estimated from the available data). Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.
Uncommon: Drug hypersensitivity
Uncommon: Weight fluctuation, decreased appetite
Uncommon: Anxiety
Common: Balance disorder, headache
Uncommon: Convulsions, somnolence
Common: Tinnitus
Uncommon: Ear congestion
Very Common: Dyspnoea, cough, dysphonia, throat irritation
Common: Haemoptysis, bronchospasm, asthma, wheezing, chest discomfort, lower respiratory tract infection, productive cough, crackles lung
Uncommon: Chest pain, dyspnoea exacerbated, pharyngolaryngeal pain, epistaxis, sputum purulent, abnormal chest sound, increased upper airway secretion
Very Common: Dysgeusia
Common: Vomiting, nausea
Uncommon: Diarrhoea, toothache, salivary hypersecretion, flatulence
Common: Arthralgia
Uncommon: Proteinuria
Common: Pyrexia, asthenia, fatigue
Uncommon: Thirst
Common: Forced expiratory volume decreased
Uncommon: Medication error
In the 24-week clinical study, where Colistimethate sodium was administered twice daily to adults and children aged 6-17, the adverse reactions identified in the paediatric population were similar to that for the overall population. The most commonly reported adverse reactions as a percent of Colistimethate sodium treated patients were: cough (55%), unpleasant taste (51%), throat irritation (34%), dyspnoea (10%) and dysphonia (10%).
© All content on this website, including data entry, data processing, decision support tools, "RxReasoner" logo and graphics, is the intellectual property of RxReasoner and is protected by copyright laws. Unauthorized reproduction or distribution of any part of this content without explicit written permission from RxReasoner is strictly prohibited. Any third-party content used on this site is acknowledged and utilized under fair use principles.
