Colistimetate (Lyophilisate, Powder) Instructions for Use

ATC Code

J01XB01 (Colistin)

Active Substance

Colistimethate sodium (Rec.INN registered by WHO)

Clinical-Pharmacological Group

Antibiotic for inhalation use

Pharmacotherapeutic Group

Antibiotic, cyclic polypeptide

Pharmacological Action

A cyclic polypeptide antibiotic produced by Bacillus polymyxa, subspecies colistinus.

The mechanism of action is mainly due to its ability to bind to phospholipids of bacterial cell membranes, leading to their destruction.

Colistimethate sodium exerts a bactericidal effect on gram-negative microorganisms, both dividing and dormant, by altering the structure and function of the outer and cytoplasmic membranes.

Caution is required when determining susceptibility breakpoints for colistimethate sodium for inhalation use according to ‘susceptible or resistant’ criteria.

Based on clinical trial experience and/or in vitro studies, Pseudomonas aeruginosa and Hemophilus influenzae are susceptible to colistimethate sodium, while Burkholderia cepacia and Staphylococcus aureus are not susceptible.

Pharmacokinetics

After inhalation, the absorption of colistimethate sodium shows significant individual variation.

The C_max in plasma after inhalation of a 2 million IU dose ranges from ‘non-measurable’ to 280 µg/L (indicating absorption of less than 2% compared to parenteral administration).

After inhalation of 2 million IU of colistimethate sodium, the mean cumulative renal excretion is about 1%.

After inhalation of 1 million IU of colistimethate sodium, its concentration in sputum after 1 hour and 4 hours is 183.6 mg/L and 22.8 mg/L, respectively.

Approximately 1.5% of the administered dose accumulates in the lungs.

Colistimethate sodium crosses the placenta and is excreted in breast milk.

Colistimethate sodium is excreted with expectorated sputum.

The small portion that enters the systemic circulation is eliminated primarily by glomerular filtration.

Within 8 hours, about 60% of the absorbed dose is excreted unchanged by the kidneys.

Indications

Respiratory tract infections in cystic fibrosis caused by Pseudomonas aeruginosa.

ICD codes

Dosage Regimen

For inhalation use only. Reconstitute the lyophilisate with sterile 0.9% sodium chloride solution. Do not use sterile water for injection. Administer the solution using a suitable jet nebulizer equipped with a mouthpiece or a suitable face mask.

The typical adult and pediatric dose (for patients 6 years and older) is 1-2 million IU, administered twice daily. The exact dose and frequency must be determined individually by a physician based on the clinical situation, severity of infection, and patient tolerance.

Premedicate with a bronchodilator prior to each inhalation if it is part of the patient’s regimen. Monitor forced expiratory volume in 1 second (FEV1) before and after administration, especially for the initial dose. The first dose should be administered under medical supervision to assess for potential bronchospasm.

Maintain a time interval between inhalation of colistimetate and other inhaled medications, such as dornase alfa. Do not mix the prepared colistimetate solution with any other drugs in the nebulizer chamber. Use the solution immediately after reconstitution; discard any unused portion.

The duration of therapy is determined by the treating physician. Regularly assess renal function during treatment. Discontinue use if acute renal failure occurs.

Adverse Reactions

Allergic reactions angioedema.

Nervous system disorders dizziness, paresthesia.

Respiratory system disorders bronchospasm, increased cough, increased sputum production, mucositis (inflammation of the respiratory tract mucosa), pharyngitis, dyspnea.

Digestive system disorders nausea, heartburn.

Urinary system disorders acute renal failure.

Contraindications

Hypersensitivity to colistimethate sodium or polymyxin B; children under 6 years of age.

With caution: bronchial asthma, renal impairment, hemoptysis; pregnancy, lactation (breastfeeding).

Use in Pregnancy and Lactation

During pregnancy, colistimethate sodium should be used only after consultation with a doctor, only for vital indications, due to the risk of nephro- and neurotoxic reactions in the fetus.

If it is necessary to use colistimethate sodium during lactation, breastfeeding should be discontinued.

Use in Renal Impairment

Should be used with caution in patients with renal impairment.

Pediatric Use

Contraindicated in children under 6 years of age.

Special Precautions

Inhalation use of colistimethate sodium in sensitive patients may cause acute bronchoconstriction.

Therefore, the first dose of this inhalation product should be administered under the supervision of experienced medical personnel, and inhalation should be preceded by the use of a bronchodilator if it is part of the patient’s therapy regimen.

Forced expiratory volume in 1 second (FEV1) should be measured before and after inhalation of colistimethate sodium.

If a patient not receiving bronchodilators shows signs of drug-induced bronchial obstruction, the test should be repeated at the next use of colistimethate sodium with the addition of a bronchodilator.

In patients with renal impairment, careful monitoring for possible development of nervous system side effects is necessary, and renal function should be regularly monitored.

A break should be taken between inhalation of dornase alfa and inhalation of colistimethate sodium.

During treatment with colistimethate sodium, the appearance of resistant strains of Pseudomonas aeruginosa is possible in rare cases.

After discontinuation and/or modification of therapy, the efficacy of colistimethate sodium may be restored.

Ethanol should not be consumed during the use of colistimethate sodium.

Effect on ability to drive vehicles and operate machinery

During treatment, one should refrain from driving vehicles and engaging in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions.

Colistimethate sodium may be used as part of combination drugs for topical use in ophthalmology.

Drug Interactions

With simultaneous use of colistimethate sodium with inhalation anesthetics (ether, halothane), muscle relaxants or curare-like drugs (tubocurarine, succinylcholine) or aminoglycosides, careful monitoring for possible development of neurotoxic reactions is necessary.

The prepared solution of colistimethate sodium should not be mixed with other drugs.

With simultaneous use of potentially nephrotoxic drugs (aminoglycosides, cephalosporins, cyclosporine) and colistimethate sodium, increased nephrotoxicity is possible.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.