Colimetat (Powder) Instructions for Use

Marketing Authorization Holder

Pharmasintez, JSC (Russia)

ATC Code

J01XB01 (Colistin)

Active Substance

Colistimethate sodium (Rec.INN registered by WHO)

Dosage Form

Colimetat

Powder for preparation of solution for inhalation 1000000 IU: vial 1, 25, 60 or 100 pcs. with solvent

Dosage Form, Packaging, and Composition

Powder for preparation of solution for inhalation white or almost white, hygroscopic.

Reconstituted solution: when 3 ml of 0.9% sodium chloride solution is added to the vial contents, upon mixing the resulting solution should be clear and colorless.

Solvent sodium chloride solution 0.9% – 3 ml (ampoules).

1000000 IU – glass type I vials with a capacity of 10 ml (1) in a set with solvent (amp. 1 pc.) – cardboard packs.
1000000 IU – glass type I vials with a capacity of 10 ml (25) in a set with solvent (amp. 25 pcs.) – cardboard packs.
1000000 IU – glass type I vials with a capacity of 10 ml (60) in a set with solvent (amp. 60 pcs.) – cardboard packs.
1000000 IU – glass type I vials with a capacity of 10 ml (100) in a set with solvent (amp. 100 pcs.) – cardboard packs.

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 the ability to bind to phospholipids of bacterial cell membranes, which leads to their destruction.

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

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.

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 at 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 excreted 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

Administer by inhalation only using a suitable nebulizer system.

Reconstitute the contents of one vial containing 1 million IU of colistimethate sodium with 3 ml of the provided 0.9% sodium chloride solvent.

Gently swirl the vial until the powder is completely dissolved; the resulting solution must be clear and colorless.

Use the entire reconstituted solution for a single inhalation session; do not mix with other medications in the nebulizer chamber.

The standard dosage for adults and children 6 years and older is 1 million IU, inhaled twice daily at approximately 12-hour intervals.

Adjust the dosing frequency and duration based on the severity of the infection and patient tolerance; the maximum daily dose is 6 million IU.

Precede each inhalation with a bronchodilator if prescribed, especially in patients with bronchial hyperreactivity.

Monitor forced expiratory volume (FEV1) before and after initial doses to assess for potential bronchospasm.

Discontinue treatment and consult a physician if severe respiratory distress or signs of hypersensitivity occur.

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.

Gastrointestinal disorders nausea, heartburn.

Renal and urinary 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 for use 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 by adding 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 inhalations of dornase alfa and inhalation of colistimethate sodium.

During treatment with colistimethate sodium, the emergence 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.

During the use of colistimethate sodium, ethanol consumption is prohibited.

Effect on ability to drive vehicles and machinery

During treatment, it is necessary to 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 products 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 medicines.

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.