Coli-M (Lyophilisate) Instructions for Use

Marketing Authorization Holder

Scientific And Production Association Innovative Pharmaceutical Technologies, LLC (Russia)

Manufactured By

Armavir Biopharmaceutical Plant, FSE (Russia)

ATC Code

J01XB01 (Colistin)

Active Substance

Colistimethate sodium (Rec.INN registered by WHO)

Dosage Forms

	Coli-M	Lyophilisate for preparation of solution for inhalation 1000000 IU (80 mg): fl. 1, 5, 10, 25 or 50 pcs.
		Lyophilisate for preparation of solution for inhalation 2000000 IU (160 mg): fl. 1, 5, 10, 25 or 50 pcs.

Dosage Form, Packaging, and Composition

Lyophilisate for preparation of solution for inhalation is a lyophilized mass from white to slightly yellowish.

1000000 IU – vials (1) – carton packs.
1000000 IU – vials (5) – contour cell packs (1) – carton packs.
1000000 IU – vials (5) – contour cell packs (2) – carton packs.
1000000 IU – vials (25) – carton box (for hospitals).
1000000 IU – vials (50) – carton box (for hospitals).

Lyophilisate for preparation of solution for inhalation is a lyophilized mass from white to slightly yellowish.

2000000 IU – vials (1) – carton packs.
2000000 IU – vials (5) – contour cell packs (1) – carton packs.
2000000 IU – vials (5) – contour cell packs (2) – carton packs.
2000000 IU – vials (25) – carton boxes (for hospitals).
2000000 IU – vials (50) – carton boxes (for hospitals).

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 resting, by altering the structure and function of the outer and cytoplasmic membranes.

Caution is required when determining susceptibility breakpoints for sodium colistimethate administered by inhalation using ‘susceptible or resistant’ criteria. Based on clinical trial experience and/or in vitro studies, Pseudomonas aeruginosa and Hemophilus influenzae are susceptible to sodium colistimethate, 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 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 in expectorated sputum. The minor portion that enters the systemic circulation is eliminated primarily by glomerular filtration. About 60% of the absorbed dose is excreted unchanged by the kidneys within 8 hours.

Indications

Respiratory tract infections in cystic fibrosis caused by Pseudomonas aeruginosa.

ICD codes

Dosage Regimen

Administer Coli-M by inhalation only using a suitable nebulizer system.

Reconstitute the lyophilisate immediately before use. For the 1,000,000 IU vial, add 4 mL of sterile 0.9% sodium chloride solution. For the 2,000,000 IU vial, add 4 mL of diluent. Gently swirl the vial until the solution is clear.

The typical adult and pediatric (over 6 years) dose is 1 to 2 million IU, administered twice daily. The maximum total daily dose is 6 million IU.

Determine the exact dose, frequency, and duration of therapy individually based on the severity of the infection and the patient’s clinical response.

Precede each inhalation with a bronchodilator if it is part of the patient’s regimen. Administer the first dose under medical supervision with FEV1 monitoring before and after administration to assess for bronchospasm.

Maintain a time interval between inhalation of dornase alfa and Coli-M; do not mix them in the nebulizer.

Use the entire contents of the reconstituted vial for a single treatment. Discard any unused solution. Do not mix the prepared solution with other drugs.

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, the use of colistimethate sodium is possible 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

Inhalational 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 administration of colistimethate sodium with the addition of a bronchodilator.

In patients with renal impairment, careful monitoring for the 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 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.

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

Effect on ability to drive vehicles and mechanisms

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 the 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.