Colimistin (Powder) Instructions for Use

Marketing Authorization Holder

Rinpharm LLC (Russia)

Manufactured By

Deko Company, LLC (Russia)

ATC Code

J01XB01 (Colistin)

Active Substance

Colistimethate sodium (Rec.INN registered by WHO)

Dosage Form

Colimistin

Powder for preparation of solution for inhalation 1 million IU: vial

Dosage Form, Packaging, and Composition

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

Vials (20) – 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 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 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 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 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 Colimistin by inhalation only using a suitable nebulizer system.

Reconstitute the powder in the vial with 4 mL of sterile 0.9% sodium chloride solution to yield a final concentration of 250,000 IU/mL.

Gently swirl the vial until the powder is completely dissolved; do not shake vigorously.

Use the entire contents of the reconstituted vial for a single inhalation session.

Discard any unused solution; do not store or reuse the prepared solution.

The standard adult and pediatric dose (for children 6 years and older) is 1 million IU, administered twice daily.

In severe infections, the dose may be increased to 2 million IU twice daily based on clinical assessment.

Always administer the dose at regular intervals, approximately every 12 hours.

The duration of therapy is determined individually based on clinical response and microbiological data.

Pre-medicate with a bronchodilator prior to each Colimistin inhalation if it is part of the patient’s regimen.

Monitor pulmonary function, specifically Forced Expiratory Volume (FEV1), before and after initial doses to assess for bronchospasm.

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

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 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 treatment 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 during the next administration of colistimethate sodium with the addition of a bronchodilator.

In patients with renal impairment, careful monitoring for possible nervous system side effects and regular monitoring of renal function is necessary.

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.

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 the possibility 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, nephrotoxicity may be enhanced.

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.