Colistimet AF (Powder) Instructions for Use

Marketing Authorization Holder

Alpharma, LLC (Russia)

Manufactured By

Deko Company, LLC (Russia)

ATC Code

J01XB01 (Colistin)

Active Substance

Colistimethate sodium (Rec.INN registered by WHO)

Dosage Forms

	Colistimet AF	Powder for solution for injection, for infusion and for inhalation 80 mg (1000000 IU): 1 vial in a set with or without a solvent
		Powder for solution for injection, for infusion and for inhalation 160 mg (2000000 IU): 1 vial in a set with or without a solvent

Dosage Form, Packaging, and Composition

Powder for solution for injection/infusion and for inhalation white or almost white, hygroscopic.

Solvent sodium chloride solution 0.9% – 5 ml (ampoules).

80 mg (1000000 IU) – type I glass vials with a capacity of 10 ml (1) – cardboard packs.
80 mg (1000000 IU) – type I glass vials with a capacity of 10 ml (1) in a set with a solvent (amp. 1 pc.) – contour cell packs (1) – cardboard packs.

Powder for solution for injection/infusion and for inhalation white or almost white, hygroscopic.

Solvent sodium chloride solution 0.9% – 5 ml (ampoules).

160 mg (2000000 IU) – type I glass vials with a capacity of 10 ml (1) – cardboard packs.
160 mg (2000000 IU) – type I glass vials with a capacity of 10 ml (1) in a set with a solvent (amp. 1 pc.) – contour cell packs (1) – cardboard packs.

Clinical-Pharmacological Group

Antibiotic for inhalation use

Pharmacotherapeutic Group

Systemic antibacterial agents; other antibacterial agents; polymyxins

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, 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 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 in 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

Administer Colistimet AF by inhalation only. Use the 80 mg (1,000,000 IU) or 160 mg (2,000,000 IU) vial for solution preparation.

Reconstitute the powder with 4 ml of 0.9% sodium chloride solution. Gently swirl the vial until the solution is clear. Do not shake vigorously.

The standard adult and pediatric dose (for children over 6 years) is 1-2 million IU, administered twice daily. The maximum daily dose is 6 million IU.

For the initial dose, administer under medical supervision. Precede inhalation with a bronchodilator if prescribed. Monitor FEV1 before and after administration.

Adjust the dose and frequency based on clinical response and tolerance. The typical treatment duration is long-term, as required for chronic suppression.

Maintain a time interval between inhalation of dornase alfa and colistimethate sodium. Do not mix the prepared solution with any other medications in the nebulizer.

Discontinue use and seek medical advice if severe bronchospasm occurs. Monitor renal function regularly during therapy, especially in patients with pre-existing impairment.

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, impaired renal function, 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 impaired renal function.

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 at the next administration of colistimethate sodium with the addition of a bronchodilator.

In patients with impaired renal function, 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 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 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 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 medicines.

With simultaneous use of potentially nephrotoxic drugs (aminoglycosides, cephalosporins, cyclosporine) and colistimethate sodium, an increase in 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.