Colitriven-APh (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 Form

Colitriven-APh

Powder for preparation of solution for intravenous administration 3000000 IU

Dosage Form, Packaging, and Composition

Powder for preparation of solution for intravenous administration

240 mg – vials – cardboard packs – By prescription

Clinical-Pharmacological Group

Antibiotic of the polypeptide group

Pharmacotherapeutic Group

Systemic antibacterial agents; other antibacterial agents; polymyxins

Pharmacological Action

Colistimethate sodium is 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, which leads to their destruction. Colistimethate sodium exerts a bactericidal effect on gram-negative microorganisms, both in the division and resting phases, by altering the structure and function of the outer and cytoplasmic membranes.

Caution is required when determining susceptibility breakpoints for the use of colistimethate sodium 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 with expectorated sputum. The minor 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 Colitriven-APh by inhalation only. The powder must be reconstituted with sterile 0.9% sodium chloride solution to prepare the inhalation solution. Do not use sterile water for injection.

The standard adult and pediatric (6 years and older) dose is 1-2 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, the patient’s clinical response, and tolerability.

Administer the first dose under medical supervision. Monitor forced expiratory volume in 1 second (FEV1) before and after inhalation to assess for bronchoconstriction.

Pre-treat with a bronchodilator 15-20 minutes prior to colistimethate sodium inhalation if the patient is on such therapy or shows signs of airway reactivity.

Maintain a time interval between inhalation of dornase alfa and colistimethate sodium.

For patients with renal impairment, use with caution. Monitor renal function regularly and adjust the dosage if necessary.

Complete the full course of therapy as prescribed, even if symptoms improve.

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.

Urinary system 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, the use of colistimethate sodium is possible only after consultation with a doctor, only for vital indications, due to the risk of developing 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

It 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 agent 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 during the next use 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 operate 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 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.