Colineb: Uses, Dosage & Side Effects

What Is Colineb and What Is It Used For?

Colineb contains the active substance colistimethate sodium, which belongs to the polymyxin class of antibiotics. Polymyxins are among the oldest antibiotics available, first discovered in the late 1940s from Paenibacillus polymyxa. They were widely used in the 1950s and 1960s but fell out of favor due to concerns about nephrotoxicity (kidney damage) and neurotoxicity when given systemically. In recent decades, however, polymyxins have experienced a significant resurgence as "last resort" antibiotics for multidrug-resistant Gram-negative bacterial infections, and inhaled formulations like Colineb have become a mainstay in cystic fibrosis care.

Colistimethate sodium is an inactive prodrug that undergoes hydrolysis in aqueous solution to release colistin (also known as polymyxin E), the active antibacterial compound. Colistin exerts its bactericidal effect primarily by binding to lipopolysaccharides (LPS) and phospholipids in the outer membrane of Gram-negative bacteria. This binding displaces divalent cations – calcium (Ca²⁺) and magnesium (Mg²⁺) – that stabilize the lipopolysaccharide layer. The resulting disruption of the outer membrane integrity increases bacterial cell permeability, causing leakage of intracellular contents and ultimately cell death. This rapid bactericidal mechanism is distinct from many other antibiotic classes and makes colistin particularly effective against organisms that have developed resistance to other antibiotics.

Pseudomonas aeruginosa is the most clinically significant pathogen in cystic fibrosis lung disease. This opportunistic Gram-negative bacterium chronically colonizes the airways of the majority of CF patients by adulthood, forming biofilms that are inherently resistant to many conventional antibiotics and to host immune defenses. Chronic Pseudomonas aeruginosa infection is strongly associated with accelerated decline in lung function, increased frequency of pulmonary exacerbations, and reduced survival in CF patients. The European Cystic Fibrosis Society (ECFS) and other international guidelines recommend long-term inhaled anti-pseudomonal antibiotics, including colistimethate sodium, as a cornerstone of maintenance therapy for patients with chronic Pseudomonas aeruginosa infection.

When administered via nebulization, Colineb delivers the active drug directly to the site of infection in the airways. This targeted delivery achieves high local concentrations of colistin in the bronchial secretions and lung tissue, far exceeding the minimum inhibitory concentration (MIC) needed to kill Pseudomonas aeruginosa, while minimizing systemic absorption. As a result, the risk of systemic side effects – particularly nephrotoxicity – is substantially lower with inhaled administration compared with intravenous use. The primary goals of inhaled colistimethate therapy in CF are to suppress bacterial density in the airways, reduce the frequency and severity of pulmonary exacerbations, slow the progressive decline of lung function, and improve overall quality of life.

What Should You Know Before Using Colineb?

Contraindications

Colineb must not be used if you have a known hypersensitivity (allergy) to colistimethate sodium, colistin, or any other polymyxin antibiotics. Cross-reactivity between polymyxin B and colistin (polymyxin E) has been reported, so individuals allergic to one polymyxin should avoid all members of this class. Allergic reactions may manifest as skin rash, urticaria (hives), facial or throat swelling (angioedema), or in severe cases, anaphylaxis. If you experience any signs of an allergic reaction during or after nebulization, stop using Colineb immediately and seek urgent medical attention.

Warnings and Precautions

Before starting Colineb, discuss the following conditions and concerns with your healthcare provider, as they may affect whether or how you can use this medication:

• Kidney problems: Colistimethate sodium can affect kidney function, even when given by inhalation. If you have pre-existing kidney disease or impaired renal function, your doctor will monitor your kidney function closely with regular blood tests. The risk of nephrotoxicity increases significantly if you are also receiving colistimethate sodium intravenously or taking other nephrotoxic medications concurrently.
• Myasthenia gravis: If you have myasthenia gravis (a condition causing muscle weakness), colistimethate sodium may worsen your symptoms. Polymyxin antibiotics can have neuromuscular blocking properties, potentially exacerbating the characteristic muscle weakness and fatigue associated with this condition. Use Colineb with extreme caution and close medical monitoring.
• Porphyria: Colistimethate sodium should be used with caution in patients with porphyria, a group of inherited disorders affecting heme synthesis, as polymyxin antibiotics may exacerbate symptoms.
• Airway hyperreactivity (asthma): Inhaling any nebulized antibiotic can trigger bronchospasm, chest tightness, and cough. Patients with asthma or a history of airway hyperreactivity are at increased risk. A bronchodilator should be administered prior to Colineb to reduce the likelihood of bronchospasm. Your doctor may also perform lung function testing before and after your first dose.
• Active hemoptysis: If you are currently coughing up blood (hemoptysis), the risks and benefits of inhaled Colineb should be carefully evaluated by your doctor before initiating or continuing treatment, as nebulized antibiotics can irritate inflamed airways and potentially worsen bleeding.

Pregnancy and Breastfeeding

There is very limited clinical data on the safety of colistimethate sodium in pregnant women. Animal studies are insufficient to fully assess reproductive toxicity. Therefore, Colineb should only be used during pregnancy when the treating physician has determined that the potential clinical benefit clearly outweighs the potential risk to the unborn child. Women who are pregnant, suspect they may be pregnant, or are planning to become pregnant should consult their doctor before using Colineb.

Colistimethate sodium may be excreted in breast milk. Although systemic absorption following inhalation is lower than with intravenous administration, a risk to the breastfed infant cannot be entirely excluded. The decision to continue or discontinue breastfeeding while using Colineb should be made in consultation with your healthcare provider, weighing the benefits of breastfeeding against the potential risk of drug exposure to the infant. Colineb should only be used during breastfeeding when clearly necessary.

Driving and Operating Machinery

Colineb may cause dizziness, confusion, and visual disturbances such as blurred vision. These effects may be more pronounced when combined with alcohol. If you experience any of these side effects, do not drive, operate machinery, or engage in activities requiring alertness and clear vision. Consult your doctor or pharmacist if you are unsure about your ability to perform these activities safely while using Colineb.

Use in Children and Neonates

Colineb can be used in children and adolescents with cystic fibrosis, including children as young as 2 years of age, at appropriate doses determined by the treating physician. Special caution is required in premature and newborn infants because their kidneys are not yet fully developed, which increases the risk of nephrotoxicity. In these vulnerable populations, renal function must be monitored very closely throughout treatment.

Important Information About Ingredients

Colineb contains less than 1 mmol (23 mg) of sodium per vial, meaning it is essentially sodium-free. This is unlikely to have any clinically meaningful effect, even in patients on a sodium-restricted diet. The product contains no other excipients – each vial contains only colistimethate sodium as the sole ingredient.

How Does Colineb Interact with Other Drugs?

Drug interactions with Colineb are primarily related to the additive toxicity that may occur when colistimethate sodium is combined with other medications that have overlapping safety profiles, particularly regarding kidney function and neuromuscular effects. It is essential to inform your doctor, pharmacist, or nurse about all medications you are currently taking, have recently taken, or may take in the future, including prescription drugs, over-the-counter medications, supplements, and herbal products.

Major Interactions

Minor Interactions

If you are using multiple inhaled therapies as part of your cystic fibrosis treatment regimen, your medical team will instruct you on the correct order of administration. Typically, a bronchodilator is inhaled first to open the airways, followed by airway clearance therapies (such as dornase alfa and chest physiotherapy), and then inhaled antibiotics such as Colineb are administered last. If you have recently inhaled dornase alfa, you should delay Colineb inhalation to a later time point in the day to optimize drug delivery and effectiveness.

What Is the Correct Dosage of Colineb?

Always use Colineb exactly as your doctor or pharmacist has instructed. Do not change the dose or frequency without consulting your healthcare provider first. The correct dose depends on your age, the severity of your infection, your kidney function, and other individual clinical factors. If you are also using other inhaled medications, your doctor will advise you on the correct order and timing of administration.

Adults

Children and Adolescents

How to Prepare and Administer Colineb

Colineb requires reconstitution before each use. The following step-by-step procedure should be followed carefully:

1. Gather your supplies: One vial of Colineb, sterile 0.9% sodium chloride solution for injection (3 mL for the 1 million IU vial or 4 mL for the 2 million IU vial), and a suitable nebulizer (e.g., PARI LC PLUS, PARI LC SPRINT, or eFlow rapid).
2. Tap the vial gently to settle the powder to the bottom, then remove the plastic cap and metal ring carefully. Remove the rubber stopper.
3. Add the saline solution to the vial containing the powder. Gently swirl or shake the vial until the powder is completely dissolved. Avoid vigorous shaking to prevent excessive foaming.
4. Inspect the solution: It should be clear and free of visible particles. Do not use the solution if you see particles or discoloration after reconstitution.
5. Pour the reconstituted solution into the nebulizer cup.
6. Sit upright in a well-ventilated room and breathe normally through the nebulizer mouthpiece until all the solution has been nebulized.
7. Clean and disinfect the nebulizer according to the manufacturer’s instructions after each use.

Missed Dose

If you forget to take a dose of Colineb, take it as soon as you remember – unless it is nearly time for your next scheduled dose. In that case, simply skip the missed dose and continue with your regular dosing schedule. Do not double up on doses to make up for a missed one. Maintaining a consistent treatment schedule is important for optimal bacterial suppression in the airways.

Overdose

If you accidentally use more Colineb than prescribed, or if a child inadvertently inhales the medication, contact your doctor, hospital emergency department, or poison control center immediately for a risk assessment and advice. Symptoms of overdose with colistimethate sodium may include:

• Temporary cessation of breathing (apnea)
• Muscle weakness
• Tingling or numbness around the lips and face
• Dizziness and vertigo (spinning sensation)
• Slurred speech
• Visual disturbances
• Confusion and mental disturbance
• Flushing (facial redness)
• Acute kidney failure

There is no specific antidote for colistimethate sodium overdose. Management is supportive, with particular attention to maintaining airway patency, respiratory support if needed, and monitoring of renal function.

Treatment Duration

Your doctor will determine how long you need to continue treatment with Colineb. In cystic fibrosis, inhaled anti-pseudomonal antibiotics are typically used as long-term maintenance therapy, often for years. It is critically important that you do not stop treatment prematurely, even if you feel well, as discontinuation can lead to regrowth of Pseudomonas aeruginosa, loss of lung function, and development of antibiotic resistance. Always consult your doctor before making any changes to your treatment regimen.

What Are the Side Effects of Colineb?

Like all medicines, Colineb can cause side effects, although not everybody who uses it will experience them. Most side effects are related to the local airway irritation caused by nebulized antibiotic delivery and are generally mild to moderate in severity. However, some side effects can be serious and require immediate medical attention.

Colineb can sometimes cause allergic reactions, including skin rash. If you develop a rash or any other signs of an allergic reaction, stop using Colineb and inform your doctor immediately. Some people may experience breathing difficulties after inhaling the nebulized solution. For this reason, your first dose should always be taken in the presence of a doctor or nurse, who can monitor your respiratory response and intervene if necessary. Your doctor may also prescribe a bronchodilator to be taken before Colineb to prevent shortness of breath and bronchospasm.

Colineb can also affect the kidneys, usually when the dose is high or when you are taking other medications that can affect kidney function. Your doctor will monitor your kidneys with regular blood tests throughout your treatment.

When to Seek Immediate Medical Attention

Contact your doctor or seek urgent medical care if you experience any of the following while using Colineb:

• Severe breathing difficulty or worsening shortness of breath after nebulization
• Facial or throat swelling (signs of angioedema)
• Widespread skin rash or hives (signs of allergic reaction)
• Significantly decreased urine output (may indicate kidney problems)
• Severe dizziness, confusion, or changes in consciousness
• Muscle weakness, particularly if you have myasthenia gravis

Reporting Side Effects

It is important to report suspected side effects after a medicine has been authorized, as this allows ongoing monitoring of its benefit-risk balance. Healthcare professionals and patients are encouraged to report any suspected adverse reactions to their national pharmacovigilance authority (for example, the MHRA Yellow Card Scheme in the UK, the FDA MedWatch program in the US, or the EMA EudraVigilance system in the EU).

How Should You Store Colineb?

Keep Colineb out of the sight and reach of children. Do not use this medicine after the expiry date stated on the carton and vial label after "EXP." The expiry date refers to the last day of the stated month.

Unopened vials: Store at or below 25°C (77°F). Do not freeze. Keep the vials in the original packaging to protect from light and moisture.

After reconstitution: The hydrolysis of colistimethate sodium accelerates significantly when the solution is diluted to a concentration below the critical micelle concentration of approximately 80,000 IU/mL. Solutions below this concentration should be used immediately after preparation. For reconstituted solutions in the original vial with a concentration at or above 80,000 IU/mL, chemical and physical stability has been demonstrated for up to 24 hours when stored at 2°C to 8°C (refrigerated). However, from a microbiological standpoint, the product should ideally be used immediately after reconstitution.

Each vial of Colineb is intended for single use only. Any remaining solution after nebulization must be discarded. Do not re-use partially used vials for subsequent doses. Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to dispose of medicines that are no longer needed. These measures help to protect the environment.

What Does Colineb Contain?

The active substance in Colineb is colistimethate sodium (also known as colistin methanesulfonate sodium or CMS). This is the inactive prodrug form of colistin (polymyxin E). There are no other excipients or inactive ingredients – each vial contains pure colistimethate sodium powder.

Physical Description

Colineb is presented as a white to off-white powder (lyophilized cake) in colorless 10 mL glass vials:

• Colineb 1 million IU: Glass vial with a red cap
• Colineb 2 million IU: Glass vial with a purple cap

Available Pack Sizes

Colineb is available in the following pack sizes: 1, 2, 10, 14, 28, or 56 vials per carton. Not all pack sizes may be marketed in your country.

Manufacturer

Colineb is manufactured by Millmount Healthcare Ltd. (Stamullen, County Meath, Ireland) and Merckle GmbH (Blaubeuren, Germany). The marketing authorization holder is Teva.