elexacaftor

Action and Spectrum

Actions and spectrum: 

Actions: 

• CFTR Modulation: elexacaftor is a CFTR corrector. It helps correct the defective CFTR protein that leads to the underlying dysfunction in cystic fibrosis. By improving folding & trafficking of CFTR to the cell surface, elexacaftor allows the protein to function more effectively in transporting chloride ions. 
• Enhanced Chloride Transport: By correcting CFTR protein function, elexacaftor enhances the transport of chloride ions across cell membranes. This helps maintain appropriate fluid balance in various tissues and organs, reducing the viscosity of mucus in the airways, digestive system, and other affected areas. 

Spectrum: 

elexacaftor is specifically indicated for individuals with cystic fibrosis who have a minimum of one F508del mutation in the CFTR gene. It is used in combination with tezacaftor and ivacaftor, which together form a triple combination therapy. This therapy is effective for a subset of individuals with CF and specific genetic mutations, primarily the F508del mutation. 

Drug Interaction

Adverse Reaction

Frequency not defined 

upper respiratory tract infections 

Increased cough 

sinus congestion 

nasal congestion. 

increased liver enzymes 

Diarrhea 

Abdominal pain. 

Acne 

Rash 

Headaches 

Dizziness 

Fatigue 

Increased Blood Pressure 

Insomnia 

Black Box Warning

Black Box Warning: 

None 

Contraindication / Caution

Contraindication/Caution: 

Contraindication: 

• Hypersensitivity: elexacaftor should not be used in individuals who have a known hypersensitivity to any of its components or to drugs of a similar class. 
• Co-Administration with Certain Medications: elexacaftor is used in a combination therapy with other medications, and there may be contraindications or interactions with certain drugs. Healthcare providers should carefully assess the patient’s medication profile and potential drug interactions before initiating elexacaftor therapy. 
• Age Restrictions: elexacaftor’s safety and efficacy have been established for specific age groups. The use of elexacaftor in individuals outside the approved age range may be contraindicated.

Caution: 

• Hepatic Impairment: elexacaftor is metabolized in the liver, so caution is advised when using it in individuals with moderate to severe hepatic impairment. Dose adjustments or close monitoring may be necessary. 
• Drug Interactions: elexacaftor is part of a combination therapy, and there may be potential drug interactions with other medications that are co-administered. Healthcare providers should carefully review the patient’s medication profile to assess for potential interactions. 
• Respiratory Symptoms: While elexacaftor aims to improve lung function and reduce respiratory symptoms in cystic fibrosis patients, there may still be a risk of respiratory-related adverse events. Any changes in respiratory symptoms should be promptly reported to a healthcare provider. 
• Pregnancy and Breastfeeding: The use of elexacaftor during pregnancy and breastfeeding may require careful consideration. Healthcare providers should weigh the potential benefits against the potential risks and make individualized decisions based on the patient’s situation. 
• Age Considerations: elexacaftor’s safety and efficacy have been established for specific age groups. Healthcare providers should ensure that it is being used within the approved age range. 
• Monitoring: Regular monitoring of clinical response, lung function, and potential adverse effects is important during elexacaftor therapy. 
• Allergic Reactions: While allergic reactions to elexacaftor are rare, patients should be monitored for any signs of hypersensitivity, such as rash, itching, swelling, or difficulty breathing.

Comorbidities: 

• Respiratory Complications: CF often leads to chronic respiratory issues, such as lung infections, bronchiectasis (damage to airway walls), and pneumonia. These respiratory complications can worsen over time and contribute to decreased lung function. 
• Gastrointestinal Issues: CF can affect the pancreas and digestive system, leading to malabsorption of nutrients, pancreatic insufficiency, and gastrointestinal symptoms like abdominal pain, bloating, and difficulty gaining weight. 
• Diabetes: CF-related diabetes (CFRD) is a common comorbidity, where individuals with CF develop diabetes due to the impact of the disease on the pancreas and insulin production. 
• Liver Disease: CF-related liver disease, including cirrhosis and bile duct abnormalities, can occur in some individuals with CF. 
• Bone Health: CF can affect bone health, leading to decreased bone density & increased risk of fractures. 
• Nutritional Deficiencies: Malabsorption of nutrients in the digestive tract can lead to deficiencies in essential vitamins and minerals. 
• Sinus and Nasal Issues: Chronic sinusitis and nasal polyps are common among CF patients, contributing to respiratory symptoms and difficulty breathing. 
• Reproductive Health: CF can affect fertility in both males and females, leading to challenges in conception and pregnancy. 

Pregnancy / Lactation

Pregnancy consideration: US FDA pregnancy category: Not assigned 

Lactation: Excreted into animal milk: Yes  

Pregnancy category: 

• Category A: well-controlled and Satisfactory studies show no risk to the fetus in the first or later trimester. 
• Category B: there was no evidence of risk to the fetus in animal studies, and there were not enough studies on pregnant women. 
• Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.   
• Category D: adequate data with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits. 
• Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women. 
• Category N: There is no data available for the drug under this category. 

Pharmacology

Pharmacology: 

elexacaftor is a medication used in combination with other drugs to treat cystic fibrosis (CF) in patients with specific genetic mutations. As a CFTR modulator, elexacaftor targets the defective CFTR protein that is impaired in CF. It helps improve the folding, trafficking, and function of CFTR at the cell surface, leading to enhanced chloride ion transport.

This action reduces the viscosity of mucus in the airways and other affected tissues, aiding in better lung clearance and improving respiratory symptoms. By addressing the underlying genetic defect, elexacaftor shows improved lung function & quality of life in eligible CF patients.  

Pharmacodynamics: 

• CFTR Modulation: elexacaftor is part of a combination therapy that includes tezacaftor and ivacaftor. It targets the CFTR protein, which is defective in CF patients with specific mutations, primarily the F508del mutation. elexacaftor helps correct the folding and trafficking of CFTR to the cell surface, allowing the protein to function more effectively as a chloride ion channel. 
• Enhanced Chloride Transport: By improving CFTR function, elexacaftor enhances the transport of chloride ions across cell membranes. This action has a direct impact on reducing the viscosity of mucus in various tissues, particularly the respiratory system. Thinning the mucus makes it easier to clear from the airways, reducing the risk of infections and improving lung function. 
• Respiratory Improvement: The improved function of CFTR and enhanced chloride transport lead to better hydration of airway surfaces. This helps maintain the normal physiological balance of fluids in the respiratory system, which contributes to improved lung clearance, reduced mucus buildup, and enhanced overall respiratory health. 
• Clinical Benefits: The pharmacodynamic effects of elexacaftor, when combined with tezacaftor and ivacaftor, result in improved lung function, reduced pulmonary exacerbations, and enhanced quality of life for eligible CF patients with specific mutations.

Pharmacokinetics: 

Absorption 

elexacaftor, when administered orally as part of the fixed-dose combination with tezacaftor and ivacaftor, is absorbed from the gastrointestinal tract. Food can affect the absorption of elexacaftor, so it is recommended to take the combination therapy with a fat-containing meal. This enhances the bioavailability of elexacaftor and supports its therapeutic effects. 

Distribution 

elexacaftor, along with tezacaftor and ivacaftor, is distributed in the body through systemic circulation. The exact distribution characteristics, such as protein binding or tissue distribution, may vary among the components of the combination therapy. 

Metabolism 

elexacaftor undergoes metabolism primarily through oxidative pathways involving cytochrome P450 (CYP) enzymes, particularly CYP3A. This metabolism can result in the formation of metabolites. The combination therapy may also influence the metabolism of elexacaftor and other components. 

Elimination and excretion 

The elimination of elexacaftor and its metabolites occurs through feces. Biliary excretion is a route of elimination, and the role of renal excretion is minor. The terminal half-life of elexacaftor may vary based on individual factors and the presence of other drugs in the combination therapy. 

Adminstartion

Administration: 

• Dosage: The dosage and administration of elexacaftor are determined based on the patient’s age, weight, medical history, and other factors. The combination therapy tablets contain specific doses of elexacaftor, tezacaftor, and ivacaftor. 
• Frequency: The combination therapy is typically taken orally once daily with a fat-containing meal. Taking it with food helps improve the absorption and effectiveness of the medication. 
• Swallowing: The tablets should be swallowed whole and should not be crushed, broken, or chewed. 
• Adherence: Adhering to the prescribed dosing schedule is important for the success of the therapy. Missing doses or altering the administration instructions may affect the therapeutic outcomes. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: elexacaftor 

Pronounced: (el-ex-uh-KAF-tor)  

Why do we use elexacaftor? 

• Cystic Fibrosis Treatment: elexacaftor, in combination with tezacaftor and ivacaftor, is indicated for the treatment of cystic fibrosis in 12 years of age and older who have minimum of one F508del mutation in the CFTR gene.  
• Lung Function Improvement: The combination therapy aims to improve lung function by addressing the underlying cause of CF-related respiratory issues. 
• Reduction of Respiratory Symptoms: CF patients often experience respiratory symptoms such as chronic cough, mucus production, and difficulty breathing.  
• Quality of Life Enhancement: The combination therapy can lead to a better quality of life for eligible CF patients by addressing the genetic defect responsible for the disease’s progression.