How Do CFTR Potentiators Work?

CFTR potentiators are medications prescribed to treat cystic fibrosis, an inherited genetic disorder that can affect many organs including the lungs. People with cystic fibrosis have mutations in the CFTR gene that encodes CFTR protein, which leads to dysfunctional CFTR protein. CFTR potentiators improve CFTR protein’s function.

Cystic fibrosis transmembrane conductance regulator (CFTR) protein maintains the balance of salt and water on many surfaces of the body. CFTR protein is an ion channel that is shaped like a tunnel, with a gate through which chloride ions flow out of the cells, attract water and maintain the right consistency of mucus and other fluids in the body.

Faulty functioning of CFTR protein prevents free movement of chloride ions to the surface and out through the channel gate, which makes the mucus that coats the lungs and other organs thick and sticky. Thick mucus in the lungs clogs up airways and traps germs leading to persistent lung infections, inflammations, and lung damage.

CFTR potentiators hold the channel’s gate open and allow the chloride ions to flow out freely. CFTR potentiators are combined with CFTR correctors, another class of medications that help the CFTR protein form the right shape and facilitate the free movement of chloride ions to the cell surface. 

The combination of CFTR potentiators and correctors makes the mucus thinner and slippery, prevents clogging of airways, and eases the symptoms of cystic fibrosis. In addition, new CFTR modulating medications known as CFTR amplifiers which can increase the production of CFTR protein are being developed.

Side effects of CFTR potentiators may include the following:

• Headache
• Oropharyngeal pain (mouth and throat pain)
• Upper respiratory tract infection
• Nasal congestion
• Dyspnea (shortness of breath)
• Nasopharyngitis (inflammation of the nasal passage and throat)
• Sinus congestion
• Rhinorrhea (nasal discharge)
• Rhinitis (nasal inflammation)
• Sinusitis (inflammation of the sinuses)
• Pharyngitis (throat inflammation)
• Sinus headache
• Bacteria in sputum
• Pharyngeal erythema (redness of the throat)
• Pleuritic pain (chest pain associated with pleura, the membrane that covers the lung)
• Wheezing
• Abnormal respiration
• Abdominal pain
• Diarrhea
• Nausea
• Flatulence
• Abdominal distension
• Increase in blood creatine phosphokinase (CPK) levels
• Increase in liver enzymes alanine aminotransferase (ALT) and aspartate aminotransferase (AST)
• Increase in blood urea nitrogen (BUN) levels
• Increase in C-reactive protein (CRP)
• Increase or decrease in blood glucose levels
• Increase in bilirubin
• Hepatic encephalopathy (brain damage caused by toxin buildup due to severe liver disease)
• Dizziness
• Fatigue
• Arthralgia (joint pain)
• Myalgia (muscle pain)
• Musculoskeletal chest pain
• Menstrual abnormalities
• Dysmenorrhea (painful menstruation)
• Urinary tract infection
• Influenza
• Rash
• Acne
• Eczema
• Pruritus (itching)
• Conjunctivitis (inflammation of the conjunctiva, the membrane on the whites of the eyes and the inner surface of eyelids)
• Tonsillitis (inflammation of the tonsils)

Information contained herein is not intended to cover all possible side effects, precautions, warnings, drug interactions, allergic reactions, or adverse effects. Check with your doctor or pharmacist to make sure these drugs do not cause any harm when you take them along with other medicines. Never stop taking your medication and never change your dose or frequency without consulting your doctor.

Generic and brand names of CFTR potentiator drugs include:

• elexacaftor/tezacaftor/ivacaftor
• ivacaftor
• Kalydeco
• lumacaftor/ivacaftor
• Orkambi
• Symdeko
• tezacaftor/ivacaftor
• Trikafta