CF Drug Therapy

CF Drug Therapy

CF drug therapy can include:

Mucolytics

Dornase alpha (Pulmozyme®) is a recombinant human deoxyribonuclease (rhDNase). In those with CF Doranse alpha hydrolyses the DNA of sputum and reduces the viscosity enabling airway clearance with the potential to increase lung function and reduce exacerbations. Dornase alpha is inhaled via a nebulizer daily.

Hydrator therapy

• Bronchitol® is a dry powder mannitol that rehydrates the airway surface by correcting the impaired mucocilliary clearance. It improves lung function by promoting clearance of retained secretions by a more effective cough. Bronchitol® delivered via a dry powder inhaler twice daily.
• Inhaled Hypertonic Saline (HTS) increases mucocilliary clearance and improves clinical outcomes in children and adults with CF. Accelerated sodium transport at the cellular level dehydrates the airway and impairs mucous clearance. Nebulized HTS increases airway hydration and mucous clearance thus improving lung function, reducing the use of antibiotics and exacerbation frequency.

Antimicrobial Therapy

Antimicrobial therapy has been strongly associated with increase survival in those with CF. Long-term use of antibiotics has been significant in slowing lung decline, we do need an awareness of the burden of care for these patients. Many patients will be taking, oral antibiotics, inhaled antibiotics, pancreatic enzymes, vitamins, physiotherapy, inhaled bronchodilators.

Parkins M, Floto, R 2015 JoCF

• Azithromycin® is often prescribed for children in subtherapeutic doses. These macrolides are thought to suppress pro -inflammatory cytokines and reduce the neutrophil burden on the lungs.
• Tobramycin Inhaled Powder (TOBI®) The introduction of inhaled tobraymicin in was a significant milestone in CF therapy. It is indicated for the management of P. aeruginosa.

CFTR (cystic fibrosis transmembrane conductance regulator) Modulator therapy

CFTR modulators are a new drug therapy that differs from other CF therapies because they aim to improve or restore the function of the defective CFTR protein rather than offer symptomatic treatment. These therapies are mutation specific. The individual modulators act in different ways to improve the mutant protein function by potentiating action at the cell surface (increasing CFTR channel opening) or correcting the defect by increasing the amount of CFTR protein at the cell surface.

• Kalydeko® – used in G551D gating mutation. Kalydeko® binds to the defective protein, potentiating the channel opening (gating) of the CFTR protein. Chloride can flow through and regulate the amount of water and cell level.
• Orkambi® – a combination corrector therapy for those with two copies of the F508 del mutation. It facilitates increased chloride transport by helping the CFTR protein to become the right shape to get to the cell membrane. Used with Kalydeko® the gate is opened and more chloride flows through and redices the symptoms of CF.
• Symdeko® – is a combination of Tezacaftor® and Orkambi®. Patients must have 2 copies of F508 del. Tezacaftor® facilitates the cellular and processing and trafficking of normal and mutant forms of CFTR which increases the amount of mature CFTR delivered to the cell surface. Orkambi can potentiate the CFTR to the cell surface by Tezacaftor thus increasing the quantity and function of the CFTR at the cell surface and improving the chloride transport.
• VX – 445 – is a next generation CFTR corrector designed to restore 508del CFTR function. Currently phase 3 clinical trials are underway testing the triple combination therapy of VX-445 with Tezacaftor® (first generation CFTR corrector) and Kalydeco® (CFTR potentiator).

Gastro Intestinal

• Pancreatic Enzymes. Creon® is prescribed for pancreatic exocrine insufficiency and the slow release formula is formulated to deliver enzymes to the duodenum. Pancreatic enzyme replacement therapy (PERT). It needs to be given with food (meals and snacks) and dose is related to fat intake/day.
• Proton pump inhibitor PPI. Long-term PPI use is common in the CF population for treatment of gastro-oesophageal reflux disease (GORD).
• Vitamin Supplementation. Those with CF especially the pancreatic insufficient are at risk of fat soluble vitamin deficiencies. VitABDECK® is a CF specific multivitamin for routine supplementation.
• Salt replacement. Because of increased sweat losses all those with CF are at risk of sodium deficiency and increased risk of dehydration. Salt replacement therapy is recommended in Western Australia and Queensland.