Cystic Fibrosis Medication

Medications used to treat patients with cystic fibrosis may include pancreatic enzyme supplements, multivitamins (particularly fat-soluble vitamins), mucolytics, antibiotics (including inhaled, oral, or parenteral), bronchodilators, anti-inflammatory agents, and CFTR potentiators.

Class Summary

These agents aid digestion when the pancreas is malfunctioning. Current pancreatic enzyme preparations are derived from porcine extracts and contain various proportions of lipase, amylase, and protease. Most of the preparations are available in multiple strengths.

A particular dose is prescribed based on clinical symptoms and age and weight and then modified according to the clinical response. Usually, the dose of pancreatic enzymes should not exceed 2000 U/kg/meal of lipase. The novel preparation TheraCLEC-Total, a highly purified microbiologically-derived enzyme preparation, is under investigation in clinical trials.

Pancrelipase (Creon, Pancreaze, Ultresa, Zenpep)

These enteric-coated pancreatic enzyme microspheres contain various amounts of lipase, protease, and amylase. Pancrelipase assists in the digestion of protein, starch, and fat.

Class Summary

Vitamins are organic substances required by the body in small amounts for various metabolic processes. They may be synthesized in small or insufficient amounts in the body or not synthesized at all, thus requiring supplementation. They are classified as fat or water soluble. Vitamins A, D, E, and K are fat soluble while biotin, folic acid, niacin, pantothenic acid, B vitamins (ie, B-1, B-2, B-6, B-12), and vitamin C are generally water soluble.

Vitamin deficiency may result from an inadequate diet, increased requirements (eg, pregnancy, lactation), or secondary to disease or drug use. Vitamins are clinically used for the prevention and treatment of specific vitamin deficiency states. Supplementation of fat-soluble vitamins is routine in cystic fibrosis because of chronic malabsorption.

Vitamins, fat soluble

Vitamins A, D, E, and K are fat-soluble vitamins and are essential for antioxidant effects and as coenzymes for biological pathways, neurodevelopment, bone development, and coagulation. Typical multivitamin preparations formulated especially for patients with CF are referred to as ADEKs. Doses vary by patient age.

Class Summary

Albuterol provides selective agonistic action on beta2-adrenoceptors. Stimulation of adenyl cyclase results in smooth muscle relaxation of the bronchi, uterus, and skeletal muscle.

Inhaled beta2-agonists are often administered before chest physical therapy for airway clearance. They also are indicated when clinical evidence of bronchial hyperresponsiveness exists. In children with CF, the use of bronchodilators must be evaluated. Children with bronchiectasis may have a paradoxic bronchodilatation in response to beta-adrenergic agents. Pulmonary function testing before and after bronchodilators is suggested to avoid these counterproductive effects.

Albuterol (AccuNeb, Proventil HFA, VoSpire ER, Ventolin HFA)

Albuterol is the most commonly used bronchodilating agent. It is available in multiple dosage forms (eg, solution for nebulization, metered-dose inhaler, PO solution). Typically, 2.5 mg of albuterol nebulizer solution is used either in premixed solution with isotonic sodium chloride solution or 0.5 mL of albuterol solution is mixed with 3 mL of 0.9% NaCl and administered before chest physical therapy.

Class Summary

Large amounts of neutrophil-derived DNA released from dead neutrophils increase sputum viscosity. Mucolytics, such as dornase alfa, an enzyme that hydrolyses the DNA, are used in patients with CF to improve airway clearance.

The Pulmonary Therapies Committee of Cystic Fibrosis Foundation recommends long-term use of hypertonic saline for patients with cystic fibrosis aged 6 years or older to improve lung function and to reduce the number of exacerbations.^[40]

Dornase alfa (Pulmozyme)

Dornase alfa is a recombinant human DNase (rhDNase) that cleaves and depolymerizes extracellular DNA and separates DNA from proteins. This allows endogenous proteolytic enzymes to break down the proteins, thus decreasing viscoelasticity and surface tension of purulent sputum.

Class Summary

Cystic fibrosis transmembrane conductance regulator (CFTR) potentiators are the first available treatment that targets the defective CFTR protein, which is the underlying cause of cystic fibrosis.

Ivacaftor (Kalydeco)

Ivacaftor potentiates the CFTR protein, a chloride channel present at the surface of epithelial cells in multiple organs. This facilitates increased chloride transport by potentiating the channel-open probability (or gating) of the G551D-CFTR protein. It is indicated for cystic fibrosis in adults and children older than 6 years who have a G551D mutation in the CFTR gene; it is not effective if the patient is homozygous for the F508del mutation in the CFTR gene.

Class Summary

Antibiotic treatment may vary from a short course of one antibiotic agent to a continuous course with multiple antibiotics administered via various routes, including oral, intravenous, or inhalation. Because patients with cystic fibrosis have a larger lean body mass, they often have a higher clearance rate for many antibiotics. Achieving effective levels in respiratory secretions is difficult; higher doses of antibiotics and monitoring of aminoglycoside levels are required.

A Cochrane review included four studies (total 328 patients) comparing once-daily dosing of aminoglycosides in the treatment of acute pulmonary exacerbation with thrice-daily dose. There were no significant differences in lung function, weight for height, and body mass index. The creatinine changes significantly favored once-daily treatment in children but not in adults. These findings support the recent trend to use once-daily intravenous aminoglycosides.^[50]

Administer aerosolized antibiotics when the airway pathogens are resistant to oral antibiotics or when the infection is difficult to control at home. Aerosolized antibiotics may reduce symptoms by reducing the organism density in the airways. Other advantages include prevention of infection or delay of chronic colonization, treatment of acute infection, and treatment of bacterial colonization in patients following transplantation to prevent infection in the transplanted lungs.

Agents used in the aerosolized form include gentamicin, aztreonam, colistin, and preservative-free high-dose tobramycin especially formulated for inhalation (ie, TOBI). Currently, clinical trials using a powder form of tobramycin and colistin are under way. These preparations use novel delivery devices and shorten the time required for dosage administration.

Cephalosporins are effective against staphylococci and Haemophilus influenzae. A small subset of third-generation cephalosporins is effective against Pseudomonas aeruginosa. Generally speaking, moving from first-generation to third-generation cephalosporins gives increasing gram-negative coverage and less gram-positive coverage.

Fluoroquinolones are effective against most gram-positive and gram-negative organisms. They are the only class of oral antibiotics effective against P aeruginosa. The most commonly used medication in this class is ciprofloxacin. No fluoroquinolones are approved for children because of concern regarding their effects on deposition in the cartilage. However, studies from Europe have reported substantial evidence of their safety in patients with CF.

In patients with colonization with P aeruginosa, azithromycin administered orally 3 times per week on a long-term basis has been shown to improve lung function and nutritional status and to reduce acute pulmonary exacerbations.^[51]

Since colonization with P aeruginosa is considered to be an unfavorable event in the clinical course of patients with cystic fibrosis, various regimens have been studied in an attempt to eradicate the organism. A group in Italy compared inhaled tobramycin plus oral ciprofloxacin with inhaled colistin plus oral ciprofloxacin. They reported 62.8% and 65.2% eradication, respectively, thus showing no superiority for either treatment.^[52]

Tobramycin (TOBI)

Preservative-free high-dose tobramycin especially formulated for inhalation (ie, TOBI) has been reported to be safe and effective in patients older than 6 months.^[53] The usual dose is 300 mg twice daily administered during alternate months. Long-term intermittent administration in patients with P aeruginosa infection improves pulmonary function and nutritional status and reduces symptomatic pulmonary exacerbation.

Systemic tobramycin is usually combined with one of the penicillins used to treat pseudomonad infections in patients with CF. It is administered intravenously.

Aztreonam inhalation (Azactam, Cayston)

Aztreonam is a monobactam antibiotic that elicits activity in vitro against gram-negative aerobic pathogens, including P aeruginosa. This agent binds to penicillin-binding proteins of susceptible bacteria, thereby inhibiting bacterial cell wall synthesis, resulting in cell death. Activity is not decreased in the presence of cystic fibrosis lung secretions.

Aztreonam is indicated to improve respiratory symptoms in patients with CF who are infected with P aeruginosa.

Gentamicin

Gentamicin is usually combined with one of the penicillins used to treat pseudomonad infections in patients with CF.

Piperacillin

Piperacillin is effective against most strains of P aeruginosa and H influenzae. It is usually not effective against staphylococci. It is administered intravenously.

Cephalexin (Keflex)

Cephalexin is a first-generation cephalosporin that arrests bacterial growth by inhibiting bacterial cell wall synthesis. It has bactericidal activity against rapidly growing organisms. Its primary activity is against skin flora.

Ceftazidime (Fortaz, Tazicef)

Ceftazidime is a third-generation cephalosporin with broad-spectrum gram-negative activity. It has lower efficacy against gram-positive organisms; higher efficacy against resistant organisms. It arrests bacterial growth by binding to one or more penicillin-binding proteins.

Ciprofloxacin (Cipro XR, Proquin XR)

Ciprofloxacin is a fluoroquinolone with activity against Pseudomonas organisms, streptococci, methicillin-resistant Staphylococcus aureus (MRSA), S epidermidis, and most gram-negative organisms, but with no activity against anaerobes. This agent inhibits bacterial DNA synthesis and, consequently, growth. Oral bioavailability is lower in younger patients with CF (65%) than in those older than 13 years (95%).

Trimethoprim and sulfamethoxazole (Bactrim DS, Septra DS)

The broad spectrum and action of trimethoprim and sulfamethoxazole (TMP-SMZ) against organisms found in patients with CF and the convenience of oral administration make this combination useful for treatment of milder infections on an outpatient basis.

Chloramphenicol

Chloramphenicol is effective against H influenzae and staphylococcal species. It may help treat P aeruginosa infection, for unclear reasons. Oral chloramphenicol is no longer available in the United States.