Treatment algorithm

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer

ACUTE

neonates with meconium ileus/partial distal intestinal obstruction

1st line – water-soluble contrast enema plus oral osmotic agents

Back
ACUTE
|
neonates with meconium ileus/partial distal intestinal obstruction
1st line – 

water-soluble contrast enema plus oral osmotic agents

Abnormal salt and water balance in the intestine can lead to inspissations of stool and intestinal mucus, usually in the terminal ileum (i.e., meconium ileus in the neonate and distal intestinal obstruction syndrome thereafter).

These are usually partial obstructions that can be managed medically using water-soluble contrast enemas and oral administration of osmotic agents, though specifics will vary by institution.[122]

Primary options

lactulose: consult specialist for guidance on dose

2nd line – surgery

Back
ACUTE
|
neonates with meconium ileus/partial distal intestinal obstruction
2nd line – 

surgery

If there is failure of medical management, surgery is indicated to resolve the obstruction.[2]​ Laparoscopic surgery may reduce complications relative to open surgery.[123]

Plus – nasogastric decompression and supportive therapy

Back
ACUTE
|
neonates with meconium ileus/partial distal intestinal obstruction
Plus – 

nasogastric decompression and supportive therapy

Treatment recommended for ALL patients in selected patient group

While the surgical team is being notified, the patient should be made nil per os. A nasogastric tube may be placed for drainage. Fluid and electrolyte balance should be maintained within normal ranges through close monitoring of serum electrolytes and the use of intravenous fluids.

complete intestinal obstruction or peritonitis

1st line – surgery

Back
ACUTE
|
complete intestinal obstruction or peritonitis
1st line – 

surgery

If there is complete intestinal obstruction or signs of peritonitis, surgery is indicated.[2]​ Laparoscopic surgery may reduce complications relative to open surgery.[123]

Plus – nasogastric decompression and supportive therapy

Back
ACUTE
|
complete intestinal obstruction or peritonitis
Plus – 

nasogastric decompression and supportive therapy

Treatment recommended for ALL patients in selected patient group

While the surgical team is being notified, the patient should be made nil per os. A nasogastric tube may be placed for drainage. Fluid and electrolyte balance should be maintained within normal ranges through close monitoring of serum electrolytes and the use of intravenous fluids.

acute respiratory infection

1st line – oral antibiotic

Back
ACUTE
|
acute respiratory infection
|
with mild exacerbation
1st line – 

oral antibiotic

Mild exacerbations generally respond to oral antibiotic therapy with or without inhaled antibiotics (tobramycin or aztreonam).[15][67]​​​ The typical duration of antibiotic therapy is 14 days.[107]

Primary options

amoxicillin/clavulanate: children: 45-90 mg/kg/day orally given in divided doses every 12 hours; adults: 875 mg orally every 12 hours

More

OR

amoxicillin: children: 80-90 mg/kg/day orally given in divided doses every 12 hours; adults: 1000 mg orally every 8 hours

OR

sulfamethoxazole/trimethoprim: children >2 months of age: 6-12 mg/kg/day orally given in divided doses every 12 hours; adults: 160-320 mg orally every 12 hours

More

OR

linezolid: children: 30 mg/kg/day orally given in divided doses every 8 hours; adults: 600 mg orally every 12 hours

Plus – increased chest physical therapy

Back
ACUTE
|
acute respiratory infection
|
with mild exacerbation
Plus – 

increased chest physical therapy

Treatment recommended for ALL patients in selected patient group

Airway clearance techniques are used to mobilize secretions from the airway walls into the lumen for expectoration, providing clear short-term benefits.[48][49]​​​​​​ Therapy should be individualized throughout life, according to developmental stage, patient preference, and clinical symptoms.[50][51]

Methods include manual chest physical therapy, active cycle of breathing, autogenic drainage, vibrating devices (e.g., flutter or high-frequency chest wall oscillators, such the Vest™), and positive expiratory pressure (PEP) devices.[52][53]​​​​​​[54][55][56]​​​​​​ These effectively increase the expectorated sputum volume, reduce its viscoelasticity, and relieve dyspnea.[57]​ Patients usually require more than one technique at a time; for example, it is common to use the Vest™ with active cycle of breathing, PEP, or huffing and coughing.[58]

Plus – inhaled bronchodilator

Back
ACUTE
|
acute respiratory infection
|
with mild exacerbation
Plus – 

inhaled bronchodilator

Treatment recommended for ALL patients in selected patient group

Short-acting bronchodilators are generally given before the use of hypertonic saline and airway clearance.[61]​ A spacer may be required for drug delivery.

Primary options

albuterol inhaled: (90 micrograms/dose metered-dose inhaler) children and adults: 90-180 micrograms (1-2 puffs) every 4-6 hours when required

Plus – inhaled mucolytic

Back
ACUTE
|
acute respiratory infection
|
with mild exacerbation
Plus – 

inhaled mucolytic

Treatment recommended for ALL patients in selected patient group

Daily use of dornase alfa is recommended for patients ages ≥6 years, with the strongest evidence for use in patients with moderate-to-severe disease.[46]​ Treatment for at least 6 months may improve lung function and decrease pulmonary exacerbations, but it may also cause voice alteration and rash.[62]

Inhaled hypertonic saline is recommended for use in patients over 6 years of age.[46]

Inhaled hypertonic saline can modestly improve lung clearance when given to children ages <6 years with CF.[63]​ One multicenter, randomized, double-blind trial found that inhaled hypertonic saline had a positive effect on lung structural changes in children ages 3-6 years with cystic fibrosis.[64]

May be delivered by nebulizer. In the absence of any device showing consistent superiority over another, choice depends on suitability for the chosen therapies, local availability, and patient preference.[59]

Primary options

dornase alfa inhaled: children and adults: 2.5 mg nebulized once or twice daily

and

hypertonic saline inhaled

Consider – noninvasive ventilation ± oxygen

Back
ACUTE
|
acute respiratory infection
|
with mild exacerbation
Consider – 

noninvasive ventilation ± oxygen

Treatment recommended for SOME patients in selected patient group

Noninvasive ventilation (NIV) may be a useful adjunct to other airway clearance techniques, particularly in people who have difficulty expectorating mucus. When used in addition to oxygen, it can improve gas exchange during sleep to a greater extent than oxygen therapy alone in moderate-to-severe disease.[60]

Consider – inhaled antibiotic

Back
ACUTE
|
acute respiratory infection
|
with mild exacerbation
Consider – 

inhaled antibiotic

Treatment recommended for SOME patients in selected patient group

Mild exacerbations generally respond to an oral antibiotic with or without inhaled tobramycin or aztreonam.

When treating an initial or new growth of Pseudomonas aeruginosa (including recurrences after at least 1 year free of infection), inhaled tobramycin for 28 days is preferred for eradication.[65]

May be delivered by nebulizer. In the absence of any device showing consistent superiority over another, choice depends on suitability for the chosen therapies, local availability, and patient preference.[59]

Primary options

tobramycin inhaled: children ≥6 years of age and adults: 300 mg inhaled (nebulizer solution) twice daily, or 112 mg inhaled (oral inhalation) twice daily; use for 28 days followed by 28 days off then repeat cycle

OR

aztreonam inhaled: children ≥7 years of age and adults: 75 mg inhaled (nebulizer solution) three times daily; use for 28 days followed by 28 days off then repeat cycle

1st line – intravenous antibiotics

Back
ACUTE
|
acute respiratory infection
|
with moderate or severe exacerbation
1st line – 

intravenous antibiotics

Moderate and severe exacerbations are usually treated with intravenous antibiotics. The typical duration of antibiotic therapy is 14 days.[107]

An aminoglycoside such as tobramycin is usually combined with one or two antibiotics that have Staphylococcus or Pseudomonas coverage, depending on suspected or known colonization and the exacerbation severity. If no improvement is observed, a different antibiotic is usually tried.[108][109]​​ 

One systematic review found little evidence that antimicrobial susceptibility testing predicts clinical response to treatment.[112]​ However, treatment typically varies with the infection. For example, S aureus is treated with oxacillin, while linezolid and vancomycin are generally reserved for methicillin-resistant S aureus. P aeruginosa and Burkholderia cepacia can both be treated with ceftazidime or piperacillin/tazobactam, but the most effective strategy is unclear.[14][15]​​[113]​​​

In severe infection with resistant strains, aztreonam, imipenem/cilastatin, or meropenem can be used.

Drug levels should be monitored appropriately. Disease-specific changes can accelerate aminoglycoside clearance and may necessitate higher doses to reach therapeutic levels. Be vigilant for adverse drug reactions.

Primary options

tobramycin: children and adults: 3.3 mg/kg intravenously every 8 hours, or 10 mg/kg intravenously every 24 hours

-- AND --

oxacillin: children: 100-200 mg/kg/day intravenously given in divided doses every 4-6 hours, maximum 12 g/day; adults: 0.25 to 1 g intravenously every 4-6 hours

or

ceftazidime sodium: children: 150 mg/kg/day intravenously given in divided doses every 8 hours; adults: 2000 mg intravenously every 8 hours

or

piperacillin/tazobactam: children: 400 mg/kg/day intravenously given in divided doses every 6 hours; adults: 4000 mg intravenously every 6 hours

More

or

aztreonam: children: 200 mg/kg/day intravenously given in divided doses every 6 hours; adults: 2000 mg intravenously every 6 hours

or

imipenem/cilastatin: children: 100 mg/kg/day intravenously given in divided doses every 6 hours; adults: 1000 mg intravenously every 6 hours

More

or

meropenem: children: 120 mg/kg/day intravenously given in divided doses every 8 hours; adults: 2000 mg intravenously every 8 hours

or

linezolid: children: 30 mg/kg/day intravenously given in divided doses every 8 hours; adults: 600 mg intravenously every 12 hours

or

vancomycin: children: 40-60 mg/kg/day intravenously given in divided doses every 6 hours; adults: 1000 mg intravenously every 12 hours

Plus – increased chest physical therapy

Back
ACUTE
|
acute respiratory infection
|
with moderate or severe exacerbation
Plus – 

increased chest physical therapy

Treatment recommended for ALL patients in selected patient group

Airway clearance techniques are used to mobilize secretions from the airway walls into the lumen for expectoration, providing clear short-term benefits.[48]​​[49]​​​​​​​ Therapy should be individualized throughout life, according to developmental stage, patient preference, and clinical symptoms.[50][51]

Methods include manual chest physical therapy, active cycle of breathing, autogenic drainage, vibrating devices (e.g., flutter or high-frequency chest wall oscillators, such the Vest™), and positive expiratory pressure (PEP) devices.[52][53]​​​​​​[54][55][56]​​​​​​ These effectively increase the expectorated sputum volume, reduce its viscoelasticity, and relieve dyspnea.[57]​ Patients usually require more than one technique at a time; for example, it is common to use the Vest™ with active cycle of breathing, PEP, or huffing and coughing.[58]

Plus – inhaled bronchodilator

Back
ACUTE
|
acute respiratory infection
|
with moderate or severe exacerbation
Plus – 

inhaled bronchodilator

Treatment recommended for ALL patients in selected patient group

Short-acting bronchodilators are generally given before the use of hypertonic saline and airway clearance.[61] A spacer may be required for drug delivery.

Primary options

albuterol inhaled: (90 micrograms/dose metered-dose inhaler) children and adults: 90-180 micrograms (1-2 puffs) every 4-6 hours when required

Plus – inhaled mucolytic

Back
ACUTE
|
acute respiratory infection
|
with moderate or severe exacerbation
Plus – 

inhaled mucolytic

Treatment recommended for ALL patients in selected patient group

Daily use of dornase alfa is recommended for patients ages ≥6 years, with the strongest evidence for use in patients with moderate-to-severe disease.[46]​ Treatment for at least 6 months may improve lung function and decrease pulmonary exacerbations, but it may also cause voice alteration and rash.[62]

Inhaled hypertonic saline is recommended for use in patients over 6 years of age.[46]

Inhaled hypertonic saline can modestly improve lung clearance when given to children ages <6 years with CF.[63]​ One multicenter, randomized, double-blind trial found that inhaled hypertonic saline had a positive effect on lung structural changes in children ages 3-6 years with cystic fibrosis.[64]

May be delivered by nebulizer. In the absence of any device showing consistent superiority over another, choice depends on suitability for the chosen therapies, local availability, and patient preference.[59]

Primary options

dornase alfa inhaled: children and adults: 2.5 mg nebulized once or twice daily

and

hypertonic saline inhaled

Consider – noninvasive ventilation ± oxygen

Back
ACUTE
|
acute respiratory infection
|
with moderate or severe exacerbation
Consider – 

noninvasive ventilation ± oxygen

Treatment recommended for SOME patients in selected patient group

Noninvasive ventilation (NIV) may be a useful adjunct to other airway clearance techniques, particularly in people who have difficulty expectorating mucus. When used in addition to oxygen, it can improve gas exchange during sleep to a greater extent than oxygen therapy alone in moderate-to-severe disease.[60]

ONGOING

respiratory disease

1st line – chest physical therapy

Back
ONGOING
|
respiratory disease
1st line – 

chest physical therapy

Airway clearance techniques are used to mobilize secretions from the airway walls into the lumen for expectoration, providing clear short-term benefits.[48][49]​​​​​​​​ Therapy should be individualized throughout life, according to developmental stage, patient preference, and clinical symptoms.[50][51]

Methods include manual chest physical therapy, active cycle of breathing, autogenic drainage, vibrating devices (e.g., flutter or high-frequency chest wall oscillators, such the Vest™), and positive expiratory pressure (PEP) devices.[52][53]​​​​​​[54][55][56]​​​​​​ These effectively increase the expectorated sputum volume, reduce its viscoelasticity, and relieve dyspnea.[57]​ Patients usually require more than one technique at a time; for example, it is common to use the Vest™ with active cycle of breathing, PEP, or huffing and coughing.[58]

Plus – inhaled bronchodilator

Back
ONGOING
|
respiratory disease
Plus – 

inhaled bronchodilator

Treatment recommended for ALL patients in selected patient group

Short-acting bronchodilators are generally given before the use of hypertonic saline and airway clearance.[61]​ A spacer may be required for drug delivery.

Primary options

albuterol inhaled: (90 micrograms/dose metered-dose inhaler) children and adults: 90-180 micrograms (1-2 puffs) before airway clearance

Plus – inhaled mucolytic

Back
ONGOING
|
respiratory disease
Plus – 

inhaled mucolytic

Treatment recommended for ALL patients in selected patient group

Daily use of dornase alfa is recommended for patients ages ≥6 years, with the strongest evidence for use in patients with moderate-to-severe disease.[46]​ Treatment for at least 6 months may improve lung function and decrease pulmonary exacerbations, but it may also cause voice alteration and rash.[62]

Inhaled hypertonic saline is recommended for use in patients over 6 years of age.[46]

Inhaled hypertonic saline can modestly improve lung clearance when given to children ages <6 years with CF.[63]​​ 

May be delivered by nebulizer. In the absence of any device showing consistent superiority over another, choice depends on suitability for the chosen therapies, local availability, and patient preference.[59]

Primary options

dornase alfa inhaled: children and adults: 2.5 mg nebulized once or twice daily

and

hypertonic saline inhaled

Consider – inhaled antibiotic (with Pseudomonas coverage)

Back
ONGOING
|
respiratory disease
Consider – 

inhaled antibiotic (with Pseudomonas coverage)

Treatment recommended for SOME patients in selected patient group

When treating an initial or new growth of Pseudomonas aeruginosa, inhaled tobramycin for 28 days is preferred, with or without oral antibiotics.[15][65]​​​​

Intravenous antibiotics offer no clear advantages over oral antibiotics for the sustained eradication of new isolates (including after at least 1 year free of infection).[66][67]​ Early infection may be easier to eradicate.

Chronic colonization with P aeruginosa is associated with a more rapid decline in lung function. Inhaled antibiotics can be used in these patients, and may improve lung function and exacerbation rates.[68]​ Evidence is stronger for patients with moderate-to-severe than mild disease.[46][69][70]​​

May be delivered by nebulizer. In the absence of any device showing consistent superiority over another, choice depends on suitability for the chosen therapies, local availability, and patient preference.[59]

Primary options

tobramycin inhaled: children ≥6 years of age and adults: 300 mg inhaled (nebulizer solution) twice daily, or 112 mg inhaled (oral inhalation) twice daily; use for 28 days followed by 28 days off then repeat cycle

Consider – anti-inflammatory agent (macrolide, ibuprofen)

Back
ONGOING
|
respiratory disease
Consider – 

anti-inflammatory agent (macrolide, ibuprofen)

Treatment recommended for SOME patients in selected patient group

Antiinflammatory agents are used to control airway inflammation, either alone or in combination based on patient need.

Prophylactic azithromycin has become increasingly important for chronic P aeruginosa colonization, where treatment can improve lung function and decrease the frequency of pulmonary exacerbations.[46][78]​​​​ Azithromycin may be given from age 3-6 months to reduce airway inflammation, pulmonary exacerbations, and hospitalizations in the first year of life, although it does not affect the extent of structural lung disease.[79]

Due to the risk of antibiotic resistance, azithromycin monotherapy should be withheld from any patient with active infection by nontuberculous mycobacteria. It is appropriate to screen patients for nontuberculous mycobacteria before starting azithromycin therapy, and at 6- or 12-month intervals thereafter.

Ibuprofen can protect against lung function decline, decrease intravenous antibiotic requirements, improve nutritional status, and improve chest radiography findings. However, it is not widely used due to frequent gastrointestinal adverse effects.[80] ​The Cystic Fibrosis Foundation recommends long-term oral ibuprofen to slow lung function decline in patients ages 6-18 years who have an FEV₁ of >60% predicted.[46][81] [ Cochrane Clinical Answers logo ] ​​ In patients ages >18 years, there is insufficient evidence to recommend for or against long-term use.

Primary options

azithromycin: children ≥6 years of age and adults: 250 mg orally three times weekly (e.g., Monday, Wednesday, Friday)

OR

ibuprofen: children ≥6 years of age and adults: 20-30 mg/kg orally twice daily, maximum 1200-2400 mg/day; consult specialist for further guidance on dose for this indication

Consider – inhaled corticosteroid

Back
ONGOING
|
respiratory disease
Consider – 

inhaled corticosteroid

Treatment recommended for SOME patients in selected patient group

Inhaled corticosteroids are often used in patients with CF and comorbid asthma or allergic bronchopulmonary aspergillosis (ABPA), rather than as a treatment for CF lung disease. More specifically they are used in patients who have significant bronchiolar reactivity and have shown a therapeutic response.[46]​ There is limited evidence as to whether they are beneficial and safe in the treatment of CF.[82]

May be delivered by nebulizer. In the absence of any device showing consistent superiority over another, choice depends on suitability for the chosen therapies, local availability, and patient preference.[59]

Primary options

fluticasone propionate inhaled: (44, 110, or 220 micrograms/dose metered-dose inhaler) children ≥4 years of age: 88 micrograms inhaled twice daily initially, adjust dose according to response, maximum 176 micrograms/day; children ≥12 years of age and adults: 88 micrograms inhaled twice daily initially, adjust dose according to response, maximum 1760 micrograms/day

OR

budesonide inhaled: (0.125 mg/mL, 0.25 mg/mL, or 0.5 mg/mL nebules) children ≥12 months of age: consult specialist for guidance on dose; children ≥12 years of age and adults: 0.5 to 2 mg nebulized twice daily

OR

budesonide inhaled: (90 or 180 micrograms/dose dry powder inhaler) children ≥6 years of age: 180-360 micrograms inhaled twice daily initially, adjust dose according to response, maximum 720 micrograms/day; adults: 180-360 micrograms inhaled twice daily initially, adjust dose according to response, maximum 1440 micrograms/day

Consider – cystic fibrosis transmembrane conductance regulator (CFTR) modulator

Back
ONGOING
|
respiratory disease
Consider – 

cystic fibrosis transmembrane conductance regulator (CFTR) modulator

Treatment recommended for SOME patients in selected patient group

Cystic fibrosis transmembrane conductance regulator (CFTR) modulators are small molecules that can partially restore function in mutated CFTR.[83] There are two main types of CFTR modulator approved for clinical use: potentiators (ivacaftor) and correctors (lumacaftor, tezacaftor, and elexacaftor).

Potentiators increase the amount of time that the CFTR channel is open and target class III and IV mutations. Correctors help the CFTR protein form so that it can move to the cell surface, and are used in combination with a potentiator to target class II mutations.

Ivacaftor is a potentiator that acts by helping the CFTR channel to open properly, thereby normalizing airway surface liquid and helping to re-establish mucociliary clearance. Ivacaftor is approved in the US for patients ages ≥1 month (age cut-off may vary in other countries) who have at least one mutation in the CFTR gene (including an R117H CFTR mutation) that is responsive to ivacaftor based on clinical and/or in-vitro assay data.[84][85][86]​ It is licensed to treat more than 95 gene mutations in patients with CF. Ivacaftor monotherapy is not effective in patients who are homozygous for the F508del mutation, the most frequent genotype in patients with CF.[87]

Lumacaftor/ivacaftor, a combination CFTR modulator, is approved in the US for patients ages ≥1 year (age cut-off may vary in other countries) who are homozygous for the F508del mutation in the CFTR gene. It is not effective for other mutations.

Tezacaftor/ivacaftor, a combination CFTR modulator, is approved in the US for patients ages ≥6 years (age cut-off may vary in other countries) who are homozygous for the F508del mutation, or who have at least one mutation in the CFTR gene that is responsive to tezacaftor/ivacaftor based on in-vitro data and/or clinical evidence.

Elexacaftor/tezacaftor/ivacaftor is a combination of three CFTR modulators. It is approved in the US for patients ages ≥2 years (age cut-off may vary in other countries) with at least one F508del mutation or a mutation in the CFTR gene responsive to elexacaftor/tezacaftor/ivacaftor based on in-vitro data.

Triple therapy (elexacaftor/tezacaftor/ivacaftor) is the preferred option.[1]​ Dual therapy (lumacaftor/ivacaftor or tezacaftor/ivacaftor) should be reserved for cases where triple therapy is not tolerated or the patient is <6 years old. Corrector monotherapy is not recommended.[1]

Oral granule formulations, which can be mixed with soft food or liquid, are available for younger children.

Primary options

elexacaftor/tezacaftor/ivacaftor and ivacaftor: children 2 to 5 years of age and <14 kg: 80 mg (elexacaftor)/40 mg (tezacaftor)/60 mg (ivacaftor) once daily in the morning and 59.5 mg (ivacaftor) once daily in the evening, doses should be approximately 12 hours apart; children 2-5 years of age and ≥14 kg: 100 mg (elexacaftor)/50 mg (tezacaftor)/75 mg (ivacaftor) once daily in the morning and 75 mg (ivacaftor) once daily in the evening, doses should be approximately 12 hours apart; children 6-11 years of age and <30 kg: 100 mg (elexacaftor)/50 mg (tezacaftor)/75 mg (ivacaftor) once daily in the morning and 75 mg (ivacaftor) once daily in the evening, doses should be approximately 12 hours apart; children ≥6 years of age and ≥30 kg and children ≥12 years of age and adults: 200 mg (elexacaftor)/100 mg (tezacaftor)/150 mg (ivacaftor) once daily in the morning and 150 mg (ivacaftor) once daily in the evening, doses should be approximately 12 hours apart

Secondary options

ivacaftor: children 1-2 months of age and ≥3 kg: 5.8 mg orally every 12 hours; children 2-3 months of age and ≥3 kg: 13.4 mg orally every 12 hours; children 4-5 months of age and ≥5 kg: 25 mg orally every 12 hours; children 6 months to 5 years of age and 5 kg to <7 kg: 25 mg orally every 12 hours; children 6 months to 5 years of age and 7 kg to <14 kg: 50 mg orally every 12 hours; children 6 months to 5 years of age and ≥14 kg: 75 mg orally every 12 hours; children ≥6 years of age and adults: 150 mg orally every 12 hours

OR

lumacaftor/ivacaftor: children 1-2 years of age and 7-8 kg: 75 mg (lumacaftor)/94 mg (ivacaftor) orally (granules) every 12 hours; children 1-2 years of age and 9-13 kg: 100 mg (lumacaftor)/125 mg (ivacaftor) orally (granules) every 12 hours; children 1-2 years of age and ≥14 kg: 150 mg (lumacaftor)/188 mg (ivacaftor) orally (granules) every 12 hours; children 2-5 years of age and <14 kg: 100 mg (lumacaftor)/125 mg (ivacaftor) orally (granules) every 12 hours; children 2-5 years of age and ≥14 kg: 150 mg (lumacaftor)/188 mg (ivacaftor) orally (granules) every 12 hours; children 6-11 years of age: 200 mg (lumacaftor)/250 mg (ivacaftor) orally (tablets) every 12 hours; children ≥12 years of age and adults: 400 mg (lumacaftor)/250 mg (ivacaftor) orally (tablets) every 12 hours

OR

tezacaftor/ivacaftor and ivacaftor: children 6-11 years of age and <30 kg: 50 mg (tezacaftor)/75 mg (ivacaftor) orally once daily in the morning and 75 mg (ivacaftor) once daily in the evening, doses should be approximately 12 hours apart; children 6-11 years of age and ≥30 kg and adults: 100 mg (tezacaftor)/150 mg (ivacaftor) orally once daily in the morning and 150 mg (ivacaftor) once daily in the evening, doses should be approximately 12 hours apart

Consider – noninvasive ventilation ± oxygen

Back
ONGOING
|
respiratory disease
Consider – 

noninvasive ventilation ± oxygen

Treatment recommended for SOME patients in selected patient group

Noninvasive ventilation (NIV) may be a useful adjunct to other airway clearance techniques, particularly in people who have difficulty expectorating mucus. When used in addition to oxygen, it can improve gas exchange during sleep to a greater extent than oxygen therapy alone in moderate-to-severe disease.[60]

2nd line – bilateral lung transplantation

Back
ONGOING
|
respiratory disease
2nd line – 

bilateral lung transplantation

Lung transplantation is reserved for candidates who have exhausted all alternatives. Referral is recommended for an FEV₁ <30% of predicted in adults and <40% of predicted in children.[116]​ Higher cut-offs are recommended in the presence of rapid decline or markers of shortened survival, including a poor 6-minute walk test, hypoxemia, hypercarbia, pulmonary hypertension, and low BMI.[116]​ In waitlist transplant candidates, obtain noninvasive CF-specific bacterial, fungal, and acid-fast bacillus respiratory cultures every 3 months, and review pathogen history to help guide the perioperative antibiotic regimen.[117]

Contraindications to lung transplantation vary between transplant centers but include sepsis, multiple organ dysfunction, documented history of nonadherence to treatment, colonization with certain genomovars of Burkholderia cepacia, class III obesity (BMI ≥40), and refractory gastroesophageal reflux. Relative contraindications in CF include renal insufficiency (GFR <25 mL/minute and/or evidence of structural renal disease), exceedingly poor functional status with inability to walk >600 feet consistently on a standard 6-minute walk test (depending on age of patient), a history of chemical pleurodesis, severe malnutrition with a BMI <16, colonization with highly virulent bacteria or fungi (or certain strains of mycobacterium), and poorly controlled diabetes mellitus. One systematic review of mortality after lung transplantation found higher rates associated with B cepacia complex, but not with FEV₁, pulmonary hypertension, CF-related diabetes, and female sex.[118]

Guidelines recommend consulting with at least two transplant centers before deciding that a patient is not a candidate for transplant.[118]​ Follow up with a multidisciplinary CF care team should resume within 6-12 months of transplant to ensure appropriate extrapulmonary CF care.[117]

gastrointestinal disease

1st line – monitoring and optimizing nutrition

Back
ONGOING
|
gastrointestinal disease
1st line – 

monitoring and optimizing nutrition

The patient should be monitored for their appetite; stooling habits, including quantity and quality; and presence of gastroesophageal reflux. An insatiable appetite along with large numbers of stools or bulky, greasy stools is consistent with fat and calorie malabsorption. A history of decreasing stool numbers over time, with or without abdominal distention or vomiting, may signal bowel obstruction. Patients are at increased risk of intussusception, which requires urgent surgical treatment.[119]

Therapy should be geared toward optimizing pancreatic enzyme replacement therapy (PERT) and good nutrition. If a patient continues to demonstrate poor weight gain or growth, oral caloric supplements may be used. Placement of a gastrostomy tube may sometimes be necessary to assist the patient in taking in enough calories to support growth.

Plus – pancreatic enzyme replacement

Back
ONGOING
|
gastrointestinal disease
|
with pancreatic insufficiency
Plus – 

pancreatic enzyme replacement

Treatment recommended for ALL patients in selected patient group

Pancreatic enzyme replacement therapy (PERT) is indicated to support growth and nutrition.[29][120]​​​ Enzyme replacements should include lipase, protease, and amylase, given with snacks and meals (“PERT treats the meal, not the pancreas”).[29]​ Adjustments are made for the patient's weight, stool frequency and character, pattern of growth, and food portions.

Stool softeners, laxatives, hydration, and at times prokinetic agents can be used alone or in combination to improve bowel habits and minimize recurrence.

Primary options

pancrelipase: dose depends on formulation and brand used; consult specialist for further guidance on dose

Consider – H2 antagonist or proton-pump inhibitor

Back
ONGOING
|
gastrointestinal disease
|
with pancreatic insufficiency
Consider – 

H2 antagonist or proton-pump inhibitor

Treatment recommended for SOME patients in selected patient group

Used to provide a more alkaline environment for pancreatic enzyme supplemental therapy, thus improving enzyme function.

Primary options

famotidine: children ≥3 months of age: 0.5 to 1 mg/kg orally twice daily, maximum 80 mg/day; adults: 20-40 mg orally once or twice daily

OR

lansoprazole: children ≥1 year of age and <30 kg body weight: 15 mg orally once daily; children ≥30 kg body weight and adults: 30 mg orally once daily

OR

omeprazole: children 5-9 kg: 5 mg orally once daily; children 10-19 kg: 10 mg orally once daily; children ≥20 kg and adults: 20 mg orally once daily

Plus – fat-soluble vitamin supplementation

Back
ONGOING
|
gastrointestinal disease
|
with pancreatic insufficiency
Plus – 

fat-soluble vitamin supplementation

Treatment recommended for ALL patients in selected patient group

Fat-soluble vitamins are given regularly according to nutritional recommendations. Cystic Fibrosis Trust (UK): diet and nutrition leaflets Opens in new window​ Serum blood levels are used to assess vitamin A, D, and E levels, while prothrombin time is used to assess vitamin K levels.

Often available in proprietary combination formulations. Consult product literature for guidance on dose.

Primary options

vitamin A (retinol)

-- AND --

ergocalciferol (vitamin D2)

or

cholecalciferol (vitamin D3)

-- AND --

alpha-tocopherol (vitamin E)

-- AND --

phytonadione (vitamin K1)

Plus – ursodiol

Back
ONGOING
|
gastrointestinal disease
|
with liver disease
Plus – 

ursodiol

Treatment recommended for ALL patients in selected patient group

CF-related liver disease presents with focal biliary fibrosis, porto-sinusoidal vascular disease, or both.

Typically, bile duct obstruction leads to periportal inflammation and fibrosis, which may develop into multilobular cirrhosis with portal hypertension.[125]​

Therapy for hepatobiliary disease is limited to oral bile acids (e.g., ursodiol).[112][126]​

Primary options

ursodiol: children and adults: 10-20 mg/kg/day orally

Consider – liver transplantation

Back
ONGOING
|
gastrointestinal disease
|
with liver disease
Consider – 

liver transplantation

Treatment recommended for SOME patients in selected patient group

Progression to liver failure (e.g., decompensated cirrhosis) is unpredictable and requires liaison with a liver transplant center.

Plus – antacid, H2 antagonist, or proton-pump inhibitor

Back
ONGOING
|
gastrointestinal disease
|
with gastroesophageal reflux
Plus – 

antacid, H2 antagonist, or proton-pump inhibitor

Treatment recommended for ALL patients in selected patient group

CF is often associated with gastroesophageal reflux and is treated with H2 antagonists first-line and proton-pump inhibitors second-line. By providing a more alkaline environment, these therapies also improve enzyme function in PERT.

Antacids are available over the counter. Consult product literature for guidance on dose.

Primary options

famotidine: children ≥3 months of age: 0.5 to 1 mg/kg orally twice daily, maximum 80 mg/day; adults: 20-40 mg orally once or twice daily

Secondary options

lansoprazole: children ≥1 year of age and <30 kg body weight: 15 mg orally once daily; children ≥30 kg body weight and adults: 30 mg orally once daily

OR

omeprazole: children 5-9 kg: 5 mg orally once daily; children 10-19 kg: 10 mg orally once daily; children ≥20 kg and adults: 20 mg orally once daily

Plus – cystic fibrosis transmembrane conductance regulator (CFTR) modulator

Back
ONGOING
|
gastrointestinal disease
|
with CFTR gene mutation
Plus – 

cystic fibrosis transmembrane conductance regulator (CFTR) modulator

Treatment recommended for ALL patients in selected patient group

Cystic fibrosis transmembrane conductance regulator (CFTR) modulators are small molecules that can partially restore function in mutated CFTR.[83] There are two main types of CFTR modulators approved for clinical use: potentiators (ivacaftor) and correctors (lumacaftor, tezacaftor, and elexacaftor).

Potentiators increase the amount of time that the CFTR channel is open and target class III and IV mutations. Correctors help the CFTR protein form so that it can move to the cell surface and are used in combination with a potentiator to target class II mutations.

​Ivacaftor is a potentiator that acts by helping the CFTR channel to open properly, thereby normalizing airway surface liquid and helping to re-establish mucociliary clearance. Ivacaftor is approved in the US for patients ages ≥1 month (age cut-off may vary in other countries) who have at least one mutation in the CFTR gene (including an R117H CFTR mutation) that is responsive to ivacaftor based on clinical and/or in-vitro assay data.[84][85][86]​​ It is licensed to treat more than 95 gene mutations in patients with CF. Ivacaftor monotherapy is not effective in patients who are homozygous for the F508del mutation, the most frequent genotype in patients with CF.[87]

Lumacaftor/ivacaftor, a combination CFTR modulator, is approved in the US for patients ages ≥1 year (age cut-off may vary in other countries) who are homozygous for the F508del mutation in the CFTR gene. It is not effective for other mutations.

Tezacaftor/ivacaftor, a combination CFTR modulator, is approved in the US for patients ages ≥6 years (age cut-off may vary in other countries) who are homozygous for the F508del mutation, or who have at least one mutation in the CFTR gene that is responsive to tezacaftor/ivacaftor based on in-vitro data and/or clinical evidence.

Elexacaftor/tezacaftor/ivacaftor is a combination of three CFTR modulators. It is approved in the US for patients ages ≥2 years (age cut-off may vary in other countries) with at least one F508del mutation or a mutation in the CFTR gene responsive to elexacaftor/tezacaftor/ivacaftor, based on in-vitro data.

Triple therapy (elexacaftor/tezacaftor/ivacaftor) is the preferred option.[1]​ Dual therapy (lumacaftor/ivacaftor or tezacaftor/ivacaftor) should be reserved for cases where triple therapy is not tolerated or the patient is <6 years old. Corrector monotherapy is not recommended.[1]

Oral granule formulations, which can be mixed with soft food or liquid, are available for younger children.

Primary options

elexacaftor/tezacaftor/ivacaftor and ivacaftor: children 2 to 5 years of age and <14 kg: 80 mg (elexacaftor)/40 mg (tezacaftor)/60 mg (ivacaftor) once daily in the morning and 59.5 mg (ivacaftor) once daily in the evening, doses should be approximately 12 hours apart; children 2-5 years of age and ≥14 kg: 100 mg (elexacaftor)/50 mg (tezacaftor)/75 mg (ivacaftor) once daily in the morning and 75 mg (ivacaftor) once daily in the evening, doses should be approximately 12 hours apart; children 6-11 years of age and <30 kg: 100 mg (elexacaftor)/50 mg (tezacaftor)/75 mg (ivacaftor) once daily in the morning and 75 mg (ivacaftor) once daily in the evening, doses should be approximately 12 hours apart; children ≥6 years of age and ≥30 kg and children ≥12 years of age and adults: 200 mg (elexacaftor)/100 mg (tezacaftor)/150 mg (ivacaftor) once daily in the morning and 150 mg (ivacaftor) once daily in the evening, doses should be approximately 12 hours apart

Secondary options

ivacaftor: children 1-2 months of age and ≥3 kg: 5.8 mg orally every 12 hours; children 2-3 months of age and ≥3 kg: 13.4 mg orally every 12 hours; children 4-5 months of age and ≥5 kg: 25 mg orally every 12 hours; children 6 months to 5 years of age and 5 kg to <7 kg: 25 mg orally every 12 hours; children 6 months to 5 years of age and 7 kg to <14 kg: 50 mg orally every 12 hours; children 6 months to 5 years of age and ≥14 kg: 75 mg orally every 12 hours; children ≥6 years of age and adults: 150 mg orally every 12 hours

OR

lumacaftor/ivacaftor: children 1-2 years of age and 7-9 kg: 75 mg (lumacaftor)/94 mg (ivacaftor) orally (granules) every 12 hours; children 1-2 years of age and 9-13 kg: 100 mg (lumacaftor)/125 mg (ivacaftor) orally (granules) every 12 hours; children 1-2 years of age and ≥14 kg: 150 mg (lumacaftor)/188 mg (ivacaftor) orally (granules) every 12 hours; children 2-5 years of age and <14 kg: 100 mg (lumacaftor)/125 mg (ivacaftor) orally (granules) every 12 hours; children 2-5 years of age and ≥14 kg: 150 mg (lumacaftor)/188 mg (ivacaftor) orally (granules) every 12 hours; children 6-11 years of age: 200 mg (lumacaftor)/250 mg (ivacaftor) orally (tablets) every 12 hours; children ≥12 years of age and adults: 400 mg (lumacaftor)/250 mg (ivacaftor) orally (tablets) every 12 hours

OR

tezacaftor/ivacaftor and ivacaftor: children 6-11 years of age and <30 kg: 50 mg (tezacaftor)/75 mg (ivacaftor) orally once daily in the morning and 75 mg (ivacaftor) once daily in the evening, doses should be approximately 12 hours apart; children 6-11 years of age and ≥30 kg and adults: 100 mg (tezacaftor)/150 mg (ivacaftor) orally once daily in the morning and 150 mg (ivacaftor) once daily in the evening, doses should be approximately 12 hours apart

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Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups. See disclaimer

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