Inhaled Corticosteroids


NAEPP

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GINA 2012

Estimated Equipotent Daily Doses of Inhaled Glucocorticosteroids for Adults and Children Older than 5 Years----

Low dose (mcg)----
Medium daily dose (mcg)----
High daily dose (mcg)----
Beclomethasone dipropionate CFC MDI----
(Not QVAR)
200-500
>500-1000
>1000-2000
Beclomethasone dipropionate HFA MDI-
100-250
>250-500
>500-1000
Budesonide
200-400
>400-800
>800-1600
Ciclesonide
80-160
>160-320
>320-1280
Fluticasone propionate
100-250
>250-500
>500-1000
Mometasone furoate
200-400
>400-800
>800-1200

Clinical usage notes:
  • Most patients achieve control with low dose of ICS, and in those who do not, only an additional 15-20% will have improved control with doubling of the dose
  • Onset of clinically significant effects
    • Symptoms improve in the first 1-2 weeks and will reach maximum improvement in 4-8 weeks
    • Lung function improvement begins in 1-2 weeks and usually plateaus at 4 weeks but may increase slightly thereafter for 6-8 weeks
    • Improvement in bronchial hyperresponsiveness requires 2-3 weeks and approaches maximum in 1-3 months but may continue to improve over 1 year
    • Maximum decrease in FeNO occurs within 1 week and returns to baseline levels within 1-2 weeks following discontinuation
    • Sensitivity to exercise challenge decreases after 4 weeks
    • Although the intensity of these responses can be dose dependent, the onset and offset of responses are not, nor do they differ significantly by which ICS is used



Symbicort SMART (Canada)

  • Single maintenance and reliever treatment, not US FDA approved
  • Instructions from Canadian package insert outlines 2 regimens adolescents/adults (12 and up):
    • 1-2 inhalations Symbicort 100 (100 mcg/6 mcg) BID or 2 inhalations QD.
      • Take 1 additional inhalation PRN if you feel symptoms. If symptoms persist after a few minutes, an additional inhalation should be taken. Not more than 6 inhalations should be taken on any single occasion.
      • The maximum recommended daily dose is 8 inhalations.
    • 1-2 inhalations Symbicort 200 Turbuhaler BID or 2 inhalations QD
      • Take 1 additional inhalation PRN if you feel symptoms. If symptoms persist after a few minutes, an additional inhalation should be taken. Not more than 6 inhalations should be taken on any single occasion.
      • The maximum recommended daily dose is 8 inhalations.



Anticholinergics

  • Spiriva HandiHaler DPI (tiotropium bromide) 18 mcg - 1 inh QD


Leukotriene Modifiers

  • Singulair (montelukast) - also approved for allergic rhinitis
    • Dosing
      • 6 months-5 years - 4 mg oral granules packet PO QD
      • 2-5 years - 4 mg chewable tablet PO QD
      • 6-14 years - 5 mg chewable tablet PO QD
      • ≥15 years - 10 mg tablet PO QD
      • ≥15 years for EIB - 10 mg tablet at least 2 hours before exercise
    • Neuropsychiatric events have been reported, including agitation, aggressive behavior or hostility, anxiousness, depression, disorientation, dream abnormalities, hallucinations, insomnia, irritability, restlessness, somnambulism, suicidal thinking and behavior (including suicide), and tremor

  • Zyflo CR (zileuton) - leukotriene synthesis (5-LO) inhibitor
    • Limited data shows benefit in aspirin-sensitive asthma, and might benefit "neutrophilic asthma" due to blockade of LTB4
    • ≥12 years - 1200 mg PO BID, within one hour after morning and evening meal
      • Contraindicated in active liver disease or persistent AST/ALT elevations ≥3x the upper limit of normal
      • Neuropsychiatric events have been reported
    • 2-4% develop hepatotoxicity, usually within first 6 months of treatment. Obtain LFTs, every month x 3 months, every 2-3 months for the remainder of the first year, and periodically (e.g. 6 months per Phil Lieberman) thereafter.
      • ALT considered the most sensitive indicator of liver injury from zileuton
      • If signs of liver dysfunction develop or transaminase elevations ≥5x upper limit of normal occur, discontinue and follow AST/ALT until normal




Anti-IgE





Related Controller Medication Issues


Asthma medications containing food allergens

  • Milk
    • Dry powder inhalers - except for Pulmicort Turbuhaler, all other DPIs (including Spiriva) available in the United States contain lactose which may be contaminated with cow's milk protein
    • Tablets
      • Singulair 4 mg granules & 10 mg tabs (but not 4 & 5 mg tabs)
      • Claritin tabs (but not liquid forms)
      • Benadryl 50 mg pink/white capsule (not caplet, chewable tabs or liquid)
      • Prednisone tabs (but not Pediapred)
    • Lactose intolerance and asthma medications - symptoms can occur if multiple lactose-containing medications are ingested. Lactose in DPIs is not likely an issue (Advair Diskus contains 12.5 mg lactose but 3 grams are needed to provoke symptoms, equivalent to amount found in 60 mL milk or 180 gram processed cheese).
  • Soy - CFC MDIs containing ipratropium (Atrovent CFC, Combivent) contain soy lecithin which may be contaminated with soy protein. New HFA forms of these inhalers and ipratropium nebulizer solutions do not contain soy lecithin.

MDI vs. Nebulizer

  • Administration of bronchodilator by MDI is 5-fold more efficient than delivery via nebulizer. (~2% of nebulized medication will reach the lungs compared with 10% an MDI dose).
  • The usual dose of albuterol delivered by nebulizer is 2.5 mg (2500 mcg) while 2 puffs from an MDI is 180 mcg. Using the above information, the dose delivered to the lung via nebulization would be 2% of 2500 mcg (50 mcg), compared with 10% of 180 mcg (18 mcg) delivered by MDI.
    • Thus, 2.5 mg albuterol via neb = ~5.5 puffs albuterol via MDI
  • Doses up to 20 puffs of albuterol is approximately equal to 2 mg oral albuterol


Sequence/timing of inhaled medications

  • There is no definitive evidence to indicate there is any advantage in using one type of inhaler before the other
    • It has been postulated that bronchodilators should be administered prior to ICS based on the rationale that bronchodilation would permit enhanced deposition of an ICS. However, bronchodilatation can take time and it is usually not achieved until 15-20 minutes after the inhalation of a SABA or formoterol and takes longer after salmeterol.
  • For most inhalers, 1-2 minutes between puffs is sufficient
  • For a bronchodilator, one might wish to wait 5-20 minutes to see if a second (or additional) inhalations are needed


Adrenal Suppression

  • Unlike other ICS medications, ciclesonide appears to have little or no suppressive effects on the HPA axis, and there is no evidence (and no case reports) of adrenal suppression with ciclesonide use
  • Adrenal suppression screening recommendations





References