Care for children with asthma is optimized when pharmacists

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1 P R A C T I C E G U I D E L I N E S Elaine Lau, BScPhm, PharmD, MSc Pharmacist-specific summary of pediatric asthma guidelines Care for children with asthma is optimized when pharmacists actively collaborate with other members of the child s health care team. To enable pharmacists to be effective respiratory health care team members, the following best practice guidelines in the management of pediatric asthma by pharmacists were adapted directly from the 2003 Canadian Pediatric Asthma Consensus Guidelines 1 and the 2006 Global Initiative for Asthma (GINA) pediatric guidelines. 2 This information applies to children up to 18 years old. The pediatric guidelines have many similarities to the adult ones, but also highlight management considerations unique to children. Avoid exposure to cigarette smoke. Advise parents not to smoke in the house or in the car. Encase mattress and box spring in an allergy-resistant cover. Wash bedding in hot water at least once a week. Replace carpets with hardwood floors or tiles. Keep pets out of the home, or at least out of the child s bedroom. Wash the pet at least once a week to control dander. Install an air filter. Use an air conditioner and keep the doors and windows shut as much as possible. Use acetaminophen instead of ibuprofen for pain or fever. I. Identify and refer children who may have asthma Asthma diagnosis in children <6 years of age depends on history and physical examination. 1,2 As frontline health care providers, pharmacists may be the first to encounter children with symptoms and can screen for patients who may need treatment. Refer children to their physicians for further assessment of asthma if they meet any of the following criteria: 1,3 Severe episode of wheezing or dyspnea Wheezing or dyspnea after 1 year of age Three or more episodes of wheezing Chronic cough, especially at night or exercise-induced Clinical response to asthma medications (e.g., inhaled bronchodilators) Colds repeatedly go to the chest or take more than 10 days to resolve II. Educate patients about triggers Pharmacists can provide advice on avoiding or reducing exposure to allergen or irritant triggers. Evaluate exposure to individualize environmental control measures. Allergy testing in children 3 and older is a reasonable measure to determine sensitivity to environmental allergens. Significant allergens include dust mites, animal dander, pollen, and mould. Nonallergic triggers include viral respiratory tract infections, cigarette smoke, exercise, cold air, chemicals, and medications such as nonsteroidal anti-inflammatory drugs (NSAIDs). Recommend the following measures to avoid or reduce exposure to known triggers: 2 Vaccinate children with asthma annually for influenza. Elaine Lau is the coordinator of Drug Information Services, Department of Pharmacy, at the Hospital for Sick Children in Toronto. Contact: elaine.lau@sickkids.ca. III. Assess a patient s asthma control according to specific criteria to optimize management Assess asthma control and the need for adjustments in maintenance therapy regularly, according to the criteria in Table 1. Assess and address reasons if asthma is uncontrolled. Common reasons for suboptimal asthma control in children are similar to those in adults and include: Lack of parental awareness about goals of asthma therapy and what adequate control is Lack of objective measurements of asthma severity; e.g., forced expiratory volume in 1 second (FEV 1 ), peak expiratory flow (PEF) Author s practice tips Identify education opportunities by targeting patients who may be at risk of uncontrolled asthma, such as newly diagnosed patients, patients who are frequently refilling their short-acting bronchodilators but not their ICS, and patients with a recent hospital visit for asthma. A high number of rescue inhalers dispensed is another indicator of poorly controlled asthma. Consider all medication changes to be trials, and re-evaluate regularly. Medication nonadherence, lack of technique follow-up, and disrupted continuity of care are common barriers to asthma management. Refer to specific manufacturer instructions for technique instructions on each device. Educating and communicating with patients concerning action plans and exacerbations is important. S 1 8

2 TABLE 1 Levels of asthma control 3 Daytime symptoms Limitation of activities Nocturnal symptoms/awakening Lung function (PEF) Controlled (all of the following) #2 times/wk Normal Partially controlled (any measure present in any week) >2 times/wk Any Any <80% predicted or personal best (if known) >2 times/wk $1/y Uncontrolled $3 features of partially controlled asthma present in any week Need for reliever/rescue treatment Exacerbations #2 times/wk 1 in any week Abbreviations: PEF = peak expiratory flow; wk = week(s); y = year(s). Note: Review maintenance treatment after any exacerbation to ensure it is adequate. By definition, an exacerbation in any week makes that an uncontrolled asthma week. Note: Lung function testing is not reliable in children 6 and younger. Note: The use of more than 12 reliever/rescue inhalers per year indicates uncontrolled asthma. Reproduced with permission from the Global Initiative for Asthma (GINA), Underuse of written action plans Underuse of inhaled corticosteroids (ICS) and overreliance on short-acting b 2 Use of anti-inflammatory agents that may be less effective than inhaled ICS as monotherapy; e.g., cromolyns, leukotriene-receptor antagonists (LTRA) Exposure to triggers Poor inhaler technique Medication nonadherence IV. Make evidence-based recommendations for maintenance drug therapy Inhaled corticosteroids Recommend ICS for maintenance therapy for children with any type of persistent asthma (symptoms 3 times per week). Consider ICS for maintenance therapy for children with symptoms <3 times per week. 1,2 table 2 Comparative dose equivalencies for inhaled corticosteroids in children <12 years of age 3,4 Drug beclomethasone dipropionate MDI (HFA) Qvar, generics budesonide DPI Pulmicort Turbuhaler budesonide nebulizer Pulmicort Nebuamp fluticasone propionate DPI or MDI plus spacer Flovent Diskus, Flovent HFA Low dose Moderate dose High dose >1000 Abbreviations: MDI = metered-dose inhaler; DPI = dry powder inhaler; HFA = hydrofluoroalkane. This table is adapted from the 5th edition of Therapeutic Choices, p. 644, copyright Canadian Pharmacists Association, Select doses of ICS according to the severity of disease (e.g., low dose for mild severity) and titrate to effect, depending on control (see Table 2). The clinical benefits of intermittent treatment with highdose ICS for children with intermittent, viral-induced wheeze remain controversial. Carefully monitor children placed on this form of therapy. If this form of therapy fails, recommend treating with inhaled steroids administered on a long-term basis, at least during the season(s) when the child is at risk of asthma exacerbations. 1 Leukotriene receptor antagonists Recommend LTRA for children who cannot or will not use ICS. Address parental concerns about ICS (e.g., side effects) and discuss the risk-benefit of using ICS vs LTRA. While LTRA may have fewer adverse effects and more convenient dosing than ICS, they are not as effective as monotherapy for maintenance treatment. 1 Monitor asthma control carefully and replace with ICS if control is not achieved. If asthma control is inadequate on low doses of ICS, recommend add-on therapy with LTRA as an alternative to increasing to moderate to high doses of the ICS. 1,2 Long-acting ß 2 Long-acting b 2 (LABA) can be used as add-on therapy in children older than 5 whose asthma is inadequately controlled on moderate doses of ICS. There is insufficient evidence to recommend LABA for add-on therapy in younger children. Avoid LABA monotherapy. 1,2 Combination inhalers Combination inhalers (ICS/LABA) are as effective as multiple single-agent inhalers, more convenient, and help to ensure compliance with ICS. 2 A budesonide/formoterol combination has recently been approved for use as both a daily maintenance and reliever therapy in patients 12 years and older according to the SMART protocol. However, it should only be used in patients whose asthma is not adequately controlled with low- to medium-dose ICS or whose disease severity warrants treatment S 1 9

3 TABLE 3 Asthma medications commonly used for children 4 Drug Dose Comments Class: Inhaled b 2, short-acting (SABA) salbutamol Airomir MDI, Ventolin Diskus, Ventolin HFA MDI, Ventolin Nebules P.F., generics MDI 100 mcg/puff: adult doses may be required due to poor deposition 4-11 y: 1 inhalation tid-qid; max 400 mcg/d $12 y: 1-2 inhalations tid-qid; max 800 mcg/d Diskus 200 mcg/blister: $4 y: 1 inhalation tid-qid; max 800 mcg/d Nebules: 5-12 y: mg as a single dose; max 5 mg. May repeat qid Prevents exercise-induced bronchospasm for up to 2-4 h. Provides relief and information on asthma control in that regular use indicates poor control, use of $1 canister per month associated with increased risk of asthma mortality. terbutaline Bricanyl Turbuhaler DPI 0.5 mg/puff: $6 y: 1 inhalation prn. Max 6 puffs/24 h See salbutamol. Inhaled b 2, long-acting (LABA) formoterol fumarate Foradil Aerolizer formoterol fumarate dihydrate Oxeze Turbuhaler salmeterol Serevent Corticosteroids, inhaled (ICS) beclomethasone Qvar, generics budesonide Pulmicort Turbuhaler, Pulmicort Nebuamp 6 ciclesonide Alvesco DPI 12 mcg/capsule: 6 16 y: 1 capsule inhaled q12h in the morning and evening; max 48 mcg/d DPI: 6 16 y: 6 12 mcg q12h; max 24 mcg/daily Diskhaler 50 mcg/blister: $4 y: 1 blister q12h Diskus 50 mcg/puff: $4 y: 1 inhalation q12h Individualize dose. Adult doses may be required due to poor deposition. MDI: mcg/d divided bid 5 11 y: 50 mcg bid; max 100 mcg bid Individualize dose. DPI: 6-12 y: mcg/d divided bid Nebules: Individualize dose. 3 mo 12 y: mg bid; may h to 1 mg bid MDI: $12 y: mcg daily. Individualize dose; max 800 mcg daily divided bid Not to be used as monotherapy. May be used to provide protection from exerciseinduced bronchospasm for 10 h, although SABA are preferred. 2 See formoterol fumarate. Not for immediate relief. May be used to provide protection from exerciseinduced bronchospasm for 10 h, although SABA are preferred. 2 Follow linear growth every 3 6 mo with regular asthma reassessments. Short-term growth rate may be slowed during first year of ICS use but is not shown to be sustained. No evidence to date that ICS impact final adult height. Dysphonia and candidiasis can be decreased by use of spacer with MDI and rinsing after use. Dose response studies show majority of corticosteroid effect on asthma control is achieved with doses under 800 mcg/day of beclomethasone dipropionate or equivalent; children requiring more than this on a regular basis should be assessed by a specialist. Regular re-evaluation required to ensure that lowest effective dose of ICS being used to maintain control. See beclomethasone. See beclomethasone. fluticasone Flovent HFA, Flovent Diskus Individualize dose. Adult doses may be required due to poor deposition. MDI, DPI: >16 y: mcg bid; max 1000 mcg bid 4 16 y: mcg bid; may h to 200 mcg bid MDI: 12 mo 4 y: mcg bid See beclomethasone. Younger children need relatively higher doses of inhaled drug compared to older children. Their smaller airways, use of spacer devices and increased nasal breathing result in reduced drug delivery efficiency. 5 S 2 0

4 Drug Dose Comments Corticosteroid/LABA combinations budesonide/formoterol fumarate dihydrate Symbicort DPI 100/6 mcg or 200/6 mcg: $12 y: 1 2 inhalations once or bid; max 4 inhalations daily for maintenance therapy, may h temporarily to 4 inhalations bid for worsening asthma Fixed-dose combination inhalers are more convenient, enhance compliance, ensure the patient receives their ICS with their LABA and are less expensive than the individual agents combined. A disadvantage is a loss in dosing flexibility. SMART strategy dosing: 1 2 inhalations bid or 2 inhalations once daily + additional doses prn rapid symptom relief (1 additional inhalation prn. If symptoms persist, an additional inhalation can be taken. No more than 6 inhalations on any single occasion. Maximum daily dose is 8 inhalations.) fluticasone/salmeterol Advair MDI, Advair Diskus Leukotriene receptor antagonists (LTRA) montelukast Singulair MDI 125/25 mcg or 250/25 mcg: $12 y: 2 inhalations bid Diskus 100/50 mcg: 4 11 y: 1 inhalation bid $15 y: 10 mg at bedtime 6 14 y: 5 mg, chewable at bedtime 2 5 y: 4 mg, chewable or granules at bedtime Fixed-dose combination inhalers are more convenient, enhance compliance, ensure the patient receives their ICS with their LABA and are less expensive than the individual agents combined. A disadvantage is a loss in dosing flexibility. Levels may i by carbamazepine, rifampin, phenytoin. zafirlukast Accolate $12 y: 20 mg bid 1 h before or 2 h after meals May h levels by ASA; may potentiate effect of warfarin; monitor INR and adjust dose as necessary; may h theophylline levels; levels may i by erythromycin, carbamazepine, rifampin, phenobarbital, phenytoin. Anti-inflammatories, miscellaneous ketotifen Zaditen, generics <3 y: 0.5 mg po bid $3 y: 1 mg po bid May require 8 12 wk for effect. Clinical effectiveness, i.e., reduction in use of rescue bronchodilator, rescue oral steroids and in exacerbations, most noted in children aged 4 mo to 18 y with mild asthma. IgE-neutralizing antibody omalizumab Xolair Glucocorticoids, oral 2,7 $12 y: Variable dosing depending on serum IgE and body weight Store at 2 8 C. Reconstituted product may be stored for up to 8 h at 2 8 C. Do not inject more than 150 mg at 1 site. After start of treatment, do not use serum IgE for dose adjustment. Omalizumab raises IgE levels, which may persist for up to a year after end of treatment. prednisone/prednisolone 1 2 mg/kg/d once daily for 3 5 days. No need to taper Although prednisone is the drug of choice for oral therapy in adults, its bitter taste has led to the use of equivalent doses of more palatable liquid preparations of prednisolone (1 2 mg/kg/d once daily) or dexamethasone ( mg/kg/d once daily) in children. dexamethasone 0.3 mg/kg/d once daily for 3 5 days. No need to taper Note: Dosage adjustment may be required in renal dysfunction. Abbreviations: DPI = dry powder inhaler; MDI = metered-dose inhaler. Note: The balance of evidence does not support the use of LABA for the prevention of exercise-induced bronchospasm. This table was adapted from the 5th edition of Therapeutic Choices, copyright Canadian Pharmacists Association, with 2 maintenance therapies. It should not be used by patients whose asthma can be managed by occasional SABA use, or ICS with occasional SABA use. 5 Inhaled short-acting ß 2 Recommend inhaled short-acting b 2 (SABA) as needed for the symptomatic treatment of acute asthma and for prophylaxis of exercise-induced asthma (given 15 to 30 minutes before exercise). SABA may be used as monotherapy in children with mild intermittent asthma and as an adjunct to maintenance therapy in children with persistent asthma. 2 V. Make evidence-based recommendations for treating acute asthma exacerbations The ICS dose may be increased two- to fourfold at the onset of an exacerbation. Recommend short courses (e.g., 3 to 5 days) of oral steroids to gain rapid control of severe acute exacerbations or for long-term prevention of symptoms of severe, persistent asthma. Repeat attempts to reduce systemic steroids and maintain control with inhaled steroids. 1,2 Consider medication therapy changes as a trial, and reevaluate periodically. If good control is sustained, consider gradual reductions in maintenance therapy to determine mini- S 2 1

5 table 4 Choosing an inhaler device for children with asthma 1 Age Preferred device Alternate device <4 years 4 6 years >6 years Metered-dose inhaler plus spacer device with face mask Metered-dose inhaler plus spacer with mouthpiece Dry powder inhaler or metered-dose inhaler ± spacer with mouthpiece Nebulizer with face mask Nebulizer with mouthpiece Nebulizer with mouthpiece Each child should be assessed individually to determine the most appropriate device. mal therapy needed to maintain control (e.g., taper ICS dose once control is achieved, at 2- to 3-month intervals). 1,2 VI. Help select the appropriate inhalation device to administer medications Aerosol therapy is now the mainstay of asthma management in children; however, delivering aerosolized drugs to young children is challenging. Be prepared to help select an age-appropriate device (including spacer if needed), teach patients and parents how to use it, and regularly assess inhaler technique regardless of the device type and patient s age. Metered-dose inhalers (MDI) with a spacer device may be used in all pediatric age groups, including infants ($6 months) and toddlers. Once children reach the age of 9 or 10, they may be able to use an MDI without a spacer device, but assess their ability to coordinate actuation and inhalation. The Aerochamber is the most commonly used spacer device in Canada, and is available with a mask in 2 pediatric sizes, as well as adult models with either a mask or a mouthpiece. The smaller orange mask is used in children up to 1 year of age. The larger yellow mask is used from 6 months to 4 years, depending on fit. Before dispensing the device, properly assess mask fit and assess if the patient is breathing with enough force to open the valves of the holding chamber, to prevent unnecessary purchases, frustration, and treatment failures. Children should switch from mask to mouthpiece as soon as they are old enough to take a slow, deep breath through the mouth (usually around 4 to 5 years old), which increases delivery efficiency. Recommend dry powder inhalers (DPI) such as the Turbuhaler or Diskus whenever possible to children over 6, as they may be simpler than MDI. Younger children do not have the inspiratory flow rates necessary to disperse the powder, particularly during acute exacerbations when drugs are needed most. Manufacturers can supply devices or whistles to verify the inspiration rate necessary to use a particular DPI. Teenagers may prefer DPI because of their discreet size. VII. Counsel patients on using inhalation devices and spacers Carefully instruct parents of young children about the importance of an optimal mask seal, good technique, and cooperation during administration. Use demonstrations and illustrated instructions to teach both children and their parents how to use inhaler devices. Check patients technique at every visit. Refer to manufacturer-specific instructions for each device. VIII. Promote education and self-management Pharmacists are in a unique position to educate children and their families about basic asthma facts, recognizing symptoms, minimizing exposure to common triggers, using reliever and preventer medications, proper inhaler technique, and monitoring and preventing medication side effects. 1 All patients should monitor their asthma using symptoms or PEF measurement and have written action plans for self-management. Work with patients and their physicians to ensure that each child has a written asthma action plan that includes the goals of therapy, clear instructions on monitoring symptoms, how and when to adjust medications in response to severity and frequency of symptoms and/or PEF measurements, and when to seek medical attention. Consider socioeconomic and cultural factors when designing asthma education programs for children. 1 n References 1. Becker A, Lemière C, Bérubé D, et al. Summary of recommendations from the Canadian Asthma Consensus Guidelines 2003 and Canadian Pediatric Asthma Consensus Guidelines CMAJ 2005;173 (Suppl 6):S1-S Global Initiative for Asthma (GINA) Global Strategy for Asthma Management and Prevention, Available: asp??l1=2&l2=1&intid=60 (accessed Sept. 19, 2007). 3. Global Initiative for Asthma (GINA). Pocket guide for asthma management and prevention in children: a pocket guide for physicians and nurses (updated 2006). Available: (accessed Sept. 19, 2007). 4. Montgomery M. Asthma in infants and children. Therapeutic Choices. 5th ed. Gray J, editor. Ottawa: Canadian Pharmacists Association; Available: www. e-therapeutics.ca (accessed June 24, 2007). 5. Symbicort Turbuhaler product monograph. In: Repchinsky C, editor. Compendium of Pharmaceuticals and Specialties. Ottawa: Canadian Pharmacists Association; 2007: p Pulmicort Nebuamp product monograph. In: Repchinsky C, editor. Compendium of Pharmaceuticals and Specialties. Ottawa: Canadian Pharmacists Association; 2007: p Lau E, ed. Hospital for Sick Children Drug handbook and formulary. 26th ed. Toronto: The Hospital for Sick Children; S 2 2