Rhinitis - Allergic (1 of 15)

1 Patient presents w/ signs & symptoms of rhinitis

2 • Consider other classiﬁ cations of rhinitis DIAGNOSIS No - Please see Rhinitis Is allergic rhinitis - Nonallergic disease conﬁ rmed? management chart

Yes

3 ASSESS DURATION & SEVERITY OF ALLERGIC RHINITIS

A Non-pharmacological therapy • Allergen avoidance • Patient education

VAS <5 VAS ≥5

B Pharmacological therapy B Pharmacological therapy • Antihistamines (oral/nasal), &/or • Corticosteroids (nasal), w/ or without • Corticosteroids (nasal), or • Antihistamines (nasal), or • Cromone (nasal), or • LTRA • Leukotriene receptor antagonists (LTRA)MIMS

TREATMENT © See next page

Speciﬁ cally for patients w/ asthma Not all products are available or approved for above use in all countries. Speciﬁ c prescribing information may be found in the latest MIMS.

B167 © MIMS Pediatrics 2020 Rhinitis - Allergic (2 of 15)

Previously treated symptomatic Previously treated symptomatic patient (VAS <5) on antihistamines patient (VAS ≥5) on intensiﬁ ed (oral/nasal) &/or corticosteroids (nasal) therapy w/ corticosteroids (nasal) w/ or without antihistamines (nasal)

Intermittent Persistent symptoms, symptoms or without allergen w/ allergen exposure exposure

B Pharmacological therapy B Pharmacological therapy • Step down or discontinue therapy • Continue or step up therapy

Untreated REASSESS DISEASE SEVERITY VAS symptomatic patient DAILY UP TO DAY 3 (VAS <5 or ≥5)

4 CONTINUE Yes THERAPY & STEP EVALUATION VAS <5 DOWN THERAPY1 Improvement of symptoms?

No VAS ≥5

B Pharmacological therapy • Step-up therapy

REASSESS DISEASE SEVERITY MIMSVAS DAILY UP TO DAY 7 4 Yes EVALUATION VAS <5 Improvement of symptoms?

No TREATMENT © VAS ≥5 See next page

Continue therapy if symptomatic; consider step-down or discontinuation of therapy if symptoms subside

Not all products are available or approved for above use in all countries. Speciﬁ c prescribing information may be found in the latest MIMS.

B168 © MIMS Pediatrics 2020 Rhinitis - Allergic (3 of 15)

PATIENTS W/ MODERATE TO SEVERE SYMPTOMS VAS ≥5

• Review diagnosis • Review compliance • Assess for infections or other causes RHINITIS - ALLERGIC

Itch/sneeze major Rhinorrhea major Blockage major symptom symptom symptom

B Pharmacological B Pharmacological B Pharmacological B Pharmacological therapy therapy therapy therapy • Add or increase • Add antihistamines • Add Ipratropium • Add decongestant corticosteroids (nasal) (nasal) or (nasal) short-term oral corticosteroid

Improvement of symptoms? CONTINUE Yes THERAPY & C Immunotherapy No Improvement of Yes symptoms? STEP DOWN THERAPY1 No

C Immunotherapy D Surgical therapy Continue therapy if symptomatic; consider step-downMIMS or discontinuation of therapy if symptoms subside. ©

Not all products are available or approved for above use in all countries. Speciﬁ c prescribing information may be found in the latest MIMS.

B169 © MIMS Pediatrics 2020 Rhinitis - Allergic (4 of 15)

1 SIGNS & SYMPTOMS OF RHINITIS

• Rhinitis: Inﬂ ammation of the nasal lining membranes Major Signs & Symptoms • Nasal itching • Rhinorrhea • Nasal congestion, w/ or without obstruction •

RHINITIS - ALLERGIC Sneezing Other Signs & Symptoms • Headache • Conjunctival symptoms, eye pruritus • Pruritus of the nose, palate, ears • Postnasal drainage • Impaired smell

2 DIAGNOSIS

Allergic Rhinitis • IgE-mediated infl ammatory disease of the nasal mucous membrane occurring after exposure to allergens & trigger factors • Diagnosis relies primarily on the clinical history & physical exam • Most prevalent in childhood & adolescence • Careful elimination of nonallergic etiologies must be done in preschool children as allergic rhinitis is unusual in <3 years Clinical History • A family or personal history of allergic & related conditions - Asthma - Infantile eczema (atopic dermatitis) - Rhinitis, rhinosinusitis - Recurrent otitis media w/ or without eff usion • Investigate onset patterns of symptoms including triggers & seasonality, & relief w/ certain treatments • Social & environmental history - Exposure to allergens & trigger factors Physical Exam • Detect other diseases (eg asthma, atopic dermatitis, cystic fi brosis, otitis media or eustachian tube dysfunction) which may occur in relation w/ allergic rhinitis Nasal Exam • Can be carried out using a nasal speculum or by endoscopy - Endoscopy is done when symptoms persist despite treatment • May reveal the following: - Swollen nasal turbinates (note size & color) - Rhinorrhea w/ clear, cloudy or colored discharge - Viral infection, sinusitis is considered if colored discharge is noted • Patient should be referred to an ENT specialistMIMS if fi ndings are more consistent w/ a structural etiology than rhinitis (eg tumors, nasal polyps, septal deviation, etc) Other Physical Findings May Include: • Conjunctival injection & edema • Allergic shiners (dark circles under the eyes) • Morgan-Dennie lines (lower eyelid creases) • Periorbital edema • Allergic salute which gives rise to nasal crease • Dental malocclusion • Open-mouth breathing or allergic gape • Cobblestoning© (lymphoid hyperplasia)

B170 © MIMS Pediatrics 2020 Rhinitis - Allergic (5 of 15)

2 DIAGNOSIS (CONT’D)

Laboratory Studies Allergy Testing • Skin test: Used to diff erentiate allergic from nonallergic rhinitis & to identify the triggering agents • Allergen-specifi c IgE identifi cation corresponding to allergen exposure & symptomatic periods is confi rmatory of allergic rhinitis - Has high sensitivity & specifi city RHINITIS - ALLERGIC • Radioallergosorbent test (RAST) may also be used for the detection of allergen-specifi c IgE - Alternative for patients w/ extensive dermatitis or dermatographism, those at high-risk for anaphylaxis, patients taking drugs that may inhibit mast cell degranulation, & those who cannot tolerate skin test Nasal Smear • Eosinophils in the nasal smear usually indicate allergy; it may support the diagnosis of allergic rhinitis

3 ASSESSMENT

• Stepwise treatment approach depends on severity, duration & frequency of allergic rhinitis Symptom Duration of Allergic Rhinitis is Classifi ed into the Following: Intermittent • Symptoms occur <4 days/week or symptoms last for <4 consecutive weeks/year Persistent • Symptoms occur >4 days/week & last for >4 consecutive weeks/year Symptom Severity of Allergic Rhinitis is Classifi ed into the Following: Moderate-Severe 1 or more of the following • Sleep disturbance • Problems w/ functioning at work or at school • Impairment of routine & leisure activities • Bothersome symptoms Mild • Normal sleep • Normal functioning at work & school • Normal conduct of routine & leisure activities • No bothersome symptoms Patterns of Exposure to Allergens: Seasonal • Dependent on a specifi c season Perennial • Year-round allergen exposure & usually present in everyday environment Episodic • Patient is exposed to allergens not normallyMIMS encountered in daily activities ©

Not all products are available or approved for above use in all countries. Speciﬁ c prescribing information may be found in the latest MIMS.

B171 © MIMS Pediatrics 2020 Rhinitis - Allergic (6 of 15)

4 EVALUATION

Evaluation of Disease Control • e following factors are considered when evaluating a patient’s response to treatment: - Symptom scores - Measures of nasal obstruction (eg peak nasal inspiratory fl ow, acoustic rhinometry, rhinomanometry) - Allergic Rhinitis & its Impact on Asthma (ARIA) severity classifi cation - Quality of Life (QOL) result - Itemized scoring - Symptom-medication scoring - VAS - A low VAS score w/ the establishment of treatment (<5) shows an amount of improvement, as indicated in Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) as well as in terms of work effi ciency, & treatment is usually maintained or continued - VAS score of <2 means well-controlled allergic rhinitis & treatment is usually stepped down - A high VAS score (≥5) shows no eff ect in symptom relief & treatment is usually stepped up MACVIA-ARIA Sentinel NetworK for Allergic Rhinitis (MASK-Rhinitis) • A clinical approach used to diagnose & classify patients based on disease severity, as well as a tool to evaluate symptom control after initiation of treatment strategies by using Information & Communications Technology (ICT) tools & a clinical decision support system (CDSS) based on ARIA guidelines • Electronic monitoring of allergic diseases include a cell phone-based VAS assessment (uses MASK aerobiology which is a simple IOS/Android app), Control of Allergic Rhinitis & Asthma Test (CARAT), an e-Allergy screening & the RhinAsthma Patient Perspective (RAPP) tool for smartphones

A NON-PHARMACOLOGICAL THERAPY

Patient Education • Provide general information about the disease & available treatments - Manage the patient’s & caregiver’s expectations from therapy & explain that a complete cure may not be possible • Provide educational materials as necessary • Educate both patient & caregiver about the proper use & timing of medications especially during times when allergen exposure is unavoidable - Possible side eff ects should also be advised - Concomitant medications should also be reviewed to determine if the patient is taking drugs that may cause oral or nasal dryness • Educate the caregiver & the patient, if possible, about the complications of allergic rhinitis (eg otitis media & chronic sinusitis) Allergen Avoidance • Identifi cation & avoidance of trigger allergens should be an integral part of allergic rhinitis management strategy • Removal of the allergen may result in diminished severity of the disease & decreased requirement for medications • Identifying specifi c causal allergens by lab testing may encourage patients to comply w/ allergen avoidance instructions • Eff ectiveness of avoidance will be measured by relief of the patient’s symptoms & by a decrease in the need for medications MIMS • In the majority of cases, it is not possible to completely avoid allergens but these measures should be considered where appropriate Pets • Do not allow animals in the house • If this is not possible, keep pets out of patient’s bedroom, bathe pets once or twice daily House Dust Mites • Major allergen found in houses • Use allergen-impermeable covers for mattresses & pillows • Wash sheets & blankets in hot water (60o C) every week • Reduce indoor© humidity to around 50% (or 40-60%) (an air conditioner may reduce humidity in the summer) • Use high effi ciency particulate air fi lter when vacuuming or dust weekly w/ mask

Not all products are available or approved for above use in all countries. Speciﬁ c prescribing information may be found in the latest MIMS.

B172 © MIMS Pediatrics 2020 Rhinitis - Allergic (7 of 15)

A NON-PHARMACOLOGICAL THERAPY (CONT’D)

Allergen Avoidance (Cont’d) Pollen • Avoid outdoor exposure on days when pollen counts are high • Use of air conditioning is advisable • Keep doors & windows closed at home & when inside vehicles

RHINITIS - ALLERGIC Others • Discourage smoking by household members & visitors • Minimize contact w/ irritants (eg perfumes, hair spray & other odors) • Reduce growth of molds in the home by decreasing humidity & eliminating sites for mold growth

B PHARMACOLOGICAL THERAPY

Principles of erapy • A step-wise approach to treatment is recommended • Step-down therapy as patient’s symptoms improve & step-up when symptoms worsen • Combination/step-up therapy may be used in patients w/ inadequate response to monotherapy - Intranasal corticosteroids & oral antihistamines: Has better symptom control than monotherapy - Oral antihistamines & oral decongestant or leukotriene modifi ers: Showed better symptom control compared to monotherapy - Intranasal corticosteroids & leukotriene modifi ers: use should be limited if symptoms lessen or disappear w/ nasal steroids alone - Intranasal corticosteroids & intranasal antihistamines or intranasal Oxymetazoline: Showed better effi cacy than monotherapy Anticholinergics • Eg Ipratropium bromide • Eff ectively controls watery rhinorrhea, no eff ect on sneezing & nasal congestion • Onset of action is fast (15-30 minutes) • Adverse eff ects are infrequent; if present, usually localized & mild (eg nasal dryness, irritation, epistaxis) Antihistamines • First-line therapy for mild to moderate intermittent & mild persistent rhinitis • H1-receptor antagonists reduce nasal itching, sneezing & rhinorrhea, but are less eff ective for nasal congestion; also relieves ocular symptoms Nasal Antihistamines • Eg Azelastine, Olopatadine, Levocabastine • Rapid onset of action (<30 minutes) but relatively short-acting • May be used in children w/ seasonal allergic rhinitis to help reduce symptoms & nasal obstruction w/ minimal side eff ects Oral Antihistamines • Eg Acrivastine, Cetirizine, Chlorpheniramine, Desloratadine, Diphenhydramine, Fexofenadine, Levocetirizine, Loratadine • Preferred route for intermittent or persistent allergic rhinitis & may be used to prevent symptoms associated w/ occasional allergy exposure MIMS • 2nd generation antihistamines are ideal as 1st-line therapy in equal preference to nasal antihistamines • Preferred over oral LTRA for treatment of preschool children w/ persistent allergic rhinitis • Use of 1st generation antihistamines should be limited; may reduce academic ability in school children • Onset of action occurs in <1 hour Intraocular Antihistamines • May be used to relieve ocular symptoms of allergic rhinitis such as pruritus & redness Anti-Immunoglobulin E Antibody • Eg Omalizumab • Has been© shown to be eff ective in seasonal allergic rhinitis

Not all products are available or approved for above use in all countries. Speciﬁ c prescribing information may be found in the latest MIMS.

B173 © MIMS Pediatrics 2020 Rhinitis - Allergic (8 of 15)

B PHARMACOLOGICAL THERAPY (CONT’D)

Corticosteroids • Have strong anti-infl ammatory capacity & reduces nasal itching, sneezing, congestion & rhinorrhea Nasal Corticosteroids • Eg Beclomethasone, Budesonide, Ciclesonide, Flunisolide, Fluticasone, Mometasone, Triamcinolone • May be considered treatment for children w/ allergic rhinitis & is preferred over oral/nasal antihistamines & oral LTRA RHINITIS - ALLERGIC • Onset of action is relatively slow (12 hours), w/ maximum effi cacy after a few days - Ciclesonide: Onset of action is within 1 hour of use - Mometasone: Onset of action is within 12 hours of use • Caution is needed due to the possible eff ect on growth; regular height measurements are advised • In severe cases, nasal corticosteroids should be administered before the start of allergy season as prophylaxis Oral/IM Corticosteroids • IM agents are more invasive & expensive, & are less preferred • Oral corticosteroids are reserved for patients w/ refractory or severe symptoms not controlled by antihistamines or topical agents - Short course for 3-5 days may be helpful • erapy must be limited to lowest eff ective dose & shortest possible time Cromones (Nasal) • Recommended as an alternative treatment to antihistamines & corticosteroids • Less eff ective than antihistamines & nasal corticosteroids • An option due to its excellent safety profi le • Most effi cient if used regularly prior to onset of allergic symptoms but may be considered for symptomatic treatment (nasopharyngeal itchiness, sneezing, rhinorrhea, conjunctivitis) Decongestants • Sympathomimetic & relieves nasal congestion • Preparations containing Ephedrine, Oxymetazoline & Xylometazoline should not be used in patients <2 years of age Nasal/Topical Decongestants • Eg Oxymetazoline, Xylometazoline • Short courses may be used to immediately reduce severe nasal congestion • Because of the risk of rebound congestion (rhinitis medicamentosa), use should be limited to <10 days • Benefi cial prior to instillation of nasal corticosteroids Oral Decongestants • Eg Pseudoephedrine, Ephedrine • Not as eff ective as nasal decongestant; consider benefi ts versus safety concerns especially in patients <6 years old • Doesn’t have rebound congestion • May be used as additional medication w/ antihistamine, effi cacy is increased than either medication alone but w/ combined side eff ects Leukotriene Receptor Antagonists (LTRA) • Eg Montelukast • A therapeutic option used either alone orMIMS in combination w/ oral antihistamines or nasal corticosteroids; not to be used as initial therapy • May be used in children w/ seasonal allergic rhinitis, preschool children w/ persistent allergic rhinitis, & those w/ coexisting asthma • Effi cacy comparable to oral antihistamines & less than nasal corticosteroids Saline Solutions • May be used as single or adjunctive agents in reducing the symptoms & improving the quality of life - Can also help clear the nose before eating & sleeping • ere is no diff erence in radiologic or symptoms score when comparing isotonic w/ hypertonic saline, although hypertonic solutions have been shown to improve mucociliary clearance • Associated© w/ mild side eff ects (eg burning, irritation, nausea)

Not all products are available or approved for above use in all countries. Speciﬁ c prescribing information may be found in the latest MIMS.

B174 © MIMS Pediatrics 2020 Rhinitis - Allergic (9 of 15)

C IMMUNOTHERAPY

• Recommended for allergy testing-positive patients w/ inadequate response to pharmacologic therapy & allergen avoidance measures Principles of erapy • Repeated administration of specifi c allergens in patients w/ IgE-mediated conditions to provide protection against allergic symptoms associated w/ exposure to these allergens • Only intervention that alters the natural history of allergic rhinitis RHINITIS - ALLERGIC • Activates regulatory T cells, thereby altering humoral response to allergens by increasing CD8+ T cells & IL-10, & reducing IL-13 production • Indicated for patients w/ the following: - Evidence of specifi c IgE antibody to allergen (positive allergy test results) - Any of the following: - Clinically diagnosed w/ both allergic rhinitis & asthma - Required medications - Poor response to avoidance measures - Adverse eff ects to medications - Prevention of asthma in allergic rhinitis patients • Initial dose should be performed in a medical facility by a trained personnel • Recommended course is usually 4-5 years Subcutaneous Immunotherapy (SCIT) • May be considered in children whose seasonal allergic rhinitis is triggered by pollen exposure, & perennial rhinitis due to house dust mite • Effi cacy for allergic rhinitis is comparable to that of nasal glucocorticoids • Limited by frequent injection on regular basis & small risk of anaphylactic reactions Sublingual Immunotherapy (SLIT) • Sublingual & intranasal allergen-specifi c immunotherapy may be considered in children w/ allergic rhinitis due to pollen exposure • A more viable treatment compared to SCIT as self-administration is encouraged w/ this form • Use should be limited to those who can tolerate systemic reactions & its treatment • Auto/self-injectable Epinephrine should be prescribed to all patients receiving SLIT • Has been associated w/ mild oral & GI symptoms & less risk for anaphylaxis compared to SCIT

D SURGICAL THERAPY

Inferior Turbinate Reduction • May be oﬀ ered to patients w/ nasal airway obstruction & hypertrophic inferior turbinates who are unresponsive to pharmacological therapy • Should be reserved for patients w/ persistentMIMS allergic rhinitis ©

Not all products are available or approved for above use in all countries. Speciﬁ c prescribing information may be found in the latest MIMS.

B175 © MIMS Pediatrics 2020 Rhinitis - Allergic (10 of 15)

Dosage Guidelines

ANTICHOLINERGIC (NASAL) Available Drug Strength Dosage Remarks RHINITIS - ALLERGIC Ipratropium 0.06% spray ≥6 yr: 42 mcg Adverse Reactions bromide each nostril • Nasopharyngeal eff ects (epistaxis, nasal dryness); GI 8-12 hrly eff ects (buccal ulceration, nausea, constipation, paralytic ileus); Other eff ects (urinary retention, paradoxical bronchospasm, immediate hypersensitivity reactions, acute angle-closure glaucoma) Special Instructions • Use w/ caution in patients w/ bladder neck obstruction, narrow-angle glaucoma, renal/hepatic impairment

ANTIHISTAMINES & ANTIALLERGICS (ALLERGEN EXTRACTS) Available Drug Strength Dosage Remarks

Grass pollen 100 IR/mL Dissolve 1 tablet under Adverse Reactions allergen extract 300 IR/mL tongue for 2 min then • Nasopharyngeal eff ects (throat irritation, swallow 24 hrly oromucosal blistering, tongue/lip/mouth edema, tonsillitis, nasal congestion); Resp eff ects (bronchitis, asthma, dyspnea); CNS eff ects (headache, dizziness); Others (conjunctivitis, GI upset, chest pain, pruritus) Special Instructions • Use w/ caution in patients w/ oral surgery, dental extraction, galactose intolerance, childn <5 yr old • Start treatment 4 mth before & maintain therapy throughout pollen season House-dust mite 10 IR/mL Initial dose: Adverse Reactions allergen extract 300 IR/mL Day 1-6 (10 IR/mL): • Nasopharyngeal eff ects (throat irritation, (D pteronyssinus Spray under the tongue oromucosal blistering, tongue/lip/mouth & D farinae) w/ increasing doses/ edema, tonsillitis, nasal congestion); Resp day: 1, 2, 4, 6, 8, 10 eff ects (bronchitis, asthma, dyspnea); CNS sprays consecutively 24 eff ects (headache, dizziness); Other eff ects hrly until Day 6 (conjunctivitis, GI upset, chest pain, Day 7-9MIMS (300 IR/mL): pruritus) Spray under the tongue Special Instructions w/ increasing doses/ • Use w/ caution in patients w/ oral cavity day: 1, 2, 4 sprays infl ammation, oral lesions, fungal infection, consecutively 24 hrly recent tooth extraction, oral surgery, Maintenance dose modifi ed diet (strict low sodium diet) Day 10 onwards • Maintain sublingually for 2 min before (300 IR/mL): Spray 4x swallowing under the tongue © 24 hrly All dosage recommendations are for children w/ normal renal & hepatic function unless otherwise stated. Not all products are available or approved for above use in all countries. Products listed above may not be mentioned in the disease management chart but have been placed here based on indications listed in regional manufacturers’ product information. Specifi c prescribing information may be found in the latest MIMS.

B176 © MIMS Pediatrics 2020 Rhinitis - Allergic (11 of 15)

Dosage Guidelines

ANTIHISTAMINES & ANTIALLERGICS (NASAL) Available Drug Strength Dosage Remarks RHINITIS - ALLERGIC Azelastine 0.1% spray >6 yr: 1 spray each Adverse Reactions (140 mcg/spray) nostril 12 hrly • CNS eff ects (headache, drowsiness, dizziness, somnolence); GI eff ects (bitter Levocabastine 0.05% nasal ≥9 yr: 1 spray each spray nostril 12 hrly taste, nausea); Resp eff ects (colds, cough, epistaxis, sinusitis, nasal irritation); CV May increase to eff ects (fl ushing, hypertension, tachycardia); 6-8 hrly if necessary Dermatologic eff ects (contact dermatitis, Olopatadine 0.6% nasal spray ≥12 yr: 2 sprays eczema) each nostril 12 hrly Special Instructions • Avoid contact w/ eyes/mouth

ANTIHISTAMINES & ANTIALLERGICS (ORAL)1

Drug Dosage Remarks

First Generation Azatadine 1-6 yr: 0.25-0.5 mg PO 12 hrly Adverse Reactions 6-12 yr: 0.5-1 mg PO 12 hrly • CNS eff ects (drowsiness, somnolence, lassitude, dizziness, Brompheniramine ≤3 yr: 0.4 -1 mg/kg/day PO divided 6 hrly headache, incoordination; 3-6 yr: 1-2 mg PO 6-8 hrly paradoxical stimulation may occur 6-12 yr: 2-4 mg PO 6-8 hrly especially at high doses); Carbinoxamine 2-3 yr: 2 mg PO 6-8 hrly Antimuscarinic eff ects (dry mouth, viscous secretions, urinary 3-6 yr: 2-4 mg PO 6-8 hrly retention, blurred vision); GI eff ects >6 yr: 4-6 mg PO 6-8 hrly (N/V, diarrhea, epigastric pain, Chlorpheniramine 2-5 yr: 1 mg PO 4-6 hrly anorexia or increased appetite); CV Max dose: 6 mg/day eff ects (palpitations, arrhythmias, rarely hazardous ventricular 6-12 yr: 2-4 mg PO 4-6 hrly arrhythmias); Dermatologic eff ects Max dose: 12 mg/day (rashes, hypersensitivity reactions) Clemastine 1-3 yr: 0.25-0.5 mg PO 12 hrly Special Instructions 3-6 yr: 0.5 mg PO 12 hrly • Use w/ caution in patients w/ 6-12 yr: 0.5-1 mg PO 12 hrly breathing problems (eg asthma, Max dose: 3 mg/day chronic bronchitis), liver disease, seizure disorder >12 yr: 1 mg PO 12 hrly • Carbinoxamine should be used w/ Max dose: 6 mg/day caution in patients <2 yr Dexchlorpheniramine 2-5 yr: 0.5 mg POMIMS 4-8 hrly Max dose: 3 mg/day 6-12 yr: 1 mg PO 4-8 hrly Max dose: 6 mg/day Diphenhydramine 2-6 yr: 6.25 mg PO 6-8 hrly 6-12 yr: 12.5 mg PO 6-8 hrly Max dose: 300 mg/day 1Antihistamines© combined w/ other cold remedies are available. Please see the latest MIMS for specifi c formulations. All dosage recommendations are for children w/ normal renal & hepatic function unless otherwise stated. Not all products are available or approved for above use in all countries. Products listed above may not be mentioned in the disease management chart but have been placed here based on indications listed in regional manufacturers’ product information. Specifi c prescribing information may be found in the latest MIMS.

Dosage Guidelines

ANTIHISTAMINES & ANTIALLERGICS (ORAL)1 (CONT’D)

Drug Dosage Remarks

RHINITIS - ALLERGIC First Generation (Cont’d) Homochlorcyclizine In some countries approved for use in Adverse Reactions childn: 5-10 mg PO 6-12 hrly • CNS eff ects (drowsiness, Mebhydrolin <2 yr: 50-100 mg/day PO in divided doses somnolence, lassitude, 2-5 yr: 50-150 mg/day PO in divided doses dizziness, headache, incoordination; paradoxical 5-10 yr: 100-200 mg/day PO in divided doses stimulation may occur >10 yr: 100-300 mg/day PO in divided doses especially at high doses); Mequitazine 5 mg PO 12 hrly Antimuscarinic eff ects (dry mouth, viscous secretions, Oxatomide 0.5 mg/kg PO 12 hrly urinary retention, blurred Pheniramine 5-10 yr: 22.5 mg PO up to 8 hrly vision); GI eff ects (N/V, diarrhea, epigastric pain, >10 yr: 15-30 mg PO 8-12 hrly anorexia or increased appetite); Max dose: 3 mg/kg/day CV eff ects (palpitations, Piprinhydrinate 3 mg PO 8 hrly arrhythmias, rarely hazardous ventricular arrhythmias); Promethazine 2-5 yr: 5-15 mg/day PO divided 12-24 hrly Dermatologic eff ects (rashes, 5-10 yr: 10-25 mg/day PO divided 12-24 hrly hypersensitivity reactions) Special Instructions • Use w/ caution in patients w/ breathing problems (eg asthma, chronic bronchitis), liver disease, seizure disorder Second Generation Acrivastine ≥12 yr: 8 mg PO 6-8 hrly Adverse Reactions • Bilastine 6-11 yr, ≥20 kg: 10 mg PO 24 hrly Cause less sedation & antimuscarinic eff ect than 1st ≥12 yr: 20 mg PO 24 hrly generation antihistamines 2 Cetirizine 1-2 yr: 2.5 mg PO 12 hrly • Palpitations, arrhythmias, 2-6 yr: 2.5 mg PO 12 hrly or 5 mg PO 24 hrly hypersensitivity reactions may >6 yr: 5 mg PO 12 hrly or 10 mg PO 24 hrly occur Desloratadine 1-5 yr: 1.25 mg PO 24 hrly - Cetirizine may cause higher incidence of drowsiness as 2.5 mg PO 24 hrly 6-11 yr: compared w/ other 2nd ≥12 yr: 5 mg PO 24 hrly generation antihistamines Ebastine 6-12 yr: 5-10 mg PO 24 hrly Special Instructions >12 yr: 10 mg PO 24 hrly • Use w/ caution in patients w/ Fexofenadine 6-11 yr: 30 mg PO 12 hrly breathing problems (eg asthma, chronic bronchitis), liver ≥12 yr: 120-180 mgMIMS PO 24 hrly disease, seizure disorder, renal Levocetirizine2 2-6 yr: 1.25 mg PO 12 hrly impairment) ≥6 yr: 5 mg PO 24 hrly Loratadine 2-12 yr: <30 kg: 5 mg PO 24 hrly >30 kg: 10 mg PO 24 hrly

Antihistamines combined w/ other cold remedies are available. Please see the latest MIMS for specifi c formulations. 2Available in combination© w/ Montelukast. Please see the latest MIMS for specifi c formulations. All dosage recommendations are for children w/ normal renal & hepatic function unless otherwise stated. Not all products are available or approved for above use in all countries. Products listed above may not be mentioned in the disease management chart but have been placed here based on indications listed in regional manufacturers’ product information. Specifi c prescribing information may be found in the latest MIMS.

Dosage Guidelines

CORTICOSTEROIDS (NASAL)1 Available Drug Strength Dosage Remarks RHINITIS - ALLERGIC Beclometasone 50 mcg/spray >6 yr: 1 spray each nostril 6-8 hrly or 2 sprays Adverse Reactions nasal spray each nostril 12 hrly • Local eff ects: Max dose: 8 sprays/day Nasal irritation, congestion, 100 mcg/ >6 yr: 1 spray each nostril 12-24 hrly spray nasal burning, epistaxis Max dose <12 yr: 0.5 mg/day • spray Headache, pharyngitis; Budesonide 32 mcg/spray >6 yr: 1 spray each nostril 12 hrly or 2 sprays Candida infection nasal spray each nostril 24 hrly Special Instructions Max dose <12 yr: 2 sprays each nostril/day • May occasionally Max dose ≥12 yr: 4 sprays each nostril/day be absorbed in Use lowest eff ective dose for maintenance suffi cient amounts 50 mcg/spray >6 yr: 2 sprays each nostril 12 hrly or 4 sprays to produce nasal spray each nostril 24 hrly systemic eff ects • Use lowest eff ective dose for maintenance Use w/ caution as corticosteroids 64 mcg/spray >6 yr: 1 spray each nostril 12 hrly or 2 sprays may aff ect linear nasal spray each nostril 24 hrly growth 100 mcg/ Use lowest eff ective dose for maintenance • Fluticasone spray nasal furoate should be spray used w/ caution in patients w/ severe Ciclesonide 50 mcg/dose Seasonal rhinitis ≥6 yr or Perennial rhinitis hepatic nasal spray ≥12 yr: 2 sprays each nostril 24 hrly impairment Max dose: 2 sprays/nostril/day Fluticasone 27.5 mcg/ 2-11 yr: 1 spray each nostril 24 hrly furoate spray nasal May be increased to 2 sprays each nostril spray 24 hrly Maintenance dose: 1 spray each nostril/day ≥12 yr: 2 sprays each nostril 24 hrly Maintenance dose: 1 spray each nostril/day Fluticasone 50 mcg/spray 4-11 yr: 1-2 sprays each nostril 24 hrly propionate nasal spray Max dose: 2 sprays each nostril/day ≥12 yr: 2 sprays each nostril 12-24 hrly Max dose: 4 sprays each nostril/day Mometasone 50 mcg/spray 2-11 yr: 1 spray each nostril 24 hrly furoate nasal spray ≥12 yr: 2 sprays each nostril 24 hrly Once symptoms are controlled, may reduce to MaintenanceMIMS dose: 1 spray each nostril 24 hrly Max dose: 4 sprays each nostril/day Triamcinolone 55 mcg/spray 4-12 yr: 1 spray each nostril 24 hrly nasal spray Maintenance dose: 1 spray each nostril 24 hrly Max dose: 2 sprays each nostril 24 hrly >12 yr: Initial dose: 2 sprays each nostril 24 hrly Maintenance dose: 1 spray each nostril 24 hrly 1Corticosteroids© combined w/ antihistamines &/or decongestants are available. Please see latest MIMS for available formulations. All dosage recommendations are for children w/ normal renal & hepatic function unless otherwise stated. Not all products are available or approved for above use in all countries. Products listed above may not be mentioned in the disease management chart but have been placed here based on indications listed in regional manufacturers’ product information. Specifi c prescribing information may be found in the latest MIMS.

Dosage Guidelines

CROMONE (NASAL) Available Drug Strength Dosage Remarks RHINITIS - ALLERGIC Cromoglicic acid 2% nasal spray 1 spray each nostril 6 hrly Adverse Reactions • (Cromolyn 4% nasal spray 3-4 sprays each nostril daily Stinging, irritation of sodium, Dose may be increased to 6 sprays daily nasal mucosa, sneezing, Disodium epistaxis cromoglycate, Sodium cromoglycate)

DECONGESTANTS (ORAL)1

Drug Dosage Remarks

Ephedrine 2-6 yr: 2-3 mg/kg/day PO or Adverse Reactions 2 100 mg/m /day PO in 4-6 divided • CNS eff ects (headache, anxiety, insomnia, doses restlessness, tremor, somnolence, dizziness, 7-11 yr: 6.25-12.5 mg PO 4 hrly agitation); CV eff ects (tachycardia, hypertension, Max dose: 75 mg/day arrhythmias); GI eff ects (nausea, dry mouth, ≥12 yr: 12.5-50 mg PO 3-4 hrly dyspepsia) Max dose: 150 mg/day Special Instructions • Use w/ caution in patients w/ phenylketonuria Pseudoephedrine 6-12 yr, ≤30 kg: 30 mg PO 12 hrly • Contraindicated in patients w/ narrow-angle 6-12 yr, >30 kg: 60 mg PO 12 hrly glaucoma, urinary retention, severe ≥12 yr: 120 mg PO 12 hrly hypertension, severe coronary disease & those on monoamine oxidase (MAO) inhibitor therapy • Should not be used in patients <2 yr

1Decongestants combined w/ antihistamines are available. Please see latest MIMS for available formulations.

LEUKOTRIENE MODIFIERS

Drug Dosage Remarks

Leukotriene Receptor Antagonists Montelukast 6 mth-2 yr: 4 mg PO 24 hrly Adverse Reactions sodium 2-5 yr: 4 mg PO 24 hrly • Headache, GI upset, mood or behavior changes 6-14 yr: 5 mg PO 24 hrly • Less commonly: Generalized pain, arthralgia, ≥15 yr: 10 mg PO 24 hrly myalgia, fever, dizziness; hypersensitivity MIMSreactions Pranlukast 3.5 mg/kg PO 12 hrly • Very rarely: Agranulocytosis, bleeding, bruising Max dose: 10 mg/kg/day not & edema, systemic eosinophilia consistent w/ exceeding 450 mg PO 24 hrly Churg-Strauss disease Special Instructions • Pranlukast: Monitor prothrombin time in patients w/ ongoing Warfarin or other © anticoagulant therapy All dosage recommendations are for children w/ normal renal & hepatic function unless otherwise stated. Not all products are available or approved for above use in all countries. Products listed above may not be mentioned in the disease management chart but have been placed here based on indications listed in regional manufacturers’ product information. Speciﬁ c prescribing information may be found in the latest MIMS.

Dosage Guidelines

MAST CELL STABILIZER/ANTIHISTAMINE

Drug Dosage Remarks

RHINITIS - ALLERGIC Ketotifen 6 mth-3 yr: 0.5 mg PO 12 hrly Adverse Reactions >3 yr: 1 mg PO 12 hrly • CNS eﬀ ects (drowsiness, dizziness, CNS Extended release: stimulation); GI eﬀ ects (dry mouth, >3 yr: 2 mg PO in the evening increased appetite, wt gain)

NASAL DECONGESTANTS & OTHER NASAL PREPARATIONS1 Available Drug Strength Dosage Remarks

Naphazoline 0.05% nasal drops, ≥12 yr: 1 spray each nostril 6 hrly Adverse Reactions nasal spray • Local eﬀ ects: Oxymetazoline 0.01% nasal drops Neonates <4 wk: 1 drop each nostril Transient irritation, 8-12 hrly sneezing, dryness of nasal mucosa; Infants <1 yr: 1-2 drops into each nostril 12 hrly rebound congestion may occur w/ 0.025% nasal drops, >1 yr: 1-2 drops each nostril extended use or nasal spray 8-12 hrly ≥10 days >2 yr: 2-3 drops/sprays each nostril • Systemic eﬀ ects: N/V, 12 hrly headache 0.05% nasal drops, ≥6 yr: 1-2 sprays each nostril Special Instructions nasal spray 8-12 hrly or 2-3 drops/sprays each • Not recommended nostril 12 hrly for extended use Tetryzoline 0.1% nasal soln >6 yr: 2-4 drops or 3-4 sprays ≥10 days (Tetrahydrozoline) 3-4 hrly 0.05% nasal soln >6 yr: 2-4 drops or 3-4 sprays 3-4 hrly Xylometazoline 0.05% nasal drops Infant & childn <6 yr: 1-2 drops each nostril 12-24 hrly Max dose: 3 drops/nostril/day 0.1% nasal drops, >6 yr: 2-3 drops or 1 spray each nasal spray nostril 6-8 hrly Max dose: 3 drops/nostril/day Others Dexpanthenol In combination w/ 1-2 sprays each nostril as needed Adverse Reactions sea water • Allergic & MIMShypersensitivity Sodium chloride 0.65% nasal drops, 1-2 drops each nostril as needed or (Sea water) nasal spray 2-4 sprays into each nostril 8 hrly, or reactions to 0.9% nasal spray as needed Dexpanthenol 2.3% nasal spray Special Instructions • Spray w/ head upright

1Decongestants combined w/ corticosteroid or antihistamine are available. Please see the latest MIMS for speciﬁ c formulations.

All dosage© recommendations are for children w/ normal renal & hepatic function unless otherwise stated. Not all products are available or approved for above use in all countries. Products listed above may not be mentioned in the disease management chart but have been placed here based on indications listed in regional manufacturers’ product information. Speciﬁ c prescribing information may be found in the latest MIMS. Please see the end of this section for the reference list.