Schedule H

Inhalation (MDI, DPI)

• Salmeterol 25 mcg + Fluticasone propionate 50 mcg per actuation

• Salmeterol 25 mcg + Fluticasone propionate 125 mcg per actuation

• Salmeterol 25 mcg + Fluticasone propionate 250 mcg per actuation

Dry Powder Inhaler (DPI/Rotacaps/Accuhaler/Diskus):

• Salmeterol 50 mcg + Fluticasone propionate 100 mcg per dose

• Salmeterol 50 mcg + Fluticasone propionate 250 mcg per dose

• Salmeterol 50 mcg + Fluticasone propionate 500 mcg per dose

Nebuliser solution: NOT AVAILABLE in India

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

1. Bronchial Asthma (Maintenance Therapy)

⚠️ IMPORTANT: Use only when ICS monotherapy is insufficient for asthma control. NOT for acute bronchospasm relief.

Adults and Adolescents (≥12 years):

Mild-Moderate Persistent (ICS-naive or low-dose ICS inadequate) MDI 25/125 mcg twice daily Assess control at 2–4 weeks; step up if needed 25/125 mcg twice daily 2 25/250 mcg twice daily

DPI 50/100 mcg twice daily Assess control at 2–4 weeks 50/250 mcg twice daily 50/500 mcg twice daily

Moderate-Severe Persistent (moderate-dose ICS inadequate) MDI 25/250 mcg twice daily Step down after 3 months of good control 25/125–250 mcg twice daily 25/250 mcg twice daily

DPI 50/250 mcg twice daily Step down after 3 months of good control 50/250 mcg twice daily 50/500 mcg twice daily

Severe Persistent DPI 50/500 mcg twice daily Maintain; consider step-down after 3–6 months stability 50/500 mcg twice daily 50/500 mcg twice daily

Key Clinical Notes:

• Always prescribe a separate SABA (salbutamol) inhaler for rescue use

• Use lowest ICS dose that maintains control

• Fixed-dose combination ensures ICS adherence (prevents LABA monotherapy)

• Step down to ICS monotherapy if stable on low-dose ICS+LABA for ≥3 months

1. Chronic Obstructive Pulmonary Disease (COPD) — Maintenance Therapy

For patients with FEV1 <60% predicted with history of frequent exacerbations (≥2/year) OR blood eosinophil count ≥300 cells/μL

Parameter DPI (Preferred) MDI

Starting dose 50/250 mcg twice daily 25/250 mcg twice daily

Titration Based on exacerbation frequency and symptom control Same

Usual maintenance dose 50/250 mcg twice daily 25/250 mcg twice daily

Maximum dose 50/500 mcg twice daily 25/250 mcg twice daily

Key Clinical Notes:

• Not recommended as first-line; use after LAMA or LAMA+LABA inadequate

• Monitor for pneumonia risk (increased with ICS in COPD)

• Consider stepping down ICS if no exacerbations for 12 months

• Add LAMA (tiotropium) for triple therapy in GOLD D patients

Secondary Indications — Adults Only (Off-label)

Indication Dose Duration Notes

Bronchiectasis with reversible airflow obstruction (OFF-LABEL) 50/250 mcg DPI twice daily Long-term Specialist only. Evidence from small RCTs; limited Indian data. Consider if concomitant asthma features present.

Chronic cough with eosinophilic bronchitis (OFF-LABEL) 50/100–250 mcg DPI twice daily 4–8 weeks trial Pulmonologist guidance. Step down after symptom control.

PAEDIATRIC DOSING (Specialist Only)

Primary Indications

1. Persistent Bronchial Asthma (Maintenance Therapy)

Only when ICS monotherapy at appropriate dose is insufficient for control

4–11 years MDI with spacer 25/50 mcg twice daily Assess at 2–4 weeks; increase ICS component if needed 25/50–100 mcg twice daily 25/125 mcg twice daily (equivalent to fluticasone 250 mcg/day)

4–11 years DPI (if capable of adequate inspiratory flow) 50/100 mcg twice daily Assess at 2–4 weeks 50/100 mcg twice daily 50/250 mcg twice daily

≥12 years MDI or DPI Adult dosing applies — — —

Key Clinical Notes:

• Minimum age: 4 years (under paediatric pulmonologist/allergist supervision)

• Spacer mandatory with MDI in children <12 years

• Always co-prescribe SABA (salbutamol) for rescue

• Monitor linear growth velocity annually during long-term therapy

• Rinse mouth after each dose to prevent oral candidiasis

• Assess inhaler technique at every visit

Secondary Indications — Paediatric (Off-label)

• No established off-label paediatric indications in Indian practice

• NOT recommended for acute bronchiolitis, viral-induced wheeze, or recurrent wheeze without documented persistent asthma

• Use below 4 years: NOT recommended except under specialist pulmonologist supervision in clinical trial settings

Clear Statement: Not recommended below age 4 years except under specialist supervision.

• Known hypersensitivity to salmeterol, fluticasone, or any excipient (including lactose in DPI formulations)

• Status asthmaticus or acute severe asthma exacerbation (NOT a rescue medication)

• Severe milk protein allergy (for lactose-containing DPI formulations)

• Use of salmeterol component as monotherapy in asthma (without concurrent ICS) — contraindicated due to increased mortality risk

• Untreated active pulmonary tuberculosis

• History of treated or latent tuberculosis — may reactivate; ensure adequate anti-TB therapy before/during use

• Active or quiescent respiratory infections (fungal, viral, bacterial)

• Cardiovascular disease: ischaemic heart disease, arrhythmias, hypertension, prolonged QTc

• Diabetes mellitus — may cause transient hyperglycaemia

• Hypokalaemia or patients on potassium-depleting therapies

• Thyrotoxicosis

• Phaeochromocytoma (rare)

• Osteoporosis or risk factors for bone loss (prolonged high-dose ICS)

• Glaucoma or cataracts (prolonged use)

• Growth suppression in children on prolonged high-dose ICS

• Immunocompromised patients — increased susceptibility to infections

• Paradoxical bronchospasm (rare but serious)

Parameter Details

Risk Category Generally considered compatible with pregnancy; inhaled route minimises systemic exposure

Preferred alternatives Budesonide (ICS monotherapy) has most human pregnancy safety data. If LABA+ICS required, salmeterol+fluticasone acceptable.

When may be used When asthma not controlled on ICS alone; uncontrolled asthma poses greater risk to fetus than medication

Monitoring Maternal symptom control (peak flow, symptom diary); fetal growth surveillance if high-dose ICS used

Parameter Details

Compatibility Compatible with breastfeeding; minimal systemic absorption from inhalation

Preferred alternatives Budesonide monotherapy if mild asthma; combination acceptable if required for control

Drug levels in milk Very low (negligible systemic absorption)

Infant monitoring No specific monitoring required; observe for oral thrush, irritability (rare)

Parameter Recommendation

Starting dose Start at lowest effective ICS strength (e.g., 50/100 mcg DPI or 25/50 mcg MDI twice daily)

Titration Slower titration; assess response at 4–6 weeks before stepping up

Special risks Increased risk of pneumonia (especially in COPD); osteoporosis with prolonged high-dose ICS; cataracts/glaucoma; oral candidiasis; assess manual dexterity and inhaler technique

Monitoring Annual ophthalmology review; bone density assessment if prolonged high-dose use; regular assessment of inhaler technique

Interacting Drug Mechanism & Effect Management

Ritonavir, Cobicistat (potent CYP3A4 inhibitors) Markedly increase fluticasone systemic levels → severe adrenal suppression, Cushing syndrome Avoid combination. If unavoidable, consider alternative ICS (beclomethasone) or close monitoring by specialist

Ketoconazole, Itraconazole (strong CYP3A4 inhibitors) Significant increase in fluticasone systemic exposure Avoid prolonged concurrent use; if essential, use lowest fluticasone dose and monitor for systemic effects

Non-selective beta-blockers (propranolol, carvedilol) Antagonise bronchodilator effect of salmeterol; risk of severe bronchospasm Avoid in asthma. If essential in COPD, use cardioselective beta-blocker (bisoprolol) with caution

MAO inhibitors, Tricyclic antidepressants Potentiate cardiovascular effects of salmeterol Avoid salmeterol within 14 days of MAOI; use with extreme caution with TCAs

Other sympathomimetics (oral beta-agonists) Additive adrenergic effects; risk of arrhythmia, hypertension Avoid concurrent use

Interacting Drug Effect Management

Moderate CYP3A4 inhibitors (erythromycin, clarithromycin, diltiazem, verapamil) May modestly increase fluticasone systemic levels Monitor for systemic corticosteroid effects with prolonged use

Rifampicin, Phenytoin, Carbamazepine (CYP3A4 inducers) May reduce fluticasone efficacy Monitor symptom control; may need dose increase

Potassium-depleting diuretics (furosemide, thiazides) Additive hypokalaemia with salmeterol Monitor serum potassium, especially in elderly and cardiac patients

Theophylline/Aminophylline Additive bronchodilation; increased arrhythmia and hypokalaemia risk Monitor heart rate, ECG, potassium

Systemic corticosteroids Additive HPA axis suppression and hypokalaemia Use lowest doses; monitor for adrenal insufficiency signs

QT-prolonging drugs (fluoroquinolones, ondansetron, antipsychotics) Salmeterol may add to QT prolongation risk ECG monitoring if combination unavoidable; correct electrolytes

• Oropharyngeal candidiasis (oral thrush)

• Dysphonia/hoarseness

• Throat irritation

• Headache

• Tremor (salmeterol-related)

• Palpitations

• Muscle cramps

• Cough on inhalation

Adverse Effect Clinical Notes

Paradoxical bronchospasm Immediate discontinuation required; treat with SABA; switch to alternative

Pneumonia (especially in COPD) Increased risk with ICS component; monitor for new or worsening symptoms

Adrenal suppression Risk with high doses (>1000 mcg/day fluticasone) or CYP3A4 inhibitors; may manifest as adrenal crisis during stress

Systemic corticosteroid effects Osteoporosis, growth suppression (children), Cushing syndrome with high doses

Glaucoma/Cataracts Risk with prolonged use; annual ophthalmology screening

Severe hypokalaemia Especially with concurrent diuretics or theophylline

Anaphylaxis/Angioedema Rare; discontinue permanently

Tachyarrhythmias Atrial fibrillation, supraventricular tachycardia (salmeterol-related)

After initiation (2–4 weeks) Symptom control (ACT score for asthma), rescue SABA use frequency, oral cavity inspection for candidiasis, inhaler technique reassessment

Long-term Spirometry every 6–12 months; annual height in children; ophthalmology review if prolonged high-dose use; bone density if high-dose ICS >12 months in elderly; serum potassium if on diuretics; monitor for pneumonia (COPD patients)

Salmeterol + Fluticasone Propionate:

• Seretide® Accuhaler/Evohaler (GSK)

• Seroflo® Rotacaps/Inhaler (Cipla)

• Combitide® (Sun Pharma)

• Airtec SF® (Glenmark)

• Maxiflo® (Cipla)

• Salbair-F® (Lupin)

• Zhale SF® (Zydus)

• Salmeter-F® (generic)

Note: Salmeterol + Fluticasone combination is included in NLEM 2022 (25/125 mcg and 25/250 mcg MDI); prices are controlled under NPPA ceiling price regulations.

1. Always prescribe SABA alongside — this is maintenance therapy ONLY; never use as rescue inhaler

1. Mouth rinsing is non-negotiable — instruct all patients to rinse mouth and spit after inhalation to prevent oral candidiasis and dysphonia

1. Spacer use with MDI — mandatory in children <12 years; beneficial in elderly and those with poor technique

1. Fixed-dose combination advantage — ensures ICS compliance and prevents dangerous LABA monotherapy in asthma

1. COPD pneumonia risk — monitor elderly COPD patients on ICS for new respiratory symptoms; consider ICS step-down if exacerbation-free for 12 months

1. Step-down when controlled — after 3–6 months of good control in asthma, attempt step-down to lower ICS strength or ICS monotherapy

1. Avoid potent CYP3A4 inhibitors — ritonavir/cobicistat combination particularly dangerous; can cause iatrogenic Cushing syndrome and adrenal crisis

asthma; COPD; ICS-LABA; inhaler; maintenance-therapy; salmeterol; fluticasone; NLEM-India; paediatric-4years; CYP3A4-interaction; pneumonia-risk

RxIndia v1.0 — 06 Jun 2025

• CDSCO Approved Drug Formulations List

• Indian Pharmacopoeia 2022

• National List of Essential Medicines (NLEM) 2022

• API Textbook of Medicine (11th Edition)

• ICMR Guidelines for Management of Bronchial Asthma (2023)

• ICMR-COPD Management Guidelines (2023)

• AIIMS Standard Treatment Guidelines 2022

• IAP Guidelines for Paediatric Asthma Management

• Product package inserts (Seretide®, Seroflo®, Maxiflo®)