Managing Seasonal & Perennial Allergic Rhinitis in India: Why Nasal Congestion Calls for Combination Therapy

Seasonal Allergic Rhinitis (SAR) and Perennial Allergic Rhinitis (PAR) - An Endemic Aero-Allergic Disease in India

Allergic rhinitis (AR) affects 35%–40% of the global population, with one-fifth residing in the Indian subcontinent [1]. AR is a multifaceted disease that requires an understanding of its subtypes. Based on the duration of allergen exposure, it is classified as seasonal AR (SAR) or perennial AR (PAR) [3].

Congestion-Dominant Allergic Rhinitis Phenotype in Indian Patients

A recent Indian expert consensus classified AR patients into "sneeze-runners" and "blockers." Congestion-dominant AR is common in Indian patients, and the "blocker" phenotype is twice as prevalent as the " sneeze-runner” phenotype [4, 5]. Effective treatment requires addressing both allergic inflammation and nasal congestion in these phenotypes.

Management of SAR and PAR – Overview, Challenges & Addressal

The World Health Organization (WHO) recommends antihistamines as first-line treatment for mild, persistent AR, although their effectiveness for nasal congestion in SAR and PAR remains uncertain. Decongestant monotherapy can temporarily reduce nasal congestion through vasoconstriction; however, it does not address the underlying allergic inflammation [6–8]. Therefore, treatments targeting both histamine-mediated inflammation and nasal vascular congestion may provide better symptom relief.

Combining Fexofenadine and Pseudoephedrine: Addressing Relief with a Bimodal Approach

The combination of second-generation non-sedating antihistamines and oral decongestants may improve AR symptom control by targeting histamine-mediated inflammation and vascular congestion. Fexofenadine, a second-generation non-sedating antihistamine, is preferred because of its favorable efficacy and safety profile[SR1.1][DS1.2]. Pseudoephedrine, a sympathomimetic amine, reduces nasal congestion by activating α1- and α2-adrenergic receptors, causing vasoconstriction of nasal blood vessels and reduced mucosal swelling (Fig. 1) [9–16].

Fig 1: Bimodal Approach of Antihistamine and Decongestant

Abbreviations: H1-Histamine, α-alpha, min-minutes, h-hours

The figure is recreated from the ref 18-23

Fexofenadine 60 mg and Pseudoephedrine 120 mg: Clinical Overview & Evidence

The short-term use of fexofenadine HCl 60 mg/pseudoephedrine HCl 120 mg in a sustained-release form is indicated for the relief of sneezing, rhinorrhea, itchy nose, and palate/throat, as well as itchy/watery/red eyes, addressing nasal congestion from inflammatory and vascular causes [10].

Recommended Dosage

• Adults and individuals aged ≥12 years: One sustained-release formulation with fexofenadine 60 mg and pseudoephedrine 120 mg twice daily on an empty stomach [10].

• Missed Dose: Resume regular dosing at the next scheduled time. Do not take two doses together [10].

Fexofenadine and Pseudoephedrine Combination: Clinical Evidence in Allergic Rhinitis Symptom Relief

A randomized study in patients with PAR (n=24) compared fexofenadine 60 mg/pseudoephedrine 120 mg (n=12) with fexofenadine 60 mg monotherapy (n=12). Nasal obstruction was assessed using nasal airflow and the visual analog scale (VAS) at 30-min intervals before and up to 8 h after dosing. The combination demonstrated an onset of action of 30 min based on increased nasal airflow (p < 0.001 vs. fexofenadine), with sustained improvement through 480 min (8 h) (p < 0.001). Reduction in nasal obstruction, as measured by VAS, showed an onset at 60 min. Overall, the combination maintained significant improvements in nasal airflow and obstruction compared with fexofenadine monotherapy [14].

In a pooled analysis (n = 786), patients with moderate-to-severe SAR treated with fexofenadine HCl 60 mg/pseudoephedrine HCl 120 mg demonstrated rapid onset of action at 45 min (P < 0.008) and sustained efficacy for 6 h (all P < 0.001). Regarding the percentage reduction in major symptom complex (MSC) scores, 77.0% of patients achieved ≥50% reduction in symptoms, 67.3% achieved ≥60%, 57.0% achieved ≥70%, and 45.5% achieved ≥80%. Similar improvements were observed in TSC scores with response rates of 76.7%, 67.0%, 55.0%, and 44.2% for ≥50%, ≥60%, ≥70%, and ≥80%, respectively [15].

Cardiovascular Safety of Sustained-Release Pseudoephedrine

A meta-analysis of 24 studies (n = 1285) showed that patients with stable, controlled hypertension do not appear to be at higher risk for BP or HR elevation, with a minimal increase in systolic blood pressure (~1 mmHg) and heart rate (~3 beats/min) without affecting diastolic pressure, particularly with immediate-release doses [17].

Studies on sustained-release pseudoephedrine in normotensive and medically controlled hypertensive subjects failed to show significant CV adverse effects, with an SBP increase of 3 mmHg and an HR change of three beats per minute [18].

Sustained-release pseudoephedrine formulations appear to be safer than immediate-release formulations, with no significant CV adverse events in subjects with stable, controlled hypertension [17-18].

In a multicentre, double-blind study including 651 allergy-treated patients receiving fexofenadine 60 mg plus pseudoephedrine HCl 120 mg combination twice daily for 2 weeks, no clinically significant changes from baseline were observed in electrocardiogram (ECG) parameters (PR interval, QRS interval, QT interval, or QTc), vital signs, or clinical laboratory values [13].

Key Takeaways

• Nasal congestion, a primary symptom of allergic rhinitis, affects quality of life and work productivity. In India, ‘blockers’ outnumber ‘sneezers’ by 2:1.

• In clinical practice, considering symptom-based phenotype assessment may guide therapeutic selection in addition to causative seasonal-based disease stratification.

• In patients with moderate-to-severe persistent allergic rhinitis or those unresponsive to monotherapy, Indian otorhinolaryngologists recommend combination therapy [4].

• Experts have suggested that combining a second-generation antihistamine with an oral decongestant can address nasal congestion. The combination of fexofenadine, an antihistamine, reduces histamine-mediated symptoms (sneezing, rhinorrhea, itchy nose, palate, and/or throat, and itchy, watery, red eyes), whereas pseudoephedrine, a decongestant, induces vasoconstriction, relieving nasal congestion associated with seasonal and perennial AR [16].

• Sustained-release pseudoephedrine provides effective congestion relief with a favorable cardiovascular safety profile when used short-term in appropriately selected patients [17, 18].

MAT-IN-2600370-v1.0-23/03/2026