Meltzer, Eli O., Paul H. Ratner, and Thomas McGraw. "Phenylephrine hydrochloride modified-release tablets for nasal congestion: a randomized, placebo-controlled trial in allergic rhinitis patients." Annals of Allergy, Asthma & Immunology 116.1 (2016): 66-71.

1. Phenylephrine modified-release
tablets for nasal congestion: A
randomized, placebo-controlled
trial in allergic rhinitis patients
Eli O. Meltzer MD, Paul H. Ratner MD
MBA, and Thomas McGraw PhD

2. Background
• Ephedrine and pseudoephedrine
decongestants can be converted into
methamphetamine.
• Phenylephrine (PE) is not used in
methamphetamine manufacture.
• Pseudoephedrine medications were moved
behind the counter (BTC) which may be a
deterrent to legitimate access.
• Work began on a 12-hour 30 mg bid modified
release PE to avoid BTC and oral PE 10 mg
immediate release 4-hour dosing
inconvenience.

3. Background
• The study formulation was evaluated in several
bioequivalence studies comparing a single dose of
30 mg 12 Hour modified-release PE tablet to three
10 mg Immediate Release PE tablets each
consecutively dosed four hours apart.
• The systemic drug levels (AUC) were higher (ratio
about 160%), whereas peak levels (Cmax) were
similar (ratio about 98%) when modified and
immediate release dosage forms were compared
(Merck & Co, Inc., data on file).
• Therefore, it can be assumed that the efficacy of
three10 mg doses every 4-hours would be similar
to one 30 mg dose over a 12-hour period.

4. Major Inclusion Criteria
• Documented or self-reported history of fall
pollen allergic rhinitis.
• Documented skin test reaction to fall pollen
allergens.
• Signs and symptoms of nasal congestion.

5. Major Exclusion Criteria
• Significant medical condition.
• Started allergen immunotherapy within 1
month of enrollment, or anticipates
immunotherapy dose change during the trial.
• Documented evidence of acute or significant
chronic sinusitis.
• Clinically significant nasal disorders.
• Asthma except mild intermittent asthma.
• Systemic, topical (>1% hydrocortisone), or
nasal corticosteroids use in the last 30 days.

6. Study Design
RQLQ: Rhinoconjunctivitis Quality of Life Questionnaire;
PEH-MR: modified-release phenylephrine HCL

7. Primary Endpoint
• Mean change from baseline in daily reflective
congestion score over the entire treatment period.
• Subject symptom assessment recorded twice
daily:
– Reflective: severity over the preceding 12 hrs.
– Instantaneous: severity right now (secondary
endpoint).
• Subjects rated congestion on a 4-point scale of
severity (0= no symptoms, 1= mild, 2= moderate
3= severe).

8. Patient Disposition
PEH-MR: modified-release phenylephrine hydrochloride.

9. Mean change from baseline in
reflective nasal congestion score
There was no statistical difference between treatment groups.

10. Discussion
• Questions raised about PE efficacy
resulted in a 2007 FDA Advisory
Committee Meeting that concluded further
efficacy data is required.
• PE was not significantly different from
placebo for the relief on nasal congestion
in allergen challenge chamber trials that
concluded pseudoephedrine (Horak 2009),
or a combination of loratadine-montelukast
(Day 2009) were effective.

11. Discussion
• PE was not significantly different from
placebo in a dose-ranging study of 10 to
40 mg doses administered every 4 hours
for 7 days in patients with nasal
congestion caused by allergic rhinitis
(Meltzer 2015).
• The results of this study provide evidence
that an oral dose of 30 mg PE does not
relieve nasal congestion.

12. Selected References
• Hendeles L., Hatton R. C. Oral phenylephrine: an ineffective replacement for
pseudoephedrine? J Allergy Clin Immunol 2006; 118: 279–80.
• Eccles R. Substitution of phenylephrine for pseudoephedrine as a nasal
decongeststant. An illogical way to control methamphetamine abuse. Br J Clin
Pharmacol 2007; 63: 10–14.
• Hatton R. C., et al. Efficacy and safety of oral phenylephrine: systematic review and
meta-analysis. Ann Pharmacother 2007; 41: 381–90.
• Horak F., et al. A placebo-controlled study of the nasal decongestant effect of
phenylephrine and pseudoephedrine in the Vienna Challenge Chamber. Ann
Allergy Asthma Immunol. 2009;102:116–120.
• Day J. H., et al. Efficacy of loratadine-montelukast on nasal congestion in patients
with seasonal allergic rhinitis in an environmental exposure unit. Ann Allergy
Asthma Immunol. 2009;102:328–338.
• Meltzer E.O., Ratner P.H., McGraw T. Oral Phenylephrine HCl for Nasal Congestion
in Seasonal Allergic Rhinitis: A Randomized, Open-label, Placebo-controlled Study.
The Journal of Allergy and Clinical Immunology: In Practice 2015; 3: 702-708, ISSN
2213-2198, http://dx.doi.org/10.1016/j.jaip.2015.05.007.