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Wise et al.

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antihistamines. (See section IX.B.10.a. Management – Pharmacotherapy – Combination therapy – Oral antihistamine and oral decongestant for additional information on this topic.) Availability of pseudoephedrine in the United States has been limited to behind-the-counter at pharmacies since 2006 due to stricter control over the distribution and sale of substances that can be used to manufacture methamphetamine. In a study by Mucha et al., 1321 pseudoephedrine resulted in significant improvement in all symptoms in adults with ragweed-induced AR (Table IX.B.3.a). Phenylephrine has been marketed as an over-the counter (OTC) medication as a substitute for pseudoephedrine for nasal decongestion. However, an RCT by Horak et al. 1322 found that while pseudoephedrine was significantly more effective at reducing nasal congestion than both placebo and phenylephrine, there was no significant difference between phenylephrine and placebo. In addition, Meltzer et al. 1323 performed a randomized, open-label, dose-range trial in 539 patients with SAR and found phenylephrine to be no more effective than placebo in reducing symptomatic nasal congestion. Known side effects of this class of medications include insomnia, nervousness, anxiety, tremors, palpitations, and increased blood pressure (BP). Two systematic reviews by Salerno et al. 1324,1325 looked at the effect of oral decongestants on blood pressure. The first study showed that phenylpropanolamine significantly increased systolic blood pressure (SBP) by 5.5 mmHg (95% CI, 3.1 to 8.0) and diastolic blood pressure (DBP) by 4.1 mmHg (95% CI, 2.2 to 6.0) with no effect on heart rate as compared to placebo. 1324 The second study found that pseudoephedrine also caused a small but significant increase in SBP by 0.99 mmHg (95% CI, 0.08 to 1.9) and heart rate (HR) by 2.83 beats/minute (95% CI, 2.0 to 3.6) with no effect on DBP. 1325 Additionally, higher doses and immediate-release preparations of pseudoephedrine were associated with greater BP elevations. 1325 Further, in a study by Kernan et al., 1326 phenylpropanolamine use in women was an independent risk factor for hemorrhagic stroke. Phenylpropanolamine is no longer available on the market. Given these cardiovascular side effects, oral decongestants should be used with caution in patients who are already at risk for hypertension and its sequelae (eg, coronary artery disease, cerebral vascular disease, hyperthyroidism, arrhythmias). Blood pressure should be closely monitored for any changes when using oral decongestants in this population. Oral decongestants are known to be effective in children older than 6 years of age. However, care should be taken in the younger population (less than 2 years of age) as this population is more prone to toxicity, and safe dosing recommendations have not yet been established for this age group. 1327 In infants and young children, oral decongestants may have central nervous system (CNS) stimulatory effects with known cases of psychosis, ataxia, and hallucinations with ingestion. 1328,1329 Evaluation of risk and benefits should be considered in patients less than 6 years old. • Aggregate Grade of Evidence: B (Level 1a: 2 studies; Level 1b: 3 studies; Level 3b: 2 studies; Level 4: 2 studies; Table IX.B.3.a). • Benefit: Reduction of nasal congestion with pseudoephedrine. No benefit with phenylephrine.

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Int Forum Allergy Rhinol . Author manuscript; available in PMC 2020 June 10.