VA Class:RE102

ATC Class:R03AA01

AHFS Class:

• Vasoconstrictors 52:32

Generic Name(s):

• Propylhexedrine

Propylhexedrine, an aliphatic amine that is structurally related to amphetamine, is a vasoconstrictor.

Nasal Congestion

Propylhexedrine is used topically for self-medication to relieve nasal congestion associated with acute or chronic rhinitis, the common cold, hay fever, or other allergies; its effectiveness appears to be similar to that of other topical vasoconstrictors.

Nasal decongestants, including propylhexedrine, are labeled and have been used for self-medication for the temporary relief of nasal congestion associated with sinusitis.101 However, because efficacy data are lacking and/or controversial,101,102,103 and because there are potential harmful effects in delaying medical evaluation and definitive treatment by a clinician,101 the US Food and Drug Administration (FDA) no longer considers oral or topical nasal decongestants appropriate for self-medication of sinusitis.101 In October 2005, the agency issued a final rule amending the final monograph for nonprescription (over-the-counter; OTC) nasal decongestant preparations to remove the indication for relief of nasal congestion associated with sinusitis from labeling and prohibiting use of the term “sinusitis” elsewhere in labeling.101 For a more complete discussion of FDA's final rule, see Uses: Nasal Congestion in Oxymetazoline 52:32.

Topical nasal decongestants provide only temporary relief of nasal congestion, and some degree of rebound congestion usually results. (See Cautions: Adverse Effects.) Some clinicians prefer topical nasal decongestants to oral preparations for the short-term treatment of nasal congestion. When nasal decongestants are required for prolonged periods, however, oral preparations may be preferable because of the propensity of topical preparations to cause mucosal irritation and more pronounced rebound congestion.

Intranasal propylhexedrine also may be used to reduce swelling and facilitate visualization of nasal and pharyngeal membranes prior to surgery or diagnostic procedures and to open obstructed eustachian ostia in patients with ear inflammation.

Administration

Propylhexedrine is administered by nasal inhalation via an inhaler. Containers of the drug should be warmed in the hands before use to increase volatility of the drug. Care should be taken to avoid contamination of the inhaler and inhalants should not be used by more than one patient. Inhalants should be inhaled through each nostril with the patient's head erect, and 3-5 minutes later the nose should be blown thoroughly.

Dosage

In adults and in children 6 years of age and older, the usual dosage is 2 inhalations (approximately 0.4-0.5 mg of the drug) through each nostril at intervals of not less than 2 hours. In children less than 6 years of age, dosage must be determined by a physician. Propylhexedrine therapy should not exceed 3-5 days in duration.

Adverse Effects

The incidence of serious adverse effects is low in patients receiving therapeutic dosages of propylhexedrine intranasal inhalations. Excessive dosage and/or prolonged or too frequent use may irritate nasal mucosa and, especially in children, cause adverse systemic effects.

Propylhexedrine may cause transient burning, stinging, or dryness of the mucosa, and sneezing. Rebound congestion, characterized by chronic redness, swelling, and rhinitis, may occur with prolonged use and may result in overuse of the drug. Prolonged use of nasal inhalations of the drug should be avoided for these reasons.

Intranasal use of propylhexedrine occasionally may cause systemic sympathomimetic effects such as headache, hypertension, nervousness, and increased ventricular rate. Overdosage following oral ingestion of propylhexedrine has been characterized by psychotic reactions, palpitation, ventricular extrasystoles, and shock.

Precautions and Contraindications

When nasal decongestants are applied topically in recommended dosages, the usual restrictions to the use of sympathomimetics in patients with hyperthyroidism, heart disease, hypertension, or diabetes mellitus or in those receiving monoamine oxidase inhibitors usually do not apply; however, some caution and observation of these patients may be warranted.

Pregnancy

Pregnancy

Safe use of propylhexedrine during pregnancy has not been established.

Pharmacology

The mechanism of action of propylhexedrine has not been conclusively determined but appears to be similar to that of amphetamine. Most pharmacologists believe that propylhexedrine indirectly stimulates α-adrenergic receptors of the sympathetic nervous system and exerts a minor stimulant effect on β-adrenergic receptors. Intranasal application of propylhexedrine results in constriction of dilated arterioles and reduction in nasal blood flow and congestion. In addition, obstructed eustachian ostia may be opened. Nasal ventilation and aeration are improved temporarily; however, rebound vasodilation and congestion usually occur to some degree.

Pharmacokinetics

Following nasal inhalation of propylhexedrine, local vasoconstriction usually occurs within 30 seconds to 5 minutes and may persist for 30 minutes to 2 hours. Occasionally, enough propylhexedrine may be absorbed to produce systemic effects. The drug is metabolized by the liver and excreted in urine as unchanged drug and as norpropylhexedrine, cyclohexylacetoxine, and 4-hydroxypropylhexedrine.

Chemistry and Stability

Chemistry

Propylhexedrine is an aliphatic amine that is structurally related to amphetamine. Propylhexedrine occurs as a clear, colorless liquid having a characteristic, amine-like odor. The drug is very slightly soluble in water and miscible with alcohol and volatilizes slowly at room temperature. Propylhexedrine inhalant consists of cylindrical rolls of a fibrous material impregnated with the drug, usually aromatized, and contained in a suitable inhaler.

Stability

Propylhexedrine inhalant should be stored in tight containers (inhalers); these containers should not be exposed to excessive heat. Because of the volatility of its contents, the inhaler should be kept closed when not in use. The inhaler usually remains potent for 2-3 months, depending on the degree of use.

Only references cited for selected revisions after 1984 are available electronically.

101. Food and Drug Administration. Cold, cough, allergy, bronchodilator, and antiasthmatic drug products for over-the-counter human use; amendment of final monograph for over-the-counter nasal decongestant drug products. 21 CFR Parts 310 and 341. Final rule. [Docket No. 2004N- 0289] Fed Regist . 2005; 70:58974-7.

102. Spector SL, Bernstein IL, Li JT et al for the Joint Task Force on Practice Parameters et al. Parameters for the diagnosis and management of sinusitis. J Allergy Clin Immunol . 1998; 102(Suppl):S107-44.

103. American Academy of Pediatrics: subcommittee on management of sinusitis and committee on quality improvement. Clinical practice guideline: Management of sinusitis. Pediatrics . 2001; 108:798-808. [PubMed 11533355]