Editing Phenylephrine (section)

== Medical uses ==

=== Decongestant ===
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Phenylephrine is used as an alternative to [[pseudoephedrine]] as a decongestant, whose availability has been restricted in some countries due to a potential for use in the illicit synthesis of [[methamphetamine]].<ref name="Presley_2018">{{cite journal | vauthors = Presley B, Bianchi B, Coleman J, Diamond F, McNally G | title = Efficiency of extraction and conversion of pseudoephedrine to methamphetamine from tamper-resistant and non-tamper-resistant formulations | journal = Journal of Pharmaceutical and Biomedical Analysis | volume = 156 | pages = 16–22 | date = July 2018 | pmid = 29684907 | doi = 10.1016/j.jpba.2018.04.016 | s2cid = 13660478 | doi-access = free }}</ref> Its efficacy as an oral decongestant has been questioned, with several independent studies finding that it provided no more relief to sinus congestion than a placebo.<ref name="danzig09">{{cite journal | vauthors = Horak F, Zieglmayer P, Zieglmayer R, Lemell P, Yao R, Staudinger H, Danzig M | title = A placebo-controlled study of the nasal decongestant effect of phenylephrine and pseudoephedrine in the Vienna Challenge Chamber | journal = Annals of Allergy, Asthma & Immunology | volume = 102 | issue = 2 | pages = 116–20 | date = February 2009 | pmid = 19230461 | doi = 10.1016/S1081-1206(10)60240-2 | publication-date = February 2009 |quote = Phenylephrine was not significantly different from placebo in the primary end point.}}</ref><ref name="yao09">{{cite journal | vauthors = Day JH, Briscoe MP, Ratz JD, Danzig M, Yao R | title = Efficacy of loratadine-montelukast on nasal congestion in patients with seasonal allergic rhinitis in an environmental exposure unit | journal = Annals of Allergy, Asthma & Immunology | volume = 102 | issue = 4 | pages = 328–38 | date = April 2009 | pmid = 19441605 | doi = 10.1016/S1081-1206(10)60339-0 |quote = There were no statistically significant differences between phenylephrine and placebo for any measures.}}</ref><ref name="Hendeles2006">{{cite journal | vauthors = Hendeles L, Hatton RC | title = Oral phenylephrine: an ineffective replacement for pseudoephedrine? | journal = The Journal of Allergy and Clinical Immunology | volume = 118 | issue = 1 | pages = 279–80 | date = July 2006 | pmid = 16815167 | doi = 10.1016/j.jaci.2006.03.002 | doi-access = free }}</ref>

A 2007 meta-analysis concluded that the evidence for its effectiveness is insufficient,<ref name="Annals">{{cite journal | vauthors = Hatton RC, Winterstein AG, McKelvey RP, Shuster J, Hendeles L | title = Efficacy and safety of oral phenylephrine: systematic review and meta-analysis | journal = The Annals of Pharmacotherapy | volume = 41 | issue = 3 | pages = 381–90 | date = March 2007 | pmid = 17264159 | doi = 10.1345/aph.1H679 | s2cid = 25627664 | url = http://www.theannals.com/cgi/content/abstract/aph.1H679v1 | format = abstract | archive-url = https://web.archive.org/web/20070227143703/http://www.theannals.com/cgi/content/abstract/aph.1H679v1 | url-status = dead | archive-date = 27 February 2007 | url-access = subscription }}(published online Jan 2007)</ref> though another meta-analysis published shortly thereafter by researchers from [[GlaxoSmithKline]] found the standard 10-mg dose to be more effective than a placebo; however, the fact that GSK markets many products containing phenylephrine has raised some speculation regarding selective publishing and other controversial techniques.<ref name="GSK">{{cite journal | vauthors = Kollar C, Schneider H, Waksman J, Krusinska E | title = Meta-analysis of the efficacy of a single dose of phenylephrine 10 mg compared with placebo in adults with acute nasal congestion due to the common cold | journal = Clinical Therapeutics | volume = 29 | issue = 6 | pages = 1057–70 | date = June 2007 | pmid = 17692721 | doi = 10.1016/j.clinthera.2007.05.021 }}</ref> A 2007 study by [[Wyeth Consumer Healthcare]] notes that 7 studies available in 1976 support the efficacy of phenylephrine at a 10&nbsp;mg dosage.<ref name="Desjardins2007">{{cite journal | vauthors = Desjardins PJ, Berlin RG | title = Efficacy of phenylephrine | journal = British Journal of Clinical Pharmacology | volume = 64 | issue = 4 | pages = 555–6; author reply 557 | date = October 2007 | pmid = 17610531 | pmc = 2048561 | doi = 10.1111/j.1365-2125.2007.02935.x }}</ref> The [[Food and Drug Administration]] withdrew the indication "for the temporary relief of nasal congestion associated with sinusitis" in 2007.<ref name=AHFS2022/>

Two studies published in 2009, examined the effects of phenylephrine on symptoms of [[allergic rhinitis]] by exposing people to pollen in a controlled, indoor environment. Neither study was able to distinguish between the effects of phenylephrine or a placebo. Pseudoephedrine and [[loratadine]]–[[montelukast]] therapy were found to be significantly more effective than both phenylephrine and placebo.<ref name="danzig09"/><ref name="yao09"/>

Pseudoephedrine was previously much more commonly available in the United States.  However, provisions of the [[Combat Methamphetamine Epidemic Act of 2005]] placed restrictions on the sale in the United States of pseudoephedrine products to prevent the [[clandestine chemistry|clandestine manufacture]] of methamphetamine. Since 2004, phenylephrine has been increasingly marketed as a substitute for pseudoephedrine; some manufacturers have changed the active ingredients of products to avoid restrictions on sales.<ref name="HeraldTribune">{{cite news|date=30 January 2007|title=All stuffed up: Reformulated cold medicines might not be able to do the job|newspaper=[[Sarasota Herald-Tribune]]|url=http://www.heraldtribune.com/apps/pbcs.dll/article?AID=/FP/20070130/HEALTHMATTERS/70129001/1025/NEWS06|url-status=dead|access-date=25 April 2023|archive-url=https://web.archive.org/web/20070301095838/http://www.heraldtribune.com/apps/pbcs.dll/article?AID=%2FFP%2F20070130%2FHEALTHMATTERS%2F70129001%2F1025%2FNEWS06|archive-date=1 March 2007|vauthors= Hillenmeyer K}}</ref> Phenylephrine has been off-patent for some time,{{when|date=April 2024}} and many generic brands are available.{{Citation needed|date=June 2020}}

In September 2023, an independent advisory committee to the U.S. [[Food and Drug Administration]] (FDA) unanimously agreed that there is insufficient evidence showing that "orally administered phenylephrine is effective as a nasal decongestant".<ref>{{cite web | title=FDA clarifies results of recent AC meeting on oral phenylephrine | website=U.S. [[Food and Drug Administration]] (FDA) | date=14 September 2023 | url=https://www.fda.gov/drugs/drug-safety-and-availability/fda-clarifies-results-recent-advisory-committee-meeting-oral-phenylephrine | archive-url=https://web.archive.org/web/20230914174151/https://www.fda.gov/drugs/drug-safety-and-availability/fda-clarifies-results-recent-advisory-committee-meeting-oral-phenylephrine | url-status=dead | archive-date=14 September 2023 | access-date=14 September 2023}}</ref> The committee also unanimously believes that this does not need further study. The FDA responded to the committee, stating it would take its advice under advisement.<ref name="christensen23">{{cite news | vauthors = Christensen J |date=12 September 2023 |title=Popular OTC medicines for colds and allergies don't work, FDA panel says |work=CNN |url=https://www.cnn.com/2023/09/12/health/phenylephrine-tablets-ineffective-fda-panel-says/index.html |access-date=12 September 2023}}</ref><ref>{{Cite web | vauthors = Constantino AK |date=2023-09-12 |title=Decongestant found in many cold, allergy medicines doesn't actually work, FDA advisors say |url=https://www.cnbc.com/2023/09/12/decongestant-phenylephrine-ineffective.html |access-date=2023-09-12 |website=CNBC }}</ref> In November 2024, the FDA proposed to remove oral phenylephrine as an active ingredient that can be used in over-the-counter (OTC) monograph drug products for the temporary relief of nasal congestion.<ref name="FDA PR 20241107" />

=== Hemorrhoids ===
[[Hemorrhoids]] are caused by swollen [[veins]] in the [[rectal]] area.<ref>{{cite web | url = http://www.mayoclinic.org/diseases-conditions/hemorrhoids/basics/definition/con-20029852 | title = Hemorrhoids | publisher = Mayo Clinic }}</ref> Phenylephrine can be used topically to prevent symptoms of hemorrhoids. Phenylephrine causes the constriction of vascular smooth muscle and is often used in the treatment of hemorrhoids to narrow the swollen veins and relieve the attendant pain. However, veins contain less vascular smooth muscle in their walls than arteries. Products for treatment may also include substances that will form a protective barrier over the inflamed area, resulting in less pain when [[feces]] are passed.<ref>{{cite web | url = https://www.webmd.com/drugs/2/drug-76444/phenylephrine-rectal/details |title = Phenylephrine HCl Suppository | work = WebMD | access-date = 4 April 2015 }}</ref>

Phenylephrine hydrochloride at 0.25% is used as a [[vasoconstriction|vasoconstrictor]] in [[suppository]] formulations for hemorrhoid treatment.<ref name="Suppository-Label">{{cite web | url = http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=a23ded81-78ba-c199-a8f0-aaf360b216ff | work = DailyMed | title = Preparation H – cocoa butter and phenylephrine hydrochloride suppository | publisher = U.S. National Institutes of Health |access-date=4 April 2015}}</ref>

=== Pupil dilation ===
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Phenylephrine is used as an eye drop to dilate the pupil to facilitate visualization of the retina. It is often used in combination with [[tropicamide]] as a synergist when tropicamide alone is not sufficient. Narrow-angle [[glaucoma]] is a [[contraindication]] to phenylephrine use. As a [[mydriasis|mydriatic]], it is available in 2.5% and 10% [[eye drop]]s. Phenylephrine eye drops are applied to the eye after a topical anesthetic is applied.<ref>{{cite web | title = Phenylephrine Hydrochloride Ophthalmic Solution, USP 2.5% — Sterile | url = http://akorn.com/documents/catalog/sell_sheets/17478-205-10.pdf | archive-url = https://web.archive.org/web/20160303234455/http://akorn.com/documents/catalog/sell_sheets/17478-205-10.pdf | archive-date = 3 March 2016 | url-status = dead | publisher = Akorn }}</ref>

=== Intraocular bleeding ===
Phenylephrine has been used as an [[intracameral injection]] into the anterior chamber of the eye to arrest [[intraocular hemorrhage|intraocular bleeding]] occurring during [[cataract]] and [[glaucoma]] [[eye surgery|surgery]].<ref>{{cite journal | vauthors = Bizrah M, Corbett MC | title = Intracameral Phenylephrine to Arrest Intraoperative Intraocular Bleeding: A New Technique | journal = Ophthalmology and Therapy | volume = 8 | issue = 1 | pages = 137–141 | date = March 2019 | pmid = 30771215 | pmc = 6393249 | doi = 10.1007/s40123-019-0165-y }}</ref>

=== Low blood pressure ===
Phenylephrine is commonly used as a [[vasopressor]] to increase the blood pressure in unstable patients with [[hypotension]] (low blood pressure), especially resulting from [[septic shock]].<ref name="MengSunZhao2024" /><ref name="LarsonAndersonThomson2021">{{cite journal | vauthors = Larson S, Anderson L, Thomson S | title = Effect of phenylephrine on cerebral oxygen saturation and cardiac output in adults when used to treat intraoperative hypotension: a systematic review | journal = JBI Evid Synth | volume = 19 | issue = 1 | pages = 34–58 | date = January 2021 | pmid = 32941358 | doi = 10.11124/JBISRIR-D-19-00352 | url = }}</ref> Such use is common in [[surgery]] and [[anesthesia]] or critical-care practices;<ref name="MengSunZhao2024" /><ref name="LarsonAndersonThomson2021" /> it is especially useful in counteracting the hypotensive effect of [[epidural]] and [[spinal anesthesia]], as well as the vasodilating effect of bacterial toxins and the inflammatory response in [[sepsis]] and [[systemic inflammatory response syndrome]].

Because of its [[vasoconstriction|vasoconstrictive]] effect, phenylephrine can cause severe [[necrosis]] if it infiltrates the surrounding tissues. Because of this, it should be given through a central line if at all possible. Damage may be prevented or mitigated by infiltrating the tissue with the alpha-blocker [[phentolamine]] by subcutaneous injection.<ref name="Cooper2008">{{cite journal | vauthors = Cooper BE | title = Review and update on inotropes and vasopressors | journal = AACN Advanced Critical Care | volume = 19 | issue = 1 | pages = 5–13; quiz 14–15 | date = 2008 | pmid = 18418098 | doi = 10.1097/01.AACN.0000310743.32298.1d | s2cid = 39192378 }}</ref>

In clinical studies, phenylephrine, administered [[intravenous administration|intravenously]], increases blood pressure, decreases [[cardiac output]], increases cerebral blood flow, and decreases cerebral tissue oxygen saturation.<ref name="MengSunZhao2024">{{cite journal | vauthors = Meng L, Sun Y, Zhao X, Meng DM, Liu Z, Adams DC, McDonagh DL, Rasmussen M | title = Effects of phenylephrine on systemic and cerebral circulations in humans: a systematic review with mechanistic explanations | journal = Anaesthesia | volume = 79 | issue = 1 | pages = 71–85 | date = January 2024 | pmid = 37948131 | doi = 10.1111/anae.16172 | url = | doi-access = free }}</ref><ref name="LarsonAndersonThomson2021" /> The decreases in cardiac output, increases in cerebral blood flow, and decreases in cerebral tissue oxygen saturation with phenylephrine are all related to the degree of blood pressure increase.<ref name="MengSunZhao2024" /> The decrease in cardiac output is primarily due to a decrease in [[heart rate]] and a modest decrease in [[stroke volume]].<ref name="MengSunZhao2024" /> The decrease in heart rate is due to activation of the [[baroreflex|arterial baroreflex]], which regulates heart rate in response to changes in blood pressure.<ref name="MengSunZhao2024" /><ref name="LarsonAndersonThomson2021" /> Because of the decrease in cardiac output, phenylephrine is a [[Inotrope#Negative inotropic agents|negative inotropic agent]].<ref name="MengSunZhao2024" /> Its effects on cardiac output and cerebral oxygenation are unfavorable, and on account of this, the use of phenylephrine in the treatment of intraoperative hypotension is now being recommended against and moved away from in favor of other agents without these adverse effects like [[ephedrine]] and [[dopamine]].<ref name="MengSunZhao2024" /><ref name="LarsonAndersonThomson2021" />

When taken orally, phenylephrine has a threshold dose of about 50{{nbsp}}mg to affect the cardiovascular system, a dose at which the drug decreases heart rate and slightly increases arterial blood pressure.<ref name="Eccles2007" /> Additionally, an [[over-the-counter drug|over-the-counter]] dose of 60{{nbsp}}mg produces a slight increase in heart rate with no detectable changes in blood pressure.<ref name="Eccles2007" /> However, other literature reports that doses over 15{{nbsp}}mg affect the cardiovascular system, including increases in blood pressure and decreases in heart rate.<ref name="AtkinsonPottsAnderson2015" /> Higher doses, like 150{{nbsp}}mg, more robustly affect the cardiovascular system.<ref name="ChuaBenrimojTriggs1989" />

===Other uses===
Phenylephrine has been used in the treatment of [[postural orthostatic tachycardia syndrome]] (POTS).<ref name="LyongaNogongeNyange2024">{{cite journal | vauthors = Lyonga Ngonge A, Nyange C, Ghali JK | title = Novel pharmacotherapeutic options for the treatment of postural orthostatic tachycardia syndrome | journal = Expert Opin Pharmacother | volume = 25 | issue = 2 | pages = 181–188 | date = February 2024 | pmid = 38465412 | doi = 10.1080/14656566.2024.2319224 | url = }}</ref> It has been found to improve [[vascular resistance]], enhance circulatory support, and improve symptoms of [[orthostatic intolerance]] in people with the condition.<ref name="LyongaNogongeNyange2024" /> It has been described as particularly effective in people with [[neuropathy|neuropathic]] POTS.<ref name="LyongaNogongeNyange2024" /> However, phenylephrine has not been specifically approved for the treatment of POTS and data on this use are limited.<ref name="LyongaNogongeNyange2024" /> This is also the case with other medications used in the treatment of POTS.<ref name="LyongaNogongeNyange2024" />

Phenylephrine has been used in the treatment of [[priapism]].<ref name="JiangChristakosFam2014">{{cite journal | vauthors = Jiang P, Christakos A, Fam M, Sadeghi-Nejad H | title = Prophylactic phenylephrine for iatrogenic priapism: a pilot study with Peyronie's patients | journal = Korean J Urol | volume = 55 | issue = 10 | pages = 665–669 | date = October 2014 | pmid = 25324950 | pmc = 4198766 | doi = 10.4111/kju.2014.55.10.665 | url = }}</ref><ref name="MartinCocchio2016">{{cite journal | vauthors = Martin C, Cocchio C | title = Effect of phenylephrine and terbutaline on ischemic priapism: a retrospective review | journal = Am J Emerg Med | volume = 34 | issue = 2 | pages = 222–224 | date = February 2016 | pmid = 26597497 | doi = 10.1016/j.ajem.2015.10.029 | url = }}</ref>

===Available forms===
Phenylephrine is available in the form of [[oral administration|oral]] [[tablet (pharmacy)|tablet]]s and [[syrup]]s for use as a [[nasal decongestant]], as an [[intravenous]] [[solution (chemistry)|solution]] to treat [[hypotension]], as an [[ophthalmology|ophthalmic]] solution, spray, or [[eye drop]] to cause [[pupil dilation]], and as a [[cocoa butter]] [[suppository]], among other forms.<ref name="Drugs@FDA">{{cite web | title=Drugs@FDA: FDA-Approved Drugs | website=accessdata.fda.gov | publisher = Food and Drug Administration | url=https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm | archive-url=https://web.archive.org/web/20161104020633/http://www.accessdata.fda.gov/scripts/cder/daf/index.cfm | url-status=dead | archive-date=4 November 2016 | access-date=21 July 2024}}</ref><ref name="DailyMed">{{cite web | title=Search Results for phenylephrine | website=DailyMed | url=https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=phenylephrine&pagesize=200&page=1 | access-date=21 July 2024}}</ref> It was also previously available as a metered [[aerosol]] for [[inhalational administration|inhalation]], but this formulation was discontinued.<ref name="Drugs@FDA" />

Phenylephrine is available both alone and in [[combination drug|combination]] with other drugs.<ref name="Drugs@FDA" /><ref name="DailyMed" /> These other drugs include [[antihistamine]]s like [[chlorpheniramine]], [[doxylamine]], [[promethazine]], and [[mepyramine]] (pyrilamine); [[analgesic]]s like [[paracetamol]] (acetaminophen), [[ibuprofen]], [[ketorolac]], and [[codeine]]; [[cough suppressant]]s like [[dextromethorphan]]; [[expectorant]]s like [[guiafenesin]]; [[anticholinergic]]s like [[cyclopentolate]] and [[tropicamide]]; and [[beta agonist|β-adrenergic receptor agonist]]s like [[isoprenaline]] (isoproterenol).<ref name="Drugs@FDA" /><ref name="DailyMed" /> It is used in combination with antihistamines and analgesics in cough and cold preparations, with anticholinergics in ophthalmic formulations, and with β-adrenergic receptor agonists in inhalational forms.<ref name="Drugs@FDA" /><ref name="DailyMed" /> Intravenous phenylephrine is always formulated by itself.<ref name="Drugs@FDA" />