Naphazoline hydrochloride

What it is

Naphazoline hydrochloride is a synthetic imidazoline drug, chemically a relative of xylometazoline and oxymetazoline, sold as a liquid rather than eaten or absorbed from food. In the United States it appears in two quite separate kinds of product: over-the-counter eye drops for redness, at 0.012% to 0.03%, and nasal sprays or drops for a blocked nose. A 2020 review records that naphazoline at 0.1% was approved by the FDA in 1974 as a prescription ocular decongestant and is now sold over the counter at lower strengths. It is listed in the US over-the-counter monographs both as an ophthalmic vasoconstrictor and as a topical nasal decongestant active ingredient.

What the research says

The evidence for naphazoline is thin and old. For red eyes it rests on case series and a handful of very small masked studies of conjunctival blanching rather than on modern randomised outcome trials, and the 2020 review that summarises the eye evidence was written by two Bausch + Lomb employees, while the 2025 review of the nasal form was funded by Procter and Gamble. It does narrow conjunctival vessels quickly and the effect lasts a few hours. For a blocked nose, naphazoline is the oldest of the imidazoline sprays and has a short duration of action, around two to six hours, which means frequent redosing. Against that sit two well-documented harms: redness or congestion that comes back worse when the drug is stopped after prolonged use, and serious poisoning in small children who swallow the liquid.

Evidence grade: Limited evidence.

How it works

Drug class: Imidazoline (imidazole-derivative) alpha-adrenergic receptor agonist used as a topical vasoconstrictor: an ocular decongestant and a nasal decongestant

Naphazoline is put on the surface of the eye, or into the nose, where it switches on alpha-adrenergic receptors on small blood vessels and makes them narrow. A 2020 review of the US over-the-counter ocular decongestants, which covers eye products only, describes naphazoline as a mixed alpha-1/alpha-2 agonist whose receptor activation starts G-protein signalling that contracts vascular smooth muscle; narrower vessels mean less blood in the lining, so the white of the eye looks less red. The 2025 Procter and Gamble-funded review of imidazoline nasal decongestants describes the same vasoconstrictor action on the submucosa of the nose, which is what reduces swelling there and makes a blocked nose feel more open. (Source 1)

What it is used for

• In a case series of more than 100 people, naphazoline 0.1% narrowed conjunctival vessels with an immediate onset lasting several hours, but that strength is higher than the 0.012% to 0.03% now sold over the counter - between about 3.3 and 8.3 times it, which the review itself describes only as substantially greater. The series had no control group, and intraocular pressure rose and pupils dilated in some cases. The head-to-head evidence is two double-masked studies of six and eight healthy adults, and a separate 40-adult safety study in which average intraocular pressure was somewhat increased with naphazoline compared with phenylephrine. Reviews note tachyphylaxis and rebound redness with sustained use. Evidence: limited. (Source 2)
• The US over-the-counter monograph lists naphazoline hydrochloride as a topical nasal decongestant active ingredient (21 CFR 341.20(b)(6), revised as of 1 April 2024). The modern trial literature for naphazoline itself is very thin: the drugs in the 15 trials of the 2016 Cochrane review of decongestant monotherapy were pseudoephedrine, oxymetazoline, phenylpropanolamine, norephedrine and xylometazoline, so no naphazoline trial was included, and what the 2025 industry-funded imidazoline review adds is descriptive only. Evidence: limited. (Source 3)
• One 2025 case report describes marked but short-lived improvement in ptosis and conjunctival congestion after thyroid surgery. A single case report cannot show that the drug works for this. Evidence: unknown. (Source 4)
• The combination is widely sold, but the comparative evidence found was a single comfort study in minimally symptomatic volunteers in which the naphazoline/pheniramine drop was less comfortable than olopatadine while producing less redness. Evidence: limited. (Source 5)

Interactions

• Monoamine oxidase inhibitors (MAOIs) (label): The monoamine oxidase inhibitor warning in the US over-the-counter nasal decongestant monograph is attached to ORAL decongestants such as pseudoephedrine and phenylephrine, not to topical naphazoline. No study or case report of an MAOI interaction with ocular or nasal naphazoline was found in the literature searched, so the concern for topical naphazoline is extrapolated rather than demonstrated. (Source 6)
• Benzalkonium chloride (the preservative in many naphazoline eye drops and nasal sprays) (clinical trial): In a randomised, double-blind study of 20 healthy volunteers, an oxymetazoline nasal spray containing benzalkonium chloride produced significantly more rebound swelling after 30 days than the same spray without it (mean 1.1 mm against 0.5 mm). That study used oxymetazoline in the nose rather than naphazoline in the eye, so it is a signal for the drug class by a different route. A 2025 review states that the maximum safe concentration of benzalkonium chloride in nasal decongestants is 0.1% and describes the wider evidence as contradictory; whether any of this matters at the concentrations used in eye drops was not established in what we read. (Source 7)
• Alcohol (theoretical): No clinical study or case report of an interaction between topical naphazoline and alcohol was found in the literature searched. What is documented is that imidazoline overdose in its own right depresses the central nervous system and breathing and slows the heart, which is the effect that any additional sedative would be added to. (Source 8)
• Existing high blood pressure and cardiovascular disease (and the medicines used for them) (case reports): A 2025 review states that imidazoline decongestants are a contraindication in people who already have high blood pressure, because the vasoconstriction is not confined to the nose or eye and can push blood pressure higher; it also notes that reported stroke risk is tied to existing cardiovascular risk plus chronic use rather than to correct dosing. (Source 9)

Stopping it

• Stopping naphazoline-type eye drops after sustained use has been associated with rebound redness. The review offers a possible explanation rather than a settled one: because these receptors sit mainly in arterial vessels, the rebound may be driven by vasoconstrictor-induced tissue ischemia and the release of vasodilators that follows. It says of the related mechanism that this is far from clear. (Source 10)
• The US Drug Facts label sets a short self-treatment window rather than a tapering schedule: it tells the user to stop and ask a doctor if they get eye pain or changes in vision, if redness or irritation continues, or if the condition worsens or symptoms last for more than 72 hours. (Source 11)
• For the nasal form, the published approach to rebound congestion after prolonged use is slow withdrawal rather than abrupt stopping, combined with saline washes and intranasal steroids; the reviews note there are no formal clinical guidelines. (Source 12)

What goes wrong

Rebound redness and loss of effect after prolonged use of naphazoline eye drops are documented in case series, including five patients diagnosed with conjunctivitis medicamentosa and a series of 70 long-term users. (Source 13)

• Case series, Low certainty.
• Size: 5 patients with conjunctivitis medicamentosa and a separate series of 70 daily users.
• Who: people using over-the-counter decongestant eye drops (naphazoline, tetrahydrozoline, phenylephrine) daily.
• How long: days, weeks or months of continuous use in the first series; a median of 3 years, mean 3.7 plus or minus 2.2 times per day, in the second.
• Result: rebound redness on discontinuation in the 5-patient series; conjunctival redness still present in 50 of 70 long-term users despite continued use, taken as evidence of loss of efficacy or rebound dilation.
• Funding: the 2020 Clinical Optometry review that reports this was written by its two authors as Bausch + Lomb staff: its Disclosure states that both are employees of Bausch Health US, LLC, and their affiliations are given as Clinical and Medical Affairs, Bausch + Lomb and Regional Director Medical Science, Bausch + Lomb. Bausch + Lomb markets both naphazoline redness drops and the competing selective alpha-2 agonist brimonidine. Medical writing assistance was provided by Synchrony Medical Communications, LLC.

In a case series of 5 patients diagnosed with conjunctivitis medicamentosa, rebound redness was observed upon discontinuation of naphazoline or tetrahydrozoline after days, weeks, or months of continuous use.

More than half of reported cases of accidental swallowing of decongestant eye drops by children under five led to hospital admission. (Source 14)

• Case series, Moderate certainty.
• Size: 96 reported cases of accidental ingestion.
• Who: children aged 1 month to 5 years, FDA Adverse Event Reporting System data.
• How long: reports collected between 1985 and 2012.
• Result: 53 of 96 cases (55.2%) resulted in hospitalisation; in 2012 the FDA warned that 1 to 2 mL swallowed by a young child may cause coma, decreased heart rate and sedation.
• Funding: the 2020 Clinical Optometry review that reports this was written by its two authors as Bausch + Lomb staff: its Disclosure states that both are employees of Bausch Health US, LLC, and their affiliations are given as Clinical and Medical Affairs, Bausch + Lomb and Regional Director Medical Science, Bausch + Lomb. Bausch + Lomb markets both naphazoline redness drops and the competing selective alpha-2 agonist brimonidine. Medical writing assistance was provided by Synchrony Medical Communications, LLC.

Data collected between 1985 and 2012 from the FDA Adverse Event Reporting System showed that 53 out of 96 cases (55.2%) of accidental ingestion of products containing tetrahydrozoline, oxymetazoline, or naphazoline by children aged 1 month to 5 years resulted in hospitalization.

A 2018 report of a 4-year-old boy given naphazoline through a therapeutic error describes paediatric naphazoline poisoning as a potentially serious picture coming on immediately, with hypotonia, deterioration of the sensory, hypothermia and bradycardia. (Source 15)

• Case report, Low certainty.
• Size: 1 child.
• Who: a 4-year-old boy who received naphazoline through a therapeutic error (the paper describes it as a dispensing error)
• How long: immediate onset after the dose.
• Result: the authors describe paediatric naphazoline intoxication as immediate hypotonia, deterioration of the sensory, hypothermia and bradycardia of variable degree of clinical compromise, and note the drug is approved from age 12 because of its toxic effects. Those four features are the authors' general description of the poisoning, not a list of this child's recorded observations: the abstract gives no findings for the child beyond the rapid and potentially severe onset.
• Funding: not stated.

It is characterized by the immediate appearance of hypotonia, deterioration of the sensory, hypothermia and bradycardia of variable degree of clinical compromise.

After a deliberate overdose of a naphazoline-containing liquid, a 27-year-old woman had marked QT prolongation, frequent ventricular contractions, reduced left ventricular function and pulmonary oedema; her QTc and ejection fraction improved during the admission. (Source 16)

• Case report, Very low certainty.
• Size: 1 patient.
• Who: a 27-year-old woman with depression and an eating disorder.
• How long: presented about 12 hours after ingestion; QTc and ejection fraction improved during the admission.
• Result: prominent QT prolongation with multiple ventricular contractions, pulmonary oedema and decreased left ventricular systolic function; QTc and ejection fraction improved during hospitalisation. The myocardial biopsy showed extensive myocardial fibrosis with a very mild inflammatory cell infiltrate, which the authors report without saying what it represents, and the naphazoline history emerged only on repeat interview, so the authors put it as something to investigate in the differential diagnosis rather than as established causation.
• Funding: not stated.

In an additional detailed medical interview, the patient admitted that she had consumed three bottles of a first-aid liquid containing naphazoline approximately ~12 h before her presentation, in a suicide attempt.

In active surveillance of 236 patients given a naphazoline 0.1% and hypromellose eye drop, 54 adverse drug reactions were reported, all expected, mild and not serious, and confined to eye irritation, blurred vision, eye itching and headache. (Source 17)

• Cohort study, Low certainty.
• Size: 236 patients, 54 adverse drug reactions.
• Who: Peruvian outpatients prescribed naphazoline 0.1% plus hypromellose 0.5%.
• How long: two telephone follow-up calls after use.
• Result: 54 adverse drug reactions, one per patient, in two system organ classes (eye disorders, nervous system disorders) and four preferred terms (eye irritation, vision blurred, eye pruritus, headache); all expected, mild and not serious; no risk factors identified.
• Funding: not stated in the abstract; this is a manufacturer-style active pharmacovigilance programme.

A total of 54 ADRs (one per patient) were reported after the use of NAPH; classified (according to the Medical Dictionary for Regulatory Activities) into two groups of System Organ Class (SOC): eye disorders and nervous system disorders; and four groups of preferred term (PT): eye irritation, vision blurred, eye pruritus and headache.

A PRISMA-compliant systematic review of swallowed ocular-surface fluid containing eye drops reports that people of all ages present pale and lethargic to emergency departments, and found only nine studies that met its inclusion criteria. (Source 18)

• Systematic review, Low certainty.
• Size: nine included studies.
• Who: people of any age who swallowed conjunctival fluid mixed with eye drops; the abstract names alpha-2 adrenergic receptor agonists and tetrahydrozoline as the substances involved and does not name naphazoline, which is a mixed alpha-1/alpha-2 agonist, so it falls under the article's general heading of imidazole-derivative alpha-adrenergic eye drops rather than among the substances the abstract lists.
• How long: not applicable.
• Result: presentation as pale and lethargic; childhood cases are accidents during play while adult cases are suicide attempts or systemic absorption; only nine studies met inclusion criteria, so the evidence base is small.
• Funding: not stated.

Victims of all ages, otherwise in good health, often present as pale and lethargic to the emergency department (ED) after unintentionally ingesting topical eye medication.

The US over-the-counter monograph requires nasal naphazoline at 0.05% to carry a warning against use in children under 12 because it may cause sedation if swallowed, and requires a three-day limit on a named list of nasal decongestants that includes naphazoline, oxymetazoline and xylometazoline. (Source 19)

• Official position, Certainty not rated.
• Size: not applicable.
• Who: users of US over-the-counter topical nasal decongestants.
• How long: monograph limit of 3 days of use.
• Result: required label warnings: a 3-day limit with a statement that frequent or prolonged use may cause nasal congestion to recur or worsen, applied to a named list (ephedrine and its salts, naphazoline hydrochloride, oxymetazoline hydrochloride, phenylephrine hydrochloride and xylometazoline hydrochloride) rather than to a drug class, and, for 0.05% naphazoline, a warning against use under age 12 because of sedation if swallowed.
• Funding: US federal regulation; a regulator's position, not a trial.

“Do not use this product in children under 12 years of age because it may cause sedation if swallowed.”

The shorter-acting imidazolines, naphazoline among them, have been observed to cause reactive hyperaemia as soon as 8 hours after a dose, which is the mechanism that pushes people to take another one. (Source 20)

• Expert review, not systematic, Low certainty.
• Size: not stated in the review.
• Who: people using short-acting imidazoline nasal decongestants.
• How long: reactive hyperaemia reported as soon as 8 hours after application.
• Result: duration of symptom relief 2 to 6 hours for naphazoline against 8 to 12 hours for oxymetazoline, with reactive hyperaemia as early as 8 hours after application; the review links this to misuse as people redose to chase relief.
• Funding: industry-funded: funded by Procter and Gamble International Operations SA, whose author also reports consulting fees from Procter & Gamble, Reckitt and Chiesi.

Interestingly, the shorter acting derivatives, including naphazoline and tetrahydrozoline have been observed to cause reactive hyperaemia as soon as 8 h after application (Hochban et al., 1999).

Squeeze-bottle nasal drops used lying down can deliver 0.5 to 1.5 mL in a single spray against 0.03 mL upright, and only about 0.15 mL can be absorbed nasally, so the rest runs down the throat and is swallowed. (Source 21)

• Expert review, not systematic, Low certainty.
• Size: not applicable, narrative review.
• Who: children given nasal decongestants, particularly in a supine position.
• How long: per dose.
• Result: 0.5 to 1.5 mL released per spray from an inverted squeeze bottle in a supine patient versus 0.03 mL upright, against a nasal absorption capacity of about 0.15 mL, with the excess draining into the oropharynx and being swallowed.
• Funding: industry-funded: funded by Procter and Gamble International Operations SA.

For example, the use of nasal decongestants in inverted spray bottles in patients in a supine position can result in the release of 0.5–1.5 mL per spray, compared to 0.03 mL being released per spray when used in an upright position (Cartabuke et al., 2021).

What the evidence supports

In a case series of more than 100 patients with red eyes of mixed causes, naphazoline 0.1% narrowed superficial conjunctival and corneal capillaries, with an immediate onset lasting several hours, but intraocular pressure rose and pupils dilated in some cases. (Source 2)

• Case series, Very low certainty.
• Size: more than 100 patients.
• Who: patients with conjunctival redness of various causes including allergic and chronic conjunctivitis, keratitis, chemical burns, trauma and post-operative states.
• How long: various dosing regimens, not reported.
• Result: constriction of superficial conjunctival and corneal capillaries with immediate onset lasting several hours; increases in intraocular pressure and pupil dilation in some cases; the 0.1% strength used is higher than the 0.012-0.03% now sold over the counter.
• Funding: the 2020 Clinical Optometry review that reports this was written by its two authors as Bausch + Lomb staff: its Disclosure states that both are employees of Bausch Health US, LLC, and their affiliations are given as Clinical and Medical Affairs, Bausch + Lomb and Regional Director Medical Science, Bausch + Lomb. Bausch + Lomb markets both naphazoline redness drops and the competing selective alpha-2 agonist brimonidine. Medical writing assistance was provided by Synchrony Medical Communications, LLC.

Naphazoline 0.1% (various dosing regimens) produced constriction of superficial conjunctival and corneal capillaries resulting in reduced redness; this effect had an immediate onset and lasted for several hours.

In a very small double-masked study of six healthy adults, naphazoline 0.02% blanched the conjunctiva more than naphazoline 0.012%, tetrahydrozoline 0.05% and phenylephrine 0.12%, with no further gain at higher naphazoline strengths. (Source 22)

• Case series, Very low certainty.
• Size: 6 healthy adults; this is the first of the three studies in the held passage - the other two, a second double-masked study in 8 adults and a 40-adult safety study, are reported in the use summary for the eye drops.
• Who: healthy adults with no ocular disease, histamine-induced erythema model.
• How long: single administration.
• Result: naphazoline 0.02% gave significantly more conjunctival blanching than 0.012% naphazoline, tetrahydrozoline and phenylephrine combined; 0.1% and 0.05% naphazoline did not differ significantly from 0.02%; the review describes this as a small double-masked study and does not state that the comparison was randomised, so it is an experiment that cannot be called a randomised trial on what is printed.
• Funding: the individual study is not given a funding statement in the review. the 2020 Clinical Optometry review that reports this was written by its two authors as Bausch + Lomb staff: its Disclosure states that both are employees of Bausch Health US, LLC, and their affiliations are given as Clinical and Medical Affairs, Bausch + Lomb and Regional Director Medical Science, Bausch + Lomb. Bausch + Lomb markets both naphazoline redness drops and the competing selective alpha-2 agonist brimonidine. Medical writing assistance was provided by Synchrony Medical Communications, LLC.

Naphazoline 0.02% demonstrated significantly more blanching of the conjunctiva compared with lower-dose naphazoline (0.012%), tetrahydrozoline, and phenylephrine (data combined for analysis); higher doses of naphazoline (0.1% and 0.05%) did not differ significantly from the 0.02% dose.

A 2025 review of imidazoline nasal decongestants records that naphazoline was identified as a treatment for nasal congestion in 1941 and that its short duration of action means it has to be given again frequently. (Source 3)

• Expert review, not systematic, Low certainty.
• Size: not applicable, narrative review.
• Who: people using imidazoline nasal decongestants.
• How long: onset about 5 minutes; stated window of activity around 2 to 6 hours.
• Result: onset of action as little as 5 minutes, window of activity around 2–6 h, with frequent redosing and a consequent risk of acute toxicity.
• Funding: industry-funded: the review series was funded by Procter and Gamble International Operations SA and one author reports consulting fees from Procter & Gamble, Reckitt and Chiesi.

Whilst, the onset of action is as little as 5 minutes, the relatively short window of activity of around 2–6 h, means naphazoline needs to be readministered relatively frequently which can result in acute toxicity

One 2025 case report describes improvement in ptosis and conjunctival congestion from Horner syndrome after thyroid surgery when naphazoline eye drops were started, with the effect lasting about two hours per application. (Source 4)

• Case report, Very low certainty.
• Size: 1 patient.
• Who: a 30-year-old woman with Horner syndrome after left thyroid lobectomy and neck dissection.
• How long: started four months after surgery; each application lasted about 2 hours.
• Result: ptosis diminished, palpebral fissure returned to normal, pupil sizes equalised and conjunctival congestion resolved, with effects lasting approximately 2 h after each application.
• Funding: not stated.

Four months postoperatively, the introduction of topical naphazoline eye drops resulted in marked improvement.

What the evidence does not support

In a Danish nationwide cohort of nearly a million births, first-trimester exposure to antazoline-naphazoline eye drops was not associated with major congenital malformations. (Source 23)

• Cohort study, Moderate certainty.
• Size: 977 706 births, of which 3061 pregnancies (0.32%) were exposed in the first trimester.
• Who: all women giving live birth in Denmark between 1997 and 2011.
• How long: exposure in the first 84 days of pregnancy; outcome assessed at birth.
• Result: malformations in 3.0% (n = 93) of exposed offspring versus 3.5% (n = 33 594) of unexposed; odds ratio 0.88, 95% CI 0.71-1.09, and no association with any specific major malformation.
• Funding: not stated.

Limit of this finding: The paper's own Results section ends with a sentence that contradicts itself: it says the number of redeemed prescriptions was “unchanged during all trimesters of pregnancy as compared to before and after pregnancy (p < 0.05)”, and a p-value below 0.05 indicates a difference rather than no change. That sentence is about how often the drops were bought, not about birth defects, and nothing in this finding rests on it. The malformation result quoted here is a different sentence and is internally consistent.

First-trimester exposure to antazoline-naphazoline was not associated with major congenital malformations overall (odds ratio: 0.88, 95% confidence interval: 0.71-1.09) or with any specific major malformation.

Where the evidence is mixed

In a comparison in minimally symptomatic volunteers, a pheniramine/naphazoline allergy drop was less comfortable on instillation than olopatadine 0.7%, although the eyes given it were less red. (Source 5)

• Cohort study, Low certainty.
• Size: 159 participants, each compared between their own two eyes.
• Who: minimally symptomatic volunteers, mean age 26.2 years, one drop in each eye in a paired within-person comparison.
• How long: comfort assessed at instillation and at 30 seconds, 1 minute and 2 minutes.
• Result: eyes given olopatadine were significantly more comfortable at instillation and were preferred for overall comfort, stinging, burning and foreign body sensation; no difference in visual acuity; eyes given the naphazoline-containing drop were less red. The abstract does not say the allocation was randomised and PubMed indexes the paper as a journal article only, though the masking was double-blind; the comparisons are within each person, between eyes.
• Funding: not stated in the abstract; the comparator is a branded olopatadine product.

The VAS found that eyes treated with Pataday were significantly more comfortable at instillation than eyes treated with VISINE.

Where the research disagrees

Whether rebound redness and rebound congestion are an inherent effect of naphazoline-type decongestants or an artefact of misuse

• Authors of a 2020 review in Clinical Optometry, both of them employees of Bausch Health US, LLC with their affiliations given as Bausch + Lomb (a company marketing both naphazoline redness drops and the competing selective alpha-2 agonist brimonidine), narrative review of case series and FDA adverse event reports: Use of α1- or mixed α1/α2-adrenergic receptor agonists has also been associated with rebound redness upon treatment discontinuation. (Source 10)
• Authors of a 2025 Frontiers in Pharmacology review series funded by Procter and Gamble International Operations SA, narrative review citing a systematic review of a different imidazoline, oxymetazoline: Indeed, a recent systematic review concluded that when used as directed, oxymetazoline does not lead to rebound congestion (Malik et al., 2025). (Source 24)

How much

• Reference intake: There is no reference intake for a drug. The US Drug Facts label for a 0.012% naphazoline eye drop (SPL version published 14 September 2026) states as its directions: “Instill 1 to 2 drops in the affected eye(s) up to four times daily.” That is the manufacturer's and regulator's position on dosing, recorded here as a position and not as guidance. (Source 11)
• Upper limit: There is no upper intake level. The US over-the-counter ophthalmic monograph sets the permitted strength range for naphazoline hydrochloride as a vasoconstrictor at “Naphazoline hydrochloride, 0.01 to 0.03 percent.” (21 CFR 349.18, revised as of 1 April 2024). That ophthalmic section sets no duration limit; the three-day labelling cap applies to nasal decongestants under a different part of the regulations (21 CFR 341.80(c)(2)(iii)) and is recorded separately among the harms. (Source 25)
• Studied: Masked ocular studies summarised in a 2020 review used naphazoline at 0.012%, 0.02%, 0.05% and 0.1%, including an exaggerated-use arm of 8 times per day for 9 days, and 4 times on the morning of Day 10. (Source 22)
• Studied: The Peruvian active surveillance programme followed patients using naphazoline 0.1% combined with hypromellose 0.5%. (Source 26)

A common belief, and what the research shows

The belief: Redness-relief drops are treating whatever is making the eye red, so it is fine to keep using them.

What the research shows: What they do is narrow blood vessels. The 2020 Clinical Optometry review’s own discussion of management is explicit that the cause is a separate matter: “Before recommending an OTC ocular decongestant, the health-care provider should make recommendations for the management of ocular redness that address the underlying cause, where known.” The label itself warns that “overuse may produce increased redness of the eye” and tells users that pupils may become temporarily enlarged, and the FDA required that overuse warning on all over-the-counter ophthalmic vasoconstrictors in 1988, after roughly 280 adverse event reports between 1969 and 1984 of which more than 90 were consumers reporting that their eyes turned redder. Reviews describe both tachyphylaxis, where “sustained use of α1- or mixed α1/α2-adrenergic receptor agonists has been associated with tachyphylaxis (tolerance or loss of effectiveness)”, and rebound redness on stopping. In one series of 70 people using decongestant drops daily for a median of three years, 50 still had conjunctival redness.

Questions and answers

What is it?

Naphazoline hydrochloride is a manufactured drug, not a nutrient or an organism. It is an imidazoline that acts on alpha-adrenergic receptors and is sold as a liquid: over-the-counter eye drops for redness and, under a separate listing in the US monograph (21 CFR 341.20(b)(6)), nasal sprays and drops for a blocked nose. In the United States the eye drops contain 0.012% to 0.03%, after the original 0.1% strength was approved as a prescription product in 1974. The review quoted here covers eye products only. (Source 27)

What does it do in the body?

It switches on alpha-adrenergic receptors on the small blood vessels of the eye surface or the nose lining, which makes those vessels contract. Less blood in the lining means the white of the eye looks whiter and the nose feels less blocked. The signalling runs through G-proteins to contraction of vascular smooth muscle. (Source 1)

Is it good or bad for you?

It depends entirely on how briefly it is used and by whom. In an active surveillance programme of 236 adults using a naphazoline eye drop, 54 adverse drug reactions were reported and all were expected, mild and not serious. Used for weeks or months it is associated with loss of effect and rebound redness. Swallowed by a small child it causes serious poisoning: in FDA adverse-event data summarised by a 2020 review, 53 of 96 reported ingestions by children under five led to hospital admission. (Source 17)

How do you get more of it?

Not a question that applies in the usual sense: naphazoline is not something the body makes or needs, so there is no way to have more of it other than buying a product containing it. The ophthalmic monograph quoted here permits it as an ophthalmic vasoconstrictor at 0.01 to 0.03 percent; a different monograph, 21 CFR 341.20(b)(6), lists it as a topical nasal decongestant active ingredient. Nothing in the diet contains it. (Source 25)

If it is harmful, what reduces it?

When the problem is rebound redness or rebound congestion from prolonged use, the published approach is to stop the drug, with slow withdrawal rather than abrupt cessation for the nasal form because sudden stopping can make rebound worse. Saline washes and intranasal steroids are used alongside the weaning, and oral steroids if needed. Reviews stress there is no standardised protocol. This paragraph says nothing about acute poisoning, which is a different situation and is covered among the harms with its own sources. (Source 12)

Why might someone be low in it or missing it?

Does not apply. Naphazoline is a manufactured drug ingredient that only enters the body when a product containing it is used, so nobody is deficient in it and there is no store of it to run down. The US monograph lists it among nasal decongestant active ingredients to be used within set dosage limits and dosage forms. (Source 28)

Which whole foods contain it or feed it?

None. Naphazoline is a synthetic imidazoline, first identified as a nasal decongestant in 1941, and it is not a constituent of any food. There are no whole foods that contain it or that feed it. (Source 3)

What happens if you do not have it?

Nothing happens from not having naphazoline: there is no deficiency state. What is left untreated is the symptom, and the evidence that the drug changes anything beyond the symptom is absent. For conjunctival redness, a 2026 narrative review notes that decongestants give effective short-term relief only, and that the mixed alpha-1/alpha-2 agonists such as naphazoline carry tachyphylaxis and rebound redness with them. That review's journal fee and medical writing were funded by Bausch + Lomb, which also reviewed the manuscript and which markets the selective alpha-2 agonist the same passage goes on to praise. (Source 29)

How can you test for it?

There is no routine clinical test for naphazoline, and no validated test for the conditions it causes. Rebound redness from decongestant drops (conjunctivitis medicamentosa) is identified clinically from the pattern of continuous use and redness that returns on stopping, as in the published case series. For the related nasal condition, reviews state plainly that there is no specific biochemical test and that diagnosis rests on examination and history. (Source 13)

We searched: Europe PMC searches for naphazoline with assay, detection, poisoning and conjunctivitis medicamentosa; the hits for naphazoline measurement were analytical chemistry method-development papers (HPLC, TLC, chemiluminescence) for quality control of eye drops, not clinical diagnostic tests

References

1. Clinical Optometry (Dove Medical Press). Over-the-Counter Ocular Decongestants in the United States - 'Mechanisms of Action', opening paragraph. 2020. PMID 32801982, DOI 10.2147/opto.s259398. Read the source
2. Clinical Optometry (Dove Medical Press). Over-the-Counter Ocular Decongestants in the United States - paragraph on the naphazoline case series. 2020. PMID 32801982, DOI 10.2147/opto.s259398. Read the source
3. Frontiers in Pharmacology. Part 1 - imidazolines and the changing face of nasal decongestants - section 'Naphazoline'. 2025. PMID 41394151, DOI 10.3389/fphar.2025.1655252. Read the source
4. The Journal of International Medical Research. Naphazoline eye drops for the treatment of Horner syndrome following radical thyroid cancer surgery: a case report - abstract. 2025. PMID 40832951, DOI 10.1177/03000605251359467. Read the source
5. Clinical and Experimental Optometry. Understanding ocular comfort differences between 0.7% olopatadine and 0.3% pheniramine maleate/0.025% naphazoline hydrochloride eye drops - Results. 2023. PMID 35815690, DOI 10.1080/08164622.2022.2090231. Read the source
6. Code of Federal Regulations, title 21, volume 5, revised as of 1 April 2024 (US Government Publishing Office). 21 CFR 341.80(c)(1)(i) - Labeling of nasal decongestant drug products: warnings, including the monoamine oxidase inhibitor drug interaction precaution, for ORAL nasal decongestants. 2024. Read the source
7. Clinical and Experimental Allergy (British Society for Allergy and Clinical Immunology). Benzalkonium chloride in a decongestant nasal spray aggravates rhinitis medicamentosa in healthy volunteers - abstract, whole. 1995. PMID 7553241, DOI 10.1111/j.1365-2222.1995.tb01069.x. Read the source
8. Frontiers in Pharmacology. Part 1 - imidazolines and the changing face of nasal decongestants - 'General toxicology', opening paragraph. 2025. PMID 41394151, DOI 10.3389/fphar.2025.1655252. Read the source
9. Frontiers in Pharmacology. Part 1 - imidazolines and the changing face of nasal decongestants - section 'Contraindicators for imidazoline nasal decongestant use'. 2025. PMID 41394151, DOI 10.3389/fphar.2025.1655252. Read the source
10. Clinical Optometry (Dove Medical Press). Over-the-Counter Ocular Decongestants in the United States - 'Tachyphylaxis and Rebound Redness', paragraph on rebound redness. 2020. PMID 32801982, DOI 10.2147/opto.s259398. Read the source
11. Prestige Brands Holdings, Inc. / DailyMed (US National Library of Medicine), SPL version 14 published 14 September 2026. Clear Eyes Redness Relief (glycerin 0.25%, naphazoline hydrochloride 0.012%) - US Drug Facts label: Uses, Warnings, Do not use, Ask a doctor before use, When using this product, Stop use and ask a doctor if, Keep out of reach of children, Directions. 2026. Read the source
12. Frontiers in Pharmacology. Part II - imidazolines and rhinitis medicamentosa - 'Treatment and prevention of rhinitis medicamentosa', paragraph on weaning and adjuncts. 2025. PMID 41394157, DOI 10.3389/fphar.2025.1655254. Read the source
13. Clinical Optometry (Dove Medical Press). Over-the-Counter Ocular Decongestants in the United States - paragraph on reported tachyphylaxis and rebound cases, held whole. 2020. PMID 32801982, DOI 10.2147/opto.s259398. Read the source
14. Clinical Optometry (Dove Medical Press). Over-the-Counter Ocular Decongestants in the United States - paragraph on accidental ingestion. 2020. PMID 32801982, DOI 10.2147/opto.s259398. Read the source
15. Archivos Argentinos de Pediatria. [Severe poisoning with naphazoline: update from a therapeutic error] - abstract. 2018. PMID 30016045, DOI 10.5546/aap.2018.e626. Read the source
16. Journal of Cardiology Cases. Naphazoline intoxication with transient QT prolongation and acute myocardial injury - abstract (one unlabelled narrative block; the source prints no 'case description' heading). 2024. PMID 38188313, DOI 10.1016/j.jccase.2023.09.004. Read the source
17. Integrated Pharmacy Research and Practice (Dove Medical Press). Real-Life Active Surveillance of a Naphazoline/Hypromellose Fixed Combination's Safety Profile in Peruvian Population - Results. 2021. PMID 34703789, DOI 10.2147/iprp.s332421. Read the source
18. Pharmaceuticals (MDPI). Ingestion of Fluids of the Ocular Surface Containing Eye Drops of Imidazole Derivatives-Alpha Adrenergic Receptor Agonists as Paragons - abstract, whole. 2024. PMID 38931425, DOI 10.3390/ph17060758. Read the source
19. Code of Federal Regulations, title 21, volume 5, revised as of 1 April 2024 (US Government Publishing Office). 21 CFR 341.80(c)(2) - Labeling of nasal decongestant drug products: warnings for topical nasal decongestants, subparagraphs (i) to (x) complete. 2024. Read the source
20. Frontiers in Pharmacology. Part 1 - imidazolines and the changing face of nasal decongestants - 'Comparative efficacy', paragraph on duration of relief and reactive hyperaemia. 2025. PMID 41394151, DOI 10.3389/fphar.2025.1655252. Read the source
21. Frontiers in Pharmacology. Part 1 - imidazolines and the changing face of nasal decongestants - 'Imidazoline nasal decongestant use in children', paragraph on systemic absorption. 2025. PMID 41394151, DOI 10.3389/fphar.2025.1655252. Read the source
22. Clinical Optometry (Dove Medical Press). Over-the-Counter Ocular Decongestants in the United States - paragraph on head-to-head studies of naphazoline and tetrahydrozoline, held whole. 2020. PMID 32801982, DOI 10.2147/opto.s259398. Read the source
23. Acta Ophthalmologica. Exposure to antazoline-naphazoline eye drops during pregnancy and the risk of congenital malformations: a Danish nationwide cohort study - Results. 2019. PMID 30479070, DOI 10.1111/aos.13980. Read the source
24. Frontiers in Pharmacology. Part 1 - imidazolines and the changing face of nasal decongestants - 'Safety measures to reduce acute risk', closing paragraph on remaining uncertainty. 2025. PMID 41394151, DOI 10.3389/fphar.2025.1655252. Read the source
25. Code of Federal Regulations, title 21, volume 5, revised as of 1 April 2024 (US Government Publishing Office). 21 CFR 349.18 - Ophthalmic vasoconstrictors. 2024. Read the source
26. Integrated Pharmacy Research and Practice (Dove Medical Press). Real-Life Active Surveillance of a Naphazoline/Hypromellose Fixed Combination's Safety Profile in Peruvian Population - Objective. 2021. PMID 34703789, DOI 10.2147/iprp.s332421. Read the source
27. Clinical Optometry (Dove Medical Press). Over-the-Counter Ocular Decongestants in the United States - section 'Ocular Decongestants', opening paragraph. 2020. PMID 32801982, DOI 10.2147/opto.s259398. Read the source
28. Code of Federal Regulations, title 21, volume 5, revised as of 1 April 2024 (US Government Publishing Office). 21 CFR 341.20 - Nasal decongestant active ingredients. 2024. Read the source
29. Ophthalmology and Therapy. Global Perspectives on Therapy for Noninfectious Conjunctival Hyperemia: A Narrative Review - abstract. 2026. PMID 41689622, DOI 10.1007/s40123-026-01310-7. Read the source