section name header

Introduction

AHFS Class:

Generic Name(s):

Tetrahydrozoline hydrochloride, an imidazoline-derivative sympathomimetic amine, is a vasoconstrictor.

Uses

Ophthalmic Disorders

Tetrahydrozoline hydrochloride is applied topically to the conjunctiva for self-medication to temporarily relieve congestion, itching, and minor irritation, and to control hyperemia in patients with superficial corneal vascularity. Ocular decongestants are ineffective in the treatment of delayed hypersensitivity reactions such as contact dermatoconjunctivitis. The vasoconstrictor effect of tetrahydrozoline may be used during some ocular diagnostic procedures, but some clinicians prefer phenylephrine to tetrahydrozoline for this use.

Dosage and Administration

Administration

Ophthalmic solutions of tetrahydrozoline hydrochloride are applied topically to the conjunctiva. Care must be taken to avoid contamination of the solution container.

Dosage

Conjunctival Congestion

To produce decongestion of the conjunctiva, 1 or 2 drops of a 0.05% ophthalmic solution of tetrahydrozoline hydrochloride may be applied topically to the conjunctiva up to 4 times daily or as directed by a physician. Treatment generally should not be continued for longer than 3-4 days unless under the direction of an ophthalmologist.

Cautions

Adverse Effects

The incidence of serious adverse effects is low in patients receiving therapeutic dosages of topical tetrahydrozoline hydrochloride. Excessive dosage and/or prolonged or too frequent use may irritate the conjunctiva and, especially in children, cause adverse systemic effects.

Use of tetrahydrozoline in the eye may cause blurred vision, irritation, and mydriasis. Conjunctival application of tetrahydrozoline, especially when high concentrations are used in geriatric patients, may liberate pigment granules, presumably from the iris. Rebound congestion, characterized by chronic redness, swelling, or reactive hyperemia, frequently occurs with prolonged use. Prolonged use of tetrahydrozoline ophthalmic solution should be avoided for these reasons.

Ophthalmic use of tetrahydrozoline occasionally may cause systemic sympathomimetic effects such as headache, hypertension, weakness, sweating, palpitation, and tremors. Overdosage of the drug may produce CNS depression with drowsiness, decreased body temperature, bradycardia, shock-like hypotension, apnea, and coma. In pediatric patients, accidental ingestion of imidazoline derivatives (i.e., tetrahydrozoline, naphazoline, oxymetazoline) has resulted in serious adverse events requiring hospitalization (e.g., coma, bradycardia, decreased respiration, sedation, somnolence).101,  1001,  1002,  1003,  1004,  1005,  1006,  1007 (See Cautions: Pediatric Precautions and also see Acute Toxicity.)

Precautions and Contraindications

Excessive dosage and/or prolonged or too frequent use of tetrahydrozoline should be avoided. In children, excessive dosage of the drug may cause severe drowsiness accompanied by profuse sweating.

When decongestants are applied topically in recommended dosage, 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.

Patients using tetrahydrozoline hydrochloride ophthalmic solutions should be advised to discontinue the drug and consult a physician if ocular pain or visual changes occur, they experience continued ocular redness or irritation, or the condition worsens or persists for more than 72 hours. Patients also should be informed that overuse of ophthalmic vasoconstrictors may produce increased redness of the eye (rebound hyperemia).

Serious adverse events requiring hospitalization have been reported in children following accidental ingestion of nonprescription (over-the-counter, OTC) ophthalmic solutions or nasal sprays containing imidazoline derivatives (i.e., tetrahydrozoline, naphazoline, oxymetazoline).1001 (See Cautions: Pediatric Precautions and also see Acute Toxicity.) If accidental ingestion of tetrahydrozoline hydrochloride ophthalmic solution occurs, a poison control center should be contacted, and patients should be advised to seek emergency help immediately.1001

Tetrahydrozoline is contraindicated in patients with a known hypersensitivity to the drug. Patients with glaucoma should be advised not to use tetrahydrozoline ophthalmic solutions except under the advice and supervision of a physician. Ophthalmic solutions of the drug should not be used in patients with angle-closure glaucoma or other serious eye diseases.

Pediatric Precautions

Tetrahydrozoline hydrochloride is contraindicated in children younger than 2 years of age. Ophthalmic solutions of tetrahydrozoline should not be used for self-medication in children younger than 6 years of age.102

Serious adverse events requiring hospitalization have been reported in children following accidental ingestion of small amounts (1-2 mL) of nonprescription ophthalmic solutions or nasal sprays containing imidazoline derivatives (i.e., tetrahydrozoline, naphazoline, oxymetazoline).1001 Patients should be advised to keep tetrahydrozoline hydrochloride ophthalmic solutions out of the reach of children.1001 (See Cautions: Precautions and Contraindications and also see Acute Toxicity.)

Pregnancy, Fertility, and Lactation

Pregnancy

Animal reproduction studies have not been performed with tetrahydrozoline hydrochloride. It is not known whether the drug can cause fetal harm when administered to pregnant women or affect reproduction capacity. Tetrahydrozoline hydrochloride should be used during pregnancy only when clearly needed.

Fertility

It is not known whether the drug can affect reproduction capacity.

Lactation

Since it is not known if tetrahydrozoline is distributed into milk, the drug should be used with caution in nursing women.

Other Information

Acute Toxicity

Pathogenesis

The minimum toxic dose of imidazoline derivatives (e.g., tetrahydrozoline, naphazoline, oxymetazoline) has not been established in pediatric patients;1003 however, ingestion of 2-5 mL of a 0.05% tetrahydrozoline solution is capable of producing coma.1001

Manifestations

Serious adverse events requiring hospitalization have been reported in pediatric patients following accidental ingestion of nonprescription (over-the-counter, OTC) ophthalmic solutions or nasal sprays containing imidazoline derivatives (i.e., tetrahydrozoline, naphazoline, oxymetazoline).1001 Between 1985 and October 2012, 96 cases of accidental ingestion were reported in children 1 month to 5 years of a the amount of drug ingested ranged from 0.6-45 mL.1001 While no deaths were reported, more than half of these cases reported serious adverse events requiring hospitalization, including nausea, vomiting, lethargy, tachycardia, decreased respiration, bradycardia, hypotension, hypertension, sedation, somnolence, mydriasis, stupor, hypothermia, drooling, and coma.1001 Respiratory depression, CNS depression, and/or lethargy were reported in a 23-month-old and a 2-year-old infant following accidental ingestion of 6 and 2-3 mL, respectively, of 0.05% tetrahydrozoline ophthalmic solution;1002,  1007 in addition, urinary incontinence was reported in a 36-month-old child following accidental ingestion of 30 mL of 0.05% tetrahydrozoline ophthalmic solution.1004

Symptoms develop rapidly in children (i.e., within 15 minutes to 4 hours following ingestion) and generally resolve within 24 hours.1002,  1003,  1004 Imidazoline derivatives stimulate central and peripheral α-adrenergic receptors; therefore, symptoms of acute intoxication in children may alternate between CNS depression and agitation or hyperactivity.1006

Treatment

Treatment of acute toxicity associated with imidazoline derivatives (e.g., tetrahydrozoline) is primarily symptomatic and supportive and is aimed at reversing the toxic cardiovascular and CNS effects of the drugs.1002 Cardiorespiratory resuscitation, including tracheal intubation and mechanical ventilation, is considered a mainstay of care for imidazoline-derivative intoxication.1002 Neurologic and hemodynamic status of the patient should be closely observed for at least 24 hours.1006

Because imidazoline derivatives are rapidly absorbed following ingestion, GI decontamination (e.g., activated charcoal, ipecac-induced emesis, gastric lavage) appears to have limited value.1002,  1006,  1007 However, if GI decontamination is used, some clinicians state that gastric lavage is preferred over induction of emesis.1002,  1007 Administration of activated charcoal and a cathartic is recommended by some clinicians; however, safety and efficacy of repeated administration of activated charcoal have not been established.1007

There is no known specific antidote for imidazoline-derivative intoxication.1006,  1007 Because symptoms of imidazoline-derivative and clonidine intoxication are similar and are mediated via the same central α2-adrenergic receptors, and because naloxone has been effective in reversing CNS depression in some instances of clonidine overdose, some clinicians have hypothesized that naloxone may be useful for the management of imidazoline-derivative intoxication.1003,  1004,  1006,  1007 However, data are limited and conflicting, and the role of naloxone in the management of imidazoline-derivative intoxication remains to be established.1002,  1004,  1006,  1007

Pharmacology

The mechanism of action of tetrahydrozoline has not been conclusively determined. Most pharmacologists believe that the drug directly stimulates α-adrenergic receptors of the sympathetic nervous system and exerts little or no effect on β-adrenergic receptors. Following topical application of tetrahydrozoline to the conjunctiva, small arterioles are constricted and conjunctival congestion is temporarily relieved, but reactive hyperemia may occur. The drug also may produce mydriasis when applied to the conjunctiva, but this effect is usually minimal with the concentrations used as ocular decongestants.

Pharmacokinetics

Following topical application of tetrahydrozoline hydrochloride solutions to the conjunctiva, local vasoconstriction usually occurs within a few minutes and may persist for 4-8 hours. Occasionally, enough tetrahydrozoline may be absorbed to produce systemic effects. Information on the distribution and elimination of the drug in humans is not available.

Chemistry and Stability

Chemistry

Tetrahydrozoline hydrochloride is an imidazoline-derivative sympathomimetic amine which is structurally and pharmacologically related to naphazoline, oxymetazoline, and xylometazoline. Tetrahydrozoline hydrochloride occurs as a white, odorless solid and has solubilities of approximately 286 mg/mL in water and 133 mg/mL in alcohol at 25°C. Tetrahydrozoline hydrochloride ophthalmic solutions are sterile, isotonic solutions of the drug in water. Tetrahydrozoline hydrochloride ophthalmic solutions have a pH of 5.8-6.5.

Stability

Tetrahydrozoline hydrochloride ophthalmic solutions should be stored in tight containers.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Tetrahydrozoline Hydrochloride

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Ophthalmic

Solution

0.05%*

Tetrahydrozoline Hydrochloride Eye Drops

Visine® Original

J&J

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Tetrahydrozoline Hydrochloride Combinations

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Ophthalmic

Solution

0.05% with Dextran 70 0.1%, Polyethylene Glycol 400 1%, and Povidone 1%*

Tetrahydrozoline Hydrochloride, Dextran, Polyethylene Glycol, and Povidone Eye Drops

Visine® Advanced

J&J

0.05% with Glycerin 0.2%, Hypromellose 0.36%, and Polyethylene Glycol 400 1%

Visine® Maximum

J&J

0.05% with Glycerin 0.2%, Hypromellose 0.36%, Polyethylene Glycol 400 1%, and Zinc Sulfate 0.25%

Visine® Totality

J&J

0.05% with Hypromellose 0.35%

Rohto® Arctic

Mentholatum

0.05% with Hypromellose 0.2% and Zinc Sulfate 0.25%

Rohto® Ice

Mentholatum

Rohto® Relief

Mentholatum

0.05% with Polyethylene Glycol 400 1%*

Tetrahydrozoline Hydrochloride and Polyethylene Glycol Eye Drops

0.05% with Polyvinyl Alcohol 0.5% and Povidone 0.6%

Clear Eyes® Triple Action Relief

Prestige Brands

0.05% with Zinc Sulfate 0.25%*

Tetrahydrozoline Hydrochloride and Zinc Sulfate Eye Drops

Visine® A.C.

J&J

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Copyright

AHFS® Drug Information. © Copyright, 1959-2025, Selected Revisions February 20, 2014. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, MD 20814.

References

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

101. Tyzine® (tetrahydrozoline hydrochloride) nasal solution prescribing information. Fairfield, NJ; 1999 Apr.

102. Pfizer. Visine® (tetrahydozoline hydrochloride 0.05%) product information. From Pfizer Visine website ([Web]). Accessed October 25, 2006.

1001. US Food and Drug Administration. FDA drug safety communication: Serious adverse events from accidental ingestion by children of over-the-counter eye drops and nasal sprays. Rockville, MD; 2012 Oct 25. From FDA website. [Web]

1002. Tobias JD. Central nervous system depression following accidental ingestion of Visine eye drops. Clin Pediatr (Phila) . 1996; 35:539-40. [PubMed 8902333]

1003. Katar S, Taskesen M, Okur N. Naloxone use in a newborn with apnea due to tetrahydrozoline intoxication. Pediatr Int . 2010; 52:488-9. [PubMed 20723124]

1004. Holmes JF, Berman DA. Use of naloxone to reverse symptomatic tetrahydrozoline overdose in a child. Pediatr Emerg Care . 1999; 15:193-4. [PubMed 10389957]

1005. Vitezic D, Rozmanic V, Franulovic J et al. Naphazoline nasal drops intoxication in children. Arh Hig Rada Toksikol . 1994; 45:25-9. [PubMed 8067910]

1006. Mahieu LM, Rooman RP, Goossens E. Imidazoline intoxication in children. Eur J Pediatr . 1993; 152:944-6. [PubMed 8276031]

1007. Higgins GL, Campbell B, Wallace K et al. Pediatric poisoning from over-the-counter imidazoline-containing products. Ann Emerg Med . 1991; 20:655-8. [PubMed 2039105]