Pi Yuan Chin

Dosage for Naphazoline must be strictly followed to avoid the risk of 'rebound' congestion or redness. According to standard clinical guidelines:

• Ophthalmic (Eye) Use: For adults and children 6 years and older, the typical dose is 1 to 2 drops of a 0.012% to 0.1% solution in the affected eye(s) up to 4 times daily. It is critical not to exceed this frequency. Use should be limited to no more than 72 consecutive hours.
• Nasal Use: For adults and children 12 years and older, the standard dose is 2 sprays or 2 drops of a 0.05% solution in each nostril as needed, not more often than every 4 to 6 hours. Similar to eye drops, nasal use should be restricted to a maximum of 3 consecutive days.

Naphazoline requires extreme caution in pediatric populations due to the risk of systemic absorption and CNS toxicity.

• Children under 6 years: Ophthalmic use is generally not recommended unless specifically directed by a pediatric ophthalmologist. Many OTC labels state 'Consult a doctor.'
• Children under 12 years: Nasal use of the 0.05% or 0.1% solution is typically discouraged. Pediatric-strength formulations (0.025%) may be available in some regions, but healthcare provider consultation is mandatory.
• Infants: Naphazoline is contraindicated (should not be used) in infants and young children, as it can cause profound coma and a dangerous drop in body temperature.

Renal Impairment

Since Naphazoline is applied topically and systemic absorption is generally low, specific dose adjustments for renal (kidney) impairment are not typically required. However, patients with severe renal disease should use the medication with caution, as any absorbed drug must be cleared by the kidneys.

Hepatic Impairment

There are no established guidelines for Naphazoline dosage adjustment in patients with hepatic (liver) impairment. Given the drug's primary local action, it is generally considered safe for short-term use, though caution is advised in patients with advanced cirrhosis.

Elderly Patients

Elderly patients may be more sensitive to the effects of sympathomimetic amines. They are at a higher risk for systemic side effects such as increased blood pressure or heart palpitations. Healthcare providers may recommend a lower frequency of use or a lower concentration for geriatric patients.

Proper administration is key to efficacy and safety:

1. 1For Eye Drops: Wash hands thoroughly. Tilt the head back and pull down the lower eyelid. Instill the prescribed number of drops into the conjunctival sac. Close the eye and apply gentle pressure to the lacrimal duct (the inner corner of the eye) for 1-2 minutes to minimize systemic absorption. Do not touch the dropper tip to any surface.
2. 2For Nasal Spray: Blow the nose gently before use. Keep the head upright. Insert the spray tip into one nostril, closing the other with a finger. Sniff briskly while squeezing the bottle. Repeat for the other nostril. Rinse the tip with hot water and dry after use.
3. 3Storage: Store at room temperature (15°C to 30°C / 59°F to 86°F). Keep the container tightly closed and protect it from light.

If you miss a dose, use it as soon as you remember. However, if it is almost time for your next scheduled dose, skip the missed dose and resume your regular schedule. Do not double the dose to catch up, as this increases the risk of toxicity.

Naphazoline overdose can be life-threatening, especially if swallowed. Signs of overdose include extreme tiredness, sweating, decreased body temperature (hypothermia), slow heart rate (bradycardia), and shallow breathing. In severe cases, particularly in children, it can lead to coma. If an overdose is suspected, contact a Poison Control Center or seek emergency medical attention immediately.

> Important: Follow your healthcare provider's dosing instructions. Do not adjust your dose or extend the duration of treatment without medical guidance.

Most patients using Naphazoline for short durations experience minimal side effects. However, common local reactions include:

• Transient Stinging or Burning: A brief, sharp sensation in the eye or nose immediately following application. This usually subsides within seconds.
• Local Irritation: Redness or itching of the nasal mucosa or conjunctiva.
• Sneezing: Frequently occurs after nasal administration as the tissue reacts to the solution.
• Dryness: Prolonged or frequent use can lead to a dry, 'crusty' feeling inside the nose or a 'gritty' sensation in the eyes.

These effects may indicate a higher level of systemic absorption or sensitivity:

• Blurred Vision: Temporary blurring may occur after using eye drops. Patients should wait for their vision to clear before driving.
• Mydriasis (Pupil Dilation): Naphazoline can cause the pupils to enlarge, which may lead to increased light sensitivity (photophobia).
• Headache: Some patients report a mild, dull headache following use.
• Nervousness or Tremor: A 'jittery' feeling similar to consuming too much caffeine.

• Palpitations: A sensation of a racing or skipping heart.
• Hypertension: A temporary increase in blood pressure.
• Nausea: Feeling sick to the stomach.
• Dizziness: A sensation of lightheadedness or spinning.

While rare with topical use, serious systemic reactions can occur, particularly in sensitive individuals or in cases of excessive use.

> Warning: Stop taking Naphazoline and call your doctor immediately if you experience any of these:

1. 1Severe Eye Pain: This may indicate an acute attack of narrow-angle glaucoma.
2. 2Vision Changes: Sudden loss of vision or seeing 'halos' around lights.
3. 3Cardiac Arrhythmia: Irregular or very fast heartbeat.
4. 4Profound Drowsiness: Especially in children, this can be a sign of CNS toxicity.
5. 5Difficulty Breathing: Signs of an allergic reaction or systemic respiratory depression.
6. 6Severe Rebound Congestion: If your nose becomes completely blocked and does not respond to the medication, stop use and seek professional help.

The most significant risk of Naphazoline is Rhinitis Medicamentosa (for nasal use) or Rebound Conjunctival Hyperemia (for eye use). When the drug is used for more than 3-5 days, the blood vessels 'forget' how to constrict on their own. As the drug wears off, the vessels dilate even more than before, leading to chronic congestion or redness. This creates a cycle of dependency where the patient must use the drug more frequently to achieve the same effect. Long-term use can also lead to permanent thickening of the nasal mucosa or chronic 'dry eye' syndrome.

No FDA black box warnings currently exist for Naphazoline. However, the FDA requires strict labeling warnings regarding use in children and the duration of use to prevent rebound effects.

Report any unusual symptoms to your healthcare provider. Monitoring for cardiovascular changes is recommended if you have pre-existing heart conditions.

Naphazoline is a potent vasoconstrictor and should be handled with the same respect as systemic medications. It is intended for temporary relief only. If symptoms persist for more than 72 hours, patients must discontinue use and consult a healthcare professional, as the underlying condition may require different treatment (e.g., antibiotics for an infection or steroid sprays for chronic allergies).

There are no FDA black box warnings for Naphazoline. However, it is classified as a 'High-Risk' medication for accidental ingestion in pediatric populations.

• Narrow-Angle Glaucoma: Naphazoline is strictly contraindicated in patients with narrow-angle glaucoma. The pupillary dilation (mydriasis) caused by the drug can trigger an acute angle-closure attack, which is a medical emergency that can lead to permanent blindness.
• Cardiovascular Disease: Patients with hypertension (high blood pressure), coronary artery disease, or arrhythmias should use Naphazoline with extreme caution. Even small amounts of systemic absorption can exacerbate these conditions.
• Diabetes Mellitus: Sympathomimetics can theoretically interfere with blood glucose control, although this is rare with topical Naphazoline.
• Thyroid Disease: Patients with hyperthyroidism (overactive thyroid) are more sensitive to the effects of sympathomimetics and may experience severe tachycardia (fast heart rate).
• Prostatic Hypertrophy: Men with an enlarged prostate may experience increased difficulty urinating due to the alpha-adrenergic effects on the bladder neck.

For standard OTC use, formal lab monitoring is not typically required. However, if a healthcare provider prescribes Naphazoline for longer-term or frequent use, they may monitor:

• Intraocular Pressure (IOP): To ensure the drug is not affecting glaucoma risk.
• Blood Pressure: Especially in patients with pre-existing hypertension.
• Nasal Mucosa Integrity: To check for signs of tissue atrophy or rhinitis medicamentosa.

Naphazoline ophthalmic drops can cause temporary blurred vision or light sensitivity. Patients should not drive or operate heavy machinery until they are certain their vision is clear and stable.

There is no direct chemical interaction between Naphazoline and alcohol. However, alcohol can dilate blood vessels, which may counteract the effects of Naphazoline. Furthermore, both alcohol and Naphazoline (if absorbed systemically) can affect the central nervous system; combining them may increase the risk of dizziness or drowsiness.

If you have used Naphazoline for longer than the recommended 3 days, do not stop 'cold turkey' if you experience severe rebound congestion. Instead, consult a doctor. They may recommend a 'weaning' process, often involving the use of a saline spray or a prescription corticosteroid spray (like fluticasone) to reduce inflammation while the blood vessels regain their natural tone.

> Important: Discuss all your medical conditions, especially heart or eye problems, with your healthcare provider before starting Naphazoline.

• Monoamine Oxidase Inhibitors (MAOIs): Drugs such as phenelzine, tranylcypromine, or selegiline must not be used with Naphazoline. MAOIs inhibit the breakdown of norepinephrine. When combined with a sympathomimetic like Naphazoline, this can lead to a 'hypertensive crisis'—a sudden, severe, and potentially fatal increase in blood pressure. This restriction applies even if the MAOI was stopped within the last 14 days.

• Tricyclic Antidepressants (TCAs): Medications like amitriptyline or nortriptyline can potentiate (increase) the pressor response of Naphazoline. This may lead to significant increases in blood pressure and heart rate.
• Maprotiline: Similar to TCAs, this medication can increase the cardiovascular effects of Naphazoline.
• Ergot Alkaloids: Used for migraines (e.g., ergotamine), these also cause vasoconstriction. Using them with Naphazoline can lead to excessive narrowing of blood vessels, increasing the risk of hypertension or reduced blood flow to extremities.

• Beta-Blockers: Drugs like propranolol or metoprolol may have their efficacy reduced by the alpha-adrenergic effects of Naphazoline. Conversely, blocking beta receptors can leave alpha-mediated vasoconstriction unopposed, leading to higher blood pressure.
• Other Decongestants: Using Naphazoline with other sympathomimetics (like pseudoephedrine) can have an additive effect, increasing the risk of insomnia, tremors, and palpitations.

• Caffeine: High intake of caffeine (coffee, tea, energy drinks) can worsen the 'jittery' side effects, nervousness, and tachycardia associated with Naphazoline.
• Alcohol: As noted, alcohol may cause vasodilation that opposes the drug’s therapeutic effect.

• St. John’s Wort: May have mild MAOI-like activity and should be used cautiously.
• Ephedra (Ma Huang): Contains ephedrine; combining this with Naphazoline significantly increases the risk of severe cardiovascular events.
• Bitter Orange: Contains synephrine, which can have additive sympathomimetic effects.

Naphazoline is not known to significantly interfere with common blood or urine laboratory tests. However, its effect on pupil size can interfere with certain ophthalmic diagnostic exams. Always inform your eye doctor if you have used Naphazoline drops before an eye exam.

Mechanism of Interaction: Most Naphazoline interactions occur via pharmacodynamic pathways, where two drugs affect the same physiological system (the sympathetic nervous system). This leads to additive effects on blood pressure and heart rate.

> Important: Tell your doctor about ALL medications, supplements, and herbal products you are taking, including those used only occasionally.

Naphazoline must NEVER be used in the following circumstances:

1. 1Narrow-Angle Glaucoma: Because Naphazoline causes mydriasis (pupil dilation), it can physically block the drainage angle of the eye in susceptible individuals, leading to a rapid, dangerous increase in intraocular pressure.
2. 2Known Hypersensitivity: If you have had a previous allergic reaction to Naphazoline or any of the inactive ingredients (such as benzalkonium chloride, a common preservative), you must avoid this drug.
3. 3MAOI Therapy: Use within 14 days of taking a Monoamine Oxidase Inhibitor is strictly forbidden due to the risk of hypertensive crisis.
4. 4Infants and Young Children: Due to the high risk of systemic toxicity, including respiratory depression and coma, Naphazoline is contraindicated in infants.

Healthcare providers will perform a risk-benefit analysis before recommending Naphazoline for patients with:

• Severe Hypertension: The risk of further elevating blood pressure may outweigh the benefit of decongestion.
• Advanced Arteriosclerosis: Narrowed arteries may be further compromised by the drug's vasoconstrictive effects.
• Hyperthyroidism: The increased sensitivity to catecholamines in these patients makes side effects much more likely.
• Chronic Rhinitis: In patients with long-term nasal issues, Naphazoline may worsen the condition through rebound effects.

Patients who are allergic or sensitive to other imidazoline derivatives (such as oxymetazoline, xylometazoline, or tetrahydrozoline) may experience cross-reactivity with Naphazoline. If you have reacted poorly to '12-hour' nasal sprays or other 'redness relief' eye drops, inform your healthcare provider before using Naphazoline.

> Important: Your healthcare provider will evaluate your complete medical history, including any history of heart disease or eye surgery, before prescribing Naphazoline.

Naphazoline is classified as FDA Pregnancy Category C. This means that animal reproduction studies have shown an adverse effect on the fetus, or there are no adequate and well-controlled studies in humans. It is unknown whether Naphazoline can cause fetal harm when administered to a pregnant woman or if it can affect reproduction capacity. Because Naphazoline is a vasoconstrictor, there is a theoretical risk that systemic absorption could reduce uterine blood flow. Naphazoline should be used during pregnancy only if clearly needed and under the direct supervision of a healthcare provider. Many clinicians recommend non-pharmacological alternatives (like saline drops) as a first-line treatment for pregnant patients.

It is not known whether Naphazoline is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from sympathomimetic amines, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother. If used, the mother should apply pressure to the tear duct (for eye drops) to minimize systemic absorption.

Pediatric patients are significantly more susceptible to the systemic effects of Naphazoline. Accidental ingestion of even small amounts of Naphazoline (such as a child chewing on a bottle) can lead to 'Imidazoline Poisoning.' Symptoms include bradycardia (slow heart rate), hypotension (low blood pressure), and CNS depression. Use in children under 6 (for eyes) or 12 (for nose) should be strictly monitored by a physician.

Clinical studies of Naphazoline did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. However, geriatric patients are generally more likely to have underlying cardiovascular disease or glaucoma, making them higher-risk candidates for Naphazoline use. Providers often suggest the lowest effective dose for the shortest possible duration.

While systemic levels are typically low, patients with end-stage renal disease (ESRD) should be monitored for signs of drug accumulation if Naphazoline is used frequently. Dialysis is not expected to significantly clear Naphazoline due to its primary local distribution.

In patients with severe hepatic impairment, the metabolism of any systemically absorbed Naphazoline may be slowed. These patients should be observed for prolonged sympathomimetic effects.

> Important: Special populations require individualized medical assessment. Never share your Naphazoline with others, especially children.

Naphazoline is a direct-acting sympathomimetic amine. Its primary molecular target is the alpha-1 adrenergic receptor. These G-protein coupled receptors are located on the smooth muscle cells of the peripheral vasculature. Upon binding, Naphazoline activates the Gq protein, which stimulates phospholipase C. This leads to an increase in intracellular calcium, resulting in muscle contraction and subsequent vasoconstriction. While it has some affinity for alpha-2 receptors, its clinical decongestant effect is almost entirely mediated through alpha-1 activation. It has negligible activity at beta-1 or beta-2 adrenergic receptors at therapeutic concentrations.

The pharmacodynamic effect of Naphazoline is characterized by rapid onset and moderate duration. The primary effect is the reduction of local blood flow and tissue volume. In the eye, it reduces conjunctival edema and hyperemia. In the nose, it reduces mucosal swelling. Tolerance (tachyphylaxis) can develop rapidly with frequent use, leading to the rebound phenomenon where the receptors become desensitized or down-regulated.

| Parameter | Value |

|---|---|

| Bioavailability | Low (Topical); High (Oral/Systemic) |

| Onset of Action | < 10 minutes |

| Duration of Effect | 2 to 6 hours |

| Tmax | Not well-defined for topical use |

| Metabolism | Hepatic (Minimal systemic levels) |

| Excretion | Renal (Primary) |

• Molecular Formula: C14H14N2 (as free base); C14H14N2·HCl (as Hydrochloride salt)
• Molecular Weight: 246.73 g/mol (Hydrochloride salt)
• Solubility: Freely soluble in water and alcohol; practically insoluble in benzene and ether.
• Structure: An imidazoline derivative consisting of a naphthalene ring attached to an imidazoline ring via a methylene bridge.

Naphazoline is a member of the Imidazoline class of vasoconstrictors. It is therapeutically categorized as a topical decongestant and an ophthalmic vasoconstrictor. Related medications include oxymetazoline (Afrin), tetrahydrozoline (Visine), and xylometazoline (Otrivin).