Oxymetazoline

Dosage for oxymetazoline depends strictly on the formulation and the condition being treated.

Nasal Congestion (0.05% Nasal Spray/Drops)

• Standard Dose: 2 to 3 sprays or drops in each nostril every 10 to 12 hours.
• Maximum Frequency: Do not exceed two doses in any 24-hour period.
• Duration Limit: Use should be strictly limited to no more than 3 consecutive days. Prolonged use can lead to 'rebound congestion' (rhinitis medicamentosa).

Facial Erythema in Rosacea (1% Cream)

• Standard Dose: Apply a pea-sized amount once daily to the entire face (forehead, nose, each cheek, and chin), avoiding the eyes and lips.

Acquired Blepharoptosis (0.1% Ophthalmic Solution)

• Standard Dose: Instill one drop into the affected eye(s) once daily.

• Children 6 to 12 years of age: Use 0.05% nasal spray/drops; 2 to 3 sprays or drops in each nostril every 10 to 12 hours, not to exceed two doses in 24 hours. Limit use to 3 days.
• Children under 6 years of age: Use is generally not recommended unless specifically directed by a pediatrician. There is a significant risk of systemic toxicity and respiratory depression in young children if the drug is absorbed or accidentally swallowed.
• Rosacea and Ptosis: Safety and efficacy have not been established in pediatric patients for these indications.

Renal Impairment

Specific dosage adjustments for renal (kidney) impairment are not typically required for topical oxymetazoline due to its low systemic absorption. However, caution should be exercised in patients with severe renal disease if systemic effects occur.

Hepatic Impairment

No specific dosage adjustments are provided for hepatic (liver) impairment. As with renal impairment, the localized nature of the drug limits systemic exposure.

Elderly Patients

Clinical trials for the 1% cream and 0.1% ophthalmic solution included elderly patients, and no overall differences in safety or effectiveness were observed. However, elderly patients may be more sensitive to the cardiovascular effects (such as increased blood pressure) of sympathomimetic amines.

Nasal Spray Instructions

1. 1Gently blow your nose to clear the passages.
2. 2Keep your head upright and insert the spray tip into one nostril.
3. 3Firmly squeeze the bottle while breathing in deeply through your nose.
4. 4Repeat in the other nostril.
5. 5Wipe the tip clean after each use and replace the cap.

Topical Cream (Rhofade) Instructions

1. 1Wash your hands before and after application.
2. 2Apply a thin layer to the face as directed by your doctor.
3. 3Avoid contact with eyes, mouth, and broken skin.

Ophthalmic Solution Instructions

1. 1Wash hands thoroughly.
2. 2Tilt your head back and pull down the lower eyelid.
3. 3Instill the prescribed number of drops without touching the dropper tip to the eye or any other surface.
4. 4Close the eye for 1-2 minutes to allow absorption.

If you miss a dose, take it as soon as you remember. However, if it is nearly time for your next scheduled dose, skip the missed dose and resume your regular schedule. Do not double the dose to catch up. For the nasal spray, missing a dose is generally not an issue as it is often used on an as-needed basis (within the 3-day limit).

Signs of oxymetazoline overdose, particularly if swallowed or used excessively, include:

• Extreme tiredness or drowsiness
• Slowed heart rate (bradycardia)
• Low blood pressure (hypotension) followed by high blood pressure (hypertension)
• Respiratory depression (slowed breathing)
• Decreased body temperature (hypothermia)

In the event of an overdose or accidental ingestion, especially by a child, 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 use without medical guidance.

When used as a nasal spray, common side effects are usually localized to the site of application and include:

• Temporary Stinging or Burning: A sharp, prickling sensation in the nasal passages immediately following use.
• Nasal Dryness: A feeling of parched or irritated membranes within the nose.
• Sneezing: An immediate reflexive response to the medication entering the nasal cavity.
• Increased Nasal Discharge: A temporary increase in 'runny nose' before the vasoconstriction takes full effect.

For the 1% topical cream (Rhofade), common side effects include application site dermatitis (skin irritation), worsening of inflammatory lesions of rosacea, and application site erythema (redness).

These effects may occur as the drug is absorbed systemically or as a reaction to the formulation:

• Headache: A dull or throbbing pain, likely due to changes in blood flow.
• Dizziness: A feeling of lightheadedness or unsteadiness.
• Nervousness or Restlessness: A mild feeling of anxiety or 'jitters.'
• Insomnia: Difficulty falling or staying asleep, particularly if the drug is used late in the evening.
• Blurred Vision: Occurs primarily with the ophthalmic formulations.

Rarely, oxymetazoline can cause systemic cardiovascular or neurological effects:

• Palpitations: A sensation that the heart is racing, fluttering, or skipping a beat.
• Tachycardia: An abnormally rapid heart rate.
• Hypertension: A sudden increase in blood pressure.
• Nausea: Feeling sick to the stomach.

> Warning: Stop taking Oxymetazoline and call your doctor immediately if you experience any of these serious symptoms.

• Rhinitis Medicamentosa (Rebound Congestion): This is a condition where the nasal passages become chronically congested because of the overuse of nasal sprays. The nasal membranes become dependent on the drug to stay constricted; when the drug wears off, the swelling returns worse than before. This can lead to permanent damage to the nasal mucosa.
• Severe Allergic Reactions: Symptoms include rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, and trouble breathing (anaphylaxis).
• Chest Pain: Any pressure or pain in the chest area, which could indicate cardiovascular strain.
• Severe Change in Vision: Sudden blurring or loss of vision when using ophthalmic drops.
• Extreme Weakness or Fainting: May indicate a significant drop in blood pressure or heart rate.

The most significant long-term risk of oxymetazoline (nasal) is the development of chronic nasal congestion and mucosal atrophy (thinning of the lining of the nose). Prolonged use can lead to the loss of the normal ciliary function (the tiny hairs that clear mucus), making the patient more prone to sinus infections and chronic irritation. For the topical cream, long-term use has been studied for up to one year, with skin irritation being the primary ongoing concern.

No FDA black box warnings currently exist for Oxymetazoline. However, the FDA does mandate strong warnings on OTC packaging regarding the duration of use (the 3-day rule) to prevent rebound congestion and warnings regarding accidental ingestion by children.

Report any unusual symptoms or persistent side effects to your healthcare provider. If you suspect you have developed a dependency on the nasal spray, consult an ear, nose, and throat (ENT) specialist for a tapering schedule.

Oxymetazoline is a potent medication that must be used with caution. The most critical safety point for patients using the nasal spray is the 3-day limit. Using the product for longer than three consecutive days can cause the nasal tissues to swell more than they did originally, creating a cycle of dependency and chronic congestion known as rhinitis medicamentosa.

There are no FDA black box warnings for Oxymetazoline. It is generally considered safe when used exactly as directed for short durations.

• Cardiovascular Disease: Oxymetazoline is a sympathomimetic amine and can cause vasoconstriction throughout the body if absorbed systemically. Patients with hypertension (high blood pressure), coronary artery disease, or arrhythmias (irregular heartbeats) should use this medication only under medical supervision.
• Diabetes Mellitus: Sympathomimetics may interfere with blood glucose control, although this is less likely with topical forms compared to oral decongestants.
• Thyroid Disease: Patients with hyperthyroidism (overactive thyroid) may be more sensitive to the effects of oxymetazoline, potentially leading to increased heart rate or blood pressure.
• Prostatic Hypertrophy: Oxymetazoline may cause urinary retention or difficulty urinating in men with an enlarged prostate (benign prostatic hyperplasia).
• Narrow-Angle Glaucoma: Ophthalmic oxymetazoline can increase intraocular pressure and should be avoided or used with extreme caution in patients with narrow-angle glaucoma.
• Accidental Ingestion: This drug is highly toxic if swallowed, especially by small children. It can cause profound CNS depression, bradycardia, and respiratory failure. Always keep oxymetazoline out of reach of children.

Routine lab tests are not typically required for short-term oxymetazoline use. However, for patients using the 1% cream or 0.1% drops long-term, doctors may monitor:

• Blood Pressure: To ensure no systemic absorption is causing hypertension.
• Skin Assessment: To check for dermatitis or worsening rosacea symptoms.
• Intraocular Pressure: For patients using the ophthalmic drops who have a history of glaucoma.

While oxymetazoline does not typically cause drowsiness, some patients may experience dizziness or blurred vision (especially with eye drops). If you experience these symptoms, do not drive or operate heavy machinery until your vision clears and you feel steady.

There is no direct interaction between alcohol and oxymetazoline. However, alcohol can cause vasodilation (widening of blood vessels), which may worsen nasal congestion or the facial redness of rosacea, potentially counteracting the effects of the medication.

If oxymetazoline nasal spray has been used for longer than 3-5 days, do not stop it abruptly if you experience severe rebound congestion. Your healthcare provider may recommend a tapering schedule, such as stopping the spray in one nostril at a time or using a saline-only spray to bridge the transition. In some cases, a short course of nasal corticosteroids may be prescribed to reduce the inflammation caused by withdrawal.

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

• Monoamine Oxidase Inhibitors (MAOIs): Oxymetazoline should not be used by patients currently taking MAOIs (such as phenelzine, selegiline, or tranylcypromine) or who have taken them within the last 14 days. MAOIs inhibit the breakdown of norepinephrine. Adding a sympathomimetic like oxymetazoline can lead to a massive accumulation of catecholamines, potentially triggering a hypertensive crisis (a dangerous, rapid rise in blood pressure).

• Tricyclic Antidepressants (TCAs): Drugs like amitriptyline and nortriptyline can potentiate the pressor (blood pressure-raising) effect of oxymetazoline. If systemic absorption occurs, the risk of hypertension and arrhythmias is significantly increased.
• Ergot Alkaloids: Medications used for migraines (e.g., ergotamine) also cause vasoconstriction. Combining them with oxymetazoline can lead to additive vasoconstrictive effects and increased risk of severe hypertension.

• Beta-Blockers: Systemic absorption of oxymetazoline may antagonize the blood pressure-lowering effects of beta-blockers (e.g., metoprolol, propranolol). Conversely, beta-blockers may leave alpha-mediated vasoconstriction unopposed, leading to higher blood pressure.
• Other Decongestants: Using oxymetazoline alongside oral decongestants (like pseudoephedrine or phenylephrine) increases the risk of sympathomimetic side effects such as jitteriness, insomnia, and palpitations.

• Caffeine: High intake of caffeine (found in coffee, tea, and energy drinks) can have additive stimulant effects when combined with oxymetazoline, potentially increasing heart rate and blood pressure.
• Alcohol: While not a direct drug-drug interaction, alcohol causes vasodilation, which can worsen the very conditions (congestion and rosacea) that oxymetazoline is intended to treat.

• Ephedra (Ma Huang): This herbal supplement contains ephedrine, a potent sympathomimetic. Using it with oxymetazoline significantly increases the risk of cardiovascular side effects.
• St. John's Wort: May have mild MAOI-like properties and could theoretically increase the risk of hypertensive effects, though this is less documented than with pharmaceutical MAOIs.
• Bitter Orange: Contains synephrine, which may have additive effects on blood pressure and heart rate.

Oxymetazoline is not known to significantly interfere with common laboratory blood or urine tests. However, its effect on intraocular pressure may interfere with tonometry tests during eye exams.

For each major interaction, the mechanism usually involves either pharmacodynamic synergy (both drugs increasing blood pressure via different or similar pathways) or interference with the clearance of neurotransmitters like norepinephrine. The clinical consequence is typically an increased risk of cardiovascular strain. The management strategy is generally to avoid the combination or to monitor blood pressure and heart rate closely during use.

> Important: Tell your doctor about ALL medications, supplements, and herbal products you are taking, including those purchased over-the-counter.

Oxymetazoline must NEVER be used in the following circumstances:

• Hypersensitivity: If you have a known allergy to oxymetazoline or any of the inactive ingredients (such as benzalkonium chloride) in the formulation. An allergic reaction can lead to skin rashes or, in severe cases, anaphylaxis.
• MAOI Use: As noted in the interactions section, use within 14 days of a Monoamine Oxidase Inhibitor is strictly contraindicated due to the risk of a fatal hypertensive crisis.
• Narrow-Angle Glaucoma (Ophthalmic Use): For the eye drop formulations, narrow-angle glaucoma is a contraindication because the drug can cause pupillary dilation (mydriasis), which may trigger an acute attack of angle-closure glaucoma, a medical emergency.

In these cases, a healthcare provider must perform a careful risk-benefit analysis:

• Severe Hypertension: Patients with uncontrolled high blood pressure are at higher risk if systemic absorption occurs.
• Advanced Arteriosclerosis: Hardening of the arteries can make the cardiovascular system less able to handle the temporary increases in pressure caused by vasoconstrictors.
• Pheochromocytoma: A rare tumor of the adrenal gland that secretes large amounts of adrenaline; sympathomimetics can trigger severe symptoms in these patients.
• Rhinitis Sicca: A chronic form of nasal inflammation characterized by dry, crusty membranes; oxymetazoline can worsen the dryness and crusting.

Patients who are allergic to other imidazoline derivatives (such as xylometazoline, naphazoline, or tetrahydrozoline) may also be allergic to oxymetazoline. If you have had a reaction to 'redness-relief' eye drops or other long-acting nasal sprays in the past, inform your healthcare provider before use.

> Important: Your healthcare provider will evaluate your complete medical history, including any history of heart disease or glaucoma, before prescribing or recommending Oxymetazoline.

Oxymetazoline 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 oxymetazoline can cause fetal harm when administered to a pregnant woman or if it can affect reproduction capacity.

• First Trimester: Caution is advised. While systemic absorption is low, excessive use should be avoided to prevent any potential uterine artery vasoconstriction.
• Third Trimester: Some studies suggest that heavy use of vasoconstrictors could potentially interfere with fetal blood flow.

Oxymetazoline should be used during pregnancy only if clearly needed and if the potential benefit justifies the potential risk to the fetus.

It is not known whether oxymetazoline is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when oxymetazoline is administered to a nursing woman. Given the low systemic absorption of topical forms, the amount reaching the infant is likely very small, but mothers should monitor the infant for any signs of restlessness or sleep disturbances.

• Nasal Use: Approved for children 6 years and older. Use in children under 6 is generally avoided due to the risk of systemic toxicity. Children are more susceptible to the sedative effects and respiratory depression that can occur if the drug is absorbed or swallowed.
• Toxicity: There have been reports of serious adverse events, including coma and severe bradycardia, in toddlers who accidentally ingested small amounts of oxymetazoline nasal spray.

Elderly patients (65 years and older) may be more prone to the side effects of sympathomimetic amines. Specifically, they have a higher prevalence of underlying cardiovascular disease, prostatic hypertrophy, and glaucoma, all of which require cautious use of oxymetazoline. In clinical trials for Rhofade and Upneeq, no specific dosage adjustments were required for the elderly, but close monitoring of blood pressure is recommended.

Oxymetazoline has not been specifically studied in patients with renal impairment. However, because only about 30% of a systemically absorbed dose is excreted by the kidneys, and systemic levels are already very low, significant accumulation is unlikely in patients with mild to moderate renal disease. No specific GFR-based adjustments are provided in the standard labeling.

There are no specific studies or dosage adjustments for oxymetazoline in patients with hepatic impairment. The drug does not appear to be heavily metabolized by the liver, suggesting that liver dysfunction should not significantly impact the clearance of the drug.

> Important: Special populations, particularly pregnant women and the elderly, require individualized medical assessment before using vasoconstrictors.

Oxymetazoline is a direct-acting sympathomimetic amine that acts as an agonist on alpha-adrenergic receptors. It has a high affinity for alpha-1A receptors, which are prevalent in the smooth muscles of the blood vessels in the nasal mucosa and the skin. It also acts on alpha-2A receptors. By binding to these receptors, oxymetazoline triggers the G-protein signaling pathway, leading to an increase in intracellular calcium and subsequent contraction of the vascular smooth muscle. This results in vasoconstriction, which reduces the volume of the nasal mucosa (nasal decongestion), reduces the diameter of facial capillaries (rosacea treatment), and contracts the Müller's muscle (eyelid elevation).

• Onset of Action: For nasal congestion, the onset is rapid, typically occurring within 5 to 10 minutes.
• Duration of Effect: Oxymetazoline is known for its long duration of action, providing relief for up to 12 hours.
• Tolerance: Tachyphylaxis (a rapid decrease in response to the drug) can occur with frequent, repeated use, which is why the 3-day limit is strictly enforced for nasal use.

| Parameter | Value |

|---|---|

| Bioavailability | Minimal (Topical/Nasal) |

| Protein Binding | Not extensively characterized |

| Half-life | 5 - 8 hours |

| Tmax | 0.5 - 2 hours (if systemic absorption occurs) |

| Metabolism | Negligible by CYP enzymes |

| Excretion | Renal 30%, Fecal 10% |

• Molecular Formula: C16H24N2O
• Molecular Weight: 260.37 g/mol (free base); 296.84 g/mol (HCl salt)
• Solubility: Soluble in water and alcohol.
• Structure: It is a substituted imidazoline derivative, chemically related to xylometazoline and clonidine.

Oxymetazoline belongs to the therapeutic class of topical nasal decongestants and the pharmacological class of alpha-adrenergic agonists. Other medications in this class include phenylephrine, naphazoline, and xylometazoline. Unlike phenylephrine, which is relatively short-acting, oxymetazoline is classified as a long-acting decongestant.