Xylometazoline

● Xylometazoline is a selective alpha-1 adrenergic agonist belonging to Nasal Decongestants.

● Xylometazoline is used in treating Nasal congestion.

● Xylometazoline is rapidly absorbed after intranasal or oral administration. When administered intranasally, xylometazoline is mainly absorbed through the nasal mucosa. When administered orally, xylometazoline is well absorbed from the gastrointestinal tract. The absolute bioavailability of xylometazoline after oral administration is approximately 33%. Xylometazoline is distributed throughout the body, with a volume of distribution of approximately 70 L. It is highly bound to plasma proteins (up to 95%), primarily to albumin. Xylometazoline undergoes extensive first-pass metabolism in the liver. It is mainly metabolized by oxidation and conjugation to form several metabolites, which are then excreted in the urine. Xylometazoline and its metabolites are primarily excreted in the urine. The elimination half-life of xylometazoline is approximately 2-3 hours. Only a small amount of the drug is excreted in the feces.

The onset of action of Xylometazoline was Within 2 minutes.

The Duration of time for Xylometazoline was within 12 hours.

The Tmax of Xylometazoline is generally 1-2 hours.

The Cmax can range from 4 to 30 nanograms per milliliter (ng/mL), depending on the dose administered. The Cmax is generally reached within 15-30 minutes after intranasal administration.

Xylometazoline shows common side effects like Headache, Nasal dryness, Nasal discomfort, Nausea, and Local irritation after using the spray

Xylometazoline is available in the form of nasal spray.

Xylometazoline is available in India, Germany, Canada, and Italy.

Nasal congestion is caused by various etiologies, such as rhinosinusitis and allergic or non-allergic rhinitis, leading to congestion of the venous sinusoids lining the nasal mucosa. Activation of α-adrenergic receptors leads to vasoconstriction of the blood vessels of the nasal mucosa and resumption of nasal airflow. As the most abundantly expressed in the human nasal mucosa, α1A- and α2B-adrenoceptors may play the most important role in vasoconstriction of the human nasal mucosa. Xylometazoline is a more selective agonist at α2B-adrenoceptors,with affinity at α1A-, α2A-, α2C-, α1B-, and α1D-adrenoceptors.Xylometazoline decreases nasal resistance during inspiration and expiration and increases the volume of nasal airflow.

Xylometazoline is available in the form of nasal spray

Intranasal: For intranasal use only. Before first use, prime the pump by spraying it several times into the air until a fine mist appears. Blow nose to clear nostrils before use. Tilt the head slightly backward and then spray the solution into each nostril. After application inhales deeply. Wipe the tip of the container clean after each use.

Xylometazoline is used in the treatment of Nasal congestion.

Xylometazoline is an imidazoline derivative with sympathomimetic and nasal decongestant activity. Xylometazoline works by binding to alpha (α)-adrenergic receptors to cause vasoconstriction of nasal blood vessels.

Xylometazoline is approved for use in the following clinical indications

Nasal Congestion: Temporary relief of nasal and nasopharyngeal mucosal congestion

Nasal

Nasal congestion

Adult: For the symptomatic relief of congestion associated with upper respiratory allergies, hay fever, common cold, sinusitis, and otitis media: As 0.05% nasal spray: Usual dose: 1-2 sprays into each nostril 2-3 times daily as necessary. Max treatment duration: 5-7 consecutive days. Alternatively, 2-3 sprays into each nostril bid for up to 3 days. Max: 2 doses per 24 hours. As 0.05% nasal drops: Usual dose: Instill 1-2 drops into each nostril 2-3 times daily. Max treatment duration: 5-7 consecutive days.

Child: As 0.01% nasal drops: ≤4 weeks Instill 1 drop into each nostril 2-3 times daily; 5 weeks to 1 year Instill 1-2 drops into each nostril 2-3 times daily. Max treatment duration: 5-7 consecutive days. As 0.025% nasal drops: 1-6 years Usual dose: Instill 1-2 drops into each nostril 2-3 times daily. Max treatment duration: 5-7 consecutive days. As 0.05% nasal drops: >6 years Same as adult dose. As 0.05% nasal spray: >12 years Usual dose: 1-2 sprays into each nostril 2-3 times daily as necessary. Max treatment duration: 5-7 consecutive days.

Xylometazoline is available in various strengths as 0.05%, 0.1%.

Xylometazoline is available in the form of nasal spray.

Nasal: Acute coronary disease, cardiac asthma, angle-closure glaucoma, rhinitis sicca, inflammation or lesions of the skin around the nostrils or nasal mucosa, phaeochromocytoma, trans-sphenoidal hypophysectomy or nasal surgery exposing the dura mater. Concomitant use or within 2 weeks after stopping treatment with MAOIs.

Concerns related to adverse effects:

• Rebound nasal congestion: Frequent or prolonged use may cause nasal congestion to recur or worsen.

Disease-related concerns:

• Cardiovascular disease: Use with caution in patients with hypertension or heart disease.

• Diabetes mellitus: Use with caution in patients with diabetes mellitus.

• Thyroid disease: Use with caution in patients with thyroid disease.

• Prostatic hyperplasia/Urinary obstruction: Use with caution in patients with prostatic hyperplasia and/or GU obstruction.

Pregnancy Category C: Teratogenicity studies have been performed in animals. 

Common Adverse effects:

• Headache • Nasal dryness • Nasal discomfort • Nausea • Local irritation after using the spray

Less Common Adverse effects:

Nosebleeds

Rare Common Adverse effects:

• Hypersensitivity including rash and pruritus • Disturbances of vision • Palpitations and increased heart rate

Enhanced adverse effects with other sympathomimetics. Risk of hypertensive crisis with MAOIs or TCAs.

The common side effects of Xylometazoline include the following Headache , Nasal dryness ,Nasal discomfort , Nausea , Local irritation after using the spray

The oral LD50 is 230 mg/kg in rats and 75 mg/kg in mice. The subcutaneous LD50 is 90 mg/kg in rats and 53 mg/kg in mice. The intraperitoneal LD50 is 43 mg/kg in rats.

Pharmacodynamic

Xylometazoline is a sympathomimetic agent that causes vasoconstriction of the nasal mucosa. In one study comprising subjects with nasal congestion associated with the common cold, the median time of onset of subjective relief of nasal congestion was about 1.7 minutes and the time of subjective peak relief of nasal congestion was 30 minutes. Previous studies reported rebound swelling, rebound nasal congestion, rhinitis medicamentosa, and a shorter duration of decongestant effect from the long-term use of xylometazoline in healthy volunteers, suggesting that the drug is most effective if used temporarily.

Pharmacokinetics

Absorption:

Xylometazoline is rapidly absorbed after intranasal or oral administration. When administered intranasally, xylometazoline is mainly absorbed through the nasal mucosa. When administered orally, xylometazoline is well absorbed from the gastrointestinal tract. The absolute bioavailability of xylometazoline after oral administration is approximately 33%.

Distribution:

Xylometazoline is distributed throughout the body, with a volume of distribution of approximately 70 L. It is highly bound to plasma proteins (up to 95%), primarily to albumin.

Metabolism:

Xylometazoline undergoes extensive first-pass metabolism in the liver. It is mainly metabolized by oxidation and conjugation to form several metabolites, which are then excreted in the urine.

Excretion:

Xylometazoline and its metabolites are primarily excreted in the urine. The elimination half-life of xylometazoline is approximately 2-3 hours. Only a small amount of the drug is excreted in the feces.

● https://clinicaltrials.gov/ct2/show/NCT04430790

● https://clinicaltrials.gov/ct2/show/NCT02820025

● https://pubmed.ncbi.nlm.nih.gov/27612991/

● https://clinicaltrials.gov/ct2/show/NCT03894189