Suprastinex^® (Tablets, Drops) Instructions for Use

ATC Code

R06AE09 (Levocetirizine)

Active Substance

Levocetirizine (Rec.INN registered by WHO)

Clinical-Pharmacological Group

Histamine H₁-receptor blocker. Antiallergic drug

Pharmacotherapeutic Group

Systemically applied antihistamines, piperazine derivatives

Pharmacological Action

Antiallergic agent. Levocetirizine, the (R)-enantiomer of cetirizine, is a selective antagonist of peripheral histamine H₁-receptors. The affinity of levocetirizine (Ki = 3.2 nmol/L) for histamine H₁-receptors is 2 times higher than that of cetirizine (Ki = 6.3 nmol/L). Pharmacokinetic studies in healthy volunteers have shown that when applied to the skin and nasal mucosa, the activity of levocetirizine at half the dose is comparable to the activity of cetirizine at the full dose.

Levocetirizine suppresses eotaxin-induced transendothelial migration of eosinophils in skin and lung cells. Pharmacodynamic studies have demonstrated three main inhibitory effects of levocetirizine at a dose of 5 mg within the first 6 hours after pollen exposure: suppression of VCAM-1 release, alteration of vascular permeability, and reduction of eosinophil activation. As with cetirizine, the effect on histamine-induced skin reactions is independent of the plasma concentrations of the drug.

Levocetirizine prevents the development and alleviates the course of allergic reactions, has an anti-exudative, antipruritic effect; it has practically no anticholinergic or antiserotonin action.

Levocetirizine at a dose of 5 mg contributes to the inhibition of the inflammatory-exudative reaction to histamine to the same extent as cetirizine at a dose of 10 mg. ECG did not reveal a significant effect of levocetirizine on the QT interval.

Pharmacokinetics

After oral administration, Levocetirizine is rapidly absorbed from the gastrointestinal tract. Food intake does not affect the completeness of absorption, although its rate decreases. C_max in plasma is reached 0.9 hours after a single oral dose. Steady state is achieved after 2 days. C_max after single and repeated (5 mg daily) administration are 270 ng/ml and 308 ng/ml, respectively.

Plasma protein binding is 90%. Data on the distribution of the drug in tissues and penetration through the blood-brain barrier are not available. V_d is 0.4 L/kg. It is excreted in breast milk.

Less than 14% of the administered dose is metabolized in the liver by oxidation of the aromatic ring, N- and O-dealkylation, and conjugation with taurine. Dealkylation is predominantly catalyzed by CYP3A4, and CYP isoforms are involved in the oxidation of the aromatic ring. Levocetirizine does not affect the activity of CYP isoenzymes 1A2, 2C9, 2C19, 2D6, 2E1, and 3A4 at concentrations far exceeding the peak concentrations after oral administration of 5 mg. Due to minimal metabolism and the absence of metabolic suppression, interaction of levocetirizine with other substances is unlikely.

T_1/2 is 7.9±1.9 hours. Total clearance is 0.63 ml/min/kg. Levocetirizine and its metabolite are excreted primarily by the kidneys (85.4% of the administered dose), through glomerular filtration and active tubular secretion. Excretion via the intestine is 12.9%.

The pharmacokinetics of levocetirizine are linear, independent of dose and time, and show little variation among different subjects. The pharmacokinetic profiles of the single enantiomer and cetirizine are similar. No chiral inversion occurs during absorption or excretion.

The total clearance of levocetirizine correlates with CrCl (this should be taken into account when determining dosing intervals in patients with moderate or severe renal impairment). In anuria, total clearance decreases by approximately 80% compared to healthy subjects. Less than 10% of levocetirizine is removed during a standard 4-hour hemodialysis procedure.

Indications

Symptomatic treatment of symptoms of perennial and seasonal allergic rhinitis (including persistent allergic rhinitis) and allergic conjunctivitis: sneezing, rhinorrhea, lacrimation, conjunctival hyperemia; hay fever (pollinosis); urticaria (including chronic idiopathic urticaria); other allergic dermatoses accompanied by itching and rash; angioedema.

ICD codes

Dosage Regimen

Administer orally, with or without food.

For adults and children over 6 years, the standard dose is 5 mg once daily.

For children aged 2 to 6 years, administer 1.25 mg twice daily.

Adjust the dose for patients with renal impairment based on creatinine clearance (CrCl).

For moderate renal impairment (CrCl 30-49 ml/min), administer 5 mg every other day.

For severe renal impairment (CrCl 10-29 ml/min), administer 5 mg every three days.

Do not use in patients with end-stage renal disease (CrCl below 10 ml/min).

No dose adjustment is required for patients with isolated hepatic impairment.

Adjust the dose for patients with combined hepatic and renal impairment.

For elderly patients with normal renal function, no dose adjustment is necessary.

The duration of therapy is determined by the indication, severity, and course of symptoms.

For seasonal allergic rhinitis (hay fever), treatment typically lasts 3 to 6 weeks.

For short-term pollen exposure, a 1-week course is often sufficient.

For chronic idiopathic urticaria, continue treatment as long as symptoms persist.

Use the oral drops formulation for accurate dosing in young children.

Avoid concomitant use with alcohol or other CNS depressants.

Monitor for adverse reactions such as headache, drowsiness, and dry mouth.

Discontinue use and seek medical attention if signs of a serious allergic reaction occur.

Adverse Reactions

From the central nervous system common – headache, drowsiness, increased fatigue; uncommon – asthenia.

From the digestive system common – dry mouth; uncommon – abdominal pain; very rare – nausea, impaired liver function tests.

Allergic reactions very rare – angioedema, itching, skin rash, urticaria, anaphylaxis.

Other very rare – weight gain, dyspnea.

Contraindications

Severe renal failure (CrCl below 10 ml/min); children under 2 years of age; hypersensitivity to levocetirizine.

Use in Pregnancy and Lactation

There are no clinical data on the use of levocetirizine during pregnancy. It is not recommended for use during pregnancy and lactation (breastfeeding).

Special Precautions

Elderly patients with moderate or severe renal impairment may require dose adjustment.

Patients with impaired renal function require dose adjustment depending on CrCl.

No dose adjustment is required for patients with isolated hepatic impairment. Dose adjustment is recommended for patients with combined hepatic and renal impairment.

Patients should refrain from consuming alcohol while taking levocetirizine.

Use in pediatrics

Levocetirizine is used in children over 2 years of age in a special dosage form.

Effect on ability to drive vehicles and operate machinery

Comparative clinical studies have not revealed signs of impaired alertness, reaction time, or ability to drive vehicles after taking recommended doses of levocetirizine. However, some patients may experience drowsiness, fatigue, or asthenia during use. Use with caution in patients driving vehicles and engaging in activities requiring quick psychomotor reactions.

Drug Interactions

A decrease in the clearance of cetirizine (16%) was observed with multiple administrations of theophylline (400 mg once daily); however, the pharmacokinetics of theophylline did not change with simultaneous administration of cetirizine.

In susceptible patients, simultaneous use of levocetirizine and ethanol or other CNS depressants may lead to potentiation of the CNS depressant effect.

Storage Conditions

Store at 2°C (36°F) to 30°C (86°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Over-the-Counter

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.