INSTRUCTIONS FOR MEDICAL USE
ALLEGRA
Trade name of the drug: Allegra
Active substance (INN): Cetirizine hydrochloride
Contents:
1 tablet contains:
active substance: Cetirizine dihydrochloride 10 mg;
Excipients: corn starch, nipagin, nipazole, lactose, talc, magnesium stearate.
Shell: hydroxypropyl methylcellulose, titanium dioxide, talc, propylene glycol 4000.
Description: Round, biconvex, white or almost white coated tablets.
Pharmacotherapeutic group: Anti-allergic agents.
ATX code: R06AE07
Pharmacological properties
Cetirizine dihydrochloride is a metabolite of hydroxyzine, belongs to the group of competitive histamine antagonists and blocks H1-histamine receptors.
The drug prevents the development and facilitates the course of allergic reactions, has antipruritic and antiexudative actions. It affects the “early” histamine-dependent stage of allergic reactions, limits the release of inflammatory mediators at the “late” stage of the allergic reaction, and also reduces the migration of eosinophils, neutrophils and basophils, stabilizes mast cell membranes. It reduces capillary permeability, prevents the development of tissue edema, relieves smooth muscle spasm. Eliminates the skin reaction to the introduction of histamine, specific allergens, as well as to cooling (in cold urticaria). Reduces histamine-induced bronchoconstriction in mild bronchial asthma.
It has no anticholinergic and antiserotonin action. In therapeutic doses the drug has no sedative effect. An effect after a single dose of 10 mg of cetirizine develops in 20 minutes in 50% of patients and in 60 minutes in 95% of patients and lasts for more than 24 hours. During a course of treatment, tolerance to the antihistamine effect of cetirizine does not develop. After discontinuation of therapy the effect lasts up to 3 days.
Pharmacokinetics
Pharmacokinetic parameters of the drug change linearly.
Absorption: after oral administration the drug is quickly and completely absorbed from the gastrointestinal tract. Food intake does not affect the completeness of absorption, although its speed decreases. In adults after a single use of the drug in a therapeutic dose, the maximum concentration (Cmax) in blood plasma is reached after 10.5 hours and is 300 ng/ml.
Distribution: cetirizine is 930.3% bound to plasma proteins. The volume of distribution (Vd) is 0.5 l/kg. No cetirizine cumulation is observed when taking the drug in a dose of 10 mg for 10 days.
Metabolism: it is metabolized in small amounts in the body by O-dealkylation (unlike other H1-histamine receptor antagonists, which are metabolized in the liver via the cytochrome system) to form a pharmacologically inactive metabolite.
Excretion: in adults the half-life (T1/2) is approximately 10 hours; T1/2 in children from 6 to 12 years is 6 hours, from 2 to 6 years is 5 hours, from 6 months to 2 years is 3.1 hours. Approximately 2/3 of the administered dose is excreted unchanged by the kidneys.
In elderly patients and patients with chronic liver diseases in single use of 10 mg dose T1/2 is increased approximately by 50%, and systemic clearance is decreased by 40%.
In patients with mild renal insufficiency (creatinine clearance (CK) 40 ml/min) pharmacokinetic parameters are similar to those in patients with normal renal function.
In patients with moderate renal insufficiency and in patients on hemodialysis (CKR 7 ml/min), in per oral administration with 10 mg dose T1/2 is prolonged by 3 times and total clearance is decreased by 70% relative to patients with normal renal function, which requires appropriate change of dosage regimen.
Cetirizine dihydrochloride is practically not eliminated from the body during hemodialysis.
Indications
For adults and children over 6 years of age:
- Treatment of symptoms of allergic year-round (persistent) and seasonal (intermittent) allergic rhinitis (hay fever, pollinosis; maximum duration of treatment of seasonal rhinitis in children is 4 weeks);
- Allergic conjunctivitis;
- Chronic idiopathic urticaria.
Dosage and administration
Treatment of allergic rhinitis.
Adults and adolescents above 12 years of age: Recommended dose is 10 mg (1 tablet) once a day.
Children 6 to 12 years of age: 10 mg (1 tablet) once a day. Maximum duration of treatment is 4 weeks.
The dose may be divided into 2 doses of 5 mg (1/2 tablet) in the morning and evening respectively.
Treatment of allergic conjunctivitis
Adults and adolescents over 12 years of age: recommended dose is 10 mg (1 tablet) once a day.
Children 6 to 12 years of age: 10 mg (1 tablet) once a day. Maximum duration of treatment is 4 weeks. The dose may be divided into 2 doses of 5 mg (1/2 tablet) in the morning and evening respectively.
Treatment of year-round rhinitis and chronic idiopathic urticaria
Adults and adolescents over 12 years of age: recommended dose is 10 mg (1 tablet) once daily.
Children 6 to 12 years of age: 10 mg (1 tablet) once daily. The dose may be divided into 2 doses of 5 mg (1/2 tablet) in the morning and evening, respectively.
Children 6 to 12 years of age: 10 mg (1 tablet) once a day. The dose may be divided into two doses of 5 mg (1/2 tablet) in the morning and evening, respectively.
Patients who require a special dosing regimen
Elderly patients
In case of age-related reduction of glomerular filtration the drug administration for elderly patients is prescribed in the same dosage as for patients with renal insufficiency.
Patients with renal failure
Intervals between doses of the drug are individually adjusted according to the degree of renal insufficiency.
Patients with hepatic impairment.
Patients with liver dysfunction only do not need to make dosage adjustment.
Administration of the drug
It should be taken in the evening, because the symptoms are more intense at this time of day. The tablet is swallowed whole, without chewing and with water.
The drug is taken regardless of food intake.
In case of mild side effects in adults and adolescents over 12 years old, it is recommended to take 5 mg (1/2 tablet) of the drug in the morning and in the evening respectively.
Side effects
Possible side effects are listed below by body system and frequency of occurrence: very common (≥1/10), common (≥1/100, <1/10), infrequent (≥1/1000, <1/100), rare (≥1/10000, <1/1000), very rare (<1/10000), frequency unknown (due to insufficient data).
Immune system disorders: rare: hypersensitivity reactions; very rare: anaphylactic shock.
Metabolic and nutritional disorders: frequency unknown: increase in appetite.
Nervous system disorders: infrequent: paresthesias; rare: seizures; very rare: perversion of taste, dyskinesia, dystonia, syncope, tremor; frequency unknown: deafness, memory impairment, amnesia.
Mental disorders: infrequent: agitation; rare: aggression, confusion, depression, hallucinations, sleep disturbance; very rare: tics; frequency unknown: suicidal ideation.
Eye: very rare: accommodation disorder, blurred vision, nystagmus; frequency unknown: vasculitis.
Hearing and balance: frequency unknown: vertigo.
Digestive system: infrequent: diarrhea.
Cardiovascular system: rare: tachycardia.
Urinary system: very rare: dysuria, enuresis; frequency unknown: urinary retention.
Blood and lymphatic system: very rare: thrombocytopenia.
Skin: infrequent: rash, itching; rare: urticaria; very rare: angioedema, persistent erythema.
Laboratory tests: rare: changes of liver function tests (increase of transaminases, alkaline phosphatase, gamma-glutamintransferase and bilirubin activity); very rare: thrombocytopenia.
General disorders: infrequent: asthenia, malaise; rarely: peripheral edema.
Metabolism: rarely: weight gain.
In case of adverse reactions, as well as reactions not mentioned in the instructions, it is necessary to consult a physician.
Contraindications
- Hypersensitivity to cetirizine, hydroxyzine or piperazine derivatives, as well as other components of the drug;
- terminal stage of renal failure (creatinine clearance 10 ml/min);
- congenital galactose intolerance, lactose deficiency and glucose-galactose malabsorption syndrome.
With caution
- Chronic renal insufficiency (in creatinine clearance >10 ml/min, dosage regimen adjustment is required);
- elderly patients (with age-related decrease in glomerular filtration);
- epilepsy and patients with increased seizure readiness;
- patients with predisposing factors to urinary retention.
Drug interactions
When concomitant use with pseudoephedrine, cimetidine, ketoconazole, erythromycin or azithromycin, no effect on the pharmacokinetics of cetirizine was found.
No pharmacokinetic interactions were observed. In vitro tests have shown that the drug does not affect the properties of warfarin to bind to proteins.
When concomitant use with azithromycin, erythromycin, ketoconazole, theophylline and pseudoephedrine no clinically significant adverse interactions were found, no changes on electrocardiogram were noted.
Simultaneous use of the drug (20 mg/day) with theophylline (400 mg/day) showed a small but stable increase of the area under the curve of concentration-time-dependence of the drug by 19%, theophylline – 11%. Moreover, maximum plasma levels reached 7.7% and 6.4% for cetirizine and theophylline, respectively. At the same time, total cetirizine clearance decreased by 16% and theophylline clearance decreased by 10% if theophylline treatment was given before cetirizine administration.
However, when initially treated with cetirizine, no significant effect on the pharmacokinetics of theophylline was detected.
After a single dose of 10 mg of cetirizine, the effects of alcohol (0.8%) were not significantly enhanced; a marked interaction was noted with diazepam 5 mg in 1 of 16 psychometric tests.
When cetirizine (10 mg) is used concomitantly daily with glipizide, the glucose index is slightly decreased. However, this has not been clinically proven. Nevertheless, it is recommended to take these drugs separately – glipizide in the morning and cetirizine in the evening.
Food intake does not affect the completeness of absorption, although its rate is reduced by 1 hour.
When ritonavir (600 mg twice daily) and cetirizine (10 mg/day) were taken repeatedly, the duration of action was increased by 40%, while the effect of ritonavir changed slightly (-11%) with subsequent administration of cetirizine.
A three-day “washout” period is recommended before allergy testing is administered.
Special indications
Use during pregnancy and lactation
At the moment there are no available clinical trials on use of the drug in pregnant women. Experimental studies on animals did not reveal any direct or indirect toxic effects of the drug on pregnancy, germinal development, embryonal development, including the postnatal period.
The potential risk to women is unknown.
Use is possible in cases when the expected benefit to the mother exceeds the potential risk to the fetus.
Cetirizine dihydrochloride is excreted with breast milk, therefore, the drug should not be taken during the period of lactation.
Effect on the ability to drive motor transport and operate machinery.
The drug may cause increased somnolence. Consequently, it affects the ability to drive vehicles and operate machinery.
Overdose
The following symptoms have been observed after a single dose of 50 mg: confusion, diarrhea, dizziness, fatigue, headache, malaise, mydriasis, pruritus, weakness, restlessness, sedation, somnolence, stupor, tachycardia, tremor, urinary retention.
Treatment: immediately after taking the drug – gastric lavage or stimulation of vomiting. Administration of activated charcoal, symptomatic and supportive therapy are recommended. There is no specific antidote. Hemodialysis is ineffective.
Form of production
10 mg coated tablets.
Storage conditions
Store in a dry, dark place at a temperature not exceeding 25 ° C. Keep out of the reach of children.
Shelf life
3 years. Do not use after the expiration date.
Conditions of dispensing from pharmacies
Released without a prescription.