Cetrin

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT CETRINE® (CETRINE)

Composition:

Active substance: cetirizine hydrochloride;

1 tablet contains cetirizine hydrochloride 10 mg;

Excipients: lactose monohydrate; corn starch; povidone; magnesium stearate; hypromellose; polyethylene glycols; titanium dioxide (E 171); talc; sorbic acid; polysorbates; dimethicone.

Pharmaceutical form. Film-coated tablets.

Main physicochemical properties: white, round, biconvex film-coated tablets with a break line on one side and smooth on the other side.

Pharmacotherapeutic group. Systemic antihistamines. Piperazine derivatives. ATC code R06A E07.

Pharmacological properties.

Pharmacodynamics.

Cetirizine is a competitive histamine antagonist, a metabolite of hydroxyzine, which blocks H1-histamine receptors. It prevents the development and alleviates the course of allergic reactions, has antipruritic and anti-exudative properties, inhibits the histamine-mediated early phase of allergic reaction, limits the release of inflammatory mediators in the late phase of allergic reaction, reduces migration of eosinophils, neutrophils, and basophils, decreases capillary permeability, prevents tissue edema development, and relieves smooth muscle spasm. It eliminates skin reactions to histamine injection, specific allergens, as well as to cold (in cold urticaria), and reduces histamine-induced bronchoconstriction in mild bronchial asthma. It has almost no anticholinergic or anti-serotonin activity. At therapeutic doses, it has minimal sedative effect. After a single 10 mg dose, onset of action occurs within 20 minutes in 50% of individuals and within 1 hour in 95% of individuals. The effect lasts at least 24 hours after a single dose. During course therapy, tolerance to the antihistaminic effect of cetirizine does not develop. After discontinuation of treatment, the effect persists for up to 3 days.

Pharmacokinetics.

Rapidly absorbed from the gastrointestinal tract; the time to reach maximum plasma concentration after oral administration is approximately 1 hour. The bioavailability of cetirizine is equivalent when administered as tablets or syrup. Food does not affect the extent of absorption but prolongs the time to maximum concentration by 1 hour and reduces the peak concentration by 23%. Plasma protein binding is 93%. It is minimally metabolized in the liver via O-dealkylation, forming a pharmacologically inactive metabolite (in contrast to other H1-histamine receptor blockers, which are metabolized in the liver via the cytochrome P450 system). It does not accumulate; approximately 2/3 of the drug is excreted unchanged by the kidneys and about 10% in feces. Systemic clearance is 53 mL/min.

The elimination half-life in adults is 7–10 hours; in children aged 6–12 years, it is 6 hours; in children aged 2–6 years, it is 5 hours.

Patients with renal impairment

Pharmacokinetics of the drug in patients with mild renal impairment (creatinine clearance below 40 mL/min) was similar to that in healthy volunteers. In patients with moderate renal impairment, the elimination half-life was three times longer, and clearance was 70% lower than in healthy volunteers.

In patients undergoing hemodialysis (creatinine clearance below 7 mL/min), following a single 10 mg dose of cetirizine, the elimination half-life was three times longer and clearance was 70% lower compared to healthy volunteers. Cetirizine is minimally removed from plasma during hemodialysis. Dose adjustment is required for patients with moderate or severe renal impairment.

Clinical characteristics.

Indications.

Cetirizine is indicated for adults and children aged 6 years and older:

• for relief of nasal and ocular symptoms of seasonal and perennial allergic rhinitis;
• for relief of symptoms of chronic idiopathic urticaria.

Contraindications.

Hypersensitivity to cetirizine, to any excipients of the medicinal product, to hydroxyzine or to any piperazine derivatives in medical history.

End-stage renal disease with estimated glomerular filtration rate (eGFR) below 15 ml/min.

Interaction with other medicinal products and other forms of interaction.

Based on the pharmacokinetics, pharmacodynamics and tolerability profile of cetirizine, the occurrence of any type of interaction when taking this antihistamine is unlikely. In particular, drug interaction studies have shown neither pharmacodynamic nor any clinically significant pharmacokinetic interaction when administered concomitantly with pseudoephedrine or theophylline (400 mg/day).

The extent of absorption of cetirizine is not reduced by food intake, although the rate of absorption is decreased.

In sensitive patients, concomitant use of alcohol or other CNS depressants may lead to additional impairment of vigilance and reduction in work capacity, although cetirizine does not potentiate the effect of alcohol (at blood alcohol levels of 0.5 g/l).

Special precautions for use

Cetirin® is excreted by the kidneys; therefore, in patients with renal impairment, the dose should be reduced to 5 mg daily. Dose adjustment is not required in elderly patients with normal renal function. No clinically significant interactions with alcohol have been observed when the drug is taken at therapeutic doses (at blood alcohol levels of 0.5 g/L). Nevertheless, concomitant use of the drug with alcohol is not recommended. The drug should be used with caution in patients with epilepsy and in those at risk of seizures. It is contraindicated in patients with hereditary galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption syndrome.

The product contains lactose monohydrate. If you have been diagnosed with an intolerance to certain sugars, consult your physician before taking this medicinal product.

Use with caution in patients predisposed to urinary retention (e.g., spinal cord injury, prostate hyperplasia), as cetirizine may increase the risk of urinary retention.

Antihistamines suppress the skin allergic response; therefore, administration of the drug should be discontinued at least 3 days prior to skin allergy testing (elimination period).

Discontinuation of cetirizine may cause pruritus and/or urticaria, even if these symptoms were not present before treatment initiation. In some cases, symptoms may be severe and require resumption of treatment. Symptoms should resolve upon resuming therapy.

Use during pregnancy or breastfeeding

Pregnancy. There is insufficient data on the use of the drug during pregnancy. Animal studies have not indicated any direct or indirect harmful effects on pregnancy, embryonic/fetal development, labor, or postnatal development. Therefore, the drug should be prescribed to pregnant women only if, in the opinion of the physician, the potential benefit outweighs the potential risk to the fetus.

Breastfeeding period. Cetirizine passes into breast milk at concentrations ranging from 25% to 90% of plasma concentrations, depending on the time elapsed after drug administration. The risk of adverse effects in breastfed infants cannot be excluded. Therefore, the drug should be administered with caution to breastfeeding women.

Fertility. Limited data are available on fertility in humans, but no safety concerns have been identified. Animal studies have not indicated any risk of impaired reproductive function in humans.

Ability to influence reaction speed when driving or operating machinery. Objective assessment of the ability to drive a vehicle, operate machinery, and degree of drowsiness has shown no clinically significant effect when the drug is used at the recommended dose of 10 mg. However, patients experiencing drowsiness should refrain from driving, performing potentially hazardous activities, or operating machinery. Patients should not exceed the recommended doses and should take into account their individual response to the drug.

Method of administration and dosage.

Take orally, regardless of food intake, with a sufficient amount of liquid (1 glass).

Children aged 6 to 12 years: 5 mg (half a tablet) twice daily.

Adults and children aged 12 years and older: 10 mg (1 tablet) once daily.

Elderly patients with normal renal function do not require dose adjustment.

For patients with impaired renal function, dosage should be individually adjusted based on creatinine clearance, age, and body weight.

Patients with renal function impairment

There are no data on the benefit-risk ratio in patients with renal function impairment. Since cetirizine is primarily excreted by the kidneys, if alternative treatment cannot be used, the intervals between doses should be individually determined according to renal function.

Dosage recommendations for adult patients according to renal function are presented in Table 1.

Table 1

Dosage adjustment for adult patients based on renal function:

Dosage should be individually adjusted in children with impaired renal function depending on renal clearance and body weight.

Dose adjustment is not required in patients with hepatic impairment (provided renal function is normal).

Dosage should be adjusted in patients with both hepatic and renal impairment (see Table 1).

The duration of treatment is determined by the physician according to the course of the disease.

Children. Cetirizine in tablet form is not recommended for the treatment of children under 6 years of age, as this dosage form does not allow for appropriate dose adjustment.

Overdose.

Symptoms. Symptoms observed following cetirizine overdose are mainly related to effects on the central nervous system or to effects indicating anticholinergic activity. Adverse effects reported after ingestion of doses at least five times higher than the recommended daily dose include: confusion, diarrhea, dizziness, fatigue, headache, malaise, mydriasis, pruritus, restlessness, sedative effect, somnolence, stupor, tachycardia, tremor, and urinary retention.

Treatment. There is no specific antidote for cetirizine. Symptomatic and supportive therapy is recommended in case of overdose. Gastric lavage should be performed as soon as possible after drug ingestion. Cetirizine is not effectively removed by hemodialysis.

Adverse reactions.

Clinical studies

Clinical studies have shown that cetirizine, at recommended doses, has a minimal effect on the central nervous system (CNS), including somnolence, increased fatigue, dizziness, and headache.

In some cases, paradoxical CNS stimulation has been reported. Although cetirizine is a selective antagonist of peripheral H₁-receptors and has almost no anticholinergic activity, isolated cases of urinary retention, accommodation disorders of the eye, and dryness of the oral mucosa have been observed. Cases of impaired liver function with elevated levels of liver enzymes, accompanied by increased bilirubin concentration, have also been reported. In most cases, these symptoms resolved after discontinuation of cetirizine.

Safety data are available from more than 3,200 subjects who participated in double-blind, controlled studies comparing cetirizine with placebo or other antihistamines at the recommended dose (10 mg of cetirizine daily). Overall, based on results from placebo-controlled studies, adverse reactions occurring with an incidence of 1.0% or greater during treatment with 10 mg cetirizine are listed below (Table 2).

Table 2

Although somnolence occurred more frequently than in the placebo group, in most cases it was of mild to moderate severity. As with other studies, results of objective assessments confirmed that administration of the recommended daily dose did not cause negative effects on everyday activities in healthy subjects.

Table 3

Adverse reactions with an incidence of 1% or greater in children aged 6 months to 12 years during placebo-controlled clinical trials:

Post-marketing experience

In addition to adverse reactions observed during clinical trials and listed above, isolated cases of the following adverse reactions to cetirizine have been reported during post-marketing use. These adverse reactions, reported less frequently, were assessed according to frequency of occurrence: uncommon (≥ 1/1000 to < 1/100); rare (≥ 1/10000 to < 1/1000); very rare (< 1/10000); or unknown (cannot be estimated from available data).

Blood and lymphatic system disorders

Very rare: thrombocytopenia.

Immune system disorders

Rare: hypersensitivity.

Very rare: anaphylactic shock.

Metabolism and nutrition disorders

Unknown frequency: increased appetite.

Psychiatric disorders

Uncommon: psychic stimulation with anxiety (agitation).

Rare: aggression, confusion, depression, hallucinations, insomnia.

Very rare: nervous tic.

Unknown frequency: suicidal thoughts, nightmares.

Nervous system disorders

Uncommon: paraesthesia.

Rare: seizures.

Very rare: dysgeusia, syncope, tremor, dystonia, dyskinesia.

Unknown frequency: amnesia, memory impairment.

Eye disorders

Very rare: accommodation disorder, blurred vision, oculogyric crisis.

Ear and labyrinth disorders

Unknown frequency: vertigo.

Cardiac disorders

Rare: tachycardia.

Gastrointestinal disorders

Uncommon: diarrhoea.

Hepatobiliary disorders

Rare: liver function abnormalities (elevated levels of transaminases, alkaline phosphatase, γ-glutamyl transferase and bilirubin).

Unknown frequency: hepatitis.

Skin and subcutaneous tissue disorders

Uncommon: pruritus, rash.

Rare: urticaria.

Very rare: angioneurotic edema, fixed drug eruption.

Unknown frequency: acute generalized exanthematous pustulosis.

Musculoskeletal and connective tissue disorders

Unknown frequency: arthralgia, myalgia.

Renal and urinary disorders

Very rare: dysuria, enuresis.

Unknown frequency: urinary retention.

General disorders and administration site conditions

Uncommon: asthenia, malaise.

Rare: edema.

Investigations

Rare: weight increase.

Description of selected adverse reactions

Cases of pruritus (intense itching) and/or urticaria have been reported after discontinuation of cetirizine.

Reporting of adverse reactions

Reporting suspected adverse reactions after authorization of a medicinal product is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals and patients, as well as patients’ legal representatives, are encouraged to report any suspected adverse reactions and lack of efficacy through the Automated Pharmacovigilance Information System at the following link: https://aisf.dec.gov.ua

Shelf life. 3 years.

Do not use after the expiry date stated on the packaging.

Storage conditions. Store in a dry, dark place, out of reach of children, at a temperature not exceeding 25 °C.

Packaging. 10 tablets in a blister pack, 2 or 3 blisters per cardboard box.

Authorization category. Over-the-counter (without prescription).

Manufacturer.

Dr. Reddy’s Laboratories Ltd, FTO – II

Manufacturer’s address and location of its business operations.

Survey No. 42R, 43, 44R, 45R, 46R, 53, 54, 83, Bachupally, Bachupally Mandal, Medchal Malkajgiri District – 500090, Telangana State, India

To report adverse reactions or lack of efficacy during use of the medicinal product, please call:

+380 44 207 51 97 or +380 50 414 39 39; or send an email to: [email protected] (available 24/7).