Rolinos

INSTRUCTION FOR MEDICAL USE OF THE MEDICINAL PRODUCT ROLINOZ (ROLINOZ)

Composition:

Active substance: cetirizine;

1 tablet contains 10 mg of cetirizine dihydrochloride;

Excipients: lactose monohydrate, microcrystalline cellulose, magnesium stearate, colloidal anhydrous silicon dioxide, sodium starch glycolate (type A).

Pharmaceutical form. Tablets.

Main physicochemical characteristics: white, round tablets with a smooth surface and a score line on one side.

Pharmacotherapeutic group.

Antihistamines for systemic use. Piperazine derivatives. ATC code R06A E07.

Pharmacological Properties

Pharmacodynamics

Cetirizine, a metabolite of hydroxyzine, is a potent and selective antagonist of peripheral H1-receptors. In vitro receptor binding studies showed no significant affinity for other receptors besides H1-receptors.

In addition to its H1-receptor antagonistic effect, cetirizine exerts anti-allergic activity: at a dose of 10 mg once or twice daily, the drug inhibited the late-phase migration of inflammatory cells (predominantly eosinophils) into the skin and conjunctiva of atopic individuals following antigen challenge.

At doses of 5 mg and 10 mg, cetirizine strongly inhibits histamine-induced wheal and flare reactions in the skin even at very high histamine concentrations, although the relationship between dose and effect has not been fully established.

Administration of cetirizine at 10 mg once daily to patients with allergic rhinitis and concomitant mild to moderate bronchial asthma improved rhinitis symptoms and had no effect on lung function, confirming the safety of cetirizine use in patients with mild to moderate bronchial asthma.

Administration of cetirizine at a high daily dose of 60 mg for one week did not cause statistically significant QT interval prolongation.

When administered at recommended doses, cetirizine improved symptoms in patients with perennial and seasonal allergic rhinitis.

In children aged 5 to 12 years, no tolerance to the antihistaminic effect of cetirizine (suppression of wheal and flare reactions) was observed. If treatment with cetirizine is discontinued after repeated dosing, skin reactivity to histamine returns to baseline within 3 days.

Pharmacokinetics

Cetirizine exhibits linear kinetics over the dose range of 5 mg to 60 mg.

Absorption

Steady-state peak plasma concentration of cetirizine is approximately 300 ng/mL, reached within 1 ± 0.5 hours. The distribution of pharmacokinetic parameters such as peak plasma concentration (Cmax) and area under the curve (AUC) is homogeneous. The extent of absorption of cetirizine is not reduced when taken with food, although the rate of absorption is decreased. Bioavailability is similar following administration of cetirizine as solution, capsules, or tablets.

Distribution

The apparent volume of distribution of cetirizine is 0.5 L/kg. Plasma protein binding is 93 ± 0.3%. Cetirizine does not affect warfarin protein binding.

Metabolism

Cetirizine undergoes no extensive first-pass metabolism.

Elimination

Approximately two-thirds of the dose is excreted unchanged in urine. The terminal elimination half-life is approximately 10 hours. No accumulation of cetirizine was observed after administration of 10 mg daily for 10 days.

Special patient populations

Patients with hepatic impairment

In patients with chronic liver disease (hepatocellular, cholestatic, and biliary cirrhosis), following a single 10 mg or 20 mg dose of cetirizine, elimination half-life increased by 50% and clearance decreased by 40% compared to healthy volunteers. Dose adjustment in patients with hepatic impairment is required only if renal impairment is also present.

Patients with renal impairment

Pharmacokinetics of cetirizine were similar in patients with mild renal impairment (creatinine clearance >40 mL/min) and healthy volunteers. In patients with moderate renal impairment, elimination half-life increased threefold and clearance decreased by 70% compared to healthy volunteers. In patients undergoing hemodialysis (creatinine clearance 7 mL/min), following a 10 mg oral dose of cetirizine, elimination half-life increased threefold and clearance decreased by 70% compared to healthy volunteers. Cetirizine is poorly removed by hemodialysis. Dose adjustment is required for patients with moderate renal impairment. Use of the drug in patients with severe renal impairment is contraindicated.

Elderly patients

After a single 10 mg oral dose of cetirizine, elimination half-life increased by nearly 50% and clearance decreased by approximately 40% compared to younger individuals. The reduced clearance of cetirizine was associated with decreased renal function.

Children

Elimination half-life of cetirizine is approximately 6 hours in children aged 6–12 years and 5 hours in children aged 2–6 years. In children aged 6 to 24 months, the half-life is reduced to 3.1 hours.

Clinical characteristics.

Indications.

• Symptomatic treatment of nasal and ocular symptoms of seasonal and perennial allergic rhinitis.
• Symptomatic treatment of chronic idiopathic urticaria.

Contraindications.

• Hypersensitivity to the active substance, any of the excipients, hydroxyzine, or to any piperazine derivatives in medical history.
• End-stage renal disease (glomerular filtration rate (GFR) < 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 co-administered with pseudoephedrine or theophylline (400 mg/day).

The extent of absorption of cetirizine is not reduced when taken with food, although the rate of absorption is decreased.

Concomitant use of the drug with alcohol or other central nervous system depressants may additionally impair attention and affect performance. However, cetirizine does not potentiate the effect of alcohol (at a blood alcohol concentration of 0.5 g/L).

Special precautions for use.

Antihistamines, including cetirizine, suppress the response to skin allergy tests; therefore, administration of the drug should be discontinued 3 days before the test (elimination period).

Cases of pruritus and/or urticaria after discontinuation of cetirizine have been reported, even if these symptoms were not observed previously. In some cases, they may be intense and require resumption of cetirizine treatment. Symptoms should resolve after restarting therapy.

Clinically significant interactions with alcohol (at blood alcohol levels of 0.5 g/L) have not been observed when cetirizine is used at therapeutic doses. However, caution should be exercised when using cetirizine concomitantly with alcohol.

The drug should be used with caution in patients predisposed to urinary retention (e.g., spinal cord injury, prostate hyperplasia), in patients with epilepsy, and in those at risk of seizures.

The drug contains lactose; therefore, it should not be administered to patients with rare hereditary galactose intolerance, lactase deficiency, or glucose-galactose malabsorption.

Use during pregnancy or breastfeeding.

Pregnancy period

Prospective data on pregnancy outcomes with cetirizine do not indicate potential toxicity for the mother or embryo/fetus. Animal studies have not shown any direct or indirect harmful effects on pregnancy, embryonic/fetal development, parturition, or postnatal development. Cetirizine should be used during pregnancy only if clearly needed and with caution.

Breastfeeding period

Cetirizine passes into breast milk at concentrations ranging from 25–90% of plasma concentrations, depending on the time interval after administration. The drug should be used with caution during breastfeeding.

Fertility

Data on the effect of cetirizine on human fertility are limited; however, no adverse effects on fertility have been observed.

Animal studies have not revealed any negative effects on fertility.

Ability to influence reaction speed when driving or operating machinery.

Objective assessments of the ability to drive, sleep latency, and performance on an assembly line have not shown any clinically significant impairment with cetirizine at the recommended dose of 10 mg.

Patients who drive or operate machinery should not exceed the recommended doses and should consider their individual response to the drug. Patients experiencing somnolence should refrain from driving or operating machinery.

Method of administration and dosage.

Method of administration

The medicinal product is intended for oral administration. Tablets should be swallowed with a glass of water.

Dosage

Adults

The medicinal product should be administered at a dose of 10 mg (1 tablet) once daily.

Pediatric population

Children aged 6 to 12 years

The medicinal product should be administered at a dose of 5 mg (½ tablet) twice daily.

Children aged 12 years and older

The medicinal product should be administered at a dose of 10 mg (1 tablet) once daily.

Dose adjustment in children with renal impairment should be individualized based on creatinine clearance, age, and body weight.

Elderly patients

Provided renal function is normal, no dosage adjustment is required in elderly patients.

Patients with hepatic impairment

No dosage adjustment is required in patients with hepatic impairment. However, in patients with both hepatic and renal impairment, dosage adjustment is recommended (see section below, «Patients with renal impairment»).

Patients with renal impairment

There are no documented data on the benefit-risk balance for patients with renal impairment. Since cetirizine is primarily excreted by the kidneys, if no alternative treatment is available, the dosage should be individualized according to renal function. Refer to the table below and adjust the dose accordingly.

Renal function status	eGFR (mL/min)	Dosage and frequency
Normal function	≥ 90	10 mg once daily
Mild impairment	60 – < 90	10 mg once daily
Moderate impairment	30 – < 60	5 mg once daily
Severe impairment	15 – < 30 (not requiring dialysis)	5 mg once every 2 days
End-stage renal disease	< 15 (requiring dialysis)	Contraindicated

Children.

The use of the drug in tablet form is not recommended for children under 6 years of age, as this pharmaceutical form does not allow appropriate dose adjustment.

Overdose.

Symptoms

Symptoms observed following significant overdose of cetirizine are mainly related to effects on the central nervous system or effects indicating anticholinergic activity. Adverse reactions reported after ingestion of doses at least 5 times higher than the recommended daily dose include: confusion, diarrhea, dizziness, increased fatigue, headache, malaise, mydriasis, itching, restlessness, sedation, somnolence, stupor, tachycardia, tremor, and urinary retention.

Treatment

In case of overdose, symptomatic and supportive therapy should be administered. Gastric lavage may be performed. Dialysis is not an effective method for removing cetirizine. There is no known specific antidote for cetirizine.

Adverse Reactions.

It is known that cetirizine, when used at recommended doses, has minimal central nervous system effects, including somnolence, increased fatigue, dizziness, and headache. In some cases, paradoxical stimulation of the central nervous system has been reported.

Although cetirizine is a selective antagonist of peripheral H1-receptors and exhibits almost no anticholinergic activity, isolated cases of urinary retention, accommodation disorders of the eye, and dry mouth have been reported.

Cases of hepatic function abnormalities characterized by elevated liver enzymes and accompanied by increased bilirubin levels have been reported. These conditions usually resolved after discontinuation of the drug.

The following adverse reactions were reported during cetirizine clinical trials in at least 1% of patients:

Psychiatric disorders – somnolence;

Nervous system disorders – dizziness, headache;

Respiratory, thoracic and mediastinal disorders – pharyngitis;

Gastrointestinal disorders – abdominal pain, dry mouth, nausea;

General disorders – increased fatigue.

Although somnolence occurred statistically more frequently than in the placebo group, in most cases it was mild or moderate in severity. As with other studies, objective testing confirmed that administration of the recommended daily dose does not impair daily functioning in healthy subjects.

The following adverse reactions were reported during cetirizine clinical trials in at least 1% of children aged 6 months to 12 years:

Psychiatric disorders – somnolence;

Respiratory, thoracic and mediastinal disorders – rhinitis;

Gastrointestinal disorders – diarrhea;

General disorders – increased fatigue.

During the use of cetirizine, the following adverse reactions have also been reported. Adverse reactions are listed by organ system classes according to MedDRA (Medical Dictionary for Regulatory Activities) and by frequency: very common (≥ 1/10); common (≥ 1/100, < 1/10); uncommon (≥ 1/1000, < 1/100); rare (≥ 1/10,000, < 1/1000); very rare (< 1/10,000); not known (frequency cannot be estimated from available data).

Blood and lymphatic system disorders:

very rare – thrombocytopenia.

Immune system disorders:

rare – hypersensitivity reactions; very rare – anaphylactic shock.

Metabolism and nutrition disorders:

not known – increased appetite.

Psychiatric disorders:

uncommon – agitation; rare – aggression, confusion, depression, hallucinations, insomnia; very rare – tic; not known – suicidal thoughts, night terrors.

Nervous system disorders:

uncommon – paresthesia; rare – seizures; very rare – dysgeusia, dyskinesia, dystonia, syncope, tremor; not known – amnesia, memory impairment.

Eye disorders:

very rare – accommodation disorders, blurred vision, involuntary eye movements.

Ear and labyrinth disorders:

not known – vertigo.

Cardiac disorders:

rare – tachycardia.

Gastrointestinal disorders:

uncommon – diarrhea.

Hepatobiliary disorders:

rare – hepatic function abnormalities (elevated levels of transaminases, alkaline phosphatase, γ-glutamyltransferase, and bilirubin); not known – hepatitis.

Skin and subcutaneous tissue disorders:

uncommon – pruritus, rash; rare – urticaria; very rare – angioneurotic edema, local drug rash; not known – acute generalized exanthematous pustulosis.

Musculoskeletal and connective tissue disorders:

not known – arthralgia, myalgia.

Renal and urinary disorders:

very rare – dysuria, enuresis; not known – urinary retention.

General disorders:

uncommon – asthenia, malaise; rare – edema.

Investigations:

rare – weight increase.

After discontinuation of cetirizine, cases of intense itching and urticaria have been reported.

Reporting of suspected adverse reactions.

Reporting suspected adverse reactions after a medicinal product's registration is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals and patients or their legal representatives should report all suspected adverse reactions and lack of efficacy via the Automated Pharmacovigilance Information System at: https://aisf.dec.gov.ua.

Shelf life.

3 years.

Storage conditions.

Store at temperatures not exceeding 25 °C in a dry place, out of reach of children.

Packaging.

10 tablets in a blister; 2 blisters per cardboard box.

Prescription status.

Over-the-counter.

Manufacturer.

ABC Farmaceutici S.p.A., Italy.

Manufacturer's address and place of business.

Via Cantone Moretti, 29 (Localita San Bernardo) – 10015 Ivrea (TO), Italy.

Marketing Authorization Holder.

WORLD MEDICINE, LLC, Ukraine.