Rolinos

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

Composition:

Active substance: cetirizine;

1 ml of solution contains cetirizine dihydrochloride 10 mg;

Excipients: glycerin; propylene glycol; sodium saccharin; methylparaben (E 218); propylparaben (E 216); sodium acetate trihydrate; glacial acetic acid; purified water.

Pharmaceutical form. Oral drops, solution.

Main physico-chemical characteristics: clear, colorless solution.

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

Pharmacological Properties

Pharmacodynamics

Cetirizine, a metabolite of hydroxyzine, is a potent selective antagonist of peripheral H1-receptors. In in vitro receptor binding studies, no significant affinity for receptors other than H1-receptors has been observed.

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 cells involved in the inflammatory response (predominantly eosinophils) into the skin and conjunctiva of atopic individuals following antigen challenge.

At doses of 5 mg and 10 mg, cetirizine strongly inhibited histamine-induced wheal and flare reactions in the skin, even at very high histamine concentrations, although a definitive dose-response relationship has not been established. 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 for at least 24 hours following a single dose.

Administration of cetirizine at a dose of 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 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 improves symptoms in patients with perennial and seasonal allergic rhinitis.

Special Patient Populations

Paediatric Population

In children aged 5 to 12 years, tolerance to the antihistaminic effect of cetirizine (inhibition of wheal and flare reactions) has not been observed. If cetirizine treatment is discontinued after repeated administration, skin reactivity to histamine returns to baseline within 3 days.

Pharmacokinetics

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

Absorption

The 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 plasma concentration-time curve (AUC) is homogeneous. The extent of cetirizine absorption 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 binding to plasma proteins.

Metabolism

Cetirizine undergoes minimal first-pass metabolism.

Elimination

Approximately two-thirds of the dose is excreted unchanged in urine. The terminal elimination half-life (t1/2) 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, t1/2 was increased by 50% and clearance reduced 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

The pharmacokinetics of cetirizine in patients with mild renal impairment (creatinine clearance >40 mL/min) are similar to those in healthy volunteers. In patients with moderate renal impairment, t1/2 was increased threefold and clearance reduced by 70% compared to healthy volunteers. In patients undergoing hemodialysis (creatinine clearance 7 mL/min), following a 10 mg oral dose of cetirizine, t1/2 was increased threefold and clearance reduced by 70% compared to healthy volunteers. Cetirizine is poorly removed by hemodialysis. Dose adjustment is required for patients with moderate renal impairment. Cetirizine is contraindicated in patients with severe renal impairment.

Elderly Patients

Following a single 10 mg oral dose, t1/2 was increased by nearly 50% and clearance reduced by approximately 40% in elderly patients compared to younger individuals. The reduced clearance of cetirizine is associated with diminished renal function.

Paediatric Population

The t1/2 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, t1/2 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, hydroxyzine, any piperazine derivatives in medical history and/or to excipients of the medicinal product.
• 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 tolerance 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 daily).

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

Concomitant use of cetirizine with alcohol or other central nervous system (CNS) depressants in sensitive patients may cause additional impairment of attention and ability to perform tasks, although 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 medicinal product should be discontinued 3 days before testing (elimination period).

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

No clinically significant interactions with alcohol (at blood alcohol concentration of 0.5 g/L) have been observed when cetirizine is used at therapeutic doses. However, caution should be exercised if alcohol is consumed during treatment with the medicinal product.

The medicinal product 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.

Methylparaben (E 218) and propylparaben (E 216) contained in the medicinal product may cause allergic reactions (possibly delayed).

The medicinal product contains less than 1 mmol (23 mg)/dose of sodium, i.e., it is practically sodium-free.

Use during pregnancy or breastfeeding

Pregnancy

Prospective data on cetirizine regarding pregnancy outcomes do not indicate potential toxicity to 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. The medicinal product should be used during pregnancy only if clearly needed and with caution.

Breastfeeding

Cetirizine passes into breast milk at concentrations ranging from 25–90% of plasma concentrations, depending on the time interval after administration. The medicinal product 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 affect reaction speed when driving or operating machinery

Objective assessment of the ability to drive, sleep latency, and performance at an assembly line has not shown any clinically significant effect of cetirizine when used at the recommended dose of 10 mg.

Patients who drive or operate machinery should not exceed the recommended doses and should take into account their individual response to the medicinal product. Patients experiencing somnolence should refrain from driving or operating machinery.

Dosage and Administration

Administration

The medicinal product is intended for oral use. The solution should be dropped onto a spoon or diluted in water. If dilution is used, it is important—especially when administering to children—to ensure that the volume of water to which the drops are added corresponds to the amount of liquid the patient can swallow. The diluted solution should be taken immediately.

Dosage

Adults

The medicinal product should be administered at a dose of 10 mg (20 drops) once daily.

Paediatric population

Children aged 12 years and older: the medicinal product should be administered at a dose of 10 mg (20 drops) once daily.

Children aged 6 to 12 years: the medicinal product should be administered at a dose of 5 mg (10 drops) twice daily.

Children aged 2 to 6 years: the medicinal product should be administered at a dose of 2.5 mg (5 drops) twice daily.

For children with impaired renal function, dosage should be individually adjusted based on the patient's creatinine clearance, age, and body weight.

Elderly patients

In patients with normal renal function, no dosage adjustment is necessary.

Patients with hepatic impairment

No dosage adjustment is required for these patients. However, for 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 of the drug in patients with renal impairment. Since cetirizine is primarily excreted by the kidneys, if no alternative treatment is available, the dosage should be individually adjusted according to renal function status. Refer to the table below and adjust the dose accordingly based on the provided information.

Children.

The medicinal product should be used in children aged 2 years and older.

Overdose.

Symptoms

Symptoms observed after significant overdose of cetirizine are mainly related to effects on the central nervous system (CNS) or effects indicating anticholinergic activity.

Adverse reactions reported after ingestion of doses at least five times higher than the recommended daily dose include confusion, diarrhea, dizziness, increased fatigue, headache, malaise, mydriasis, pruritus, 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 elimination of cetirizine. There is no known specific antidote for cetirizine.

Adverse Reactions.

It is known that cetirizine, when used 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 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 impairment have been observed, characterized by elevated liver enzyme levels accompanied by increased bilirubin levels. These conditions usually resolved after discontinuation of cetirizine.

The following adverse reactions occurred during clinical trials of cetirizine 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 test results confirmed that administration of the recommended daily dose of cetirizine does not impair daily functioning in healthy subjects.

The following adverse reactions occurred during clinical trials of cetirizine 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 post-marketing use of cetirizine, the following adverse reactions have also been reported. Adverse reactions are listed by organ system class according to MedDRA (Medical Dictionary for Regulatory Activities) and 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); frequency not known (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:

frequency not known – increased appetite.

Psychiatric disorders:

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

Nervous system disorders:

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

Eye disorders:

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

Ear and labyrinth disorders:

frequency not known – vertigo.

Cardiac disorders:

rare – tachycardia.

Gastrointestinal disorders:

uncommon – diarrhea.

Hepatobiliary disorders:

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

Skin and subcutaneous tissue disorders:

uncommon – pruritus, rash; rare – urticaria; very rare – angioedema, localised drug rash; frequency not known – acute generalized exanthematous pustulosis.

Musculoskeletal and connective tissue disorders:

frequency not known – arthralgia, myalgia.

Renal and urinary disorders:

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

General disorders:

uncommon – asthenia, malaise; rare – swelling.

Investigations:

rare – weight gain.

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

Reporting suspected adverse reactions

Reporting of suspected adverse reactions after registration of the medicinal product 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 the following link: https://aisf.dec.gov.ua.

Shelf life.

3 years.

Storage conditions.

Store at temperatures not exceeding 25 °C, in a place inaccessible to children.

Packaging.

20 mL in a bottle with dropper cap and closure; 1 bottle in a cardboard box.

Pharmaceutical category.

Over-the-counter (without prescription).

Manufacturer.

UORLД MEDICIN ILAC SAN. VE TİC. A.Ş. /
WORLD MEDICINE ILAC SAN. VE TIC. A.S.

Manufacturer's address and location of operations.

15 Temmuz Mahallesi Cami Yolu Caddesi No:50 Gunesli Bagcilar/Istanbul, Turkey.

Marketing Authorisation Holder.

LLC «WORLD MEDICINE», Ukraine /
WORLD MEDICINE, LLC, Ukraine.