Rolinos

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

Composition:

Active substance: cetirizine;

1 ml of solution (20 drops) contains cetirizine dihydrochloride 10 mg;

Excipients: glycerol (85 %); propylene glycol; sodium saccharin; methylparaben (E 218); propylparaben (E 216); sodium acetate, trihydrate; glacial acetic acid; purified water.

Pharmaceutical form. Oral drops.

Main physicochemical characteristics: clear, colorless liquid.

Pharmacotherapeutic group.

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

Pharmacological properties.

Pharmacodynamics.

Mechanism of action.

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

Pharmacodynamic effects.

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

Clinical efficacy and safety.

At doses of 5 mg and 10 mg, cetirizine strongly inhibits histamine-induced wheal and flare reactions in the skin, although the dose–response relationship has not been fully 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 after a single dose.

Administration of cetirizine to patients with allergic rhinitis and concomitant mild to moderate bronchial asthma at a dose of 10 mg once daily improved rhinitis symptoms and had no adverse 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.

At recommended doses, cetirizine improves symptoms in patients with perennial and seasonal allergic rhinitis.

Special patient groups.

Children.

In children aged 5 to 12 years, tolerance to the antihistaminic effect of cetirizine (inhibition of wheal and flare reactions) was not 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 the dose range of 5 mg to 60 mg.

Absorption.

The steady-state maximum plasma concentration of cetirizine is approximately 300 ng/mL and is 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 cetirizine absorption is not reduced when taken with food, although the rate of absorption is decreased. Bioavailability is similar following administration of cetirizine in solution, capsule, or tablet form.

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 minimal first-pass metabolism.

Elimination.

Approximately two-thirds of the administered 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 groups.

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 function is also impaired.

Patients with renal impairment.

The 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 in patients with moderate renal impairment. The use of cetirizine is contraindicated in patients with severe renal impairment.

Elderly patients.

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

Children.

The 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 6–24 months, the half-life is reduced to 3.1 hours.

Clinical characteristics.

Indications.

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

Contraindications.

• Hypersensitivity to the active substance, to any other component of the medicinal product, to 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 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 administered concomitantly with pseudoephedrine or theophylline (400 mg/day).

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

Concomitant use of cetirizine with alcohol or other agents that depress the central nervous system may result in additional impairment of attention and reduction in performance ability, although cetirizine does not potentiate the effect of alcohol (at blood alcohol levels 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 prior to testing (elimination period).

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

No clinically significant interactions with alcohol (at blood alcohol levels of 0.5 g/L) have been observed when cetirizine is used at therapeutic doses. However, caution should be exercised when cetirizine is used concomitantly with alcohol.

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

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

The 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. Nevertheless, cetirizine should be used with caution during pregnancy.

Breastfeeding

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

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

Patients who drive vehicles or operate machinery should not exceed the recommended doses and should take into account their individual response to the drug.

Patients experiencing somnolence should refrain from driving vehicles or operating machinery.

Method of Administration and Dosage

Method of Administration

The medicinal product is intended for oral use. The solution should be administered by drops into a spoon or diluted in water. If dilution is used, it is important—especially when treating 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 creatinine clearance, age, and body weight.

Elderly Patients

In the presence of normal renal function, no dosage adjustment is necessary for elderly patients.

Patients with Hepatic Impairment

No dosage adjustment is required for patients with hepatic impairment. For patients with concomitant hepatic and renal impairment, dosage adjustment is recommended (see section below, «Patients with Renal Impairment»).

Patients with Renal Impairment

There are no documented data confirming the efficacy/safety ratio 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. Refer to the table below and adjust the dose accordingly based on the provided information.

Renal function status	CrCl (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 medicinal product should be used in children from 2 years of age.

Overdose.

Symptoms.

Symptoms observed after 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 a dose at least 5 times higher than the recommended daily dose include: confusion, diarrhea, dizziness, increased fatigue, headache, malaise, mydriasis, pruritus, restlessness, sedation, somnolence, stupor, tachycardia, tremor, 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 impairment characterized by elevated liver enzyme levels associated with increased bilirubin levels have been reported. Usually, the condition normalized 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 activities 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 the use of cetirizine, the following adverse reactions have also been reported. The 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 (≥ 1/10000, < 1/1000); very rare (<1/10000); 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 disorder, blurred vision, involuntary eye movements.

Ear and labyrinth disorders:

not known – vertigo.

Cardiac disorders:

rare – tachycardia.

Gastrointestinal disorders:

uncommon – diarrhea.

Hepatobiliary disorders:

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

Skin and subcutaneous tissue disorders:

uncommon – pruritus, rash; rare – urticaria; very rare – angioedema, 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 gain.

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

Reporting of suspected adverse reactions.

Reporting of suspected adverse reactions after drug registration is important. It allows continuous monitoring of the benefit-risk balance of the medicinal product. Healthcare and pharmaceutical professionals, as well as patients or their legal representatives, should report all suspected adverse reactions and lack of efficacy through the Automated Pharmacovigilance Information System at: https://aisf.dec.gov.ua.

Shelf life.

3 years.

After first opening of the bottle, use drops within 21 months.

Storage conditions.

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

Packaging.

20 ml in a glass bottle with a dropper cap, 1 bottle in a cardboard box.

Prescription status.

Over-the-counter.

Manufacturer.

ABC Farmaceutici S.p.A., Italy.

Manufacturer's address.

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

Marketing Authorization Holder.

WORLD MEDICINE, LLC, Ukraine.