FRI-AL (Tablets) Instructions for Use

Marketing Authorization Holder

Alsi Pharma, JSC (Russia)

Contact Information

ALSI Pharma JSC (Russia)

ATC Code

R06AE09 (Levocetirizine)

Active Substance

Levocetirizine (Rec.INN registered by WHO)

Dosage Form

FRI-AL

Film-coated tablets, 5 mg: 10, 20 or 30 pcs.

Dosage Form, Packaging, and Composition

Film-coated tablets white, round, biconvex; the inner layer is white or almost white on the cross-section.

Excipients: microcrystalline cellulose – 53.2 mg, croscarmellose sodium – 3.8 mg, pregelatinized starch – 32.04 mg, colloidal silicon dioxide (aerosil) – 0.48 mg, magnesium stearate – 0.48 mg.

Shell composition Opadry II (series 31F28678 White) – 3.8 mg (lactose monohydrate – 1.37 mg, hypromellose – 1.06 mg, titanium dioxide – 0.99 mg, macrogol 3000 – 0.38 mg).

10 pcs. – blister packs (1) – cardboard packs.
10 pcs. – blister packs (2) – cardboard packs.
10 pcs. – blister packs (3) – cardboard packs.

Clinical-Pharmacological Group

Histamine H₁-receptor blocker. Antiallergic drug

Pharmacotherapeutic Group

Antiallergic agent – H₁-histamine receptor blocker

Pharmacological Action

The active substance of the drug FRI-AL – Levocetirizine – is the R-enantiomer of cetirizine; a competitive histamine antagonist; it blocks histamine H₁-receptors, with an affinity 2 times higher than that of cetirizine. Levocetirizine affects the histamine-dependent stage of allergic reactions; reduces eosinophil migration, reduces vascular permeability, and limits the release of inflammatory mediators.

It prevents the development and alleviates the course of allergic reactions, has anti-exudative, antipruritic effects; it has practically no anticholinergic or antiserotonin effects. In therapeutic doses, it has practically no sedative effect.

Pharmacokinetics

The pharmacokinetic parameters of levocetirizine change linearly depending on the dose and are practically no different from the pharmacokinetics of cetirizine.

Absorption

It is rapidly and completely absorbed after oral administration. Food intake does not affect the completeness of absorption but reduces its rate. C_max in blood plasma is reached in 0.9 hours and is 270 ng/ml.

A constant concentration level of levocetirizine is reached after two days of administration. Bioavailability reaches 100%.

Distribution

Plasma protein binding is 90%. Vd is 0.4 l/kg. It penetrates into breast milk.

Metabolism

Less than 14% of the drug is metabolized in the liver by N- and O-dealkylation to form a pharmacologically inactive metabolite.

Due to the low level of metabolism and lack of metabolic potential (the cytochrome system is minimally involved in its metabolism), interaction of levocetirizine with other drugs seems unlikely.

Elimination

In adults, T_1/2 is 7.9±1.9 hours, and the total clearance is 0.63 ml/min/kg; in young children, T_1/2 is shortened.

About 85.4% of the administered dose of the drug is excreted by the kidneys, about 12.9% – through the intestines.

Pharmacokinetics in special clinical cases

Patients with renal impairment. In renal impairment (CrCl<40 ml/min), clearance decreases (by 80% in patients on hemodialysis), T_1/2 is prolonged.

Less than 10% of levocetirizine is removed during a standard 4-hour hemodialysis procedure.

Children. Data from a study of the pharmacokinetics of the drug in 14 children aged 6 to 11 years with a body weight of 20 to 40 kg after a single oral dose of 5 mg of levocetirizine showed that C_max and AUC values are approximately 2 times higher than those in healthy adults in a cross-over study.

Data obtained during the analysis showed that administration of the drug at a dose of 1.25 mg in children aged 6 months to 5 years leads to a plasma concentration corresponding to that in adults taking the drug at a dose of 5 mg once/day.

Elderly patients. Data on pharmacokinetics in elderly patients are limited.

Upon repeated administration of levocetirizine at a dose of 30 mg once/day for 6 days in 9 elderly patients (age from 65 to 74 years), the total clearance was approximately 33% lower than that in younger adults.

It has been shown that the distribution of the cetirizine racemate depends more on renal function than on age. This statement may also be applicable to levocetirizine, since both drugs – both Levocetirizine and cetirizine – are excreted primarily in the urine.

Therefore, in elderly patients, the dose of levocetirizine should be adjusted depending on renal function.

Indications

• Treatment of symptoms of perennial (persistent) and seasonal (intermittent) allergic rhinitis and allergic conjunctivitis, such as itching, sneezing, nasal congestion, rhinorrhea, lacrimation, conjunctival hyperemia;
• Hay fever;
• Urticaria;
• Other allergic dermatoses accompanied by itching and rashes.

If necessary, please consult your doctor before using the drug.

ICD codes

Dosage Regimen

The drug is taken orally with meals or on an empty stomach, without chewing, with a small amount of water. The daily dose is recommended to be taken in one dose.

Adults and children over 6 years the daily dose is 5 mg. The maximum daily dose is 5 mg.

Children under 6 years tablets are not prescribed: another, liquid dosage form is used for them.

Since Levocetirizine is excreted by the kidneys, when prescribing the drug to patients with renal impairment and elderly patients, the dose should be adjusted depending on the CrCl value.

CrCl for men can be calculated based on serum creatinine concentration using the following formula

Creatinine clearance for women can be calculated by multiplying the obtained value by a coefficient of 0.85

For patients with renal and hepatic impairment dosing is carried out according to the table above. If the patient has impaired liver function only, then no adjustment of the dosage regimen is required.

In the treatment of seasonal (intermittent) rhinitis (symptoms present for less than 4 days per week or their total duration is less than 4 weeks), the duration of treatment depends on the duration of symptoms: treatment can be stopped when symptoms disappear and resumed when symptoms appear.

In the treatment of perennial (persistent) allergic rhinitis (symptoms present for more than 4 days per week and their total duration is more than 4 weeks), treatment can continue throughout the period of allergen exposure.

There is clinical experience of continuous use of the drug FRI-AL in the dosage form of film-coated tablets, 5 mg, in adult patients for up to 6 months.

Use the drug only according to the method of application and in the doses indicated in the instructions.

If you forget to take the drug, do not take a double dose to compensate for the missed one, take the next dose at the usual time.

If improvement does not occur after treatment or new symptoms appear, it is necessary to consult a doctor.

Adverse Reactions

Clinical studies

During clinical studies in men and women aged 12-71 years with a frequency of 1% and more ( common ≥ 1/100,<1/10), the following side effects occurred: headache, drowsiness, dry mouth, fatigue, uncommon (≥ 1/1000,<1/100) asthenia and abdominal pain occurred.

During clinical studies in children aged 6 to 12 years with a frequency of 1% and more ( common ≥1/100, <1/10) headache and drowsiness occurred.

Post-registration studies

The frequency of side effects is unknown (cannot be estimated from the available data).

Immune system disorders: hypersensitivity reactions, including anaphylaxis.

Metabolism and nutrition disorders: increased appetite.

Psychiatric disorders: anxiety, aggression, agitation, depression, hallucinations, insomnia, suicidal thoughts.

Nervous system disorders: convulsions, dural sinus thrombosis, paresthesia, dizziness, syncope, tremor, dysgeusia.

Ear and labyrinth disorders vertigo.

Eye disorders visual impairment, blurred vision, inflammatory manifestations.

Cardiac disorders angina pectoris, tachycardia, palpitations, jugular vein thrombosis.

Respiratory, thoracic and mediastinal disorders dyspnea, worsening of rhinitis symptoms.

Gastrointestinal disorders: nausea, vomiting, diarrhea.

Hepatobiliary disorders: hepatitis, changes in liver function tests.

Renal and urinary disorders: dysuria, urinary retention.

Skin and subcutaneous tissue disorders angioedema, fixed drug eruption, pruritus, rash, urticaria, hypotrichosis, fissures, photosensitivity.

Musculoskeletal and connective tissue disorders: myalgia, arthralgia.

General disorders and administration site conditions peripheral edema, weight increased.

Other cross-reactivity.

If any of the side effects listed in the instructions get worse, or you notice any other side effects not listed in the instructions, tell your doctor.

Contraindications

• Hypersensitivity to the active substance, cetirizine, hydroxyzine, any piperazine derivative or to any other excipient of the drug;
• Lactase deficiency, lactose intolerance, glucose-galactose malabsorption;
• End-stage renal failure (CrCl less than 10 ml/min);
• Children under 6 years of age (for tablets, due to limited data on efficacy and safety).

With caution

Caution is required in the following conditions: chronic renal failure (dose adjustment is necessary); in elderly patients (with age-related decrease in glomerular filtration rate), with simultaneous use with alcohol (see also the section “Drug Interactions”); in patients with spinal cord injury, prostatic hyperplasia, as well as in the presence of other predisposing factors for urinary retention, since Levocetirizine may increase the risk of urinary retention; when prescribed to pregnant women and during breastfeeding.

Use in Pregnancy and Lactation

Pregnancy

Data on the use of levocetirizine during pregnancy are virtually absent or limited (less than 300 pregnancy outcomes). However, the use of cetirizine, the racemate of levocetirizine, during pregnancy (more than 1000 pregnancy outcomes) was not accompanied by malformations and intrauterine and neonatal toxic effects.

Animal studies have not revealed direct or indirect adverse effects on pregnancy, embryonic and fetal development, childbirth and postnatal development.

Caution should be exercised when prescribing levocetirizine to pregnant women.

Breastfeeding period

Cetirizine, the racemate of levocetirizine, is excreted in breast milk. Therefore, excretion of levocetirizine in breast milk is also likely. Breastfed infants may experience adverse reactions to Levocetirizine. Therefore, caution should be exercised when prescribing levocetirizine during breastfeeding.

Fertility

Clinical data on levocetirizine are lacking.

Use in Renal Impairment

Contraindication: end-stage renal failure (CrCl less than 10 ml/min).

Pediatric Use

Contraindication: children under 6 years of age (for tablets, due to limited data on efficacy and safety).

Special Precautions

The intervals between doses should be selected individually depending on renal function.

In patients with predisposing factors for urinary retention (e.g., spinal cord injury, prostatic hyperplasia), caution should be exercised, as Levocetirizine may increase the risk of urinary retention.

During treatment, it is recommended to refrain from consuming ethanol (alcohol).

The FRI-AL tablet formulation contains lactose monohydrate; it should not be prescribed to patients with lactose intolerance, hereditary lactase deficiency, or glucose-galactose malabsorption syndrome.

Effect on ability to drive vehicles and machinery

Levocetirizine may lead to increased drowsiness, therefore, the drug may affect the ability to drive a car or operate machinery. During the period of taking FRI-AL, it is advisable to refrain from performing potentially hazardous activities that require increased concentration and speed of psychomotor reactions (including driving vehicles and operating machinery).

Overdose

Symptoms: drowsiness (in adults), agitation and restlessness, followed by drowsiness (in children).

Treatment: immediately after oral administration of the drug, gastric lavage or induction of vomiting is necessary. Symptomatic and supportive therapy is recommended. There is no specific antidote. Hemodialysis is ineffective.

Drug Interactions

Studies of the interaction of levocetirizine with other drugs have not been conducted. When studying the drug interaction of the cetirizine racemate with antipyrine, pseudoephedrine, cimetidine, ketoconazole, erythromycin, azithromycin, glipizide and diazepam, no clinically significant undesirable interaction was found.

With simultaneous use with theophylline (400 mg/day), the total clearance of cetirizine decreases by 16% (the kinetics of theophylline does not change).

With simultaneous use of ritonavir (600 mg 2 times/day) and cetirizine (10 mg/day), a study showed that the exposure of cetirizine increased by 40%, and the exposure of ritonavir changed slightly (-11%).

In some cases, simultaneous use of levocetirizine with alcohol or drugs that have a depressant effect on the central nervous system may cause lethargy and decreased performance.

Storage Conditions

The drug should be stored out of the reach of children, at a temperature not exceeding 25°C (77°F) in the original packaging (blister pack in a carton).

Shelf Life

Shelf life – 18 months.

Dispensing Status

The drug is dispensed without a prescription.

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.