Active ingredients: Bilastine
AYRINAL 20mg Tablets
Why is Ayrinal used? What is it for?
AYRINAL tablets contain the active ingredient bilastine which is an antihistamine. AYRINAL 20 mg tablets are used to relieve the symptoms of hay fever (sneezing, itching, runny nose, stuffy nose and red and watery eyes) and other forms of allergic rhinitis. It can also be used to treat itchy skin rashes (such as hives).
Contraindications When Ayrinal should not be used
Do not take AYRINAL 20 mg tablets if:
you are allergic (hypersensitive) to bilastine or any of the other ingredients of AYRINAL 20 mg tablets (see section 6, Further Information).
Precautions for use What you need to know before taking Ayrinal
Take special care with AYRINAL 20 mg tablets
If you have moderate or severe kidney impairment and are taking other medicines (see below)
It is not intended for use in children under 12 years of age
Do not exceed the recommended dose. If symptoms persist, consult your doctor.
Interactions Which drugs or foods may change the effect of Ayrinal
Taking AYRINAL 20 mg tablets with other medicines
Tell your doctor or pharmacist if you are taking or have recently taken any other medicines, including medicines obtained without a prescription.
In particular, consult your doctor if you are taking any of the following medicines:
- Ketoconazole (an antifungal drug)
- Erythromycin (an antibiotic)
- Diltiazem (for the treatment of angina)
- Ciclosporin (to reduce the activity of the immune system in order to avoid transplant rejection or to reduce the activity of autoimmune and allergic diseases, such as psoriasis, atopic dermatitis or rheumatoid arthritis)
- Ritonavir (to treat AIDS)
- Rifampicin (an antibiotic)
Taking AYRINAL 20 mg tablets with food and drink
The tablets should not be taken with food or grapefruit juice or other fruit juices, as this diminishes the effect of bilastine.
To prevent this from happening, he can:
- take the tablet and wait for one hour before consuming any food or fruit juice
- if you have consumed food or fruit juice, wait two hours before taking the tablet
Warnings It is important to know that:
Pregnancy and breastfeeding
Consult your doctor if you are pregnant, if you may be pregnant, or if you are breastfeeding.
Ask your doctor or pharmacist for advice before taking any medicine.
Driving and using machines
A study conducted to establish the effects of bilastine on the ability to drive showed that treatment with doses of 20 mg of bilastine does not affect the ability to drive. However, very rarely some people have experienced somnolence, which may affect the ability to drive and use machines.
Alcohol intake
Bilastine, at the recommended dose (20 mg), does not increase the drowsiness produced by alcohol.
Dose, Method and Time of Administration How to use Ayrinal: Posology
Adults, including the elderly and adolescents 12 years of age and older
- Take one tablet a day.
- The tablet should be taken on an empty stomach, for example in the morning before breakfast. Do not eat for 1 hour after taking bilastine.
- Swallow the tablet with a glass of water.
- The score line is not used to divide the tablet into equal doses. It can be used to break the tablet and make it easier to take.
Regarding the duration of treatment, your doctor will determine the type of disease you suffer from and will decide how long you should take AYRINAL 20 mg tablets.
Overdose What to do if you have taken too much Ayrinal
If you take more AYRINAL 20 mg tablets than you should
If you or someone else have taken too much AYRINAL 20 mg tablets, contact your doctor or pharmacist immediately.
If you forget to take AYRINAL 20 mg tablets
Do not take a double dose to make up for a forgotten dose.
If you forget to take a dose, take it as soon as possible and then return to your regular dosing schedule.
If you have any further questions on the use of AYRINAL 20 mg tablets, ask your doctor or pharmacist.
Side Effects What are the side effects of Ayrinal
Like all medicines, AYRINAL 20 mg tablets can cause side effects, although not everybody gets them.
The side effects that can occur are the following:
Common: affects 1 to 10 users in 100
- headache
- drowsiness
Uncommon: affects 1 to 10 users in 1,000
- abnormal electrocardiographic trace (ECG)
- blood tests that indicate changes in the functioning of the liver
- dizziness
- stomach pains
- tiredness
- increased appetite
- irregular heartbeat
- weight gain
- nausea (feeling sick)
- anxiety
- feeling of dryness or discomfort in the nose
- bellyache
- diarrhea
- gastritis (inflammation of the stomach wall)
- vertigo (a feeling of dizziness)
- feeling of weakness
- thirst
- dyspnoea (difficulty in breathing)
- dry mouth
- indigestion
- itch
- oral herpes
- fever
- tinnitus (ringing in the ears)
- difficulty falling asleep
- blood tests that indicate changes in kidney function
- increased fat in the blood
If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.
Expiry and Retention
Keep out of the reach and sight of children.
Do not use AYRINAL 20 mg tablets beyond the expiry date which is stated on the carton and blister. The expiry date refers to the last day of that month.
This medicine does not require any special storage conditions.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. This will help protect the environment.
Composition and pharmaceutical form
What AYRINAL 20 mg tablets contain:
- The active ingredient is bilastine. Each tablet contains 20 mg of bilastine.
- The other ingredients are microcrystalline cellulose, sodium starch glycolate type A (derived from potatoes), anhydrous colloidal silica, magnesium stearate.
What AYRINAL 20 mg tablets look like and contents of the pack:
AYRINAL 20 mg tablets are white, oval, biconvex and scored.
The tablets are supplied in blisters of 10, 20, 30, 40 or 50 tablets.
Not all pack sizes may be marketed.
Source Package Leaflet: AIFA (Italian Medicines Agency). Content published in January 2016. The information present may not be up-to-date.
To have access to the most up-to-date version, it is advisable to access the AIFA (Italian Medicines Agency) website. Disclaimer and useful information.
01.0 NAME OF THE MEDICINAL PRODUCT
ARYNAL 20 MG TABLETS
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION
Each tablet contains 20 mg of bilastine.
For the full list of excipients, see section 6.1
03.0 PHARMACEUTICAL FORM
Tablet.
White, oval, biconvex tablets with score line.
The score line on the tablet is only to facilitate breaking for easier swallowing of the tablet e Not to divide it into equal doses.
04.0 CLINICAL INFORMATION
04.1 Therapeutic indications
Symptomatic treatment of allergic rhinoconjunctivitis (seasonal and perennial) and urticaria.
04.2 Posology and method of administration
Route of administration:
Oral use
Adults and adolescents (12 years and over)
20 mg (1 tablet) once daily to relieve the symptoms of allergic rhinoconjunctivitis (SAR and PAR) and urticaria.
The tablet should be taken orally one hour before or two hours after food or fruit juice. It is recommended to take the daily dose in a single administration.
Senior citizens
No dosage adjustments are required in elderly patients (see sections 5.1 and 5.2). Experience in patients over 65 years of age is poor.
Children under 12 years old
The safety and efficacy of bilastine in children under the age of 12 have not yet been established.
Renal impairment
No dosage adjustments are required in patients with renal impairment. (see section 5.2).
Hepatic impairment
There is no clinical experience in patients with hepatic impairment. Since bilastine is not metabolised and renal clearance is the major route of elimination, hepatic impairment is not expected to increase systemic exposure beyond the safety margin. Therefore, no dosage adjustment is necessary in patients with hepatic impairment. (see section 5.2).
Duration of treatment
For allergic rhinitis, treatment should be limited to the period of exposure to the allergens. For seasonal allergic rhinitis, treatment can be stopped after the symptoms have disappeared and resumed when they reappear. In perennial allergic rhinitis, continued treatment may be offered to patients during the period of exposure to allergens. In urticaria, the duration of treatment depends on the type, duration and course of the complaints.
04.3 Contraindications
Hypersensitivity to the active substance bilastine or to any of the excipients.
04.4 Special warnings and appropriate precautions for use
The safety and efficacy of bilastine in children below 12 years of age have not been established.
In patients with moderate to severe renal impairment, co-administration of bilastine with P-glycoprotein inhibitors, such as ketoconazole, erythromycin, cyclosporine, ritonavir or diltiazem, may increase the plasma levels of bilastine and therefore increase the risk of adverse effects. . Therefore, co-administration of bilastine and P-glycoprotein inhibitors should be avoided in patients with moderate to severe renal impairment.
04.5 Interactions with other medicinal products and other forms of interaction
Interaction with food: food significantly reduces the oral bioavailability of bilastine by 30%.
Interaction with grapefruit juice: Concomitant intake of 20 mg bilastine with grapefruit juice decreases the bioavailability of bilastine by 30%. This effect may also occur with other fruit juices. The degree of decrease in bioavailability may vary according to different producers and fruits. The mechanism of this interaction is inhibition of OATP1A2, an uptake transporter for which bilastine is a substrate (see section 5.2). Medicinal products that are substrates or inhibitors of OATP1A2, such as ritonavir or rifampicin, may similarly have the potential to decrease the plasma concentration of bilastine.
Interaction with ketoconazole or erythromycin: Concomitant intake of bilastine and ketoconazole or erythromycin increased the AUC of bilastine by 2-fold and the Cmax by 2-3-fold. These changes may be explained by the interaction with intestinal efflux transporters, as bilastine is a substrate for P-gp and is not metabolised (see section 5.2). These changes do not appear to affect the safety profile of bilastine and ketoconazole. or erythromycin, respectively Other medicinal products that are substrates or inhibitors of P-gp, such as cyclosporine, may similarly have the potential to increase the plasma concentration of bilastine.
Interaction with diltiazem: Concomitant intake of bilastine 20 mg and diltiazem 60 mg increased the Cmax of bilastine by 50%. This effect may be explained by the interaction with intestinal efflux transporters (see section 5.2) and does not appear to have an effect on the profile of safety of bilastine.
Interaction with alcohol: The psychomotor performance after the concomitant intake of alcohol and 20 mg bilastine was similar to that observed after the intake of alcohol and placebo.
Interaction with lorazepam: Concomitant intake of bilastine 20 mg and lorazepam 3 mg for 8 days did not potentiate the CNS sedative effects of lorazepam.
04.6 Pregnancy and lactation
Fertility: there are no clinical data or they are limited in number. A study conducted in rats did not indicate any adverse effects on fertility (see section 5.3).
Pregnancy: data on the use of bilastine in pregnant women do not exist or are limited in number.
Animal studies do not indicate the presence of direct or indirect adverse effects with respect to reproductive toxicity, parturition or postnatal development (see section 5.3). As a precautionary measure, it is preferable to avoid the use of Ayrinal during pregnancy.
Feeding time: it is not known whether bilastine is excreted in human milk. The excretion of bilastine in milk has not been studied in animals. A decision must be made whether to continue / discontinue breastfeeding or to continue / discontinue Ayrinal therapy taking into account the benefit of breastfeeding for the child and the benefit of therapy with the bilastine for the mother.
04.7 Effects on ability to drive and use machines
A study performed to evaluate the effects of bilastine on the ability to drive showed that treatment with 20 mg did not affect the ability to drive. However, patients should be warned that somnolence has occurred very rarely in some people, which may affect the ability to drive or use machines.
04.8 Undesirable effects
The number of adverse events occurring in patients with allergic rhinoconjunctivitis or chronic idiopathic urticaria treated with 20 mg of bilastine in clinical trials was comparable to that in placebo-treated patients (12.7% versus 12.8% ).
The most commonly reported adverse events by patients who received bilastine 20 mg during phase II and III clinical trials were headache, somnolence, dizziness and fatigue. These adverse events occurred with a comparable frequency in placebo-treated patients.
Adverse events at least possibly related to bilastine and reported in over 0.1% of patients treated with bilastine 20 mg during clinical development are presented in the table below.
Frequencies are assigned as follows:
very common (≥1 / 10);
common (≥1 / 100 to
uncommon (≥1 / 1,000 to
rare (≥1 / 10,000 to
very rare (
not known (frequency cannot be estimated from the available data).
Rare, very rare and of unknown frequency were not included in the table.
04.9 Overdose
Information regarding acute overdose is limited to experiences gathered in clinical trials conducted during the development of bilastine. Following administration of bilastine at doses higher than 10 or 11 times the therapeutic dose (220 mg (single dose); or 200 mg / day for 7 days) to healthy volunteers, the frequency of adverse events occurring during treatment was two. times higher than placebo. The most frequently reported adverse reactions were dizziness, headache and nausea. No serious adverse events and no significant QTc prolongation were reported.
A critical evaluation of the effect of multiple doses of bilastine (100 mg x 4 days) on ventricular repolarization using a "thorough QT / QTc cross-study" involving 30 healthy volunteers did not reveal significant QTc prolongation.
In the event of an overdose, symptomatic and supportive treatment is recommended.
There is no known antidote to bilastine.
05.0 PHARMACOLOGICAL PROPERTIES
05.1 Pharmacodynamic properties
Pharmacotherapeutic group: antihistamines for systemic use, other antihistamines for systemic use.
ATC code RO6AX29.
Bilastine is a non-sedating, long-acting histaminergic antagonist with selective peripheral H1-receptor antagonist affinity and no muscarinic affinity.
Bilastine inhibited histamine-induced wheal-erythematous skin reactions for 24 hours following single dose administration.
In clinical trials performed in adult and adolescent patients with allergic rhinoconjunctivitis (seasonal and perennial), bilastine 20 mg, administered once daily for 14-28 days, was effective in relieving symptoms such as sneezing, nasal discomfort, nasal itching. , nasal congestion, itchy eyes, watery eyes and red eyes Bilastine effectively controlled symptoms for 24 hours.
In two clinical trials conducted in patients with chronic idiopathic urticaria, bilastine 20 mg, administered once daily for 28 days was effective in "relieving" the intensity of itching and the number and size of hives, as well as disorders caused by the "urticaria. Sleep conditions and quality of life improved in patients.
Clinically relevant prolongation of the QTc interval or any other cardiovascular effect was not observed in clinical trials with bilastine, even at doses of 200 mg per day (10 times the clinical dose) for 7 days in 9 subjects, or even when co-administered with P-gp inhibitors such as ketoconazole (24 subjects) and erythromycin (24 subjects) In addition, a thorough QT study was performed on 30 volunteers.
In controlled clinical trials at the recommended dose of 20 mg once daily, the CNS safety profile of bilastine was similar to placebo and the incidence of somnolence was not statistically different from placebo. Bilastine at doses up to 40 mg each day did not affect psychomotor performance in clinical trials and did not affect driving ability in a standard driving test.
In elderly patients (≥ 65 years) included in phase II and III studies, there were no differences in efficacy or safety compared to younger patients.
05.2 Pharmacokinetic properties
Absorption
Bilastine is rapidly absorbed after oral administration reaching maximum plasma concentration in approximately 1.3 hours. No accumulation phenomenon was observed. The mean bioavailability of bilastine after oral administration is 61%.
Distribution
Education in vitro And in vivo showed that bilastine is a substrate for Pgp (see section 4.5 Interaction with ketoconazole, erythromycin and diltiazem) and OATP (see section 4.5 Interaction with grapefruit juice). Bilastine does not appear to be a substrate of the BCRP transporter or the renal transporters OCT2, OAT1 and OAT3. Based on studies in vitro, bilastine is not expected to inhibit the following transporters in the systemic circulation: P-gp, MRP2, BCRP, BSEP, OATP1B1, OATP1B3, OATP2B1, OAT1, OAT3, OCT1, OCT2 and NTCP, as only modest inhibition was detected for P-gp, OATP2B1 and OCT1, with an estimated IC50 ≥ 300 mcM, much higher than the calculated clinical plasma CMAX and therefore these interactions will not be clinically relevant. However, on the basis of these results, the inhibitory action of bilastine on transporters present in the intestinal mucosa, for example P-gp, cannot be excluded.
At therapeutic doses, bilastine is 84-90% bound to plasma proteins.
Biotransformation
Bilastine did not induce or inhibit the activity of CYP450 isoenzymes in the studies in vitro.
Elimination
In a mass balance study conducted in healthy volunteers, following administration of a single 20 mg dose of 14C-bilastine, nearly 95% of the administered dose was recovered in urine (28.3%) and faeces (66 , 5%) as unchanged bilastine, thus confirming that bilastine is not significantly metabolised in humans. The calculated mean elimination half-life in healthy volunteers was 14.5 h.
Linearity
Bilastine exhibits linear pharmacokinetics in the dose range studied (5 to 220 mg), with low interindividual variability.
Patients with renal impairment:
In a study in subjects with renal impairment, the mean (SD) AUC0- ¥ increased from 737.4 (± 260.8) ngxh / mL in subjects without impairment (GFR:> 80 mL / min / 1.73 m2) to: 967.4 (± 140.2) ngxh / ml in mildly impaired subjects (GFR: 50-80 ml / min / 1.73 m2), 1384.2 (± 263.23) ngxh / ml in subjects with moderate impairment (GFR: 30 - 2), and 1708.5 (± 699.0) ngxh / ml in subjects with severe impairment (GFR: 2). The mean (SD) half-life of bilastine was 9.3 h (± 2.8) in subjects without impairment, 15.1 h (± 7.7) in subjects with mild impairment, 10.5 h (± 2.3) in subjects with moderate impairment, and 18.4 h (± 11.4 ) in subjects with severe impairment. Urinary excretion of bilastine was essentially complete after 48 to 72 h in all subjects. These pharmacokinetic changes are not expected to have a clinically relevant influence on the safety of bilastine, as plasma bilastine levels in patients with renal impairment fall within still in the safe range of bilastine.
Patients with hepatic impairment:
There are no pharmacokinetic data for subjects with hepatic impairment. Bilastine is not metabolised in humans. Since the results of the renal impairment study indicate that renal elimination is the major contributor to elimination, biliary excretion is expected to be involved only marginally in the elimination of bilastine. Alterations in liver function are not expected to have a clinically relevant influence on bilastine pharmacokinetics.
Elderly patients:
Only a limited amount of data is available in subjects over 65 years of age. No statistically significant differences in bilastine pharmacokinetics were observed in elderly versus young subjects.
05.3 Preclinical safety data
Non-clinical data on bilastine reveal no special hazard for humans based on conventional studies of safety pharmacology, repeated dose toxicity, genotoxicity and carcinogenic potential.
In reproductive toxicity studies, the effects of bilastine on the fetus (pre- and post-implantation loss in rats and incomplete ossification of the cranial bones, sternum and limbs in rabbits) were observed only at maternally toxic doses. No Observed Adverse Effect Level (NOAEL) exposure levels are sufficiently in excess (> 30-fold) of human exposure at the recommended therapeutic dose.
In a fertility study in rats, bilastine administered orally up to 1000 mg / kg / day had no effect on the male and female reproductive organs. Mating, fertility and pregnancy indices were not affected.
As shown in a distribution study in rats by determining drug concentrations by autoradiography, bilastine does not accumulate in the CNS.
06.0 PHARMACEUTICAL INFORMATION
06.1 Excipients
Microcrystalline cellulose
Sodium Starch Glycolate (Type A) (derived from potatoes)
Anhydrous colloidal silica
Magnesium stearate
06.2 Incompatibility
Not relevant.
06.3 Period of validity
5 years
06.4 Special precautions for storage
This medicine does not require any special storage conditions.
06.5 Nature of the immediate packaging and contents of the package
The medicine is packaged in a blister, which consists of two parts:
laminate, composed of oriented polyamide (external side of the laminate), aluminum and PVC (internal side of the laminate)
Aluminum sheet
The aluminum sheet is heat-sealed with a heat-sealing lacquer (PVC-PVAC copolymer and butyl methacrylate resins) to the laminate after forming and filling with tablets.
Each blister contains 10 tablets. The blisters are packed in cardboard boxes.
Packs of 10, 20, 30, 40 or 50 tablets.
Not all pack sizes may be marketed.
06.6 Instructions for use and handling
No special instructions.
Unused medicine and waste derived from this medicine must be disposed of in accordance with local regulations.
07.0 MARKETING AUTHORIZATION HOLDER
Menarini International Operations Luxembourg S.A.
1, Avenue de la Gare, L-1611 - Luxembourg
Dealer for sale: Malesci Istituto Farmacobiologico S.p.A.
Via Lungo l "Ema, 7 - Loc. Ponte a Ema, Bagno a Ripoli - Florence
08.0 MARKETING AUTHORIZATION NUMBER
Ayrinal 20 mg tablets:
10 tablets - A.I.C. 040854010 / M
20 tablets - A.I.C. 040854022 / M
30 tablets - A.I.C. 040854034 / M
40 tablets - A.I.C. 040854046 / M
50 tablets - A.I.C. 040854059 / M
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION
Date of first authorization: 3 April 2012
10.0 DATE OF REVISION OF THE TEXT
April 2012
