Consumer medicine information

Allertine Tablets

Bilastine

BRAND INFORMATION

Brand name

Allertine

Active ingredient

Bilastine

Schedule

S2

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Allertine Tablets.

SUMMARY CMI

ALLERTINE® tablets

Consumer Medicine Information (CMI) summary

The full CMI on the next page has more details. If you are worried about taking this medicine, speak to your pharmacist or doctor.

▼ This medicine is new or being used differently. Please report side effects. See the full CMI for further details.

1. Why am I taking ALLERTINE?

ALLERTINE contains the active ingredient bilastine. ALLERTINE is used to relieve the symptoms of hayfever and other forms of allergic rhinitis. It may also be used to treat itchy skin rashes.

For more information, see Section 1. Why am I taking ALLERTINE? in the full CMI.

2. What should I know before I take ALLERTINE?

Do not use if you have ever had an allergic reaction to bilastine or any of the ingredients listed at the end of the CMI.

Talk to your pharmacist or doctor if you have kidney problems or are taking any other regular medicines listed in Section 3. What if I am taking other medicines?.

Talk to your pharmacist or doctor if you are pregnant, likely to become pregnant or are breastfeeding.

For more information, see Section 2. What should I know before I take ALLERTINE? in the full CMI.

3. What if I am taking other medicines?

Some medicines may interfere with ALLERTINE and affect how it works.

A list of these medicines is in Section 3. What if I am taking other medicines? in the full CMI.

4. How do I take ALLERTINE?

  • Adults and adolescents 12 years & over: Take one tablet daily, as required to manage your symptoms.
  • Swallow the tablet with a glass of water, on an empty stomach (at least 1 hour before or 2 hours after meals or fruit juices).

More instructions can be found in Section 4. How do I take ALLERTINE? in the full CMI.

5. What should I know while taking ALLERTINE?

Things you should do
  • Discuss any side effects that concern you with your pharmacist or doctor.
  • If you are started on a new medicine, remind your doctor or pharmacist that you are taking ALLERTINE.
  • If symptoms persist or appear to worsen, check with your pharmacist or doctor for advice.
Driving or using machines
  • ALLERTINE has been shown not to affect adult driving performance. However, as medicine responses for each person can vary, check how this medicine affects you before driving or operating machinery.
Looking after your medicine
  • Keep your medicine in a cool dry place where the temperature stays below 30°C.
  • Keep your medicine in the original pack until it is time to take.

For more information, see Section 5. What should I know while taking ALLERTINE? in the full CMI.

6. Are there any side effects?

The most common side effects of ALLERTINE are headache, sleepiness and stomach pain.

Serious side effects may include difficulty breathing, swelling of face, lips or tongue, sudden or rapidly developing rash or itching of skin or collapsing or losing consciousness.

For more information, including what to do if you have any side effects, see Section 6. Are there any side effects? in the full CMI.

▼ This medicine is subject to additional monitoring. This will allow quick identification of new safety information. You can help by reporting any side effects you may get. You can report side effects to your doctor, or directly at www.tga.gov.au/reporting-problems.



FULL CMI

ALLERTINE® tablets

Active ingredient: bilastine

Consumer Medicine Information (CMI)

This leaflet provides important information about taking ALLERTINE. You should also speak to your pharmacist or doctor if you would like further information or if you have any concerns or questions about taking ALLERTINE.

Where to find information in this leaflet:

1. Why am I taking ALLERTINE?
2. What should I know before I take ALLERTINE?
3. What if I am taking other medicines?
4. How do I take ALLERTINE?
5. What should I know while taking ALLERTINE?
6. Are there any side effects?
7. Product details

1. Why am I taking ALLERTINE?

ALLERTINE contains the active ingredient bilastine.
ALLERTINE is one of a group of medicines called non-drowsy antihistamines.

ALLERTINE is used to relieve the symptoms of hayfever (sneezing, itchy, runny, blocked nose, red watery and itchy eyes) and other forms of allergic rhinitis. It may also be used to treat itchy skin rashes (hives or urticaria).

2. What should I know before I take ALLERTINE?

Warnings

Do not use ALLERTINE if:

  • you are allergic to bilastine, or any of the ingredients listed at the end of this leaflet.

Always check the ingredients to make sure you can use this medicine.

Check with your pharmacist or doctor if you:

During treatment, you may be at risk of developing certain side effects. It is important you understand these risks and how to monitor for them. See additional information under Section 6. Are there any side effects?

Pregnancy and breastfeeding

Check with your pharmacist or doctor if you are pregnant or likely to become pregnant.

Talk to your pharmacist or doctor if you are breastfeeding or intend to breastfeed.

Do not take ALLERTINE if you are pregnant or breastfeeding unless your doctor has advised you to.

Use in Children

Do not give ALLERTINE to a child under the age of 12 years.

The safety of ALLERTINE and how well it works has not been studied in children younger than 12 years of age.

3. What if I am taking other medicines?

Tell your pharmacist or doctor if you are taking any other medicines, including any medicines, vitamins or supplements that you buy without a prescription from your pharmacy, supermarket or health food shop.

Some medicines and ALLERTINE may interfere with each other and affect how well each works. These include:

  • Diltiazem, a medicine for the treatment of high blood pressure and angina.
  • Cyclosporine, a medicine used to reduce the activity of the immune system.
  • Ketoconazole, a medicine used to treat fungal infections.
  • Erythromycin, a medicine used to treat a wide variety of bacterial infections.

Check with your pharmacist or doctor if you are not sure about what medicines, vitamins or supplements you are taking and if these affect ALLERTINE.

4. How do I take ALLERTINE?

How much to take

  • Adults and adolescents 12 years & over: Take one tablet daily, as required to manage your symptoms.
  • Swallow the tablet with a glass of water.
  • If you have difficulty swallowing, the tablet may be halved along the score line.

When to take ALLERTINE

  • Take ALLERTINE on an empty stomach, at least 1 hour before or 2 hours after food or fruit juice (particularly grapefruit juice).

Food and fruit juice can interfere with the absorption of ALLERTINE by the body.

How long to take ALLERTINE

ALLERTINE helps control your condition, but it does not cure it. You can stop taking ALLERTINE when you know you are no longer exposed to your hayfever/ allergy triggers, or you know you have obtained sufficient relief from your symptoms. ALLERTINE can be restarted if your symptoms recur or are expected to recur.

If you take too much ALLERTINE

If you think that you have taken too much ALLERTINE, you may need urgent medical attention.

You should immediately:

  • phone the Poisons Information Centre
    (by calling 13 11 26 in Australia), or
  • contact your doctor, or
  • go to the Emergency Department at your nearest hospital.

You should do this even if there are no signs of discomfort or poisoning.

5. What should I know while taking ALLERTINE?

Things you should do

  • Discuss any side effects that concern you with your pharmacist or doctor.
  • If you are started on a new medicine, remind your doctor or pharmacist that you are taking ALLERTINE.
  • If your symptoms persist or appear to worsen, do not take extra tablets. Check with your pharmacist or doctor for advice.
  • Tell your pharmacist or doctor immediately if you become pregnant while you are taking this medicine.

Driving or using machines

It has been demonstrated that bilastine does not affect adult driving performance. However, the response from each patient to the medicine may be different. Therefore, as for any new medicine, you should check how this medicine affects you, before driving or operating machinery.

Looking after your medicine

  • Keep your medicine where the temperature stays below 30°C.
  • Keep your medicine in the original pack until it is time to take.

Follow the instructions on the carton on how to take care of your medicine properly.

Store it in a cool dry place away from moisture, heat or sunlight; for example, do not store it:

  • in the bathroom or near a sink, or
  • in the car or on window sills.

Keep it where young children cannot reach it.

Getting rid of any unwanted medicine

If you no longer need to use this medicine or it is out of date, take it to any pharmacy for safe disposal.

Do not use this medicine after the expiry date.

6. Are there any side effects?

All medicines can have side effects. If you do experience any side effects, most of them are minor and temporary. However, some side effects may need medical attention.

See the information below and, if you need to, ask your pharmacist or doctor if you have any further questions.

Do not be alarmed by the following list of side effects. You may not experience any of them. Similar side effects were seen in patients taking ‘dummy’ or placebo tablets during the clinical studies.

Less serious side effects

Less serious side effectsWhat to do
COMMON:
General body-related:
  • headache
  • sleepiness, drowsiness or tiredness
  • dizziness
LESS COMMON:
Stomach and bowel-related:
  • mild stomach upsets such as stomach or belly pain, nausea or diarrhoea
Heart-related:
  • fast or irregular heartbeat
Other:
  • tinnitus (ringing in the ears)
  • vertigo (a strong feeling of dizziness or spinning)
Speak to your pharmacist or doctor if you have any of these less serious side effects and they worry you.

Serious side effects

Serious side effectsWhat to do
Allergic reaction-related:
  • sudden or rapidly developing rash, swelling, itchiness or hives on the skin
  • shortness of breath, wheezing or difficulty breathing or swallowing
  • swelling of face, lips, tongue, throat or other parts of the body
  • fainting, collapsing or losing consciousness
Call your doctor straight away, or go straight to the Emergency Department at your nearest hospital if you notice any of these serious side effects.

Tell your pharmacist or doctor if you notice anything else that may be making you feel unwell.

Other side effects not listed here may occur in some people.

Reporting side effects

After you have received medical advice for any side effects you experience, you can report side effects to the Therapeutic Goods Administration online at www.tga.gov.au/reporting-problems. By reporting side effects, you can help provide more information on the safety of this medicine.

7. Product details

This medicine is available over-the-counter without a doctor's prescription.

What ALLERTINE contains

Active ingredient
(main ingredient)		Each tablet contains 20 mg of bilastine.
Other ingredients
(inactive ingredients)
  • microcrystalline cellulose
  • sodium starch glycollate type A
  • colloidal anhydrous silica
  • magnesium stearate

Do not take this medicine if you are allergic to any of these ingredients.

ALLERTINE does not contain lactose, sucrose, gluten, tartrazine or any other azo dyes.

What ALLERTINE looks like

ALLERTINE is a white, oval, biconvex and scored tablet
(AUST R 387574).

Available in blister packs of 4, 10, 20, 30, 40, 50, 60, 70, 80, 90 or 100 tablets.

Not all pack sizes may be supplied.

Who distributes ALLERTINE

A. Menarini Australia Pty. Ltd.,
Level 8, 67 Albert Avenue,
Chatswood, NSW 2067
Phone 1800 644 542

For further information or the most up-to-date version of this leaflet visit www.allertine.com.au

® Trademark

[CMI vA03-0]

This leaflet was prepared in September 2023.

Published by MIMS November 2023

BRAND INFORMATION

Brand name

Allertine

Active ingredient

Bilastine

Schedule

S2

 

1 Name of Medicine

Bilastine.

2 Qualitative and Quantitative Composition

Each tablet contains 20 mg of bilastine.
For the full list of excipients, see Section 6.1.

3 Pharmaceutical Form

Allertine is supplied as oval, biconvex, scored white tablets.
The score line allows for splitting of the tablet to facilitate the ease of swallowing.

4 Clinical Particulars

4.1 Therapeutic Indications

Allertine is indicated for the symptomatic treatment of allergic rhinoconjunctivitis (AR - both seasonal allergic rhinitis (SAR) and perennial allergic rhinitis (PAR)) and/or urticaria.

4.2 Dose and Method of Administration

AR and urticaria.

Adults and adolescents (12-17 years of age).

Take one Allertine tablet daily, as required for symptom control according to allergen exposure, symptom severity and expected course of symptoms.
No dosage adjustment is required in renal or hepatic impairment or in the elderly.

Method of administration.

Allertine should be swallowed whole, with a glass of water, at least 1 hour before or 2 hours after intake of food or fruit juice (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).

4.3 Contraindications

Hypersensitivity to bilastine or to any of the excipients.

4.4 Special Warnings and Precautions for Use

Use in hepatic impairment.

No dosage adjustment is required in patients with hepatic impairment (see Section 5.2 Pharmacokinetic Properties) since bilastine is not metabolised and is eliminated unchanged in urine and faeces. Hepatic impairment is not expected to increase systemic exposure above the safety margin.

Use in renal impairment.

No dosage adjustment is required in patients with renal impairment (see Section 5.2 Pharmacokinetic Properties).
In patients with moderate or severe renal impairment, co-administration of Allertine with P-glycoprotein inhibitors such as cyclosporine or diltiazem should be approached with caution as elevated bilastine plasma levels and higher incidence of adverse reactions such as dizziness, headache and nausea may occur (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).

Use in the elderly.

No dosage adjustment is required in elderly patients (see Section 5.1 Pharmacodynamic Properties; Section 5.2 Pharmacokinetic Properties). Data from phase 2, 3 and post-authorisation studies found no difference in efficacy or safety in elderly patients over 65 years of age compared to younger adults.

Paediatric use.

No difference in efficacy and safety was observed in clinical trials with Allertine in adolescents 12 to 17 years compared to the adult population.
There is currently no data on the use of bilastine in children aged 2 years or under for allergic rhinoconjunctivitis or urticaria. The safety and efficacy of Allertine in children below 12 years has not yet been established.

Effects on laboratory tests.

No data available.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Interaction with food.

Food reduces the oral bioavailability of Allertine by 25% to 30%, although it is not certain if this interaction is clinically significant particularly when food has a low-fat content (see Section 5.1 Pharmacodynamic Properties).

Interactions mediated by transporters or CYP450.

In vitro and in vivo studies have shown that bilastine is a substrate of P-gp and OATP1A2. Bilastine does not appear to be a substrate of the transporter BCRP or renal transporters OCT2, OAT1 and OAT3. Based on in vitro studies, 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.
Bilastine did not induce or inhibit activity of CYP450 isoenzymes in in vitro studies.

Interaction with grapefruit juice.

Concomitant intake of Allertine and grapefruit juice decreased bilastine bioavailability by 30%. This effect may also apply to other fruit juices. The mechanism for this interaction is an inhibition of OATP1A2, an uptake transporter for which bilastine is a substrate. Medicinal products that are substrates or inhibitors of OATP1A2, such as ritonavir or rifampicin, may likewise have the potential to decrease plasma concentrations of bilastine.

Interaction with ketoconazole or erythromycin.

Concomitant intake with ketoconazole or erythromycin increased bilastine AUC 2-fold and Cmax 2-3 fold, but these changes do not appear to affect the safety profile of bilastine and ketoconazole or erythromycin, respectively. These changes can be explained by interaction with intestinal efflux transporters since bilastine is a substrate for P-gp and is not metabolised (see Section 5.2 Pharmacokinetic Properties).
Other medicinal products that are substrates or inhibitors of P-gp, such as cyclosporine, may likewise have the potential to increase plasma concentrations of bilastine.
Importantly, no clinically relevant prolongation of the QTc interval or any other cardiovascular effect has been observed in interaction studies with ketoconazole and erythromycin, or when repeat doses of bilastine 200 mg daily (i.e. 10 times the therapeutic dose) are taken.

Interaction with diltiazem.

Concomitant intake of Allertine and diltiazem 60 mg increased Cmax of bilastine by 50%, but it does not appear to affect the safety profile of Allertine. This effect can be explained by interaction with intestinal efflux transporters (see Section 5.2 Pharmacokinetic Properties).

Interaction with lorazepam.

Concomitant intake of Allertine and lorazepam 3 mg for 8 days did not potentiate the CNS depressant effects of lorazepam.

Interaction with alcohol.

No differences were observed in psychomotor performance after intake of alcohol with either Allertine or placebo.

Paediatric population.

While interaction studies were performed in adults, similar effects are expected in adolescents 12 to 17 years of age.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

There are limited clinical data available. In a fertility study in rats, bilastine administered orally up to 1000 mg/kg/day did not induce any effect on female or male reproductive organs. Mating, fertility and pregnancy indices were not affected. A reduction in sperm motility and abnormal sperm morphology were observed in dogs treated with bilastine for 52 weeks with oral doses of 800 mg/kg/day (approximately 380 times the clinical exposure based on AUC), with no effects at 125 mg/kg/day (approximately 130 times the clinical exposure based on AUC).
(Category B3)
There are limited data available on the use of bilastine in pregnant women.
Bilastine was studied for effects on embryofetal development in pregnant rats and rabbits given oral doses of 75, 275 and 1000 mg/kg/day and 30, 110 and 400 mg/kg/day respectively, during organogenesis. In rabbits, an increased incidence of skeletal variations (incomplete ossification of cranial bones, sternebrae and limbs) were observed at a maternotoxic dose of 400 mg/kg/day (approximately 250 times the clinical exposure based on AUC), with no effects on embryofetal development at 110 mg/kg/day (approximately 40 times the clinical exposure based on AUC). Bilastine had no effect on pre- and postnatal development of rats treated with oral doses up to 1000 mg/kg/day. As a precautionary measure, it is preferable to avoid the use of Allertine during pregnancy.
 The excretion of bilastine in milk has not been studied in humans. Available pharmacokinetic data in rats administered a single oral dose (20 mg/kg) has identified excretion of bilastine in milk. Concentrations of bilastine in milk were about half of those in maternal plasma. The relevance of those results for humans is unknown.
A decision on whether to use Allertine should be made taking into account the benefit of breast-feeding to the child and the benefit of Allertine therapy to the mother.

4.7 Effects on Ability to Drive and Use Machines

The CNS safety profile and incidence of somnolence of Allertine at the recommended dose was similar to placebo in clinical trials. Higher doses of bilastine up to 40 mg once daily did not affect psychomotor performance in clinical trials or driving performance in a standard driving test.
Although Allertine is no more likely than placebo to cause sedation and/or decreased mental alertness, individual response should be determined before driving or using machines.

4.8 Adverse Effects (Undesirable Effects)

Summary of safety profile.

The incidence of adverse events in patients suffering from allergic rhinoconjunctivitis or chronic idiopathic urticaria treated with Allertine in clinical trials was comparable with the incidence in patients receiving placebo (12.7% versus 12.8%).
Phase 2 and 3 clinical trials performed during the clinical development included 2599 patients treated with single or multiple doses of bilastine, up to 40 mg. Of these trials, double-blind multiple-dose trials included 1358 patients who received 20 mg (Allertine), 1362 who received placebo, and 1093 who received active control. Adverse events most commonly reported for Allertine were headache, somnolence and abdominal pain (see Table 1). These adverse events occurred with a frequency comparable to that for placebo.

Tabulated summary of adverse events.

Adverse events with a frequency of very common (≥ 1/10) and common (≥ 1/100 to < 1/10) related to Allertine during the clinical development in double-blind multiple-dose phase 2 and 3 studies (n = 1358) are tabulated in Table 1. Adverse events with a frequency less than 1% (< 1/100) have not been included in Table 1.
Other adverse reactions at least possibly related to Allertine and reported at a frequency of uncommon (≥ 1/1,000 to < 1/100) during the clinical development include:

Infections and infestations.

Oral herpes.

Metabolism and nutrition disorders.

Increased appetite.

Psychiatric disorders.

Anxiety, insomnia.

Ear and labyrinth disorders.

Tinnitus, vertigo.

Cardiac disorders.

Right bundle branch block, sinus arrhythmia, electrocardiogram QT prolonged, other ECG abnormalities.

Respiratory, thoracic and mediastinal disorders.

Dyspnoea, nasal discomfort, nasal dryness.

Gastrointestinal disorders.

Upper abdominal pain, nausea, stomach discomfort, dry mouth, dyspepsia, gastritis.

Skin and subcutaneous tissue disorders.

Pruritus.

General disorders and administration site conditions.

Thirst, improved pre-existing condition, pyrexia, asthenia.

Investigations.

Increased gamma-glutamyltransferase, alanine aminotransferase increased, aspartate aminotransferase increased, blood creatinine increased, blood triglycerides increased, increased weight.
Although ECG abnormalities and other cardiac disorders were reported during clinical trials of bilastine, the incidences were not significantly different from those reported when taking placebo (also see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions; Section 4.9 Overdose).

Adolescent population.

During the clinical development of Allertine the frequency, type and severity of adverse reactions in adolescents (12 years to 17 years) were the same as seen in adults. The safety information collected in this population (adolescents) during post-marketing surveillance has confirmed clinical trial findings.

Post-marketing experience.

Information collected during post-marketing surveillance confirmed the Allertine safety profile observed during clinical development.
Palpitations, tachycardia, hypersensitivity reactions (such as anaphylaxis, angioedema, dyspnoea, rash, localised oedema/local swelling, and erythema) and vomiting have been observed during the Allertine post-marketing period.

Reporting suspected adverse effects.

Reporting 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 are asked to report any suspected adverse reactions at www.tga.gov.au/reporting-problems.

4.9 Overdose

For information on the management of overdose, contact the Poison Information Centre on 13 11 26 (Australia).
Information regarding acute overdose of bilastine is based on experience from clinical trials conducted during the development and post-marketing surveillance. In clinical trials, after administration of bilastine at doses 10 to 11 times the therapeutic dose (220 mg as single dose or 200 mg/day for 7 days) to healthy volunteers, frequency of treatment emergent adverse events was two times higher than with placebo, with dizziness, headache and nausea most frequently reported. No serious adverse events and no significant prolongation in the QTc interval were reported.
Critical evaluation of bilastine's multiple dose (100 mg x 4 days) effect on ventricular repolarization by a "thorough QT/QTc cross-over study" involving 30 healthy volunteers did not show significant QTc prolongation.
There is no known specific antidote to bilastine. In the event of overdose, symptomatic and supportive treatment is recommended.

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Bilastine is a non-sedating, long-acting histamine antagonist with selective peripheral H1 receptor antagonist affinity and no affinity for muscarinic receptors. Single doses of Allertine demonstrated sustained inhibition of histamine-induced wheal and flare skin reactions for 24 hours. Duration of activity in AR as measured by efficacy at 22-26 hours post-dose was at least 26 hours for Allertine. This end of the dosing period efficacy was also significantly greater for Allertine than for the active comparator fexofenadine (p=0.0012). Allertine also demonstrated a fast 1 hour onset of action equivalent to other non-sedating antihistamines (cetirizine, fexofenadine).

Clinical trials.

Allergic rhinoconjunctivitis (SAR and PAR).

In clinical trials with adults and adolescents (12-17 years) with AR (SAR and PAR), Allertine 20 mg once daily for 14-28 days demonstrated effective relief of nasal (sneezing, nasal discharge, nasal itching and nasal congestion) and non-nasal symptoms (ocular redness and tearing ± itching of ears, palate and/or eyes) symptoms. Bilastine effectively controlled symptoms for 24 hours. The primary efficacy measurement was mean reduction in total symptom scores (TSS), with mean reductions in sum of nasal symptom scores (NSS) and/or sum of non-nasal symptom scores (NNSS) included as secondary measures. Given SAR and PAR are considered pharmacodynamically comparable conditions that differ principally in symptom duration with many PAR patients having concomitant SAR, efficacy and safety data are considered for AR as a whole.
In study #1003, Allertine 20 mg once daily was compared to the active comparator desloratadine 5 mg once daily and placebo in 720 SAR patients for 14 days. Allertine had comparable efficacy to desloratadine from day 1, with mean reductions in TSS significantly greater than that for placebo (p < 0.001) over the study period. In addition, the percentage reduction of NSS (p=0.001) and NNSS (p=0.003) from baseline to day 14 was significantly greater with Allertine compared to placebo, supporting the efficacy of bilastine for the range of AR symptoms. No differences were observed when comparing the efficacy of Allertine with the active comparator. Allertine also demonstrated an excellent safety profile with an adverse events profile equivalent to that for placebo (28.3% vs 25.3%, p=0.199).
In study #1704, 683 SAR patients were treated with Allertine 20 mg, placebo or the active comparator cetirizine 10 mg, once daily for 14 days. Mean reductions in TSS at 14 days were significantly greater with Allertine and cetirizine compared to placebo (p < 0.001). Allertine also significantly decreased both NSS (p < 0.001) and NNSS (p < 0.001) compared to placebo. After 14 treatment days, the reported mean TSS at the end of the dose period (prior to the next morning dose) was compared to that measured the prior evening. As no difference in TSS was observed between these time points for Allertine (p=0.2032) while a significant difference was observed for placebo (p < 0.0001), there is strong evidence of Allertine's sustained 24-hour efficacy and duration of action. In addition, Allertine demonstrated a favourable safety profile, with an incidence of adverse events similar to that of placebo (14.5% vs 19.5% respectively), and superior adverse events profile to that of cetirizine 10 mg (overall incidence 24.7% vs 36.0% respectively, p=0.031).
In study #1503, 650 patients with PAR were randomised to Allertine 20 mg, the active comparator cetirizine 10 mg or placebo, once daily for 28 days. Due to regional differences in the response, no significant differences in mean reduction of TSS across treatment groups were observed. However, when the data was reanalysed by excluding a region with very high placebo response, both Allertine and cetirizine significantly reduced TSS compared to placebo over the 28-day treatment period (p=0.039). The 28-day double-blind phase was followed by an additional 12 month open-label safety extension in 513 patients receiving Allertine. A trend in mean reduction of NSS and NNSS were observed throughout the 12 months follow-up, although there were no comparison groups. There were no significant differences in overall adverse events incidence with Allertine compared to cetirizine or placebo. No serious adverse reactions were reported with Allertine.

Urticaria.

In clinical study #2006, 522 adults suffering from Chronic Idiopathic Urticaria (CIU) with a documented history of symptoms for at least 6 weeks were treated with either Allertine 20 mg, the active comparator levocetirizine 5 mg or placebo once daily for 28 days. Efficacy was defined as mean reduction in TSS (which is comprised of number and size of wheals as well as itching intensity and discomfort due to urticaria) at 4 weeks. Both Allertine and levocetirizine significantly reduced TSS compared to placebo (p < 0.001), with similar secondary quality of life outcomes reported for both active treatments. Results obtained for the secondary efficacy variables were consistent with those reported for the primary efficacy variable and in general, efficacy of both Allertine and levocetirizine was superior to placebo with high statistical significance. Similarly, Allertine demonstrated a favourable safety profile, with similar incidence of adverse events to that for levocetirizine (overall incidence 35.8% vs 37.0% respectively, p=0.319).

5.2 Pharmacokinetic Properties

Absorption.

Bilastine is rapidly absorbed after oral administration with a time to maximum plasma concentration of around 1.3 hours. No accumulation has been observed. Mean bilastine oral bioavailability is 61%.
The effect of food on bioavailability of bilastine was investigated in two phase 1 studies. The first assessed the influence of a high fat meal on bioavailability compared to a fasted state. The second study compared bioavailability after a high-fat meal, a standard (low-fat) meal and in a fasted state. It appears that high-fat and standard low-fat meals significantly reduce the oral bioavailability of bilastine by 30% and 25% respectively (see Section 4.2 Dose and Method of Administration; Section 4.5 Interactions with Other Medicines and Other Forms of Interactions, Interaction with grapefruit juice). Nevertheless, as the low-fat meal studied included orange juice and the apparent bioavailability reduction with low-fat meals and with juices is similar, it is possible that low-fat meal interactions are not clinically significant.

Distribution.

At therapeutic doses bilastine is 84-90% bound to plasma proteins.

Metabolism.

Metabolism of bilastine was limited in animal species and humans. Minimal to no metabolism of bilastine by animal or human microsomes or hepatocytes. No metabolism was detected in Caco-2 cells, with and without induction of CYP1A1 and CYP3A4, indicating the absence of intestinal metabolism.

Excretion.

In a mass balance study performed in healthy volunteers, after administration of a single dose of 20 mg 14C-bilastine, almost 95% of the administered dose was recovered in urine (28.3%) and faeces (66.5%) as unchanged bilastine, confirming that bilastine is not significantly metabolised in humans. The mean elimination half-life in healthy volunteers was 14.5 h.

Linearity.

Bilastine presents linear pharmacokinetics in the dose range studied (5 to 220 mg), with a low inter-individual variability.

Patients with renal impairment.

In a study in subjects with renal impairment the mean (SD) AUC0-∞ increased from 737.4 (± 260.8) nanogram.hr/mL in subjects without impairment (GFR: > 80 mL/min/1.73 m2) to: 967.4 (± 140.2) nanogram.hr/mL in subjects with mild impairment (GFR: 50 - 80 mL/min/1.73 m2), 1384.2 (± 263.2) nanogram.hr/mL in subjects with moderate impairment (GFR: 30 - < 50 mL/min/1.73 m2), and 1708.5 (± 699.0) nanogram.hr/mL in subjects with severe impairment (GFR: < 30 mL/min/1.73 m2). 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 48-72 h in all subjects. These pharmacokinetic changes are not expected to have a clinically relevant influence on the safety of bilastine, since bilastine plasma levels in patients with renal impairment are still within the safety range of bilastine.

Patients with hepatic impairment.

There are no pharmacokinetic data in subjects with hepatic impairment. Bilastine is not metabolised in humans. Since the results of the renal impairment study indicate renal elimination to be a major contributor in the elimination, biliary excretion is expected to be only marginally involved in the elimination of bilastine. Changes in liver function are not expected to have a clinically relevant influence on bilastine pharmacokinetics.

Elderly patients.

There are limited pharmacokinetic data for subjects older than 65 years which shows no statistically significant differences in pharmacokinetics compared to adults aged between 18 and 35 years.

Paediatric population.

No pharmacokinetic data are available in adolescents (12 years to 17 years) as the extrapolation from adult data was deemed appropriate for this product.

5.3 Preclinical Safety Data

Genotoxicity.

Bilastine was not mutagenic in a bacterial reverse mutation assay (Ames test) using S. typhimurium, or clastogenic in human lymphocytes in vitro. Systemic exposure to bilastine did not induce chromosomal aberrations in an in vivo micronucleus assay conducted in mice.

Carcinogenicity.

Bilastine was not carcinogenic to mice or rats when administered orally for 2-years in the diet at dose levels up to 2000 mg/kg/day in mice and 1200 mg/kg/day in rats (greater than 100 times the clinical exposure based on AUC).

6 Pharmaceutical Particulars

6.1 List of Excipients

Microcrystalline cellulose, sodium starch glycollate type A, colloidal anhydrous silica, magnesium stearate.

6.2 Incompatibilities

Not applicable.

6.3 Shelf Life

In Australia, information on the shelf life can be found on the public summary of the Australian Register of Therapeutic Goods (ARTG). The expiry date can be found on the packaging.

6.4 Special Precautions for Storage

Store below 30°C.

6.5 Nature and Contents of Container

Allertine is packaged in PVC-PVAC-Al blister packs containing 4, 10, 20, 30, 40, 50, 60, 70, 80, 90 or 100 tablets. Not all pack sizes may be marketed.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of by taking to your local pharmacy.

6.7 Physicochemical Properties

Chemical structure.


Chemical name: 2-[4-(2-(4-(1-(2-ethoxyethyl)-1H-benzimidazol-2-yl)piperidin-1-yl) ethyl) phenyl]-2-methylpropionic acid or p-[2-[4-[1-(2-ethoxyethyl)-2-benzimidazolyl] piperidino] ethyl]-α-methylhydratropic acid.
Molecular formula: C28H37N3O3.
Molecular weight: 463.61 g/mol.
AAN: Bilastine.

CAS number.

202189-78-4.

7 Medicine Schedule (Poisons Standard)

Schedule 2 (Pharmacy Medicine).

Summary Table of Changes