1. Generic Name

Bilastine Tablets

2. Qualitative & Quantitative Composition

BILAFAV

Each uncoated tablet contains:

Bilastine ……………………………20 mg

Excipients…………………………. q.s.

3. Dosage Form & Strength

Tablet for Oral use

20 mg Tablet

4. Clinical Particulars

4.1 Therapeutic Indications

Bilastine tablet is indicated for the treatment of seasonal allergic rhinitis and urticaria in adults and adolescents (12 years of age and over).

4.2 Posology & Method of Administration12 Years of Age and Over

One tablet (20 mg) once daily for the relief of symptoms of urticaria and allergic rhinitis. The tablet should be taken by oral route one hour before or two hours after intake of food or fruit juice.

Duration of Treatment

For urticaria the duration of treatment depends on the type, duration and course of the complaints.

For allergic rhinitis, the treatment should be limited to the period of exposure to allergens. For seasonal allergic rhinitis treatment, could be discontinued after the symptoms have resolved and reinitiated upon their reappearance. In perennial allergic rhinitis, continued treatment may be proposed to the patients during the allergen exposure periods.

Method of Administration

The tablet is to be swallowed with water. It is recommended to take the daily dose in one single intake.

4.3 Contraindication

Hypersensitivity to the active substance or to any of the excipients

4.4 Special warnings & Precaution for Use

Efficacy and safety of bilastine in children under 12 years of age have not been established.

In patients with moderate or severe renal impairment co-administration of bilastine with P-glycoprotein inhibitors, such as e.g., ketoconazole, erythromycin, cyclosporine, ritonavir or diltiazem, may increase plasmatic levels of bilastine and therefore increase the risk of adverse effects of bilastine. Therefore, co-administration of bilastine and P-glycoprotein inhibitors should be avoided in patients with moderate or severe renal impairment.

4.5 Drug Interactions

Interaction with Ketoconazole or Erythromycin

Concomitant intake of Bilastine and ketoconazole or erythromycin increased Bilastine AUC 2-fold and C_max 2-3-fold. These changes can be explained by interaction with intestinal efflux transporters, since Bilastine is substrate for P-gp and not metabolized. 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 likewise have the potential to increase plasma concentrations of bilastine.

Interaction with Diltiazem

Concomitant intake of Bilastine 20 mg and Diltiazem 60 mg increased C_max of Bilastine by 50%. This effect can be explained by interaction with intestinal efflux transporters, and does not appear to affect the safety profile of bilastine.

Interaction with Lorazepam

Concomitant intake of Bilastine 20 mg and lorazepam 3 mg for 8 days did not potentiate the depressant CNS effects of lorazepam.

Interaction with Alcohol

The psychomotor performance after concomitant intake of alcohol and 20 mg Bilastine was similar to that observed after intake of alcohol and placebo.

Interaction with Grapefruit Juice

Concomitant intake of Bilastine 20 mg and grapefruit juice decreased Bilastine bioavailability by 30%. This effect may also apply to other fruit juices. The degree of bioavailability decrease may vary between producers and fruits. 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 Food

Food significantly reduces the oral bioavailability of bilastine by 30%.

4.6 Use in Special Population

Pregnancy

There are no adequate and well controlled studies on pregnancy outcome with bilastine in pregnant women.

Studies in animals do not indicate direct or indirect harmful effects with respect to reproductive toxicity, parturition or postnatal development. As a precautionary measure, it is preferable to avoid the use of bilastine during pregnancy.

There are no or limited amount of clinical data on fertility. A study in rats did not indicate any negative effect on fertility.

Lactation

The excretion of bilastine in milk has not been studied in humans. Available pharmacokinetic data in animals have shown excretion of bilastine in milk.

A decision on whether to discontinue/abstain from bilastine therapy must be made considering the benefit of breast-feeding for the child and the benefit of bilastine therapy for the mother.

Paediatric Population

Drug interaction studies have only been performed in adults. Extent of interaction with other medicinal products and other forms of interaction is expected to be similar in paediatric population from 12 to 17 years of age.

Children under 12 Years

The safety and efficacy of bilastine in children under 12 years of age have not yet been established.

Geriatrics

No dosage adjustments are required in elderly patients.

Renal Impairment

No dosage adjustment is required in patients with renal impairment.

Hepatic Impairment

There is no clinical experience in patients with hepatic impairment. Since bilastine is not metabolized and renal clearance is its major elimination route, hepatic impairment is not expected to increase systemic exposure above the safety margin. Therefore, no dosage adjustment is required in patients with hepatic impairment.

4.7 Effects on Ability to Drive and Use Machines

A study performed to assess the effects of bilastine on the ability to drive demonstrated that treatment with 20 mg did not affect the driving performance. However, patients should be informed that very rarely some people experience drowsiness, which may affect their ability to drive or use machines

4.8 Undesirable Effects

The below adverse effects were determined based on data from the Bilastine clinical studies and frequencies are defined as: very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1,000 to < 1/100), rare (≥ 1/10,000 to < 1/1,000), very rare (<1/10,000) and not known (cannot be estimated from the available data).

Infections and Infestations

Uncommon: Oral herpes

Metabolism and Nutrition Disorders

Uncommon: Increased appetite

Psychiatric Disorders

Uncommon: Anxiety, insomnia

Ear and Labyrinth Disorders

Uncommon: Tinnitus, vertigo

Cardiac Disorders

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

Nervous System Disorders

Common: Somnolence, headache

Uncommon: Dizziness

Respiratory, Thoracic and Mediastinal Disorders

Uncommon: Dyspnea, nasal discomfort, nasal dryness

Gastrointestinal Disorders

Uncommon: Upper abdominal pain, nausea, stomach discomfort, diarrhea, dry mouth, dyspepsia and gastritis

Skin and Subcutaneous Tissue Disorders

Uncommon: Pruritus

General Disorders and Administration Site Conditions

Uncommon: Fatigue, thirst, improved pre-existing condition, pyrexia and asthenia.

Investigations

Uncommon: Increased gamma-glutamyltranferase, alanine aminotransferase increased, aspartate aminotransferase increased, blood creatinine increased, blood triglycerides increased and increased weight.

Frequency not known (cannot be estimated from the available data): Palpitations, tachycardia and hypersensitivity reactions (such as anaphylaxis, angioedema, dyspnoea, rash, localised oedema/local swelling, and erythema) have been observed during the post-marketing period.

If you experience any side-effects, talk to your doctor or pharmacist or write to drugsafety@cipla.com. You can also report side effects directly via the national pharmacovigilance program of India by calling on 18002677779 (Cipla Number) or you can report to PvPI on 1800 180 3024.

By reporting the side effects, you can help provide more information on the safety of this product.

4.9 Overdose

Information regarding acute overdose is limited to experience from clinical trials conducted during the development of bilastine. After administration of bilastine at doses 10 to 11 times the therapeutic dose 220 mg (single dose); or 200 mg/day for 7 days) to healthy volunteer’s frequency of treatment emergent adverse events was two times higher than with placebo. The adverse reactions most frequently reported were dizziness, headache and nausea. No serious adverse events and no significant prolongation in the QTc interval were reported. Critical evaluation of bilastine 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. In the event of overdose symptomatic and supportive treatment is recommended.

There is no known specific antidote to Bilastine.

5. Pharmacological Properties

5.1 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.

5.2 Pharmacodynamics Properties

Bilastine is a second generation H₁-antihistamine, indicated for the treatment of allergic rhinitis and chronic urticaria. Bilastine, or 2- piperidin-1-yl] ethyl] phenyl]-2-methylpropionic acid is a novel molecule with a molecular weight of 463.6 daltons and a chemical structure is 

It belongs to piperidine derivatives and is not structurally derived from any other currently available antihistamines. It exerts a potent and specific H1‑antihistamine activity. It has high specificity for H1‑receptors. It is a non-sedating, long-acting histamine antagonist with selective peripheral H₁ receptor antagonist affinity and no affinity for muscarinic receptors. The affinity for the H1 receptor is 3 and 6 times higher than for cetirizine and fexofenadine. Additional in vitro trials demonstrated that bilastine had no significant antagonist activity at a diverse range of other receptors: H2, H3, and H4, 5-HT2A, bradykinin B1, leukotriene D4, N-type voltage-dependent calcium receptors, α1- and β2-adrenoceptors, and M1–M5 muscarinic receptors

Bilastine inhibited histamine-induced wheal and flare skin reactions for 24 hours following single doses

5.3 Pharmacokinetic properties

Absorption

Bilastine is rapidly absorbed after oral administration with a time to maximum plasma concentration of around 1.3 hours. No accumulation was observed. The mean value of Bilastine oral bioavailability is 61%.

Distribution

In vitro and in vivo studies have shown that bilastine is a substrate of P-gp and OATP. Bilastine does not appear to be a substrate of the transporter BCRP (Breast cancer resistance proteins) 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, since only mild inhibition was detected for P-gp, OATP2B1 and OCT1, with an estimated IC₅₀ ≥ 300 μM, much higher than the calculated clinical plasma C_max and therefore these interactions will not be clinically relevant. However, based on these results inhibition by bilastine of transporters present in the intestinal mucosa, e.g. P-gp, cannot be excluded. At therapeutic doses bilastine is 84-90% bound to plasma proteins.

Metabolism

Bilastine did not induce or inhibit activity of CYP₄₅₀ isoenzymes in in vitro studies.

Elimination

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 metabolized in humans. The mean elimination half-life calculated in healthy volunteers was 14.5 h.

Linearity

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

6. Non-Clinical Properties

6.1 Animal toxicology or pharmacology

Non-clinical data with bilastine reveal no special hazard for humans based on conventional studies of safety pharmacology, repeated dose toxicity, genotoxicity and carcinogenic potential.

In reproduction toxicity studies effects of bilastine on the foetus (pre-and post-implantation loss in rats and incomplete ossification of cranial bones, sternebrae and limbs in rabbits) were only observed at maternal toxic doses. The exposure levels at the NOAELs are sufficiently in excess (> 30-fold) to the human exposure at the recommended therapeutic dose.

In a lactation study, bilastine was identified in the milk of nursing rats administered a single oral dose (20 mg/kg). Concentrations of bilastine in milk were about half of those in maternal plasma. The relevance of those results for humans is unknown.

In a fertility study in rats, bilastine administered orally up to 1000 mg/kg/day did not induce any effect on female and male reproductive organs. Mating, fertility and pregnancy indices were not affected.

As seen in a distribution study in rats with determination of drug concentrations by autoradiography, bilastine does not accumulate in the CNS.

7. Pharmaceutical Particulars

7.1 Incompatibilities

Not applicable.

7.2 Shelf Life

See on pack.

7.3 Packaging Information

Pack of 10 tablets

7.4 Storage & Handling Instruction

Store in a temperature not exceeding 30°C

Protect from light and moisture.

Keep out of the reach of children.

8. Patient Counselling Information

8.1 What is BILAFAV and what it is used for?

BILAFAV contains the active substance bilastine which is an antihistamine. Bilastine is used to relieve the symptoms of hay fever (sneezing, itchy, runny, blocked-up nose and red and watery eyes) and other forms of allergic rhinitis. It may also be used to treat itchy skin rashes (hives or urticaria).

8.2 What you need to know before you take BILAFAV 20 mg tablets?

Do not take BILAFAV:

If you are allergic to bilastine or any of the other ingredients of this medicine.

Warnings and Precautions

Talk to your doctor before using BILAFAV, if you have moderate or severe renal impairment and in addition you are taking other medicines (see “Other medicines and BILAFAV – Drug Interactions”).

Children

Do not give this medicine to children under 12 years of age

Do not exceed the recommended dose. If symptoms persist, consult your doctor.

Other medicines and BILAFAV

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines, including medicines obtained without a prescription. Please discuss with your doctor if you are taking any of the following medicines:

• Ketoconazole (an antifungal medicine)
• Erythromycin (an antibiotic)
• Diltiazem (to treat angina)
• Cyclosporine (to reduce the activity of your immune system, thus avoiding transplant rejection or reducing disease activity in autoimmune and allergic disorders, such as psoriasis, atopic dermatitis or rheumatoid arthritis)
• Ritonavir (to treat AIDS)
• Rifampicin (an antibiotic)

BILAFAV with food, drink and alcohol

These tablets should not be taken with food or with grapefruit juice or other fruit juices, as this will decrease the effect of bilastine. To avoid this, you can:

 take the tablet and wait for one hour before taking food or fruit juice or

• if you have taken food or fruit juice, wait for two hours before taking the tablet.

Bilastine, at the recommended dose (20 mg), does not increase the drowsiness produced by alcohol.

Pregnancy, Breast-feeding and Fertility

There are no or limited amount of data from the use of bilastine in pregnant women and during breast-feeding and on the effects on fertility. If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor for advice before taking this medicine.  Ask your doctor for advice before taking any medicine.

Driving and Using Machines

A study performed to establish the effect of bilastine on the ability to drive demonstrated that treatment with 20 mg bilastine does not affect the driving performance. However very rarely some people experience drowsiness, which may affect their ability to drive or use machines.

8.3 How should I take BILAFAV?

Always take this medicine exactly as your doctor have told you. Check with your doctor if you are not sure. The recommended dose in adults, including the elderly and adolescents aged 12 years and over, is 1 tablet (20 mg) a day.

• The tablet is for oral use.
• The tablet must be taken on an empty stomach, for example in the morning prior to breakfast. You must not eat for 1 hour after taking bilastine
• Swallow your tablet with a glass of water.
• The score line is only here to help you break the tablet if you have difficulty swallowing it whole

Regarding the duration of treatment, your physician will determine the type of disease you are suffering from and will determine for how long you should take BILAFAV

Use in children

Do not give this medicine to children under 12 years of age.

If you take more BILAFAV than you should

If you, or anyone else, have taken too many BILAFAV tablets, contact your doctor immediately.

If you forget to take BILAFAV

Do not take a double dose to make up for a forgotten dose. If you forget to take your dose on time, take it as soon as possible, and then go back to your regular dosing schedule. If you have any further questions on the use of this medicine, ask your doctor.

8.4 What are the possible side effects?

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Side effects that may be experienced are:

Common: may affect up to 1 in 10 people

• headache
• drowsiness

Uncommon: may affect up to 1 in 100 people

• Abnormal ECG heart tracing
• blood tests which show changes in the way the liver is working
• dizziness
• stomach pain
• tiredness
• increased appetite
• irregular heartbeat
• increased weight
• nausea (the feeling of being sick)
• anxiety
• dry or uncomfortable nose
• belly pain
• diarrhoea
• gastritis (inflammation of the stomach wall)
• vertigo (a feeling of dizziness or spinning)
• feeling of weakness
• thirst
• dyspnoea (difficulty in breathing)
• dry mouth
• indigestion
• itching
• cold sores (oral herpes)
• fever
• tinnitus (ringing in the ears)
• difficulty in sleeping
• blood tests which show changes in the way kidney is working
• blood fats increased

Frequency not known: cannot be estimated from the available data

• palpitations (feeling your heart beat)

• tachycardia (fast heart beat)
• allergic reactions the signs of which may include difficulty in breathing, dizziness, collapsing or losing consciousness, swelling of your face, lips, tongue or throat, and/or swelling and redness of the skin. If you notice any of these serious side effects, stop taking the medicine and seek urgent medical advice straight away.
• vomiting

8.5 How should I store BILAFAV?

• Keep this medicine out of the sight and reach of children.
• Do not use this medicine after the expiry date which is stated on the carton and the blisters after EXP. The expiry date refers to the last day of that month.
• This medicine does not require any special storage conditions. However, store in a temperature not exceeding 30°C. Protect from light and moisture.
• Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help to protect the environment.

9. Details of Manufacturers

Marketed by:

CIPLA Ltd.

Cipla House, Peninsula Business Park,

Ganpatrao Kadam Marg, Lower Parel

Mumbai-400 013 INDIA

 

Manufactured by:

M/s Hetero Labs Ltd, Unit III Baddi

Details of License Number with Date

MNB/06/328

MF-ND-21/2019 

DATE: 18/3/2019

Last updated: May 2019

Last reviewed: May 2019