Consumer medicine information

LIVOSTIN Eye Drops and Nasal Spray

Levocabastine

BRAND INFORMATION

Brand name

Livostin Nasal Spray

Active ingredient

Levocabastine

Schedule

S2

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using LIVOSTIN Eye Drops and Nasal Spray.

What is in this leaflet

This leaflet answers some common questions about LIVOSTIN. It does not contain all the available information. It does not take the place of talking to your doctor or pharmacist.

All medicines have risks and benefits. Your doctor has weighed the risks of you using LIVOSTIN against the benefits this medicine is expected to have for you.

If you have any concerns about using LIVOSTIN, ask your doctor or pharmacist.

Keep this leaflet with your medicine. You may need to read it again.

What LIVOSTIN is used for

LIVOSTIN eye drops are used to relieve watery, itchy, swollen eyelids or red eyes caused by allergies to grass, pollen, moulds, dust or other substances.

LIVOSTIN nasal spray is used to relieve sneezing, runny nose or irritation of the nose caused by allergies to grass, pollen, moulds, dust or other substances.

LIVOSTIN contains levocabastine which belongs to a group of medicine called antihistamines. It provides rapid and long lasting relief for symptoms of allergy. It works by blocking the effect of histamine which is a chemical released by the body that causes most of the symptoms.

Your doctor may have prescribed LIVOSTIN for another use. Ask your doctor if you have any questions about why this medicine has been prescribed for you.

Before you use LIVOSTIN

When you must not use it

Do not use LIVOSTIN if

  • you have an allergy to LIVOSTIN or any of the ingredients. See Product description at the end of this leaflet for a list of ingredients.
  • if the packaging is torn or shows signs of tampering
  • beyond the expiry date (month and year) printed on the pack.

Before you start to use it

You must tell your doctor if

  • you are pregnant or planning to become pregnant.
  • you are breast feeding or wish to breast feed.
  • you have or have ever had kidney disease.
  • you wear soft contact lenses. As with all eye drops containing benzalkonium chloride, you are advised not to wear soft contact lenses while being treated with LIVOSTIN eye drops.

There is limited experience of use of LIVOSTIN in children under 6 years of age. Ask your doctor for further information if you have any questions on the use of this medicine in children.

If you have not told your doctor or pharmacist about any of the above, tell them before you start using LIVOSTIN.

Your doctor will advise you whether or not to use LIVOSTIN or if you need to adjust the dose or adapt your treatment.

Taking other medicines

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

The decongestant oxymetazoline for example may reduce the absorption of nasal levocabastine.

Effects on driving and operating machinery

  • LIVOSTIN does not usually affect alertness or concentration. However, should you feel drowsy be careful while driving or operating machinery.

Effects of alcohol

  • At the usual dose, LIVOSTIN nasal spray does not usually increase the effect of alcohol.

Using LIVOSTIN

How much to use

Eye drops -
Adults and children 6 years of age and over: the usual dose is 1 drop of LIVOSTIN eye drops in each eye, twice daily. If necessary, the dose may be increased to 1 drop 3 or 4 times daily.

Do not use for more than 8 weeks.

Nasal spray -
Adults and children 6 years of age and over: the usual dose is 2 sprays of LIVOSTIN nasal spray in each nostril, twice daily. If necessary, the dose may be increased to 2 sprays 3 or 4 times daily.

Do not use for more than 8 weeks.

How to use LIVOSTIN eye drops

You may find it easier to put eye drops in your eye while you are sitting or lying down.

  1. Shake the bottle well before removing the cap. To open a new bottle, twist off the plastic protective cap and the seal will break.
  2. Hold the bottle upside down in one hand between your thumb and index finger. Using your other hand, gently pull down your lower eyelid to form a pouch.
  3. Tilt your head back and look up.
  4. Put the tip of the bottle close to your eye. Do not let it touch your eye.
  5. Release one drop onto your eye by gently squeezing the bottle. Close your eye. Do not blink or rub your eye.
  6. While your eye is closed, apply gentle pressure for a few minutes with your fingers to the bridge of your nose to prevent medication from being drained from the eye.
  7. Repeat the above steps for the other eye.
  8. Place the cap on the bottle and close it tightly.

How to use LIVOSTIN nasal spray

Place your index and middle fingers on the white collar of the bottle. Hold the bottle upright by placing your thumb at the bottom of the bottle.

For each new bottle of LIVOSTIN nasal spray, remove the cap and press the white collar of the spray downwards once or twice until a fine spray appears in the air.

  1. Gently blow your nose to clear the nostrils.
  2. Shake the bottle well and remove the cap.
  3. Lean your head slightly forward. Keep one nostril tightly closed. Insert the nozzle into the other nostril.
  4. Press the white collar down to release each spray. Breathe in through the same nostril between each spray.
  5. Repeat steps 3 and 4 for the other nostril.
  6. After use, wipe the nozzle with a tissue and replace the cap.

If you do not understand the instructions provided with this medicine, ask your doctor or pharmacist for help.

If you forget to use it

  • Use your dose as soon as you remember, and then continue to use it as you would normally.
  • If it is almost time for your next dose, skip the dose you missed and use your next dose when you are meant to.
  • Do not use a double dose to make up for the one you missed.

If you have missed more than one dose, or are not sure what to do, check with your doctor or pharmacist.

If you have trouble remembering when to use your medicine, ask your pharmacist for some hints.

If you have used too much (overdose)

Immediately telephone your doctor or the Poisons Information Centre for advice, or go to Accident and Emergency at your nearest hospital.

Do this even if there are no signs of discomfort or poisoning. You may need medical attention.

Poisons Information Centre telephone numbers:

  • Australia: 13 11 26
  • New Zealand: 0800 764 766

Keep these telephone numbers handy.

If, by accident, you use or drink a whole bottle of LIVOSTIN, you may feel drowsy.

In the meantime, the best thing to do is to drink a lot of water.

While you are using LIVOSTIN

Things you must do

  • Always follow your doctor's instructions carefully.
  • Tell your doctor if you become pregnant while using LIVOSTIN.
  • If you are about to start taking a new medicine, tell your doctor and pharmacist that you are using LIVOSTIN.

Things you must not do

  • Do not use LIVOSTIN to treat any other complaint unless your doctor says so.
  • Do not give this medicine to anyone else, even if their symptoms seem similar to yours.

Side effects

All medicines can have side effects. Sometimes they are serious, most of the time they are not. You may need medical treatment if you get some side effects. Do not be alarmed by this list of possible side effects. You may not experience any of them.

Ask your doctor or pharmacist to answer any questions you may have.

Tell your doctor if you experience any of the following:

  • slight irritation to your eyes e.g. eye pain, itching, burning or redness of the eyes, conjunctivitis, swelling of the eye, inflammation of the eyelid, watery eyes
  • congestion of blood in the eye
  • slight irritation to your nose e.g. nasal congestion, nasal discomfort, pain, burning or dryness
  • headache
  • drowsiness
  • nose bleeds
  • blurred vision
  • hives
  • allergic reaction (swelling of the lips, eyelids and tongue, shortness of breath)
  • nausea
  • cough
  • dizziness
  • fatigue
  • throat pain
  • achiness
  • difficulty breathing
  • abnormally fast heartbeats
  • skin irritation
  • hypersensitivity
  • a general feeling of being unwell

Rarely, allergic reactions may occur. Should this happen discuss the matter with your doctor or pharmacist.

Other side effects not listed above may also occur in some people. Tell your doctor if you notice any other effects.

After using LIVOSTIN

Storage

  • Keep LIVOSTIN in a cool, dry place where the temperature stays below 25°C.
  • Do not store LIVOSTIN or any medicines in the bathroom or near a sink. Do not leave medicines in the car or on window sills. Heat and dampness can destroy some medicines.
  • Keep your medicines where young children cannot reach them. A locked cupboard at least one-and-a-half metres (1.5m) above the ground is a good place to store medicines.

Disposal

Discard LIVOSTIN eye drops one month after the date of first opening. If your doctor tells you to stop using LIVOSTIN, or your medicine has passed its expiry date, ask your pharmacist what to do with any medicine which may be left over.

Product description

What it looks like

LIVOSTIN eye drops contains 4 mL of liquid in a 5 mL volume plastic bottle. LIVOSTIN nasal spray contains 10 mL of liquid in a 15 mL volume plastic bottle.

Ingredients

LIVOSTIN

  • contains levocabastine 0.5 milligrams per millilitre.
  • The eye drops also contain propylene glycol, polysorbate 80, sodium phosphate dibasic, sodium phosphate monobasic, hypromellose, water and benzalkonium chloride, disodium edetate as preservatives.
  • The nasal spray also contains propylene glycol, polysorbate 80, sodium phosphate dibasic, sodium phosphate monobasic, hypromellose, water and benzalkonium chloride, disodium edetate as preservatives.

Sponsor

Johnson & Johnson Pacific
45 Jones Street,
Ultimo NSW 2007
AUSTRALIA
and
Auckland,
NEW ZEALAND

For further information call our toll free info lines:
AUS: 1800 029 979
NZ: 0800 446 147

This leaflet was prepared in December 2014.

Published by MIMS June 2016

BRAND INFORMATION

Brand name

Livostin Nasal Spray

Active ingredient

Levocabastine

Schedule

S2

 

1 Name of Medicine

Levocabastine hydrochloride.

2 Qualitative and Quantitative Composition

Livostin Eye Drops.

Active ingredients: levocabastine hydrochloride equivalent to levocabastine 0.5 mg/mL.
Excipients with known effect: benzalkonium chloride and disodium edetate (both 0.15 mg/mL) as preservatives.
Excipients: propylene glycol, polysorbate 80, sodium phosphate dibasic, sodium phosphate monobasic, hypromellose and water as inactive excipients.

Livostin Nasal Spray.

Active ingredients: levocabastine hydrochloride equivalent to levocabastine 0.5 mg/mL.
Excipients with known effect: benzalkonium chloride and disodium edetate (both 0.15 mg/mL) as preservatives.
Excipients: propylene glycol, polysorbate 80, sodium phosphate dibasic, sodium phosphate monobasic, hypromellose and water as inactive excipients.

3 Pharmaceutical Form

Eye drops: a sterile white ophthalmic microsuspension (pH 6-8).
Nasal spray: a white microsuspension (pH 6-8).

4 Clinical Particulars

4.1 Therapeutic Indications

Eye drops.

Symptomatic treatment of seasonal allergic conjunctivitis.

Nasal spray.

Symptomatic treatment of seasonal or perennial allergic rhinitis.

4.2 Dose and Method of Administration

As Livostin eye drops and nasal spray are available as a microsuspension, the bottle should be shaken before each application.

Eye drops.

As with all ophthalmic preparations containing benzalkonium chloride, patients are advised not to wear soft (hydrophilic) contact lenses while under treatment with Livostin eye drops.

Adults and children 6 years of age and over.

The usual dose is one drop of Livostin eye drops per eye, twice daily. If necessary, the dose may be increased to one drop 3 to 4 times daily. The bottle should be well shaken before use. The duration of treatment should be limited to 8 weeks.
Systemic absorption of levocabastine is very low. However, the systemic absorption of drugs from ophthalmic solutions can be minimised by pressure on the tear duct immediately after application.
Livostin eye drops should be used within one month of first opening of the bottle. Patients should be instructed to take appropriate measures to avoid contamination of the container.

Nasal spray.

Adults and children 6 years of age and over.

The usual dose is two sprays of Livostin nasal spray per nostril, twice daily. If necessary, the dose may be increased to two sprays 3 to 4 times daily. The duration of treatment should be limited to 8 weeks.
Patients should be instructed to clear the nasal passages prior to administering the spray and to inhale through the nose during spraying. Before using the pump delivery system for the first time, the pump reservoir should be filled by priming until a fine spray is delivered.

4.3 Contraindications

Hypersensitivity to any of the ingredients.

4.4 Special Warnings and Precautions for Use

Mental alertness.

In clinical trials there was no significant difference in the incidence of slowed patient reactions with Livostin compared to placebo and active comparator drugs. Livostin, therefore, would not be expected to interfere with the ability to drive a motor vehicle or operate machinery. Should drowsiness occur, caution is advised.

Renal impairment.

After a single oral dose of 0.5 mg levocabastine in solution, the terminal half-life of levocabastine in moderate to severe renal impairment (creatinine clearance 10 - 50 mL/min) increased from 36 hours to 95 hours. Overall exposure to levocabastine based on AUC was increased by 56%.

Nasal spray.

Limited data are available on the use of oral levocabastine. Caution should be exercised when administering Livostin nasal spray to patients with renal impairment (see Section 5.2 Pharmacokinetic Properties).

Eye drop.

Given the extremely low plasma concentrations after ocular application, a dose adjustment is unlikely to be required in patients with renal impairment receiving levocabastine eye drops. However, dose reduction should be considered in patients with renal disease during prolonged treatment with levocabastine nasal spray. As hepatic metabolism of levocabastine is negligible, dose adjustments in patients with impaired hepatic function should not be necessary.

Use in the elderly.

In the elderly, after multiple nasal administrations of 0.4 mg levocabastine for 14 days, the terminal half-life of levocabastine was increased by 15% and the peak plasma level was increased by 26%.

Paediatric use.

No data available on use in children less than six years of age.

Effects on laboratory tests.

No data available.

4.5 Interactions with Other Medicines and Other Forms of Interactions

No interactions have been seen with Livostin eye drops. With Livostin nasal spray there were no reports of interaction with alcohol in clinical trials. In psychomotor performance studies there was no significant potentiation of the effects of alcohol on performance and subjective test measures with Livostin nasal spray used at normal doses.

Pharmacokinetic interactions.

The decongestant oxymetazoline may transiently reduce the absorption of nasal levocabastine.
Co-administration of the CYP3A4 inhibitors ketoconazole (200 mg) and erythromycin (333 mg) as a single dose had no impact on the pharmacokinetics of intranasal levocabastine.
Intranasal levocabastine did not change the pharmacokinetics of loratadine.

4.6 Fertility, Pregnancy and Lactation

(Category B3)
In pregnant rats, levocabastine readily crossed the placental barrier and was distributed extensively in foetal tissues. Reproductive studies in mice and rats showed that levocabastine was embryolethal at oral doses greater than 40 mg/kg/day in both species, and teratogenic at oral doses greater than 40 mg/kg/day in mice and 20 mg/kg/day in rats. The main foetal malformations observed were open eyes in mice, and polydactyly, hydrocephalus, anophthalmia/microphthalmia, hydronephrosis and arthrogryposis in rats. There are limited postmarketing data on the use of Livostin eye drops or nasal spray in pregnant women. The risk for humans is unknown. Therefore Livostin eye drops and nasal spray should not be used during pregnancy.
 Based on determinations of levocabastine concentrations in saliva and breast milk in a nursing woman, who received a single oral dose of 0.5 mg levocabastine, it is expected that approximately 0.6% of the total intranasally and approximately 0.3% of the total ophthalmically administered dose of levocabastine may be transferred to a nursing infant. However, due to the limited nature of the clinical and experimental data, it is recommended that Livostin nasal spray or eye drops be avoided in breast-feeding mothers.

Effects on fertility.

No data available.

4.7 Effects on Ability to Drive and Use Machines

The effects of this medicine on a person's ability to drive and use machines were not assessed as part of its registration.

4.8 Adverse Effects (Undesirable Effects)

Clinical trial data.

Eye drops.

The safety of Livostin eye drops was evaluated in 508 subjects who participated in 4, placebo-controlled clinical trials and one open-label clinical trial. All adverse drug reactions (ADRs) reported by subjects in Livostin eye drops clinical trials are presented in Table 1.

Nasal spray.

The safety of Livostin nasal spray was evaluated in 2328 subjects who participated in 12 double-blind, placebo-controlled clinical trials. Adverse drug reactions (ADRs) reported in ≥ 1% of subjects in these trials are presented in Table 2.
Additional ADRs reported for < 1% of Livostin Nasal Spray treated subjects in the 12 clinical trials are presented in Table 3.

Postmarketing data.

Additional adverse drug reactions first identified during postmarketing experience with Livostin eye drops and nasal spray are included in Table 4 (eye drops) and Table 5 (nasal spray). Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Therefore, the frequencies are provided according to the following convention (3,4). Very common: ≥ 1/10; common: ≥ 1/100 and < 1/10; uncommon: ≥ 1/1000 and < 1/100; rare: ≥ 1/10,000 and < 1/1000; very rare: ≥ 1/10,000, including isolated reports.
In Tables 4 and 5, ADR's are presented by frequency category based on incidence in clinical trials or epidemiology studies when known.

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: https://www.tga.gov.au/reporting-problems.

4.9 Overdose

There has been no experience with overdose of Livostin eye drops or nasal spray to date. After accidental intake of the contents of the bottle, sedation may occur. In case of overdose, the patient should be advised to drink plenty of water in order to accelerate the renal elimination of levocabastine. For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Livostin eye drops contain levocabastine, a potent, fast-acting and highly selective histamine H1-antagonist with a sustained duration of action. After topical application to the eyes, it (almost immediately and for several hours) relieves the typical symptoms of allergic conjunctivitis (itching, redness, chemosis, eyelid swelling, tearing).
Livostin nasal spray contains levocabastine, a potent, fast-acting and highly selective histamine H1-antagonist with a sustained duration of action. After topical application to the nose, it almost immediately and for several hours relieves the typical symptoms of allergic rhinitis (sneezing, itchy nose, rhinorrhoea).

Clinical trials.

Clinical studies have shown that Livostin eye drops and nasal spray are effective for the indications listed above. The duration of treatment with the eye drops alone was generally 2-4 weeks but lasted up to 3 months in two studies and 4 months in one study. Duration of treatment with the nasal spray alone was also generally 2-4 weeks, but lasted up to 10 weeks in some instances. The duration of treatment in studies using a combination of the eye drops and nasal spray was 8 weeks.

5.2 Pharmacokinetic Properties

Absorption.

After intranasal and ocular application, the absorption of levocabastine is incomplete with a systemic bioavailability ranging from 60 to 80% for the nasal spray and from 30 to 60% for the eye drops. However, as the amount of levocabastine applied intranasally and ocularly is small, the levocabastine plasma concentrations achieved are very low. Steady-state concentrations of levocabastine are attained within 7 to 10 days following multiple dosage and are predictable from single-dose pharmacokinetics.

Distribution.

After single intravenous dosing, levocabastine is rapidly distributed over the tissues, and the terminal half-life is 33 h. The total steady-state volume of distribution is 82 L (1.14 L/kg) with a total plasma clearance of 30 mL/min.
The plasma protein binding of levocabastine is 55% with albumin being the main binding protein.

Excretion.

Levocabastine undergoes minimal hepatic metabolism, i.e. ester glucuronidation, and is predominantly cleared by the kidneys. 70% of the parent drug is recovered unchanged in the urine, and 10% of the dose is excreted in the urine as the acylglucuronide of levocabastine. The remaining 20% is excreted unchanged in the faeces.

5.3 Preclinical Safety Data

Genotoxicity.

No data available.

Carcinogenicity.

In female mice, dietary administration of levocabastine for 20 months stimulated the development of pituitary adenomas and mammary adenocarcinomas. The no-effect dose level for the pituitary tumours was 3 mg/kg/day, but a no-effect dose level has not been established for the mammary tumours. In female rats, there was an equivocal increase in the incidence of mammary tumours at the highest dose level of 34 mg/kg/day administered in the diet for 24 months. There was no evidence of carcinogenic activity in male rats or mice. The mechanism of the carcinogenic effects of levocabastine in female mice (and possibly rats) may involve antagonism of dopamine D2-receptors in the pituitary gland and subsequent elevation of serum prolactin levels.

6 Pharmaceutical Particulars

6.1 List of Excipients

See Section 2 Qualitative and Quantitative Composition.

6.2 Incompatibilities

Incompatibilities were either not assessed or not identified as part of the registration of this medicine. See Section 4.5 Interactions with Other Medicines and Other Forms of Interactions.

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 25°C.

6.5 Nature and Contents of Container

Livostin eye drops: 4 mL in 5 mL bottle.
Livostin nasal spray: 10 mL in 15 mL bottle.

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

Levocabastine hydrochloride is a white powder, insoluble in water except at higher pH and only fairly soluble in other solvents such as acetone.

Chemical structure.


Chemical Name: Levocabastine, (-)-[3S-[1(cis),3 alpha, 4 beta]]- 1-[4-cyano- 4-(4-fluorophenyl) cyclohexyl]- 3-methyl- 4-phenyl- 4-piperidine-carboxylic acid monohydrochloride, is a highly selective histamine H1-antagonist for topical use.
Chemical formula: C26H29FN2O2.HCl.
MW: 456.99.

CAS number.

CAS-79547-78-7.

7 Medicine Schedule (Poisons Standard)

Pharmacy Medicine (S2).

Summary Table of Changes