LEVOCABASTINE HYDROCHLORIDE Eye drops, Nasal spray Ref.[9896] Active ingredients: Levocabastine

Mental Alertness

In clinical trials there was no significant difference in the incidence of slowed patient reactions with ZYRTEC compared to placebo and active comparator drugs. ZYRTEC, 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 0.5mg levocabastine in solution, the terminal half-life of levocabastine in moderate to severe renal impairment (Creatinine Clearance 10-50mL/min) increased from 36 hours to 95 hours. Overall exposure to levobabastine 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 ZYRTEC nasal spray to patients with renal impairment (refer to pharmacokinetics-renal impairment).

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 0.4mg 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.

No interactions have been seen with ZYRTEC eye drops. With ZYRTEC 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 ZYRTEC 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 (200mg) and erythromycin (333mg) as a single dose had no impact on the pharmacokinetics of intranasal levocabastine.

Intranasal levocabastine did not change the pharmacokinetics of loratadine.

Use in pregnancy

Pregnancy 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 ZYRTEC eye drops or nasal spray in pregnant women. The risk for humans is unknown. Therefore, ZYRTEC eye drops and nasal spray should not be used during pregnancy.

Use in lactation

Based on determinations of levocabastine concentrations in saliva and breast milk in a nursing woman, who received a single oral dose of 0.5mg 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 ZYRTEC nasal spray or eye drops be avoided in breast-feeding mothers.

Effects on fertility

No data available.

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

Clinical Trial Data

Eye Drops

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

Table 1. Adverse Drug Reactions Reported by ZYRTEC Eye Drops Treated Subjects in 5 Clinical Trials:

Nasal Spray

The safety of ZYRTEC 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.

Table 2: Adverse Drug Reactions Reported by ≥1% ZYRTEC Nasal Spray Treated Subjects in 12 Double-Blind, Placebo-Controlled Clinical Trials:

Additional ADRs reported for <1% of ZYRTEC Nasal Spray treated subjects in the 12 clinical trials are presented in Table 2.

Table 2. Adverse Drug Reactions Reported by <1% ZYRTEC Nasal Spray Treated Subjects in 12 Double-Blind, Placebo-Controlled Clinical Trials:

MedDRA System Organ Class:
MedDRA PT

General Disorders and Administrative Site Conditions:
Application site irritation
Application site pain
Application site dryness
Application site burn
Application site discomfort

Respiratory, Thoracic, and Mediastinal Disorders:
Nasal discomfort
Nasal congestion

Postmarketing Data

Additional adverse drug reactions first identified during postmarketing experience with ZYRTEC eye drops and nasal spray are included in Table 3 (nasal spray) and Table 4 (eye drops). 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: ≥1/10000 and <1/1000, Very rare: ≥1/10000, including isolated reports.

In the tables below ADR’s are presented by frequency category based on incidence in clinical trials or epidemiology studies when known.

Table 3. Adverse Drug Reactions Identified During Postmarketing Experience with ZYRTEC Eye Drops by Frequency Category Estimated from Spontaneous Reporting Rates:

Cardiac Disorders

Very Rare: Palpitations

Eye Disorders

Very Rare: Eye pain, Conjunctivitism Eyelid oedema, Eye swelling, Blepharitis, Ocular hyperaemia, Vision blurred

General Disorders and Administrative Site Conditions

Very Rare: Application site reaction including eye burning sensation, eye redness, eye pain, eye swelling, eye itching, watery eyes and vision blurred.

Immune System Disorders

Very Rare: Anaphylaxis, Angioneurotic oedema, Hypersensitivity

Skin and Subcutaneous Tissue Disorders

Very Rare: Contact dermatitis, Urticaria

Nervous System Disorders

Very Rare: Headache

Table 4. Adverse Drug Reactions Identified During Postmarketing Experience with ZYRTEC Nasal Spray by Frequency Category Estimated from Spontaneous Reporting Rates:

Cardiac Disorders

Very Rare: Palpitations, Tachycardia

Eye Disorders

Very Rare: Eyelid Oedema

General Disorders and Administrative Site Conditions

Very Rare: Malaise

Immune System Disorders

Very Rare: Anaphylaxis, Hypersensitivity

Respiratory, Thoracic, and Mediastinal Disorders

Very Rare: Bronchospasm, Dyspnoea, Nasal oedema

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.

Incompatibilities were either not assessed or not identified as part of the registration of this medicine. Refer to section 4.5: Interactions with other medicines and other forms of interactions.