Source: Υπουργείο Υγείας (CY) Revision Year: 2020 Publisher: Delorbis Pharmaceuticals Ltd., 17 Athinon Street, Ergates Industrial Area, 2643 Ergates, P.O. Box 28629, 2081 Lefkosia, Cyprus, European Union
Hypersensitivity to the active substance, to cetirizine, to hydroxyzine, to any other piperazine derivatives or to any of the other excipients listed in section 6.1.
Severe renal impairment at less than 10 ml/min creatinine clearance.
Precaution is recommended with concurrent intake of alcohol (see section 4.5).
Caution should be taken in patients with predisposing factors of urinary retention (e.g. spinal cord lesion, prostatic hyperplasia) as levocetirizine may increase the risk of urinary retention.
Caution should be taken in patients with epilepsy and patients at risk of convulsion as levocetirizine may cause seizure aggravation.
Response to allergy skin tests are inhibited by antihistamines and a wash-out period (of 3 days) is required before performing them.
Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicine.
Pruritus may occur when levocetirizine is stopped even if those symptoms were not present before treatment initiation. The symptoms may resolve spontaneously. In some cases, the symptoms may be intense and may require treatment to be restarted. The symptoms should resolve when the treatment is restarted.
The use of the film-coated tablet formulation is not recommended in children aged less than 6 years since this formulation does not allow for appropriate dose adaptation. It is recommended to use a paediatric formulation of levocetirizine.
No interaction studies have been performed with levocetirizine (including no studies with CYP3A4 inducers); studies with the racemate compound cetirizine demonstrated that there were no clinically relevant adverse interactions (with antipyrine, azithromycin, cimetidine, diazepam, erythromycin, glipizide, ketoconazole and pseudoephedrine). A small decrease in the clearance of cetirizine (16%) was observed in a multiple dose study with theophylline (400 mg once a day); while the disposition of theophylline was not altered by concomitant cetirizine administration.
In a multiple dose study of ritonavir (600 mg twice daily) and cetirizine (10 mg daily), the extent of exposure to cetirizine was increased by about 40% while the disposition of ritonavir was slightly altered (-11%) further to concomitant cetirizine administration.
The extent of absorption of levocetirizine is not reduced with food, although the rate of absorption is decreased.
In sensitive patients, the concurrent administration of cetirizine or levocetirizine and alcohol or other CNS depressants may cause additional reductions in alertness and impairment of performance.
There are no or limited amount of data (less than 300 pregnancy outcomes) from the use of levocetirizine in pregnant women. However, for cetirizine, the racemate of levocetirizine, a large amount of data (more than 1000 pregnancy outcomes) on pregnant women indicate no malformative or feto/neonatal toxicity. Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryo/fetal development, parturition or postnatal development (see section 5.3).
The use of levocetirizine may be considered during pregnancy, if necessary.
Cetirizine, the racemate of levocetirizine, has been shown to be excreted in human. Therefore, the excretion of levocetirizine in human milk is likely. Adverse reactions associated with levocetirizine may be observed in breastfed infants. Therefore, caution should be exercised when prescribing levocetirizine to lactating women.
For levocetirizine no clinical data are available.
Comparative clinical trials have revealed no evidence that levocetirizine at the recommended dose impairs mental alertness, reactivity or the ability to drive.
Nevertheless, some patients could experience somnolence, fatigue and asthenia under therapy with Zobral. Therefore, patients intending to drive, engage in potentially hazardous activities or operate machinery should take their response to the medicinal product into account.
In therapeutic studies in women and men aged 12 to 71 years, 15.1% of the patients in the levocetirizine 5 mg group had at least one adverse drug reaction compared to 11.3% in the placebo group. 91.6% of these adverse drug reactions were mild to moderate.
In therapeutic trials, the dropout rate due to adverse events was 1.0% (9/935) with levocetirizine 5 mg and 1.8% (14/771) with placebo.
Clinical therapeutic trials with levocetirizine included 935 subjects exposed to the medicinal product at the recommended dose of 5 mg daily. From this pooling, following incidence of adverse drug reactions were reported at rates of 1% or greater (common: ≥1/100 to <1/10) under levocetirizine 5 mg or placebo:
| Preferred Term (WHOART) | Placebo (n=771) | Levocetirizine 5 mg (n=935) |
|---|---|---|
| Headache | 25 (3.2%) | 24 (2.6%) |
| Somnolence | 11 (1.4%) | 49 (5.2%) |
| Mouth dry | 12 (1.6%) | 24 (2.6%) |
| Fatigue | 9 (1.2%) | 23 (2.5%) |
Further uncommon incidences of adverse reactions (uncommon ≥1/1,000 to <1/100) like asthenia or abdominal pain were observed.
The incidence of sedating adverse drug reactions such as somnolence, fatigue, and asthenia was altogether more common (8.1%) under levocetirizine 5 mg than under placebo (3.1%).
In two placebo-controlled studies in paediatric patients aged 6-11 months and aged 1 year to less than 6 years, 159 subjects were exposed to levocetirizine at the dose of 1.25 mg daily for 2 weeks and 1.25 mg twice daily respectively. The following incidence of adverse drug reactions was reported at rates of 1% or greater under levocetirizine or placebo.
| System Organ Class and Preferred Term | Placebo (n=83) | Levocetirizine (n=159) |
|---|---|---|
| Gastrointestinal disorders | ||
| Diarrhoea | 0 | 3 (1.9%) |
| Vomiting | 1 (1.2%) | 1 (0.6%) |
| Constipation | 0 | 2 (1.3%) |
| Nervous system disorders | ||
| Somnolence | 2 (2.4%) | 3 (1.9%) |
| Psychiatric disorders | ||
| Sleep disorder | 0 | 2 (1.3%) |
In children aged 6-12 years double blind placebo controlled studies were performed where 243 children were exposed to 5 mg levocetirizine daily for variable periods ranging from less than 1 week to 13 weeks. The following incidence of adverse drug reactions was reported at rates of 1% or greater under levocetirizine or placebo.
| Preferred Term | Placebo (n=240) | Levocetirizine 5 mg (n=243) |
|---|---|---|
| Headache | 5 (2.1%) | 2 (0.8%) |
| Somnolence | 1 (0.4%) | 7 (2.9%) |
Adverse reactions from post-marketing experience are per System Organ Class and per frequency. The frequency is defined as follows: 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), not known (cannot be estimated from the available data).
Not known: hypersensitivity including anaphylaxis
Not known: increased appetite
Not known: aggression, agitation, hallucination, depression, insomnia, suicidal ideation, nightmare
Not known: convulsion, paraesthesia, dizziness, syncope, tremor, dysgeusia
Not known: vertigo
Not known: visual disturbances, blurred vision, oculogyration
Not known: palpitations, tachycardia
Not known: dyspnoea
Not known: nausea, vomiting, diarrhoea
Not known: hepatitis
Not known: dysuria, urinary retention
Not known: angioneurotic oedema, fixed drug eruption, pruritus, rash, urticaria
Not known: myalgia, arthralgia
Not known: oedema
Not known: weight increased, abnormal liver function tests
After levocetirizine discontinuation, pruritus has been reported.
Reporting suspected adverse reactions after authorisation 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 to the Pharmaceutical Services, Ministry of Health, CY-1475, www.moh.gov.cy/phs, Fax: +357 22608649.
Not applicable.
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