Approval Date.
Levocetirizine Hydrochloride Capsules Instructions
Please read the instructions carefully and use under the guidance of a doctor
Drug Name]
Generic name: Levocetirizine Hydrochloride Capsules
Trade name: Chang Ran
English name: Levocetirizine Dihydrochloride Capsules
Hanyu Pinyin: Yansuan Zuoxitiliqin Jiaonang
Ingredients
The active ingredient of this product is levocetirizine hydrochloride.
Chemical name: (+)-2-[2-[4-[(4-chlorophenyl)phenylmethyl]-1-piperazinyl]ethoxy]acetic acid-dihydrochloride.
Chemical structure formula.
Molecular formula: C21H25ClN2O3-2HCl
Molecular weight: 461.8
Properties] The contents of this product are white or off-white granules or powder.
Indications】This product is used for the treatment of allergy-related symptoms of the following diseases: allergic rhinitis (including seasonal persistent allergic rhinitis and perennial persistent allergic rhinitis) and chronic idiopathic urticaria.
Specification】5mg
Dosage and Administration
1) Route of administration: Oral.
2） Dosage and method of administration
Adults, children aged 6 years and above: 1 capsule (5mg) daily by mouth, either on an empty stomach or during or after a meal.
Patients with renal impairment: No dose adjustment is required for patients with mild renal impairment; dosage for patients with moderate to severe renal impairment is adjusted according to the following table.
Patient renal function status creatinine clearance (ml/min)a Dose and number of doses Moderate renal impairment 30-49 every 2 days, 5mg Severe renal impairment<30 every 3 days, 5mg Patients with advanced renal disease – using dialysis therapy<10 Contraindications
Patients with hepatic impairment: For patients with hepatic impairment only, no dose adjustment is required; for patients with renal impairment, please refer to the dosage in “Patients with Renal Impairment”.
Geriatric patients: For elderly patients with moderate or severe renal impairment, dose adjustment is recommended, please refer to “Patients with Renal Impairment” dosage.
Adverse Reactions
Clinical studies of the original product
Pediatric patients.
Two placebo-controlled studies were completed in pediatric patients 6-11 months of age and 1-6 years of age, in which 159 subjects were exposed to levocetirizine at a dose of 1.25 mg twice daily for 2 weeks, with an incidence of 1% or more of the following adverse drug reactions in the placebo control or levocetirizine treatment groups.
System organ classification and preferred terminology Placebo (n=83) Levocetirizine (n=159) Gastrointestinal disorders Diarrhea 03 (1.9%) Vomiting 1 (1.2%) 1 (0.6%) Constipation 02 (1.3%) Neurological disorders Somnolence 2 (2.4%) 3 (1.9%) Psychiatric disorders Sleep disorders 02 (1.3%) A double-blind study of the original product completed in children 6-12 years of age placebo-controlled study with 243 children exposed to 5 mg of levocetirizine for varying durations of administration (1 week-13 weeks). The incidence of the following adverse drug reactions was 1% or more in the placebo-controlled or levocetirizine treatment groups.
Preferred term placebo (n=240) 5 mg levocetirizine (n=243) Headache 5 (2.1%) 2 (0.8%) Sleepiness 1 (0.4%) 7 (2.9%) Adults and children 12 years of age and older.
The original investigational product had at least 1 adverse drug reaction in 15.1% of patients and 11.3% of patients in the therapeutic study 5 mg levocetirizine treatment group and placebo control group completed in male and female patients aged 12-71 years. 91.6% of the adverse drug reactions were mild to moderate in severity. In the therapeutic study 5 mg levocetirizine treatment group and the placebo control group, the rate of shedding due to adverse events was 1.0% (9/935) and 1.8% (14/771), respectively.
The clinical therapeutic study of the original levocetirizine included 935 subjects exposed to 5 mg of the original product daily. After pooled analysis, adverse drug reactions with an incidence of 1% or more (common: ≥1/100, <1/10) in the 5 mg levocetirizine treatment group or the placebo control group were reported as follows.
Preferred term (WHOART) Placebo (n=771) 5 mg levocetirizine (n=935) Headache 25 (3.2%) 24 (2.6%) Drowsiness 11 (1.4%) 49 (5.2%) Dry mouth 12 (1.6%) 24 (2.6%) Fatigue 9 (1.2%) 23 (2.5%) Further uncommon adverse reactions were observed to occur (uncommon: ≥1 /1000, <1/100) (e.g., malaise or abdominal pain). The following sedative adverse drug reactions occurred more frequently in the 5 mg levocetirizine treatment group (8.1%) compared to the placebo control group (3.1%): drowsiness, fatigue, and malaise.
Post-marketing experience with the original product
In addition to the adverse reactions reported during the clinical study and those described above, the following adverse drug reactions have been reported in postmarketing experience. Due to insufficient data, it is not possible to predict the incidence of these adverse reactions in the treated population.
Immune system disorders: hypersensitivity reactions, including anaphylactic reactions.
Metabolic and nutritional disorders: increased appetite.
Psychiatric disorders: anxiety, aggression, agitation, hallucinations, depression, insomnia, suicidal ideation, nightmares.
neurological disorders: convulsions, abnormalities of venous sinus thrombosis sensation, dizziness, syncope, tremors, taste disturbances.
Diseases of the ear and vagus: vertigo.
Visual system: inflammation, visual disturbances, blurred vision, actinic nerve crisis.
Diseases of the heart: angina pectoris, palpitations, tachycardia.
vascular diseases: jugular vein embolism.
respiratory, thoracic and mediastinal diseases: exacerbation of rhinitis, dyspnea.
gastrointestinal disorders: nausea, vomiting.
Diseases of the liver and gallbladder: hepatitis.
diseases of the kidneys and urinary system: difficulty in urination, retention of urine
skin and subcutaneous tissue disorders: angioneurotic edema, hair thinning, fixed drug rash, pruritus, rash, chancroid, urticaria, photosensitivity reaction/toxicity.
systemic discomfort: ineffective drug therapy, drug interactions, dry mucous membranes.
Skeletal muscle, connective tissue and bone disorders: myalgia, arthralgia.
systemic disorders and administration sites: edema.
Interference detection methods: cross-reactivity.
Physical examination: weight gain, abnormal liver function test results.
Description of selected adverse reactions.
Pruritus has been reported in a few patients after discontinuation of the original product.
[Contraindication].
Contraindicated in persons with hypersensitivity to levocetirizine or any component of this product or to hydroxyzine, piperazine derivatives.
Contraindicated in patients with advanced renal disease with creatinine clearance <10ml/min.
Contraindicated in patients with specific genetic disorders including rare galactose intolerance, primary lactase deficiency (lapp lactase) or glucose-galactose malabsorption.
[Precautions].
1. This product is not recommended for use in children under 6 years of age because it is currently not available at half strength. levocetirizine pediatric dosage form is recommended for children under 6 years of age.
2. Caution should be advised when using after drinking alcohol.
3. Caution should be used in patients with predisposing factors for urinary retention (e.g., spinal cord injury, prostate enlargement) because levocetirizine may increase the risk of urinary retention.
4. Effects on the ability to drive and operate machinery: Levocetirizine may cause increased drowsiness. Thus, it may affect the ability to drive a vehicle and operate machinery, and its combination with alcohol or other CNS depressants may result in decreased alertness and impaired ability to operate.
5. Patients at risk for seizures and convulsions should use caution as levocetirizine may cause exacerbation of seizures.
[For pregnant and lactating women].
Pregnant women
Only limited study data (prospectively collected from 300 cases in the Pregnancy Outcome Study) are available, and these results all suggest no clear causal relationship with malformations or fetal/neonatal toxicity of levocetirizine. Animal studies have not demonstrated direct or indirect deleterious effects in pregnancy, embryo/fetus development, delivery, or postpartum development. Use with caution in pregnant women.
Lactation
Although data are not available on whether levocetirizine is secreted into breast milk, it is expected that the former will also be secreted into breast milk given that cetirizine is secreted into breast milk. Levocetirizine should not be used during lactation. Adverse reactions associated with levocetirizine may be observed in breastfed infants.
Fertility
Clinical data on the effects of levocetirizine on fertility have not been obtained, and no animal data on fertility effects exist.
For [Pediatric Use] see [Dosage] item. In pediatric patients with impaired renal function, dose adjustment should be individualized based on the patient’s renal clearance and body weight.
For geriatric use, see [Dosage and Administration].
Drug Interactions] There have been no studies of drug interactions with levocetirizine (including studies without CYP3A4 inducers); previous studies of cetirizine racemization have shown no clinically relevant interdrug adverse reactions (with antipyrine, pseudoephedrine, cimetidine, ketoconazole, erythromycin, azithromycin, glipizide, diazepam). In a study of multiple doses of cetirizine combined with theophylline (400 mg/day), a 16% decrease in cetirizine clearance was found, while theophylline clearance was not altered by the combination of cetirizine. In a multiple dosing study of ritonavir (600 mg twice daily) with cetirizine (10 mg daily), cetirizine exposure increased by approximately 40%, and ritonavir distribution was also slightly altered (-11%) with the combination. Although studies have shown that the racemic cetirizine does not potentiate the effects of alcohol (0.5 g/l blood level), co-administration of cetirizine or levocetirizine with alcohol or other CNS depressants may lead to a further decrease in alertness and affect mental performance. Eating may cause a decrease in the rate of absorption of levocetirizine, the degree of absorption will not be reduced.
[Drug overdose].
Symptoms: Drowsiness in adults, initial euphoria followed by drowsiness in children.
Treatment: No specific antidote is available. After overdose, symptomatic treatment and supportive therapy are recommended; gastric lavage may be considered if freshly taken; dialysis cannot completely remove levocetirizine.
Pharmacology and Toxicology
Levocetirizine
Pharmacological effects
This product is the active enantiomer of cetirizine, an oral selective histamine H1 receptor antagonist. It has no significant anticholinergic and anti-5-hydroxytryptamine effects, and has a small central inhibitory effect.
Toxicological studies
Reproductive toxicity: Oral administration of levocetirizine to rats and rabbits at doses up to 200 and 120 mg/kg (approximately 320 and 390 times the maximum recommended daily oral dose for adults, respectively, based on body surface area) was not shown to be teratogenic.
In lactating mice (females), oral administration of cetirizine at doses up to 96 mg/kg (approximately 40 times the clinically recommended maximum daily oral dose for adults, based on body surface area) caused delayed weight gain in the litter.
Genotoxicity: The original Ames test, human lymphocyte staining aberration test, mouse lymphoma test and mouse micronucleus test were all negative.
Cetirizine
Toxicological studies
Reproductive toxicity: The results of fertility and general toxicity tests in mice suggest that cetirizine does not impair fertility when administered orally at a dose of 64 mg/kg (approximately 25 times the maximum recommended daily oral dose for adults, based on body surface area).
Carcinogenicity: Levocetirizine has not been tested for carcinogenicity. The cetirizine carcinogenicity test can assess the potential carcinogenicity of levocetirizine. In a carcinogenicity test in rats administered orally for 2 consecutive years, doses up to 20 mg/kg (equivalent to approximately 15 times the clinically recommended maximum daily oral dose for adults or children aged 6 months to 5 years, or 4 times the clinically recommended maximum daily dose for children aged 6-11 years) caused an increased incidence of benign liver tumors in male animals; doses of 4 mg/kg (equivalent to approximately No increase in the incidence of benign tumors was observed at a dose of 4 mg/kg (equivalent to approximately 2 times the clinically recommended maximum daily oral dose for adults or children aged 6 months to 5 years, or equivalent to the clinically recommended maximum daily oral dose for children aged 6 to 11 years). The clinical significance of these findings is unclear.
Pharmacokinetics]
The pharmacokinetics of levocetirizine is characterized by a linear relationship between plasma concentration levels and dose administered, with minimal inter-individual variation.
The absorption of levocetirizine in the body is rapid and complete. Food intake may cause a decrease in the absorption rate of levocetirizine, but the total absorption does not decrease, and the degree of absorption of levocetirizine is independent of the administered dose. The results of clinical trials showed that the relative bioavailability of 5 mg levocetirizine tablets was nearly 100%, with peak blood concentrations in adults at approximately 0.9 hours after administration; levocetirizine was firmly bound to plasma proteins, with a plasma protein binding rate of approximately 90% and an apparent volume of distribution of 0.4 L/kg; the plasma elimination half-life was 7.9 ± 1.9 hours, and after 2 days of once-daily administration of 5 mg The steady-state blood concentration was reached after once daily administration of 5 mg for 2 days; the peak blood concentration was 270 ng/ml after single dose administration of 5 mg, and the peak steady-state blood concentration was 308 ng/ml after readministration of 5 mg.
The metabolism of levocetirizine has no first-pass effect and its metabolic rate in humans is less than 14% of the administered dose. Therefore, individual differences in liver enzymes or the combination of liver enzyme inhibitors have little effect on levocetirizine, and the possibility of interaction with other substances is low. Levocetirizine is excreted on average 85.4% in the urine and 12.9% in the feces as a prototype. Levocetirizine is not converted to dexcetirizine during absorption and clearance.
Storage】Seal and store in a dry place below 25℃. Keep out of the reach of children.
Package】Polyvinyl chloride solid pharmaceutical hard tablets/pharmaceutical aluminum foil, plus polyester/aluminum/polyethylene pharmaceutical composite film bag. 6 capsules/plate/bag/box, 6 capsules/plate/bag×2 bags/box, 6 capsules/plate/bag×3 bags/box, 6 capsules/plate/bag×4 bags/box, 8 capsules/plate/bag/box, 10 capsules/plate/bag/box, 12 capsules/plate/bag/box, 12 capsules/plate/bag×2 bags/box, 18 capsules/plate/bag/box. Bag/box.
Expiry date】12 months
【Marketing license holder
Company name: Hunan Jiudian Pharmaceutical Co.
Production Address: Hunan Liuyang Biomedical Park
Postal Code: 410331
Telephone number: 0731-88220220 88220228
Fax number: 0731-88220238
Website: http://www.hnjiudian.com
Manufacturer
Company name: Hunan Jiudian Pharmaceutical Co.
Production Address: Hunan Liuyang Biomedical Park
Postal Code: 410331
Telephone number: 0731-88220220 88220228
Fax number: 0731-88220238
Website: http://www.hnjiudian.com