Approval date: xxxx, xx, xx, xx
Modification date: xxxx xx date
Desloratadine tablets instructions
Please read the instructions carefully and use under the guidance of a physician
Drug Name]
Generic name: Desloratadine Tablets
Trade name: Flibriptine
English Name: Desloratadine Tablets
Hanyu Pinyin: DilüleitadingPian
Ingredients
The active ingredient of this product is: Desloratadine
Chemical name: 8-chloro-6,11-dihydro-11-(4-piperidinylidene)-5H-benzo-[5,6]cycloheptane[1,2-b]pyridine
Chemical structure formula.
Molecular formula: C19H19ClN2
Molecular weight: 310.82
Properties]: This product is a light blue film-coated tablet, which appears white or off-white after removing the coating.
Indications】For the relief of symptoms related to chronic idiopathic urticaria and allergic rhinitis.
Specification】5mg.
Dosage and Administration
Adults and adolescents 12 years of age or older: Take 1 tablet orally once daily. Eating does not affect the effect of taking the medicine. For patients with intermittent allergic rhinitis (symptoms occurring less than 4 days per week or for less than 4 weeks), the patient’s history should be evaluated before treatment is scheduled, and treatment should be discontinued when the patient’s recurrent symptoms have resolved and recovered. For patients with persistent allergic rhinitis (episodes of symptoms 4 days per week or more and duration of illness greater than 4 weeks), continuous treatment is recommended during acute episodes.
[Adverse reactions].
In a series of clinical trials with allergic rhinitis and chronic idiopathic urticaria as indications, patients taking desloratadine at the recommended dose of 5 mg per day had a 3% higher incidence of adverse reactions in the trial group than in the placebo group. The most common adverse reactions that exceeded those in the placebo group were fatigue (1.2%), dry mouth (0.8%), and headache (0.6%). In a clinical trial with 578 adolescent subjects aged 12 to 17 years, the most common adverse reaction was headache; it occurred in 5.9% of patients in the desloratadine treatment group compared with 6.9% in the placebo treatment group. The following extremely rare adverse reactions have been reported post-marketing: hallucinations, dizziness, drowsiness, insomnia, hyperactivity, seizures, tachycardia, palpitations, abdominal pain, nausea, vomiting, dyspepsia, diarrhea, elevated liver enzymes, elevated bilirubin, hepatitis, increased appetite, myalgia, and allergic reactions (e.g., anaphylaxis, angioedema, dyspnea, pruritus, rash, and urticaria).
Contraindication】It is contraindicated for those who are allergic to the active ingredients or excipients of this product and loratadine.
Precautions】
No effect of loratadine on the ability to drive or operate machinery has been observed. However, it should be noted that a very small number of patients experience drowsiness, which may affect their ability to drive and use machinery.
Use with caution in patients with severe renal insufficiency.
Desloratadine should be used with caution in patients with a history or family history of epilepsy. Young children, in particular, may be more likely to have seizures during desloratadine treatment. Healthcare providers may consider discontinuing desloratadine if the patient has seizures during treatment.
Use in Pregnant and Lactating Women
Because there are no clinical data on the use of desloratadine in pregnant women, the safety of desloratadine use during pregnancy has not been established. Desloratadine should not be used during pregnancy unless the potential benefits outweigh the possible risks.
Desloratadine is excreted through breast milk and therefore is not recommended for nursing women.
Administration of 34 times the recommended human clinical dose of desloratadine has not been found to affect overall fertility in rats, and no teratogenic or mutagenic effects of desloratadine have been observed in animal studies.
Pediatric Use
The efficacy and safety of Desloratadine Tablets in pediatric patients under 12 years of age have not been established.
Geriatric Use]
There is a lack of data on the use of Desloratadine in elderly patients.
Drug Interactions]
No clinically relevant interactions with desloratadine have been identified in clinical trials. No clinically significant changes in plasma concentrations were observed in multiple-dose drug interaction tests with ketoconazole, erythromycin, azithromycin, fluoxetine, and cimetidine. However, the metabolizing enzymes of desloratadine have not been determined and therefore interactions with other drugs cannot be completely ruled out.
Consumption of food or grapefruit juice had no effect on the distribution of desloratadine.
The impairing effect of alcohol on human behavior is not enhanced by the concomitant use of desloratadine with alcohol.
Overdose]
In case of overdose, standard therapeutic measures should be considered to remove the unabsorbed active substance. Symptomatic and supportive treatment is recommended.
In a multi-dose clinical trial in adults and adolescents, subjects received up to 45 mg of desloratadine (9 times the actual clinical dosage) with no clinically relevant adverse effects.
Desloratadine cannot be eliminated by hemodialysis; whether it can be eliminated by peritoneal dialysis is unclear.
Pharmacology and Toxicology
Pharmacological effects
Desloratadine is a non-sedating, long-acting histamine antagonist with potent, selective antagonism of peripheral H1 receptors. Desloratadine has been shown to have anti-allergic, antihistamine and anti-inflammatory effects. After oral administration, desloratadine is effectively rejected from the central nervous system (CNS) and therefore selectively blocks peripheral histamine H1 receptors.
In vitro studies have shown that in addition to antihistamine effects, desloratadine also displays anti-allergic and anti-inflammatory effects. These studies suggest that desloratadine can inhibit multiple aspects of the initial and progressive phases of allergic inflammation, including inhibition of the release of pro-inflammatory response cytokines such as: IL-4, IL-6, IL-8 and IL-13 from human host cells/basophils, as well as inhibition of the expression of adhesion molecules such as selectin P on endothelial cells. The clinical relevance of these observations remains to be further confirmed.
In clinical trials with multiple doses of desloratadine 20 mg/day x 14 days, no statistically or clinically relevant cardiovascular effects were observed. In clinical pharmacology trials, no prolongation of the QTc interval was seen with desloratadine 45 mg/day (9 times the clinical dose) x 10 days.
Desloratadine is not readily transmissible through the central nervous system. The incidence of drowsy reactions at the recommended dose of 5 mg/day did not exceed that of placebo. In clinical trials, desloratadine did not affect mental performance even at a dose of 7.5 mg/day. A single dose of desloratadine 5 mg had no effect on the ability to fly an aircraft (including exacerbation of drowsiness or behaviors related to flying an aircraft).
In clinical pharmacology trials, dexloratadine did not exacerbate drowsiness or the impairing effects of alcohol on behavioral performance when taken with alcohol. There were no significant differences in psychomotor tests between the desloratadine and placebo groups, either alone or with alcohol.
In patients with allergic rhinitis, this product is effective in relieving symptoms of allergic rhinitis such as sneezing, runny and itchy nose; congestion/nasal congestion of the nasal mucosa; itchy, watery and congested eyes; and itchy palate. This product is effective in controlling the above symptoms within 24 hours. There is limited information on clinical studies of the effectiveness of this product in adolescent subjects aged 12-17 years.
In addition to seasonal and perennial allergic rhinitis, intermittent allergic rhinitis and persistent allergic rhinitis can be classified according to the duration of symptoms. Intermittent allergic rhinitis occurs less than four days per week or lasts less than four weeks. Persistent allergic rhinitis occurs four or more days per week and lasts for more than four weeks.
In two four-week clinical trials in patients with seasonal allergic rhinitis complicated by asthma, desloratadine was effective in relieving symptoms of seasonal allergic rhinitis (runny, stuffy, itchy and sneezy nose; itchy and burning eyes; tearing; congestion; itchy palate or itchy ears) and asthma (coughing, wheezing and dyspnea), and in reducing the use of beta agonists. The first second exertional expiratory volume (FEV1) was unchanged in both the desloratadine and placebo groups.
Questionnaires in patients with allergic rhinoconjunctivitis showed that desloratadine tablets were effective in relieving the burden of patients with seasonal allergic rhinitis and were able to significantly improve the daily inconvenience caused by symptoms.
In two six-week placebo-controlled treatment trials in patients with chronic idiopathic urticaria, desloratadine tablets relieved pruritus and reduced the size and number of urticaria, with efficacy evident at the first dosing interval. In each trial, the therapeutic effect was maintained beyond the 24-hour dosing interval. Similar to other clinical trials of antihistamines in the treatment of chronic idiopathic urticaria, the few patients who did not respond to antihistamines were excluded. 55% of patients in the dexloratadine treatment group had improvement in pruritus in approximately 50% or more of patients, compared to 19% of patients in the placebo treatment group. Treatment with Desloratadine also significantly reduced interference with sleep and daytime activity as measured by a four-point rating scale.
Toxicological studies
Acute toxicity: Death occurred in rats at 250 mg/kg orally and in mice at 353 mg/kg orally. no death occurred in monkeys at 250 mg/kg orally.
Genotoxicity: No potential genotoxicity was observed in the revertant mutation test (Salmonella/E. coli mammalian microsomal bacterial mutation test) and chromosomal aberration test (human peripheral blood lymphocyte lytic cleavage test and mouse skeletal micronucleus test).
Reproductive toxicity: Oral administration of up to 24 mg/kg/day (exposure to desloratadine and its metabolites is approximately 130 times the AUC at the recommended clinical daily oral dose) had no effect on fertility in female rats; oral administration of up to 12 mg/kg (exposure to desloratadine is approximately 45 times the AUC at the recommended clinical daily oral dose) showed decreased fertility in female rats, decreased sperm count, decreased spermatozoa in males, and decreased spermatozoa in males. Male rats showed decreased sperm count, reduced sperm viability and histological changes in the testes, indicating reduced fertility in male rats; oral administration at a dose of 3 mg/kg/day (exposure to desloratadine and its metabolites was approximately 8 times the AUC of the clinical daily recommended oral dose) had no effect on fertility in rats.
No teratogenic effects were observed in rats and rabbits given orally at doses of 48 and 60 mg/kg/day (exposure to desloratadine and its metabolites at approximately 210 and 230 times the AUC of the recommended clinical daily oral dose). In male rats administered at 24 mg/kg (exposure to desloratadine and its metabolites at approximately 120 times the AUC of the recommended daily oral dose), an increase in preimplantation loss and a decrease in the number of implants and embryos were observed; at 9 mg/kg/day (exposure to desloratadine and its metabolites at approximately 50 times the AUC of the recommended daily oral dose) or more, a At a dose of 3 mg/kg/day (exposure to desloratadine and its metabolites is approximately 7 times the AUC of the recommended daily oral dose), there was no effect on the development of the litter. However, there are no adequate and rigorously controlled clinical studies in pregnant women because animal reproduction tests are not always predictive of human response, and this product should not be used during pregnancy unless truly needed. This product can be secreted through breast milk, so the decision to discontinue breastfeeding or discontinue the drug should be based on the importance of the drug to the mother.
Carcinogenicity: The potential carcinogenicity of this product has been evaluated by studies with loratadine. The incidence of hepatocellular tumors (including adenomas and carcinomas) was significantly higher in mice and rats administered loratadine orally for 18 months and 2 years, respectively, at doses up to 40 mg/kg/day in male mice (exposure to loratadine and its metabolites was approximately three times the AUC at the recommended clinical daily dose) than in controls. The incidence of hepatocellular tumors was significantly higher in male rats administered at a dose of 10 mg/kg/day (exposure to desloratadine and its metabolites was approximately 7 times the AUC at the recommended clinical daily oral dose) and in female and male rats administered at a dose of 25 mg/kg/day. The relevance of the above findings to clinical trials of long-term administration of desloratadine is unclear.
Pharmacokinetics]
The plasma concentration of desloratadine can be measured 30 minutes after oral administration and is well absorbed, reaching peak blood concentration after about 3 hours. The degree of accumulation of desloratadine is consistent with its half-life (approximately 27 hours) and the number of once-daily doses. The bioavailability of desloratadine is proportional to the dose in the range of 5 mg-20 mg.
In a pharmacokinetic trial in which patients had basic information similar to the general population of patients with seasonal allergic rhinitis, 4% of the subjects achieved high blood concentrations of desloratadine. This percentage varied by ethnicity. At 7 hours of dosing, desloratadine blood levels could be up to 3 times higher, with a terminal half-life of approximately 89 hours, and the safety profile of these subjects did not differ from the general population.
Desloratadine is moderately bound to plasma proteins (83%-87%). No clinically relevant drug accumulation was observed with once-daily dosing of desloratadine (5 mg-20 mg) for 14 days.
The enzyme dependence of desloratadine metabolism has not been established, thus interactions with other drugs are not completely excluded. Desloratadine does not inhibit CYP3A4. In vitro tests have shown that it does not inhibit CYP2D6, which is neither a substrate nor an inhibitor of P-glycoprotein.
In a single-dose trial with 7.5 mg of desloratadine, food (high-fat, high-calorie breakfast) had no effect on the distribution of desloratadine. In another study, grapefruit juice had no effect on the distribution of desloratadine.
Storage】Storage in dry place below 30℃.
Package】Double aluminum package, (1) 3 tablets/box; (2) 6 tablets/box; (3) 12 tablets/box; (4) 18 tablets/box; (5) 24 tablets/box.
【Expiration date】18 months
【Execution standard
【Approval Number】State Drug Certificate H20020088
【Manufacturing enterprise】 【Approval number】 【Primary standard
Company Name: Hainan Puri Pharmaceutical Co.
Production Address: Guilin Yang Economic Development Zone, Meilan District, Haikou City, Hainan Province
Postal code: 571127
Telephone number: 0898-65710369
Fax number：0898-65710298
Customer service hotline：4007-118-15804
Website: http://www.hnpoly.com