Desloratadine

Description

Desloratadine Tablets are light blue, round tablets containing 5 mg of desloratadine, an antihistamine intended for oral administration. Each tablet includes excipients such as microcrystalline cellulose NF, pregelatinized starch NF, croscarmellose sodium NF, talc USP, zinc stearate USP, and FD&C Blue #2 HT at a concentration of 11-14%. Desloratadine is characterized as a white to off-white powder, exhibiting slight solubility in water and high solubility in ethanol and propylene glycol. The empirical formula of desloratadine is C19H19ClN2, with a molecular weight of 310.8. Its chemical name is 8-chloro-6,11-dihydro-11-(4-piperdinylidene)-5H-benzo5,6cyclohepta1,2-bpyridine.

Uses and Indications

Desloratadine Tablets are indicated for the relief of symptoms associated with seasonal allergic rhinitis and perennial allergic rhinitis in patients 12 years of age and older. This medication provides relief from both nasal and non-nasal symptoms.

Additionally, Desloratadine Tablets are indicated for the symptomatic relief of chronic idiopathic urticaria in patients 12 years of age and older, including the reduction of pruritus and the number and size of hives.

There are no teratogenic or nonteratogenic effects associated with the use of this medication.

Dosage and Administration

Desloratadine is indicated for use in adults and adolescents aged 12 years and over. The recommended dosage is one 5 mg tablet administered orally once daily.

It is advised that the tablet be taken with or without food, according to the patient's preference. Healthcare professionals should ensure that patients are informed about the importance of adhering to the prescribed dosing schedule to achieve optimal therapeutic outcomes.

Contraindications

Use of this product is contraindicated in individuals with a known hypersensitivity to any of its components (4, 6.2).

Warnings and Precautions

Hypersensitivity reactions have been reported in patients taking Desloratadine Tablets. These reactions may manifest as rash, pruritus, urticaria, edema, dyspnea, or, in severe cases, anaphylaxis. In the event of any hypersensitivity reaction, it is imperative to discontinue the use of Desloratadine Tablets immediately and consider alternative treatment options.

Healthcare professionals are advised to monitor patients for signs of hypersensitivity, particularly during the initial stages of treatment. Prompt recognition and management of these reactions are crucial to ensure patient safety and to mitigate potential complications.

Side Effects

Patients may experience a range of adverse reactions while using Desloratadine Tablets. Common adverse reactions observed in clinical trials include pharyngitis, dry mouth, myalgia, fatigue, somnolence, and dysmenorrhea. These reactions were reported with varying frequencies among participants.

In addition to the common adverse reactions, hypersensitivity reactions have been noted. These may manifest as rash, pruritus, urticaria, edema, dyspnea, and in rare cases, anaphylaxis. It is crucial for healthcare providers to monitor for these serious reactions. Should any hypersensitivity reaction occur, it is recommended that Desloratadine Tablets be discontinued immediately, and alternative treatments should be considered.

Drug Interactions

Co-administration of desloratadine with certain medications may lead to increased plasma concentrations of desloratadine and its active metabolite, 3-hydroxydesloratadine. However, clinical studies have shown that these interactions do not result in any clinically significant changes to the safety profile of desloratadine.

Pharmacokinetic Interactions:

• Antifungals:

  • Ketoconazole: Co-administration with desloratadine has been shown to increase plasma concentrations of both desloratadine and 3-hydroxydesloratadine. No clinically relevant safety concerns were noted.

• Macrolide Antibiotics:

  • Erythromycin and Azithromycin: Similar to ketoconazole, these antibiotics also resulted in increased plasma levels of desloratadine and its metabolite, without any significant safety implications.

• Selective Serotonin Reuptake Inhibitors (SSRIs):

  • Fluoxetine: The combination with desloratadine led to elevated plasma concentrations of desloratadine and 3-hydroxydesloratadine, yet no clinically relevant safety issues were observed.

• Histamine H2-Receptor Antagonists:

  • Cimetidine: Co-administration resulted in increased plasma concentrations of desloratadine and its metabolite, with no clinically significant changes in safety.

Given the absence of clinically relevant safety concerns, no dosage adjustments are necessary when desloratadine is used in conjunction with the aforementioned medications. However, monitoring may be warranted in specific patient populations or under unique clinical circumstances.

Packaging & NDC

The table below lists all NDC Code configurations of Desloratadine, the U.S. brand-name prescription product. Columns show Packaging, Formulation Type, and Active Ingredient Strength.

Pediatric Use

The recommended dose of Desloratadine Oral Solution in pediatric patients is determined through cross-study comparisons of plasma concentrations between adults and pediatric subjects. Safety has been established in a clinical evaluation involving 246 pediatric subjects aged 6 months to 11 years across three placebo-controlled studies. However, the safety and effectiveness of Desloratadine Tablets or Desloratadine Oral Solution have not been demonstrated in pediatric patients younger than 6 months of age.

Geriatric Use

Clinical studies of desloratadine did not include a sufficient number of subjects aged 65 and over to determine whether they respond differently from younger subjects. However, other reported clinical experience has not identified significant differences in response between elderly patients and younger patients.

In general, dose selection for geriatric patients should be approached with caution. This is due to the greater frequency of decreased hepatic, renal, or cardiac function in this population, as well as the potential for concomitant diseases or other drug therapies that may affect drug metabolism and efficacy. Therefore, careful monitoring and consideration of individual patient factors are recommended when prescribing desloratadine to elderly patients.

Pregnancy

The available data regarding the use of desloratadine in pregnant patients is limited and does not provide sufficient evidence to establish a drug-associated risk for major birth defects or miscarriage. There are no adequate and well-controlled studies in pregnant women. Animal studies have shown that desloratadine, when administered during organogenesis, did not result in teratogenic effects in pregnant rats or rabbits at exposure levels significantly higher than the recommended human daily dose (RHD) of 5 mg/day. Specifically, in pregnant rats, no fetal malformations were observed at doses of 6, 24, and 48 mg/kg/day, which correspond to approximately 50, 200, and 320 times the summed area under the concentration-time curve (AUC)-based exposure at the RHD. Similarly, in pregnant rabbits, no adverse fetal effects were noted at doses of 15, 30, and 60 mg/kg/day, approximately 30, 70, and 230 times the AUC-based exposure at the RHD.

However, reduced fetal weights and skeletal variations were observed in rats at doses of 24 and 48 mg/kg/day, likely due to maternal toxicities, including reduced body weight gain and food consumption. In a peri- and post-natal development study, desloratadine administered to rats during the perinatal period through lactation resulted in reduced body weight and slow righting reflex in F1 pups at doses of 9 mg/kg/day or greater, which is approximately 70 times or greater than the summed AUC-based exposure at the RHD. Notably, no adverse effects on F1 pup development were observed at a dose of 3 mg/kg/day, approximately 10 times the summed AUC-based exposure at the RHD.

The estimated background risk of major birth defects and miscarriage in the U.S. general population is 2-4% and 15-20%, respectively. Given the limited data, healthcare professionals should weigh the potential benefits against the risks when considering the use of desloratadine in pregnant patients.

Lactation

Desloratadine passes into breast milk. There are insufficient data on the effects of desloratadine on breastfed infants or on milk production.

The decision regarding whether to discontinue nursing or to discontinue desloratadine should be made by considering the developmental and health benefits of breastfeeding, the clinical need of the nursing mother, and any potential adverse effects on the breastfed infant from desloratadine or from the underlying maternal condition.

Renal Impairment

There is no specific information available regarding dosage adjustments, special monitoring, or safety considerations for patients with renal impairment. Healthcare professionals should exercise caution when prescribing to patients with reduced kidney function, as the absence of detailed guidance necessitates careful clinical judgment. Regular monitoring of renal function may be advisable in this patient population.

Hepatic Impairment

Patients with hepatic impairment have not been specifically studied in relation to the use of this medication. Consequently, there are no established dosage adjustments, special monitoring requirements, or precautions outlined for individuals with compromised liver function. It is recommended that healthcare providers exercise caution when prescribing this medication to patients with hepatic impairment, given the lack of data on its safety and efficacy in this population. Regular monitoring of liver function may be prudent in these cases, although specific parameters are not defined in the available information.

Overdosage

In the event of an overdose, it is essential to implement standard measures to remove any unabsorbed drug from the gastrointestinal tract. Symptomatic and supportive treatment should be initiated as necessary. It is important to note that neither desloratadine nor its active metabolite, 3-hydroxydesloratadine, are eliminated through hemodialysis.

Current knowledge regarding acute overdosage is primarily derived from post-marketing adverse event reports and clinical trials conducted during the development of the desloratadine product. In a dose-ranging trial, somnolence was reported at doses of 10 mg and 20 mg per day. However, in another study involving normal male and female volunteers, no clinically relevant adverse events were observed when participants received single daily doses of 45 mg of desloratadine for a duration of 10 days.

Healthcare professionals should remain vigilant for potential symptoms of overdose and provide appropriate management based on the clinical presentation of the patient.

Nonclinical Toxicology

The carcinogenic potential of desloratadine was evaluated through studies involving loratadine in rats and desloratadine in mice. In a two-year study with rats, loratadine was administered in the diet at doses up to 25 mg/kg/day, which corresponds to approximately 45 times the summed AUC-based exposure of desloratadine and its metabolite at the recommended human dose (RHD). A significantly higher incidence of hepatocellular tumors, including both adenomas and carcinomas, was observed in male rats receiving 10 mg/kg/day of loratadine, which is approximately 10 times the summed AUC-based exposure of desloratadine and its metabolite at the RHD. Additionally, both male and female rats given 25 mg/kg/day of loratadine exhibited similar tumor incidences. The clinical significance of these findings regarding the long-term use of desloratadine remains undetermined. In a separate two-year dietary study in mice, administration of desloratadine at doses of up to 16 mg/kg/day for males and 32 mg/kg/day for females, corresponding to approximately 30 and 70 times the summed AUC-based exposure of desloratadine and its metabolite at the RHD, did not result in significant increases in tumor incidence.

Genotoxicity studies conducted with desloratadine revealed no evidence of genotoxic potential. This was demonstrated through a reverse mutation assay (Salmonella/E. coli mammalian microsome bacterial mutagenicity assay) and two assays for chromosomal aberrations, including a human peripheral blood lymphocyte clastogenicity assay and a mouse bone marrow micronucleus assay.

In terms of fertility impairment, a study involving female rats administered desloratadine orally for 14 days prior to and throughout mating until Gestation Day 7 at doses of 6, 12, and 24 mg/kg/day indicated an increase in preimplantation loss and a decrease in the number of implantations and fetuses at the 24 mg/kg dose. This effect was likely attributed to maternal toxicities, including reduced body weight gain and food consumption, and corresponds to approximately 200 times the summed AUC-based exposure of desloratadine and its metabolite at the RHD. In a male fertility study, desloratadine was given orally to male rats for 70 days prior to mating and throughout the mating period at doses of 3, 12, and 40 mg/kg/day. At the 40 mg/kg/day dose, reduced body weight gain, decreased food consumption, and lower absolute organ weights of the testes, epididymis, and cauda epididymis were observed. A male-specific decrease in fertility was noted at doses of 12 mg/kg or greater, which is approximately 65 times or greater than the summed AUC-based exposure of desloratadine and its metabolite at the RHD, as evidenced by reduced female conception rates, decreased sperm numbers and motility, and histopathological changes in the testes and epididymis. No effects on male fertility were observed at the 3 mg/kg/day dose, which corresponds to approximately 10 times the summed AUC-based exposure of desloratadine and its metabolite at the RHD.

Postmarketing Experience

Reports of adverse events have been received through voluntary reporting and surveillance programs. Healthcare professionals and patients are encouraged to report any side effects to Virtus Pharmaceuticals, LLC at 1-888-848-3593 or to the FDA at 1-800-FDA-1088 or via the website www.fda.gov/medwatch. This information contributes to the ongoing monitoring of the product's safety profile.

Patient Counseling

Patients should be advised to read the FDA-approved patient labeling (Patient Information) carefully. It is important for patients to use Desloratadine Tablets as directed by their healthcare provider. Since there are no food effects on the bioavailability of the medication, patients can be instructed that Desloratadine Tablets may be taken without regard to meals.

Healthcare providers should emphasize that patients must not increase the dose or dosing frequency, as studies have not demonstrated increased effectiveness at higher doses, and somnolence may occur. Patients are encouraged to discuss any questions regarding the use of this medicine with their doctor.

Patients should inform their healthcare provider about all medications they are taking, including prescription and non-prescription medicines, vitamins, and herbal supplements. Desloratadine may interact with other medications, affecting their efficacy, and vice versa. It is advisable for patients to maintain an updated list of their medications and present it to their doctor and pharmacist when receiving new prescriptions.

Patients must take Desloratadine Tablets exactly as prescribed and should not alter their dosage or frequency of administration. In the event of an overdose, patients should seek medical attention immediately.

Patients should be instructed to stop taking Desloratadine Tablets and contact their doctor or seek emergency help if they experience symptoms such as rash, itching, hives, swelling of the lips, tongue, face, or throat, or shortness of breath or difficulty breathing. They should also report any side effects that are bothersome or persistent to their healthcare provider.

This Patient Information leaflet summarizes the most important information about Desloratadine Tablets. For additional information, patients are encouraged to consult their doctor or pharmacist for resources intended for healthcare professionals. Lastly, patients should be reminded to keep Desloratadine Tablets and all other medications out of the reach of children.

Storage and Handling

Desloratadine Tablets are supplied in a tight, light-resistant container as defined by the United States Pharmacopeia (USP), equipped with a child-resistant closure.

For optimal storage, these tablets should be maintained at a temperature of 25°C (77°F), with permissible excursions between 15° and 30°C (59° and 86°F) in accordance with USP Controlled Room Temperature guidelines. It is crucial to avoid exposure to temperatures at or above 30°C (86°F) due to the heat-sensitive nature of the product.

Additional Clinical Information

No further data are available.

FDA Insert (PDF)

This document is the official FDA-approved prescribing information for Desloratadine as submitted by Virtus Pharmaceuticals, LLC. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)