Desloratadine

Description

Desloratadine tablets, USP are light blue, circular, film-coated tablets containing 5 mg of desloratadine, an antihistamine intended for oral administration. Each tablet includes excipients such as corn starch, low substituted hydroxypropyl cellulose, colloidal silicon dioxide, betadex, butylated hydroxyanisole, croscarmellose sodium, magnesium stearate, and opadry blue. The opadry blue coating consists of hypromellose, titanium dioxide, polyethylene glycol 6000, F D&C Blue # 2, and polysorbate 80.

Desloratadine, USP is characterized as a pale yellow powder that is freely soluble in dichloromethane. The molecular formula of desloratadine is C19H19ClN2, with a molecular weight of 310.8. The chemical name for desloratadine is 8-chloro-6,11-dihydro-11-(4-piperidinylidene)-5H-benzo5,6cyclohepta1,2-bpyridine. It is important to note that FDA-approved dissolution test specifications may differ from those established by the USP.

Uses and Indications

This drug is indicated for the relief of nasal and non-nasal symptoms associated with seasonal allergic rhinitis in patients 12 years of age and older. It is also indicated for the relief of nasal and non-nasal symptoms related to perennial allergic rhinitis in the same patient population. Additionally, this drug provides symptomatic relief of pruritus and reduces both the number and size of hives in patients 12 years of age and older diagnosed with chronic idiopathic urticaria.

There are no teratogenic or nonteratogenic effects associated with this drug.

Dosage and Administration

Adults and adolescents aged 12 years and over are recommended to take one 5 mg tablet of desloratadine orally once daily. It is important to ensure that the tablet is swallowed whole with water and not chewed or crushed. Consistent daily administration at the same time is advised to maintain optimal therapeutic levels.

Contraindications

Use is contraindicated in patients with a known hypersensitivity to the product or any of its components.

Warnings and Precautions

Hypersensitivity reactions have been reported in patients receiving desloratadine. 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 desloratadine immediately and consider alternative therapeutic 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 essential to ensure patient safety and to mitigate potential complications associated with desloratadine use.

Side Effects

Patients may experience a range of adverse reactions while receiving treatment. Common adverse reactions reported include pharyngitis, dry mouth, myalgia, fatigue, somnolence, and dysmenorrhea. These reactions were observed in clinical trials and are considered to be of lower severity.

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. Such hypersensitivity reactions warrant immediate medical attention and should be closely monitored in patients.

It is important for healthcare providers to be aware of these potential adverse reactions to ensure appropriate management and support for patients during treatment.

Drug Interactions

Co-administration of desloratadine with certain medications may lead to increased plasma concentrations of desloratadine and its active metabolite, 3-hydroxydesloratadine. The following interactions have been observed:

Pharmacokinetic Interactions:

• Antifungals and Macrolides: The concomitant use of desloratadine with ketoconazole, erythromycin, or azithromycin has been shown to elevate plasma levels of desloratadine and 3-hydroxydesloratadine. However, no clinically significant alterations in the safety profile of desloratadine were noted.

• Selective Serotonin Reuptake Inhibitors (SSRIs): Co-administration with fluoxetine also resulted in increased plasma concentrations of desloratadine and 3-hydroxydesloratadine, with no clinically relevant changes in safety observed.

• Histamine H2-Receptor Antagonists: The use of cimetidine alongside desloratadine similarly led to increased plasma concentrations of both desloratadine and 3-hydroxydesloratadine, without any clinically significant changes in the safety profile.

In light of these interactions, while dosage adjustments may not be necessary, it is advisable to monitor patients for any potential side effects when desloratadine is used in conjunction with the aforementioned medications.

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 for pediatric patients is determined through cross-study comparisons of plasma concentrations in both 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.

Effectiveness in these age groups is supported by data from adequate and well-controlled studies of desloratadine tablets in adults. However, the safety and effectiveness of desloratadine tablets or 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, healthcare providers are advised to carefully consider these factors when prescribing desloratadine to elderly patients, ensuring appropriate monitoring and adjustments as necessary.

Pregnancy

The available data regarding the use of desloratadine in pregnant patients is limited and insufficient to establish a definitive 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 and rabbits at exposure levels significantly higher than the recommended human daily dose (RHD) of 5 mg/day. Specifically, in pregnant rats, doses of desloratadine at 6, 24, and 48 mg/kg/day (approximately 50, 200, and 320 times the AUC-based exposure at the RHD) did not produce fetal malformations. Similarly, in pregnant rabbits, doses of 15, 30, and 60 mg/kg/day (approximately 30, 70, and 230 times the AUC-based exposure at the RHD) also did not show adverse fetal effects.

However, reduced fetal weights and skeletal variations were observed in rats at higher doses, likely attributable to maternal toxicities such as reduced body weight gain and food consumption. In a peri- and post-natal development study, desloratadine was administered to pregnant rats from Gestation Day 6 through lactation, revealing reduced body weight and slow righting reflex in F1 pups at doses of 9 mg/kg/day or greater (approximately 70 times the AUC-based exposure at the RHD). Notably, no developmental toxicity was observed in F2 pups from F1 offspring that were subsequently mated.

The estimated background risk of major birth defects and miscarriage in the U.S. general population is approximately 2 to 4% and 15 to 20%, respectively. Given the limited data, healthcare professionals should weigh the potential benefits against the risks when considering desloratadine for use 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 to discontinue nursing or to discontinue desloratadine should be made by lactating mothers, 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 regarding renal impairment, dosage adjustments, special monitoring, or safety considerations for patients with reduced kidney function. Healthcare professionals should exercise caution and consider individual patient factors when prescribing to patients with renal impairment, as the absence of detailed guidance necessitates careful clinical judgment.

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 desloratadine and its active metabolite, 3-hydroxydesloratadine, are not 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 desloratadine at 45 mg 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

No teratogenic effects were observed in the studies conducted.

In a female fertility study, desloratadine was administered orally to female rats at doses of 6, 12, and 24 mg/kg/day for 14 days prior to mating and throughout the mating period until Gestation Day 7. At the highest dose of 24 mg/kg/day, an increase in preimplantation loss and a decrease in the number of implantations and fetuses were noted. These effects were likely attributed to maternal toxicities, including reduced body weight gain and food consumption.

A male fertility study involved the oral administration of desloratadine to male rats for 70 days prior to mating and throughout the mating period, totaling 106 to 108 days, at doses of 3, 12, and 40 mg/kg/day. At the highest dose of 40 mg/kg/day, 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 evident at doses of 12 mg/kg/day or greater, characterized by reduced female conception rates, decreased sperm numbers and motility, and histopathologic changes in the testes and epididymis. No effects on male fertility were noted at 3 mg/kg/day.

The carcinogenic potential of desloratadine was evaluated through studies involving loratadine in rats and desloratadine in mice. In a two-year study in rats, loratadine was administered in the diet at doses up to 25 mg/kg/day. A significantly higher incidence of hepatocellular tumors (combined adenomas and carcinomas) was observed in male rats receiving 10 mg/kg/day and in both male and female rats receiving 25 mg/kg/day. The clinical significance of these findings during long-term use of desloratadine remains uncertain. In a two-year dietary study in mice, males and females receiving up to 16 mg/kg/day and 32 mg/kg/day of desloratadine, respectively, did not exhibit significant increases in tumor incidence.

Genotoxicity studies indicated no evidence of genotoxic potential for desloratadine. This was demonstrated in a reverse mutation assay and in two assays for chromosomal aberrations, including a human peripheral blood lymphocyte clastogenicity assay and a mouse bone marrow micronucleus assay.

Postmarketing Experience

Postmarketing experience with desloratadine tablets has identified several commonly reported side effects among adults and children aged 12 years and older with allergic rhinitis. These include sore throat, dry mouth, muscle pain, tiredness, sleepiness, and menstrual pain.

Increased levels of sleepiness or tiredness have been noted, particularly in instances where dosages exceed those prescribed by a healthcare professional.

Patients are advised to communicate any side effects that are bothersome or persistent to their healthcare provider. It is important to note that the side effects listed are not exhaustive. For further information, patients should consult their doctor or pharmacist. Additionally, side effects may be reported to the FDA at 1-800-FDA-1088.

Patient Counseling

Healthcare providers should advise patients to read the FDA-approved patient labeling (Patient Information) prior to initiating treatment with desloratadine tablets and each time they receive a refill, as there may be new information available. Patients should be instructed to use desloratadine tablets strictly as directed by their healthcare provider.

It is important to inform patients that desloratadine tablets can be taken without regard to meals, as there are no food effects on bioavailability. Patients should be cautioned against increasing the dose or frequency of dosing, as studies have not shown increased effectiveness at higher doses, and somnolence may occur.

Patients should be encouraged to discuss any questions or concerns regarding the use of desloratadine tablets with their healthcare provider. Prior to taking this medication, patients must inform their doctor if they have any liver or kidney problems. Additionally, patients who are pregnant, plan to become pregnant, or are breastfeeding should communicate this to their healthcare provider, as it is not known if desloratadine will harm an unborn baby or if it can pass into breast milk.

Patients should be reminded to disclose all medications they are currently taking, including prescription and non-prescription drugs, vitamins, and herbal supplements, as desloratadine may interact with other medications. Keeping an updated list of all medications and sharing it with their healthcare provider and pharmacist is advisable.

Patients must take desloratadine tablets exactly as prescribed and should not alter their dosage or frequency without consulting their healthcare provider. In the event of an overdose, patients should seek medical attention immediately.

Patients should be instructed to stop taking desloratadine tablets and contact their healthcare provider or seek emergency help if they experience symptoms such as rash, itching, hives, swelling of the lips, tongue, face, or throat, or difficulty breathing. They should also report any bothersome or persistent side effects to their healthcare provider. While this information summarizes potential side effects, patients are encouraged to consult their healthcare provider or pharmacist for further details and may report side effects to the FDA at 1-800-FDA-1088.

Desloratadine tablets should be stored between 20° to 25°C (68° to 77°F) and protected from moisture and heat, with a warning not to store above 30°C (86°F). Patients should keep desloratadine tablets and all medications out of the reach of children and should not use this medication for any condition for which it was not prescribed, nor should they share it with others, as it may be harmful to them.

Storage and Handling

The product is supplied in a tight, light-resistant container as defined by the United States Pharmacopeia (USP), equipped with a child-resistant closure. It is essential to store the product at a temperature range of 20° to 25°C (68° to 77°F) to maintain its integrity. Care should be taken to avoid exposure to temperatures at or above 30°C (86°F), as this may compromise the product's quality.

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 Bionpharma Inc.. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)