Desloratadine

Description

Desloratadine orally disintegrating tablets, USP, are available in two strengths: 2.5 mg and 5 mg. The 2.5 mg tablets are light red, speckled, round, flat, uncoated, and have beveled edges, debossed with “R” on one side and “551” on the other. The 5 mg tablets share the same physical characteristics but are debossed with “RDY” on one side and “360” on the other.

Each orally disintegrating tablet contains either 2.5 mg or 5 mg of desloratadine, a white to light pink powder with a molecular formula of C19H19ClN2 and a molecular weight of 310.8. Desloratadine is soluble in dichloromethane and is chemically designated as 8-chloro-6,11-dihydro-11-(4-piperdinylidene)-5H-benzo5,6cyclohepta1,2-bpyridine.

Inactive ingredients in the formulation include anhydrous citric acid, aspartame, colloidal silicon dioxide, crospovidone, ferric oxide, mannitol, lactose anhydrous, microcrystalline cellulose, polacrilex resin, sodium stearyl fumarate, talc, and tutti frutti flavor.

Uses and Indications

Desloratadine is indicated for the relief of symptoms associated with seasonal allergic rhinitis in patients aged 2 years and older. It is also indicated for the relief of symptoms associated with perennial allergic rhinitis in patients aged 6 months and older. Additionally, desloratadine is indicated for the symptomatic relief of chronic idiopathic urticaria, including pruritus and the reduction in the number and size of hives, in patients aged 6 months and older.

There are no teratogenic or nonteratogenic effects associated with desloratadine.

Dosage and Administration

Adults and adolescents aged 12 years and over are recommended to take one 5 mg desloratadine orally disintegrating tablet once daily.

For children aged 6 to 11 years, the recommended dosage is one 2.5 mg desloratadine orally disintegrating tablet once daily.

The orally disintegrating tablets should be placed on the tongue and allowed to dissolve completely before swallowing. No additional water is required for administration.

Contraindications

Use of this product is contraindicated in individuals with a known hypersensitivity to any of its components. Due to the potential for severe allergic reactions, it is essential to avoid administration in such cases.

Warnings and Precautions

Hypersensitivity reactions have been reported in patients using desloratadine orally disintegrating tablets. These reactions may manifest as rash, pruritus, urticaria, edema, dyspnea, and in severe cases, anaphylaxis. In the event of any hypersensitivity reaction, it is imperative to discontinue the use of 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 crucial to ensure patient safety and to mitigate potential complications associated with severe allergic responses.

Side Effects

Patients may experience a range of adverse reactions while using desloratadine orally disintegrating tablets. Common adverse reactions reported include pharyngitis, dry mouth, myalgia, fatigue, somnolence, and dysmenorrhea.

In addition to these common reactions, hypersensitivity reactions have been observed. These may manifest as rash, pruritus, urticaria, edema, dyspnea, and in rare cases, anaphylaxis. In instances of hypersensitivity, it is crucial to discontinue the use of desloratadine orally disintegrating tablets immediately and consider alternative treatments.

Healthcare providers should monitor patients for these adverse reactions and manage them appropriately to ensure patient safety and comfort.

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 the plasma levels of desloratadine and 3-hydroxydesloratadine. However, these changes do not result in any clinically significant alterations in the safety profile of desloratadine.

• Selective Serotonin Reuptake Inhibitors (SSRIs): Co-administration with fluoxetine, an SSRI, similarly leads to increased plasma concentrations of desloratadine and 3-hydroxydesloratadine, without clinically relevant changes in safety.

• Histamine H2-Receptor Antagonists: The use of cimetidine alongside desloratadine also results in elevated plasma concentrations of desloratadine and 3-hydroxydesloratadine, with no significant impact on 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 these 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 desloratadine orally disintegrating 2.5 mg tablet has not been evaluated in pediatric patients. However, pharmacokinetic data support the use of this 2.5 mg dose strength in pediatric patients aged 6 to 11 years. Bioequivalence has been established between the desloratadine orally disintegrating tablet and the previously marketed orally disintegrating tablet in adults. Caution is advised when considering the use of this formulation in younger populations due to the lack of specific pediatric evaluation.

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 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 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 to assess the safety of desloratadine during pregnancy.

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 6, 24, and 48 mg/kg/day (approximately 50, 200, and 320 times the summed area under the concentration-time curve AUC-based exposure at the RHD) did not produce fetal malformations. However, reduced fetal weights and skeletal variations were observed at the higher doses, likely due to maternal toxicities such as reduced body weight gain and food consumption.

Similarly, in pregnant rabbits, desloratadine administered at doses of 15, 30, and 60 mg/kg/day (approximately 30, 70, and 230 times the AUC-based exposure at the RHD) did not show adverse fetal effects, although reduced maternal body weight gain was noted at the highest dose.

In a peri-and post-natal development study, desloratadine was given to pregnant rats from Gestation Day 6 through lactation at doses of 3, 9, and 18 mg/kg/day. At doses of 9 mg/kg/day or greater (approximately 70 times or greater than the summed AUC-based exposure at the RHD), reduced body weight and slow righting reflex were reported in F1 pups. No developmental effects were observed in F1 pups at 3 mg/kg/day (approximately 10 times the summed AUC-based exposure at the RHD). Maternal toxicities were noted at 18 mg/kg/day for F0 dams, but F1 offspring showed no developmental toxicity when subsequently mated.

The estimated background risk of major birth defects and miscarriage in the U.S. general population is 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 is excreted in breast milk; however, the effects on breastfed infants are not well established. In animal studies, desloratadine was administered to pregnant rats during organogenesis through lactation, leading to reduced body weight and slow righting reflex in F1 pups at exposure levels approximately 70 times or greater than the recommended human daily oral dose (RHD).

In a peri-and post-natal development study, doses of 9 mg/kg/day or greater resulted in similar adverse effects on F1 pups, while no developmental effects were observed at a dose of 3 mg/kg/day, which corresponds to approximately 10 times the summed AUC-based exposure of desloratadine and its metabolite at the RHD.

Given the potential for adverse effects observed in animal studies, caution is advised when considering the use of desloratadine in lactating mothers. The decision to use this medication should involve a careful assessment of the benefits and risks, taking into account the health of the mother and the potential impact on the breastfed infant.

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 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 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, there was an increase in preimplantation loss and a decrease in the number of implantations and fetuses. These effects were likely attributed to maternal toxicities, which included 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 of dosing at 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 noted. A male-specific decrease in fertility was observed at doses of 12 mg/kg/day or greater, characterized by reduced female conception rates, decreased sperm numbers and motility, and histopathological 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 2-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 separate 2-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 did not result in significant increases in tumor incidence.

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

Information regarding animal pharmacology and toxicology is encompassed within the nonclinical toxicology section, specifically under the carcinogenicity studies and impairment of fertility studies as detailed above.

Postmarketing Experience

Desloratadine has been associated with serious side effects, including allergic reactions. Patients are advised to discontinue use and seek immediate medical attention if they experience symptoms such as rash, itching, hives, swelling of the lips, tongue, face, or throat, as well as shortness of breath or difficulty breathing.

In postmarketing surveillance, the most frequently reported side effects in adults and children aged 12 years and older with allergic rhinitis include sore throat, dry mouth, muscle pain, tiredness, sleepiness, and menstrual pain. It has also been noted that increased sleepiness or tiredness may occur if desloratadine is taken in excess of the prescribed dosage.

Patients are encouraged to inform their healthcare provider of any side effects that are bothersome or persistent. It is important to note that the aforementioned side effects do not encompass all possible adverse reactions associated with desloratadine. For further information, patients should consult their doctor or pharmacist. Side effects can be reported to the FDA at 1-800-FDA-1088.

Patient Counseling

Patients should be advised to read the FDA-approved patient labeling (Patient Information) prior to starting desloratadine and each time they receive a refill, as there may be new information. It is important for patients to use desloratadine as directed by their healthcare provider. They can be informed that desloratadine orally disintegrating tablets may be taken without regard to meals, as there are no food effects on bioavailability.

Healthcare providers should counsel patients not to increase the dose or dosing frequency of desloratadine, as studies have not demonstrated increased effectiveness at higher doses, and somnolence may occur. Patients who are phenylketonurics should be made aware that desloratadine orally disintegrating tablets contain phenylalanine (10.08 mg per 5 mg or 5.04 mg per 2.5 mg).

Patients should be encouraged to discuss any questions or concerns about taking desloratadine with their healthcare provider. Before initiating treatment, patients must inform their doctor if they have liver or kidney problems, any other medical conditions, or if they are pregnant, planning to become pregnant, or breastfeeding.

It is essential for patients to provide their healthcare provider with a complete list of all medications they are taking, including prescription and non-prescription medicines, vitamins, and herbal supplements. Patients should be advised to keep this list updated and to show it to their doctor and pharmacist when obtaining new medications.

Patients should take desloratadine exactly as prescribed and not alter the dosage or frequency without consulting their healthcare provider. They should place the orally disintegrating tablet on their tongue and allow it to dissolve before swallowing, with or without water, and take it immediately after opening the blister.

In the event of an overdose, patients should be instructed to contact their doctor or seek medical attention immediately. They should also be informed to stop taking desloratadine and seek emergency help if they experience any allergic reactions, such as rash, itching, hives, swelling of the lips, tongue, face, or throat, or difficulty breathing.

Patients should report any bothersome side effects to their healthcare provider and may also report side effects to the FDA at 1-800-FDA-1088. It is important to store desloratadine orally disintegrating tablets at 20°C to 25°C (68°F to 77°F), with permissible excursions between 15°C to 30°C (59°F to 86°F), and to keep all medications out of the reach of children. Patients should be cautioned against using desloratadine for any condition for which it was not prescribed and should not share their medication with others, as it may be harmful to them.

Storage and Handling

Orally disintegrating tablets are supplied in a package configuration that includes NDC numbers for identification. These tablets should be stored at a temperature range of 20°C to 25°C (68°F to 77°F). Temporary excursions are permissible, allowing storage between 15°C to 30°C (59°F to 86°F), in accordance with USP Controlled Room Temperature guidelines. It is essential to ensure that the storage conditions are maintained within these specified limits to preserve the integrity and efficacy 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 Dr. Reddy's Laboratories Limited. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)