Desloratadine Oral Solution

Description

Desloratadine oral solution is a clear, colorless to slightly yellow solution containing 0.5 mg/mL desloratadine. The formulation includes the following inactive ingredients: bubble gum flavor, butylated hydroxyanisole, citric acid anhydrous, glycerin, maltitol solution, polyethylene glycol 400, propylene glycol, purified water, sodium benzoate, sodium citrate dihydrate, sorbitol solution, and sucralose powder. Desloratadine, USP is a white to beige powder that is slightly soluble in water, but very soluble in ethanol and propylene glycol. Its empirical formula is C19H19ClN2, and it has a molecular weight of 310.8. The chemical name for desloratadine is 8-chloro-6,11-dihydro-11-(4-piperdinylidene)-5H-benzo5,6cyclohepta1,2-bpyridine.

Uses and Indications

This drug is indicated for the relief of nasal and non-nasal symptoms associated with seasonal allergic rhinitis in patients aged 2 years and older. It is also indicated for the relief of nasal and non-nasal symptoms associated with perennial allergic rhinitis in patients aged 6 months and older. Additionally, this drug provides symptomatic relief of pruritus and reduces both the number and size of hives in patients with chronic idiopathic urticaria who are 6 months of age and older.

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 2 teaspoonfuls (5 mg in 10 mL) once daily. For children aged 6 to 11 years, the recommended dosage is 1 teaspoonful (2.5 mg in 5 mL) once daily. In children aged 12 months to 5 years, the appropriate dosage is ½ teaspoonful (1.25 mg in 2.5 mL) once daily.

The medication should be administered orally. It is advised to measure the dosage accurately using a calibrated measuring device to ensure proper dosing.

Contraindications

Use is contraindicated in patients with hypersensitivity to the active ingredient or any of the excipients.

Warnings and Precautions

Hypersensitivity reactions have been reported in patients receiving desloratadine. 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 desloratadine immediately and consider alternative therapeutic options.

Healthcare professionals are advised to monitor patients closely for any 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.

Side Effects

In clinical trials involving adults and adolescents, the most commonly reported adverse reactions for patients with allergic rhinitis included pharyngitis (4.1%), dry mouth (3%), and somnolence (2.1%). Other reactions observed were myalgia, dysmenorrhea, and fatigue, each occurring in 2.1% of participants. For those with chronic idiopathic urticaria, headache was reported in 14% of subjects, with nausea (5%), fatigue (5%), and dizziness (4%) also noted. Pharyngitis and dyspepsia were reported in 3% of participants, while myalgia occurred in 3% as well.

In pediatric populations, adverse reactions varied by age group. For children aged 6 to 11 years, no individual adverse event was reported by 2% or more of subjects. In the 2 to 5 years age group, fever was reported in 5.5% of subjects, alongside urinary tract infections (3.6%) and varicella (3.6%). Among children aged 12 to 23 months, fever (16.9%), diarrhea (15.4%), and upper respiratory tract infections (10.8%) were the most common reactions. Coughing, appetite increase, emotional lability, epistaxis, parasitic infections, pharyngitis, and maculopapular rash were each reported in 3.1% of subjects.

For infants aged 6 to 11 months, upper respiratory tract infections (21.2%) and diarrhea (19.7%) were the most frequently reported adverse reactions. Other notable reactions included fever (12.1%), irritability (12.1%), and coughing (10.6%). Somnolence was reported in 9.1% of subjects, while bronchitis, otitis media, and vomiting were each reported in 6.1%. Additional reactions included anorexia, pharyngitis, insomnia, rhinorrhea, erythema, and nausea.

Post-marketing experience has revealed additional adverse reactions, including cardiac disorders such as tachycardia and palpitations, respiratory issues like dyspnea, and skin reactions including rash and pruritus. Nervous system disorders reported include psychomotor hyperactivity, movement disorders (including dystonia, tics, and extrapyramidal symptoms), and seizures, which have occurred in patients both with and without a known seizure disorder. Immune system disorders such as hypersensitivity reactions (urticaria, edema, and anaphylaxis) have also been documented. Investigations have shown elevated liver enzymes, including bilirubin, and cases of hepatitis have been reported. Metabolic and nutritional disorders, such as increased appetite, were also noted.

In cases of hypersensitivity reactions, including rash, pruritus, urticaria, edema, dyspnea, and anaphylaxis, it is advised to discontinue desloratadine immediately and consider alternative treatments.

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:

Antifungals and Antibiotics

• Ketoconazole: Increased plasma concentrations of desloratadine and 3-hydroxydesloratadine were noted; however, no clinically relevant changes in the safety profile were observed.

• Erythromycin: Similar to ketoconazole, co-administration resulted in increased plasma concentrations without significant safety concerns.

• Azithromycin: This antibiotic also led to elevated levels of desloratadine and its metabolite, with no clinically relevant safety implications.

Antidepressants

• Fluoxetine: The combination with desloratadine resulted in increased plasma concentrations of both desloratadine and 3-hydroxydesloratadine, but again, no clinically relevant changes in safety were reported.

Histamine H2 Antagonists

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

In all cases, while increased plasma concentrations were observed, there were no clinically significant alterations in the safety profile of desloratadine. Therefore, routine dosage adjustments or enhanced monitoring may not be necessary; however, clinical judgment should guide individual patient management.

Packaging & NDC

The table below lists all NDC Code configurations of Desloratadine Oral Solution (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 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 patients. However, other reported clinical experiences have not identified significant differences in response between elderly patients and their younger counterparts.

In general, dose selection for geriatric patients should be approached with caution. This is particularly important due to the increased likelihood of decreased hepatic, renal, or cardiac function in this population, as well as the potential for concomitant diseases or other drug therapies. Therefore, healthcare providers are advised to consider these factors when prescribing desloratadine to elderly patients, ensuring appropriate monitoring and adjustments as necessary to optimize safety and efficacy.

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 oral 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, although reduced fetal weights and skeletal variations were noted at the higher doses, likely due to maternal toxicities such as reduced body weight gain and food consumption.

In pregnant rabbits, desloratadine was also not associated with adverse fetal outcomes at doses of 15, 30, and 60 mg/kg/day, although reduced maternal body weight gain was observed at the highest dose. In a peri-and post-natal development study, desloratadine was administered to rats during the perinatal period through lactation, revealing reduced body weight and slow righting reflex in F1 pups at doses of 9 mg/kg/day or greater. However, no adverse effects on F1 pup development were noted at a dose of 3 mg/kg/day, which corresponds to approximately 10 times the summed area under the concentration-time curve (AUC)-based exposure of desloratadine and its metabolite at the RHD.

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 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 in lactating mothers.

The decision 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

Patients with renal impairment may require dosage adjustments to ensure safety and efficacy. It is recommended to refer to the Dosage and Administration (2.5) and Clinical Pharmacology (12.3) sections for specific guidance on dosing modifications based on the degree of renal function. Monitoring of renal function is advised to optimize treatment outcomes in this patient population.

Hepatic Impairment

Patients with hepatic impairment may require dosage adjustments to ensure safety and efficacy. It is recommended that healthcare providers refer to the Dosage and Administration section (2.5) and the Clinical Pharmacology section (12.3) for specific guidance on dosage modifications. Close monitoring of liver function is advised in this patient population to mitigate potential risks associated with compromised liver function.

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 to manage any adverse effects.

Desloratadine and its active metabolite, 3-hydroxydesloratadine, are not eliminated through hemodialysis, which should be taken into consideration when managing an overdose situation.

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 single daily doses of desloratadine 45 mg were administered for a duration of 10 days.

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

Nonclinical Toxicology

There is no information available regarding teratogenic effects associated with desloratadine.

In terms of non-teratogenic effects, studies in rats indicated that female fertility was unaffected at desloratadine doses up to 24 mg/kg/day, with estimated exposures approximately 130 times the area under the curve (AUC) in humans at the recommended daily oral dose. However, a male-specific decrease in fertility was observed at an oral dose of 12 mg/kg, characterized by reduced female conception rates, decreased sperm numbers and motility, and histopathologic changes in the testes. This exposure level corresponded to approximately 45 times the AUC in humans at the recommended daily oral dose. Conversely, no effects on fertility were noted at an oral dose of 3 mg/kg/day, which represented an estimated exposure of about 8 times the AUC in humans.

The carcinogenic potential of desloratadine was evaluated through studies involving loratadine in rats and desloratadine in mice. In a 2-year dietary study in rats, loratadine was administered at doses up to 25 mg/kg/day, leading to a significantly higher incidence of hepatocellular tumors (adenomas and carcinomas) in males receiving 10 mg/kg/day and in both males and females receiving 25 mg/kg/day. The estimated exposures in these rats were approximately 30 times the AUC in humans at the recommended daily oral dose, with the 10 mg/kg group showing exposures around 7 times the AUC. The clinical significance of these findings in the context of long-term desloratadine use remains unclear. In a separate 2-year dietary study in mice, neither males nor females receiving up to 16 mg/kg/day and 32 mg/kg/day of desloratadine exhibited significant increases in tumor incidence, with estimated exposures of 12 and 27 times the AUC in humans, respectively.

Genotoxicity assessments of 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.

Postmarketing Experience

Adverse events have been reported voluntarily from a population of uncertain size, making it challenging to reliably estimate their frequency or establish a causal relationship to drug exposure. The following spontaneous adverse events have been documented during the marketing of desloratadine:

Cardiac disorders, including tachycardia and palpitations, have been noted. Respiratory, thoracic, and mediastinal disorders such as dyspnea have also been reported. Skin and subcutaneous tissue disorders include rash and pruritus.

Nervous system disorders encompass psychomotor hyperactivity, movement disorders (which include dystonia, tics, and extrapyramidal symptoms), and seizures, with reports occurring in both patients with and without a known seizure disorder.

Immune system disorders have included hypersensitivity reactions, such as urticaria, edema, and anaphylaxis. Investigations have revealed elevated liver enzymes, including bilirubin. Hepatobiliary disorders, specifically hepatitis, have been reported, along with metabolism and nutrition disorders characterized by increased appetite.

Patient Counseling

Patients should be instructed to use desloratadine as directed, adhering strictly to the prescribed dosage. It is important to inform patients that there are no food effects on the bioavailability of desloratadine, allowing them to take the oral solution without regard to meals.

Healthcare providers should emphasize that patients must not increase the dose or dosing frequency. Studies have not demonstrated increased effectiveness at higher doses, and doing so may lead to somnolence. It is crucial for patients to understand the importance of following the recommended dosing guidelines to ensure both safety and efficacy.

Storage and Handling

The product is supplied in accordance with the National Drug Code (NDC) specifications. It should be stored at a temperature range of 20° to 25° C (68° to 77° F), adhering to the guidelines set forth by the United States Pharmacopeia (USP) for Controlled Room Temperature.

It is essential to protect the product from light to maintain its integrity and efficacy. Proper handling and storage conditions must be observed to ensure optimal quality.

Additional Clinical Information

Post-marketing experience has revealed several adverse reactions associated with the use of desloratadine. Clinicians should be aware of potential cardiac disorders such as tachycardia and palpitations, as well as respiratory issues including dyspnea. Skin reactions may manifest as rash and pruritus. Neurologically, patients may experience psychomotor hyperactivity, movement disorders (including dystonia, tics, and extrapyramidal symptoms), and seizures, which have been reported in both patients with and without a known seizure disorder. Additionally, hypersensitivity reactions (e.g., urticaria, edema, and anaphylaxis) have been noted, along with elevated liver enzymes and hepatitis. Patients may also report increased appetite.

For patient counseling, it is essential to refer to the FDA-approved patient labeling. Patients should be instructed to use desloratadine as directed and informed that there are no food effects on its bioavailability, allowing for administration without regard to meals. It is important to advise patients against increasing the dose or frequency, as higher doses have not shown increased effectiveness and may lead to somnolence.

FDA Insert (PDF)

This document is the official FDA-approved prescribing information for Desloratadine Oral Solution as submitted by INA Pharmaceutics, Inc.. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)