Desloratadine

Uses and Indications

Desloratadine is indicated for the relief of nasal and non-nasal symptoms associated with seasonal allergic rhinitis and perennial allergic rhinitis in patients of varying ages. Specifically, it is indicated for:

Seasonal Allergic Rhinitis

• Relief of nasal and non-nasal symptoms in patients 2 years of age and older.

Perennial Allergic Rhinitis

• Relief of nasal and non-nasal symptoms in patients 6 months of age and older.

Chronic Idiopathic Urticaria

• Symptomatic relief of pruritus, reduction in the number of hives, and size of hives in patients 6 months of age and older.

Desloratadine tablets are specifically indicated for patients 12 years of age and older for all the above conditions.

Limitations of Use

No teratogenic or nonteratogenic effects have been mentioned in the available data.

Dosage and Administration

Adults and adolescents 12 years of age and over are recommended to take one 5 mg tablet of Desloratadine, orally, once daily. This dosage applies to both standard and orally disintegrating tablet forms.

For the oral solution, adults and adolescents 12 years of age and over should take 2 teaspoonfuls (5 mg in 10 mL) once daily.

Children aged 6 to 11 years should receive 1 teaspoonful (2.5 mg in 5 mL) of the oral solution or one 2.5 mg orally disintegrating tablet once daily.

For children aged 12 months to 5 years, the recommended dosage is ½ teaspoonful (1.25 mg in 2.5 mL) of the oral solution once daily.

Children aged 6 to 11 months may be given 2 mL (1 mg) of the oral solution once daily.

All formulations should be administered orally.

Contraindications

Use of Desloratadine is contraindicated in individuals with hypersensitivity to the active substance or any of its excipients. This contraindication is critical due to the potential for severe allergic reactions in susceptible patients.

Warnings and Precautions

Hypersensitivity reactions, including rash, pruritus, urticaria, edema, dyspnea, and anaphylaxis, have been reported with the use of Desloratadine in various formulations, including tablets, film-coated tablets, orally disintegrating tablets, and oral solutions. In the event of such reactions, it is imperative to discontinue Desloratadine immediately and consider alternative treatments.

Serious Warnings

• Patients should be monitored for signs of hypersensitivity. If any symptoms occur, discontinue the medication and seek medical attention.

Monitoring Requirements

• Regular assessment for any adverse reactions is recommended, particularly in patients with a history of hypersensitivity to similar medications.

Side Effects

Common adverse reactions reported in clinical trials and post-marketing experience for Desloratadine include:

• Pharyngitis

• Dry mouth

• Myalgia

• Fatigue

• Somnolence

• Dysmenorrhea

In clinical trials, the following adverse reactions were observed with varying frequencies:

• Allergic Rhinitis (Adults and Adolescents):

  • Pharyngitis (4.1%)

  • Somnolence (2.1%)

  • Dry Mouth (3%)

  • Myalgia (2.1%)

  • Dysmenorrhea (2.1%)

  • Fatigue (2.1%)

• Chronic Idiopathic Urticaria:

  • Headache (14%, 13%)

  • Nausea (5%, 2%)

  • Fatigue (5%, 1%)

  • Dizziness (4%, 3%)

  • Pharyngitis (3%, 2%)

  • Dyspepsia (3%, 1%)

  • Myalgia (3%, 1%)

In pediatric populations, specific adverse reactions included:

• Ages 2 to 5 years:

  • Fever (5.5%, 5.4%)

  • Urinary tract infection (3.6%, 0%)

  • Varicella (3.6%, 0%)

• Ages 12 months to 23 months:

  • Fever (16.9%, 12.9%)

  • Diarrhea (15.4%, 11.3%)

  • Upper respiratory tract infections (10.8%, 9.7%)

  • Coughing (10.8%, 6.5%)

  • Appetite increased (3.1%, 1.6%)

  • Emotional lability (3.1%, 0%)

  • Epistaxis (3.1%, 0%)

  • Parasitic infection (3.1%, 0%)

  • Pharyngitis (3.1%, 0%)

  • Rash maculopapular (3.1%, 0%)

• Ages 6 months to 11 months:

  • Upper respiratory tract infections (21.2%, 12.9%)

  • Diarrhea (19.7%, 8.1%)

  • Fever (12.1%, 1.6%)

  • Irritability (12.1%, 11.3%)

  • Coughing (10.6%, 9.7%)

  • Somnolence (9.1%, 8.1%)

  • Bronchitis (6.1%, 0%)

  • Otitis media (6.1%, 1.6%)

  • Vomiting (6.1%, 3.2%)

  • Anorexia (4.5%, 1.6%)

  • Pharyngitis (4.5%, 1.6%)

  • Insomnia (4.5%, 0%)

  • Rhinorrhea (4.5%, 3.2%)

  • Erythema (3%, 1.6%)

  • Nausea (3%, 0%)

Hypersensitivity reactions have been reported, including:

• Rash

• Pruritus

• Urticaria

• Edema

• Dyspnea

• Anaphylaxis

In cases of hypersensitivity, it is advised to discontinue Desloratadine immediately and consider alternative treatments.

Additional adverse reactions noted in post-marketing experience include:

• Cardiac disorders: Tachycardia, palpitations

• Respiratory disorders: Dyspnea

• Skin disorders: Rash, pruritus

• Nervous system disorders: Psychomotor hyperactivity, movement disorders (including dystonia, tics, and extrapyramidal symptoms), seizures (reported in patients with and without a known seizure disorder)

• Immune system disorders: Hypersensitivity reactions (such as urticaria, edema, and anaphylaxis)

• Investigations: Elevated liver enzymes including bilirubin

• Hepatobiliary disorders: Hepatitis

• Metabolism and nutrition disorders: Increased appetite

It is important for patients to be aware of these potential adverse reactions and to consult healthcare professionals if they experience any concerning symptoms.

Drug Interactions

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

Pharmacokinetic Interactions

• Antifungals and Antibiotics: Co-administration with ketoconazole, erythromycin, or azithromycin resulted in increased plasma concentrations of desloratadine and 3-hydroxydesloratadine. However, no clinically relevant changes in the safety profile were observed.

• Selective Serotonin Reuptake Inhibitors (SSRIs): The combination of desloratadine with fluoxetine led to increased plasma concentrations of desloratadine and 3-hydroxydesloratadine, with no clinically significant alterations in the safety profile.

• Histamine H2-Receptor Antagonists: Co-administration with cimetidine also resulted in increased plasma concentrations of desloratadine and 3-hydroxydesloratadine, without any clinically relevant changes in safety.

Overall, while these interactions may lead to increased plasma levels of desloratadine, they do not appear to result in clinically significant safety concerns. No additional drug interactions or laboratory test interactions have been reported.

Pediatric Use

The recommended dose of Desloratadine Oral Solution in the pediatric population is based on cross-study comparisons of plasma concentrations in adults and pediatric subjects. The safety of Desloratadine Oral Solution has been established in 246 pediatric subjects aged 6 months to 11 years through three placebo-controlled clinical studies. The effectiveness of Desloratadine Oral Solution in these age groups is supported by evidence from adequate and well-controlled studies of Desloratadine Tablets in adults.

The safety and effectiveness of Desloratadine Tablets or Desloratadine Oral Solution have not been demonstrated in pediatric patients less than 6 months of age. Additionally, the Desloratadine orally disintegrating 2.5 mg tablet has not been evaluated in pediatric patients, although pharmacokinetic data supports the use of this dose strength in pediatric patients aged 6 to 11 years. The CLARINEX Oral Solution has similar dosing recommendations and safety profiles, with the same age restrictions for use in patients under 6 months. The CLARINEX RediTabs 2.5-mg tablet has not been evaluated in pediatric patients.

Geriatric Use

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

In general, dose selection for elderly patients should be approached with caution, taking into account the increased likelihood of decreased hepatic, renal, or cardiac function, as well as the presence of concomitant diseases or other drug therapies. Monitoring for potential adverse effects and therapeutic efficacy is recommended in this population.

Pregnancy

The available data regarding desloratadine in pregnant patients are limited and insufficient to establish a definitive drug-associated risk for major birth defects and miscarriage. There are no adequate and well-controlled studies in pregnant women.

Animal studies indicate that desloratadine was not teratogenic when administered during organogenesis to pregnant rats and rabbits at exposure levels approximately 320 times and 230 times, respectively, the recommended human daily oral dose (RHD) of 5 mg/day. 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 such as reduced body weight gain and food consumption. In pregnant rabbits, no adverse fetal effects were noted at doses of 15, 30, and 60 mg/kg/day, although reduced maternal body weight gain was observed at the highest dose.

During a peri- and post-natal development study, desloratadine was administered to pregnant rats from Gestation Day 6 through lactation. Reduced body weight and slow righting reflex were reported in F1 pups at doses of 9 mg/kg/day or greater (approximately 70 times the AUC-based exposure at the RHD). No effects on F1 pup development were noted at 3 mg/kg/day (approximately 10 times the AUC-based exposure at the RHD). Maternal toxicities, including reduced body weight gain and food consumption, were observed at 18 mg/kg/day for F0 dams. Importantly, F1 offspring were subsequently mated, and no developmental toxicity for F2 pups was observed.

The estimated background risk of major birth defects and miscarriage in the U.S. general population is approximately 2-4% and 15-20%, respectively. Given the lack of adequate human data and the potential risks observed in animal studies, desloratadine should be used during pregnancy only if clearly needed.

Lactation

Desloratadine is excreted in breast milk, and there is insufficient data regarding its effects on breastfed infants or on milk production. Healthcare professionals should consider the developmental and health benefits of breastfeeding alongside the nursing mother's clinical needs when deciding whether to continue desloratadine or breastfeeding.

In animal studies, desloratadine administered to pregnant rats during lactation resulted in reduced body weight and delayed reflexes in offspring at high doses (approximately 70 times the recommended human daily dose). However, no adverse effects on pup development were observed at lower doses (3 mg/kg/day), which is approximately 10 times the human exposure at the recommended dose.

Given the lack of comprehensive data on the impact of desloratadine on breastfed infants, careful consideration is warranted to weigh the potential risks against the benefits of continued breastfeeding.

Renal Impairment

For patients with renal impairment, specific considerations regarding the use of Desloratadine are limited. The available data indicates that dosage adjustments are recommended for patients with renal impairment when using the Desloratadine Oral Solution. However, no detailed information is provided regarding dosage modifications, special monitoring, or safety precautions for patients with reduced kidney function in the other formulations of Desloratadine, including tablets and film-coated tablets.

Healthcare professionals should exercise caution and consider individual patient circumstances when prescribing Desloratadine to patients with renal impairment, particularly in the absence of comprehensive guidelines. Regular monitoring of renal function may be prudent to ensure patient safety and therapeutic efficacy.

Hepatic Impairment

Patients with hepatic impairment may require dosage adjustments when using Desloratadine Oral Solution. Specific recommendations for dosage adjustments can be found in the Dosage and Administration and Clinical Pharmacology sections of the product labeling. However, for other formulations of Desloratadine, including tablets and film-coated tablets, no specific information regarding dosage adjustments, special monitoring, or precautions for patients with liver problems is provided. Therefore, healthcare professionals should exercise caution and consider individual patient factors when prescribing Desloratadine to patients with hepatic impairment.

Overdosage

In the event of an overdose of desloratadine, standard measures should be considered to remove any unabsorbed drug. Symptomatic and supportive treatment is recommended. It is important to note that desloratadine and its metabolite, 3-hydroxydesloratadine, are not eliminated by hemodialysis.

Information 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. Additionally, another study indicated that no clinically relevant adverse events occurred in normal male and female volunteers who received single daily doses of desloratadine at 45 mg for 10 days.

Animal studies have shown that lethality occurred in rats at oral doses of 250 mg/kg or greater, with estimated desloratadine and metabolite exposures approximately 120 times the area under the curve (AUC) in humans at the recommended daily oral dose. The oral median lethal dose in mice was found to be 353 mg/kg, with estimated exposures around 290 times the human daily oral dose on a mg/m² basis. However, no deaths were reported in monkeys at oral doses up to 250 mg/kg, which corresponded to estimated exposures approximately 810 times the human daily oral dose on a mg/m² basis.

Monitoring for symptoms such as somnolence is advised following an overdose, and appropriate medical intervention should be initiated as necessary.

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenicity Studies

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, 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 (combined adenomas and carcinomas) was observed in male rats receiving 10 mg/kg/day (approximately 10 times the summed AUC-based exposure) and in both male and female rats at 25 mg/kg/day. The clinical significance of these findings during long-term use of desloratadine remains undetermined. 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 (approximately 30 and 70 times the summed AUC-based exposure at the RHD, respectively) did not result in significant increases in tumor incidence.

Genotoxicity Studies

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 (human peripheral blood lymphocyte clastogenicity assay and mouse bone marrow micronucleus assay).

Impairment of Fertility

In studies assessing fertility, desloratadine was administered to female rats at doses of 6, 12, and 24 mg/kg/day for 14 days prior to and throughout mating until Gestation Day 7. An increase in preimplantation loss and a decrease in the number of implantations and fetuses were noted at the highest dose of 24 mg/kg (approximately 200 times the summed AUC-based exposure at the RHD), likely due to maternal toxicities such as reduced body weight gain and food consumption. In male fertility studies, desloratadine was given 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 40 mg/kg/day, reduced body weight gain, food consumption, and 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 or greater (approximately 65 times the summed AUC-based exposure), 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 observed at a dose of 3 mg/kg/day (approximately 10 times the summed AUC-based exposure at the RHD).

Teratogenic Effects

Desloratadine was not found to be teratogenic in rats at doses up to 48 mg/kg/day (approximately 210 times the AUC in humans at the RHD) or in rabbits at doses up to 60 mg/kg/day (approximately 230 times the AUC in humans at the RHD). However, an increase in pre-implantation loss and a decrease in the number of implantations and fetuses were noted in female rats at 24 mg/kg (approximately 120 times the AUC in humans at the RHD). Additionally, reduced body weight and slow righting reflex were reported in pups at doses of 9 mg/kg/day or greater, while no effects on pup development were observed at 3 mg/kg/day (approximately 7 times the AUC in humans at the RHD).

Storage and Handling

Desloratadine is supplied in various forms, including tablets, film-coated tablets, orally disintegrating tablets, and an oral solution.

Desloratadine Tablets and Film-Coated Tablets should be stored at 25°C (77°F), with permissible excursions between 15°C and 30°C (59°F to 86°F) as defined by USP Controlled Room Temperature. These tablets are heat sensitive and must be protected from exposure at or above 30°C (86°F). They should be dispensed in a tight, light-resistant container that complies with USP standards and includes a child-resistant closure.

Desloratadine Oral Solution is to be stored at a temperature range of 20°C to 25°C (68°F to 77°F), also adhering to USP Controlled Room Temperature guidelines. It is essential to protect this solution from light.

Orally disintegrating tablets of Desloratadine should be stored at 20°C to 25°C (68°F to 77°F), with excursions allowed between 15°C and 30°C (59°F to 86°F) as per USP Controlled Room Temperature recommendations.

All formulations should be safeguarded from excessive moisture and heat to maintain their efficacy and safety.