Clarinex

Description

CLARINEX (desloratadine) Tablets are light blue, round, film-coated tablets containing 5 mg of desloratadine, an antihistamine intended for oral administration. The tablets include excipients such as dibasic calcium phosphate dihydrate USP, microcrystalline cellulose NF, corn starch NF, talc USP, carnauba wax NF, white wax NF, and a coating material composed of lactose monohydrate, hypromellose, titanium dioxide, polyethylene glycol, and FD&C Blue #2 Aluminum Lake.

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

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

For adults and adolescents aged 12 years and over, the recommended dosage of CLARINEX is one 5 mg tablet, one 5 mg RediTabs tablet, or 2 teaspoonfuls (5 mg in 10 mL) of the oral solution, all administered once daily.

In children aged 6 to 11 years, the dosage is adjusted to one teaspoonful (2.5 mg in 5 mL) of the oral solution or one 2.5 mg RediTabs tablet, both given 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, administered once daily.

In infants aged 6 to 11 months, the dosage is 2 mL (1 mg) of the oral solution, also given once daily.

Healthcare professionals should ensure that the appropriate formulation is selected based on the patient's age and weight, and that the medication is administered at the same time each day for optimal efficacy.

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 CLARINEX, including but not limited to rash, pruritus, urticaria, edema, dyspnea, and anaphylaxis. In the event of any hypersensitivity reaction, it is imperative to discontinue CLARINEX immediately and consider alternative treatment options.

Healthcare professionals should remain vigilant for signs of these reactions and ensure that patients are informed about the potential for hypersensitivity. Monitoring for these adverse effects is essential, and appropriate interventions should be initiated promptly if they occur.

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 common reactions, hypersensitivity reactions have been noted. These may manifest as rash, pruritus, urticaria, edema, dyspnea, and in rare cases, anaphylaxis. The occurrence of hypersensitivity reactions necessitates careful monitoring of patients, as they can vary in severity and may require immediate medical attention.

Overall, healthcare providers should be vigilant in assessing patients for both common and hypersensitivity reactions to ensure timely management and intervention when necessary.

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 increased plasma concentrations of both desloratadine and 3-hydroxydesloratadine, with no significant impact on the safety profile.

In all cases, while plasma concentrations may be elevated, there are no recommended dosage adjustments or additional monitoring requirements due to the absence of clinically relevant safety concerns.

Packaging & NDC

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

Pediatric Use

The recommended dose of CLARINEX Oral Solution for pediatric patients is determined through cross-study comparisons of plasma concentrations in both adults and pediatric subjects. The safety of CLARINEX Oral Solution has been established in a clinical population of 246 pediatric subjects aged 6 months to 11 years, evaluated in three placebo-controlled studies.

However, the safety and effectiveness of CLARINEX Tablets or CLARINEX Oral Solution have not been demonstrated in pediatric patients younger than 6 months of age. Additionally, the CLARINEX RediTabs 2.5-mg tablet has not been evaluated in this population. Pharmacokinetic data supports the use of the 2.5-mg dose strength of CLARINEX RediTabs in pediatric patients aged 6 to 11 years.

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 CLARINEX (desloratadine) in pregnant women are limited and insufficient to establish a drug-associated risk for major birth defects or miscarriage. There are no adequate and well-controlled studies in this population.

Animal studies have shown that desloratadine, administered during organogenesis, did not result in teratogenic effects in pregnant rats and rabbits at exposure levels significantly higher than the recommended human daily oral dose (RHD) of 5 mg/day. Specifically, in pregnant rats, desloratadine was given at doses of 6, 24, and 48 mg/kg/day, corresponding to approximately 50, 200, and 320 times the summed area under the concentration-time curve (AUC)-based exposure at the RHD, with no fetal malformations observed. However, reduced fetal weights and skeletal variations were noted at the higher doses, likely due to maternal toxicities, including reduced body weight gain and food consumption.

In pregnant rabbits, desloratadine was administered at doses of 15, 30, and 60 mg/kg/day (approximately 30, 70, and 230 times the AUC-based exposure at the RHD), with no adverse fetal effects reported. Nonetheless, reduced maternal body weight gain was observed 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. Reduced body weight and slow righting reflex were observed in F1 pups at doses of 9 mg/kg/day or greater (approximately 70 times or greater than the summed AUC-based exposure at the RHD). No developmental effects were noted in F1 pups at the lowest dose of 3 mg/kg/day (approximately 10 times the summed AUC-based exposure).

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 CLARINEX 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

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.

Data regarding acute overdosage primarily derive from post-marketing adverse event reports and clinical trials conducted during the development of the CLARINEX 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 CLARINEX 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

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 is 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 (approximately 10 times the summed AUC-based exposure of desloratadine and its metabolite at the RHD) and in both male and female rats given 25 mg/kg/day. The clinical significance of these findings in relation to the long-term use of desloratadine remains uncertain. 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 (approximately 30 and 70 times the summed AUC-based exposure of desloratadine and its metabolite at the RHD, respectively) 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 highest dose of 24 mg/kg (approximately 200 times the summed AUC-based exposure of desloratadine and its metabolite at the RHD). These effects were likely attributed to maternal toxicities, including reduced body weight gain and food consumption. 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 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 noted at doses of 12 mg/kg or greater (approximately 65 times or greater than the summed AUC-based exposure of desloratadine and its metabolite at the RHD), 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 of desloratadine and its metabolite at the RHD).

Postmarketing Experience

Postmarketing experience with CLARINEX 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 in instances where the dosage of CLARINEX exceeded the prescribed amount.

Healthcare professionals are advised to be vigilant regarding these side effects and to provide appropriate medical guidance. Additionally, 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 CLARINEX and each time they receive a refill, as there may be new information. It is important for patients to use CLARINEX as directed by their healthcare provider. They can be informed that CLARINEX Tablets, Oral Solution, or RediTabs Tablets may be taken without regard to meals, as there are no food effects on bioavailability.

Patients should be cautioned against increasing the dose or dosing frequency, as studies have not demonstrated increased effectiveness at higher doses and somnolence may occur. For those who are phenylketonurics, it should be noted that CLARINEX RediTabs Tablets contain phenylalanine.

Healthcare providers should encourage patients to discuss any questions or concerns regarding the use of CLARINEX with their doctor, especially if they have liver or kidney problems, are pregnant or planning to become pregnant, or are breastfeeding or planning to breastfeed, as CLARINEX can pass into breast milk and its effects on an unborn baby are not fully known.

Patients should be instructed to maintain an updated list of all medications they are taking and to share this list with their healthcare provider and pharmacist when obtaining new medications. They must take CLARINEX exactly as prescribed and should not change their dose or frequency without consulting their doctor.

For specific administration instructions, patients should be informed that CLARINEX RediTabs Tablets should be placed on the tongue and allowed to dissolve before swallowing, and they can be taken with or without water. The CLARINEX Oral Solution should be measured using a dropper or oral syringe that can accurately measure 2 mL or 2.5 mL, which can be obtained from a pharmacist if needed.

Patients should be advised to seek medical attention immediately if they take too much CLARINEX and to report any bothersome or persistent side effects to their doctor. They may also report side effects to the FDA at 1-800-FDA-1088.

It is essential to store CLARINEX Tablets between 59°F to 86°F (15°C to 30°C), protecting them from heat and moisture, and to keep all forms of CLARINEX and other medications out of the reach of children. Patients should not use CLARINEX for any condition for which it was not prescribed and should not share it with others, as it may cause harm.

Storage and Handling

The product is supplied in Unit-of-Use packaging and a Unit-Dose Hospital Pack. It is essential to protect these packages from excessive moisture to maintain product integrity.

Storage conditions require the product to be kept at a temperature of 25°C (77°F), with permissible excursions between 15°C to 30°C (59°F to 86°F) in accordance with USP Controlled Room Temperature guidelines. The product is heat sensitive; therefore, exposure to temperatures at or above 30°C (86°F) should be strictly avoided to ensure optimal efficacy.

Additional Clinical Information

No further data are available.

FDA Insert (PDF)

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

View full prescribing information (PDF)