Desloratadine is a non-sedating, potent, second-generation long-acting antihistamine (H1-blocker). Desloratadine is the active metabolite of loratadine, with a relative potency of 10 to 20 times that of loratadine in vitro. Both loratadine and desloratadine are non-sedating; however, desloratadine does not cause QT prolongation, even when given in doses 4 to 9 times the recommended dose in adults. Desloratadine is utilized in adults and adolescents to relieve symptoms associated with seasonal allergic rhinitis, perennial allergic rhinitis, and chronic spontaneous urticaria. Desloratadine was originally FDA approved in December 2001.
Administration
May administer desloratadine with or without food.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Route-Specific Administration
Oral Administration
Oral Solid Formulations
-Tablets: Swallow tablets whole, do not chew.
-Disintegrating Tablets: Administer by placing on the tongue. The tablet will dissolve rapidly until it can be swallowed in the saliva. Food or water do not affect bioavailability.
Oral Liquid Formulations
-Oral syrup (0.5 mg/mL): Measure dose using a calibrated oral syringe, cup, or dropper.
Poor penetration into the central nervous system (CNS) and a low affinity for CNS H1-receptors help limit CNS effects of desloratadine, a non-sedating H1 blocker. While fatigue (2.1% to 5%) and somnolence (2.1% adults; 9.1% pediatrics) do occur in some patients, the risk of drowsiness is relatively low as compared to standard, sedating antihistamines. During pre-marketing clinical trials, other adverse reactions reported in 2% or more of adult and pediatric patients receiving desloratadine and that were more frequently experienced as compared to placebo-treated patients include headache (14%), pharyngitis (3% to 4.1% adults; 3.1% to 4.5% pediatrics), xerostomia (3%), dizziness (4%), dry throat (2%), flu-like symptoms (2%), myalgia (2.1% to 3%), and dysmenorrhea (2.1%).
The following spontaneous adverse events have been reported during marketing of desloratadine: tachycardia (sinus tachycardia), palpitations and rarely hypersensitivity reactions (such as rash (unspecified), pruritus, urticaria, edema, dyspnea, and anaphylactoid reactions), elevated hepatic enzymes including bilirubin (hyperbilirubinemia), and rare cases of hepatitis.
Respiratory and infectious adverse reactions reported in pediatric patients aged 6 months to 5 years receiving desloratadine and that were more frequently experienced as compared to placebo-treated patients include fever (5.5% to 16.9%), upper respiratory tract infection (10.8% to 21.2%), cough (10.6% to 10.8%), bronchitis (6.1%), otitis media (6.1%), rhinorrhea (4.5%), urinary tract infection (3.6%), varicella (3.6%), epistaxis (3.1%), and parasitic infection (3.1%).
Nausea (5% adults; 3% pediatrics) is the most common gastrointestinal adverse reaction reported in desloratadine clinical trials. Dyspepsia was reported by 3% of adult subjects. In pediatric patients aged 6 months to 5 years, the following GI adverse events were more experienced more frequently in patients who received desloratadine than those who received placebo: diarrhea (15.4% to 19.7%), vomiting (6.1%), anorexia (4.5%), and appetite stimulation (3.1%).
Central nervous system adverse reactions reported in pediatric patients aged 6 months to 5 years receiving desloratadine and that were more frequently experienced as compared to placebo-treated patients include irritability (12.1%), insomnia (4.5%), and emotional lability (3.1%). Seizures, psychomotor hyperactivity (restlessness), and involuntary movements including dystonic reaction, tics, and extrapyramidal symptoms have been reported during postmarketing use of desloratadine.
Dermatologic adverse reactions reported in pediatric patients aged 6 months to 5 years receiving desloratadine and that were more frequently experienced as compared to placebo-treated patients include maculopapular rash (3.1%) and erythema (3%).
Desloratadine products are contraindicated in patients who are hypersensitive to desloratadine or to any of the product ingredients or to loratadine.
The anticholinergic activity of H1-antagonists may result in thickened bronchial secretions in the respiratory tract thereby aggravating asthma or an asthmatic attack. However, these anticholinergic effects do not preclude the use of H1-antagonists in all asthmatic patients, particularly if the upper respiratory symptom is not a primary component of the illness. Because desloratadine possesses only weak anticholinergic properties, it would not be expected to adversely affect the respiratory status of most asthmatic patients.
Use desloratadine with caution in pediatric patients with hepatic disease or renal impairment; dosage adjustments may be necessary, Desloratadine dosage adjustments are recommended for adults with hepatic disease, renal impairment, or renal failure due to increased serum concentrations of desloratadine in these patients.
The safety and effectiveness of desloratadine in infants less than 6 months have not been established. Antihistamines generally should not be used in neonates due to the possibility of paradoxical CNS stimulation or other adverse reactions. In January 2007, the CDC warned caregivers and healthcare providers of the risk for serious injury or fatal overdose from the administration of cough and cold products to children and infants less than 2 years of age. The report estimated that 1,519 children less than 2 years of age were treated in emergency departments during 2004 to 2005 for adverse events related to cough and cold medications; some cases were due to inadvertent inappropriate use. In January 2008, the FDA issued a Public Health Advisory recommending that non-prescription cough and cold products not be used in infants and children less than 2 years. If prescription or non-prescription ncough and cold products are used in children, labels should be read carefully, caution should be used when administering multiple products, and only measuring devices specifically designed for use with medications should be used. While some combination cough/cold products containing these ingredients are available by prescription only and are not necessarily under scrutiny by the FDA, clinicians should thoroughly assess each patient's use of similar products, both prescription and nonprescription, to avoid duplication of therapy and the potential for inadvertent overdose.
No teratogenic or mutagenic effects were observed in animal studies of desloratadine use during pregnancy in rats or rabbits. Loratadine and cetirizine are often preferred second generation antihistamines based on their excellent safety data and recommendation in multiple guidelines for use during pregnancy. Desloratadine is the major metabolite of loratadine. Results of a large cohort study of desloratadine use in human pregnancy concluded that the safety profile of desloratadine is similar to loratadine and cetirizine.
Desloratadine may be used during breast-feeding. It is distributed into breast milk. Literature with loratadine, the parent drug, suggests that because of its expected low milk levels and lack of sedation and anticholinergic effects, maternal use of desloratadine is unlikely to affect a breast-fed infant or milk production. In one study, a single loratadine dose of 40 mg was administered to 6 lactating women (note that the suggested daily dose of desloratadine is 5 mg). Average loratadine peak milk concentrations, 2 hours after administration, were 29.2 mcg/L (range 20.4 to 39 mcg/L); average desloratadine peak milk concentrations, 5.3 hours after loratadine administration, were 16 mcg/L (range 9 to 29.6 mcg/L). The total amount excreted in milk over 48 hours was 11.7 mcg of loratadine and desloratadine. However, as noted above, the dose administered was 4 times greater than the usual adult dose of the drug; a total dose of about 3 mcg would be expected with a 10 mg dose. The calculated average and maximum expected doses of loratadine and desloratadine in milk were 0.46% and 1.1% of the maternal weight-adjusted dose, respectively, after the 40 mg dose. Loratadine is considered to be compatible with breast-feeding. The British Society for Allergy and Clinical Immunology recommends loratadine or cetirizine at the lowest dose as a preferred antihistamine in breast-feeding women. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally ingested drug, healthcare providers are encouraged to report the adverse effect to the FDA.
Desloratadine is generally non-sedating. However, the drug may cause drowsiness or somnolence in individual patients; therefore, patients receiving desloratadine should be advised to avoid activities requiring concentration and coordination, such as driving or operating machinery, until the effects of the drug are known.
Desloratadine oral disintegrating tablets contain aspartame, a source of phenylalanine. Caution should be used and the source of phenylalanine taken into account in patients with phenylketonuria.
For the management of symptoms of seasonal allergies or perennial allergies, including allergic rhinitis:
Oral dosage (tablet):
Adults: 5 mg PO once daily.
Children and Adolescents 12 years and older: 5 mg PO once daily.
Oral dosage (orally disintegrating tablet):
Adults: 5 mg PO once daily.
Children and Adolescents 12 years and older: 5 mg PO once daily.
Children 6 to 11 years: 2.5 mg PO once daily.
Oral dosage (oral solution):
Adults: 5 mg PO once daily.
Children and Adolescents 12 years and older: 5 mg PO once daily.
Children 6 to 11 years: 2.5 mg PO once daily.
Children 1 to 5 years: 1.25 mg PO once daily. NOTE: Desloratadine is not FDA-approved for the treatment of seasonal allergic rhinitis in children less than 2 years.
Infants 6 months and older: 1 mg PO once daily. NOTE: Desloratadine is not FDA-approved for the treatment of seasonal allergic rhinitis in infants.
For the management of symptoms of chronic spontaneous urticaria (e.g., relief of pruritus, reduction in the size and number of hives):
Oral dosage (tablet):
Adults: 5 mg PO once daily.
Children and Adolescents 12 years and older: 5 mg PO once daily.
Oral dosage (orally disintegrating tablet):
Adults: 5 mg PO once daily.
Children and Adolescents 12 years and older: 5 mg PO once daily.
Children 6 to 11 years: 2.5 mg PO once daily.
Oral dosage (oral solution):
Adults: 5 mg PO once daily.
Children 6 to 11 years: 2.5 mg PO once daily.
Children and Adolescents 12 years and older: 5 mg PO once daily.
Children 1 to 5 years: 1.25 mg PO once daily.
Infants 6 months and older: 1 mg PO once daily.
Maximum Dosage Limits:
-Adults
5 mg/day PO.
-Geriatric
5 mg/day PO.
-Adolescents
5 mg/day PO.
-Children
12 years: 5 mg/day PO.
6 to 11 years: 2.5 mg/day PO.
1 to 5 years: 1.25 mg/day PO.
-Infants
6 to 11 months: 1 mg/day PO.
Less than 6 months: Safety and efficacy have not been established.
Patients with Hepatic Impairment Dosing
In adults with hepatic impairment, a starting dose of 5 mg PO every other day is recommended. Recommendations for dosage adjustments in pediatric patients with hepatic impairment are not available, but dosage interval adjustment may be necessary.
Patients with Renal Impairment Dosing
CrCl 50 mL/minute or less: In adults, 5 mg PO every other day is recommended. Recommendations for dosage adjustments in pediatric patients with renal impairment are not available, but dosage interval adjustment may be necessary.
Intermittent hemodialysis
Desloratadine and its metabolite are not removed by hemodialysis. See dosage for CrCl 50 mL/minute or less.
*non-FDA-approved indication
Acetaminophen; Aspirin; Diphenhydramine: (Minor) Although desloratadine is considered a 'non-sedating' antihistamine, dose-related sedation has been noted. For this reason, it would be prudent to monitor for drowsiness during concurrent use of desloratadine with CNS depressants such as other H1-blockers.
Acetaminophen; Caffeine; Pyrilamine: (Minor) Although desloratadine is considered a 'non-sedating' antihistamine, dose-related sedation has been noted. For this reason, it would be prudent to monitor for drowsiness during concurrent use of desloratadine with CNS depressants such as other H1-blockers.
Acetaminophen; Chlorpheniramine: (Minor) Although desloratadine is considered a 'non-sedating' antihistamine, dose-related sedation has been noted. For this reason, it would be prudent to monitor for drowsiness during concurrent use of desloratadine with CNS depressants such as other H1-blockers.
Acetaminophen; Chlorpheniramine; Dextromethorphan: (Minor) Although desloratadine is considered a 'non-sedating' antihistamine, dose-related sedation has been noted. For this reason, it would be prudent to monitor for drowsiness during concurrent use of desloratadine with CNS depressants such as other H1-blockers.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: (Minor) Although desloratadine is considered a 'non-sedating' antihistamine, dose-related sedation has been noted. For this reason, it would be prudent to monitor for drowsiness during concurrent use of desloratadine with CNS depressants such as other H1-blockers.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Minor) Although desloratadine is considered a 'non-sedating' antihistamine, dose-related sedation has been noted. For this reason, it would be prudent to monitor for drowsiness during concurrent use of desloratadine with CNS depressants such as other H1-blockers.
Acetaminophen; Chlorpheniramine; Phenylephrine : (Minor) Although desloratadine is considered a 'non-sedating' antihistamine, dose-related sedation has been noted. For this reason, it would be prudent to monitor for drowsiness during concurrent use of desloratadine with CNS depressants such as other H1-blockers.
Acetaminophen; Dextromethorphan; Doxylamine: (Minor) Although desloratadine is considered a 'non-sedating' antihistamine, dose-related sedation has been noted. For this reason, it would be prudent to monitor for drowsiness during concurrent use of desloratadine with CNS depressants such as other H1-blockers.
Acetaminophen; Diphenhydramine: (Minor) Although desloratadine is considered a 'non-sedating' antihistamine, dose-related sedation has been noted. For this reason, it would be prudent to monitor for drowsiness during concurrent use of desloratadine with CNS depressants such as other H1-blockers.
Acetaminophen; Pamabrom; Pyrilamine: (Minor) Although desloratadine is considered a 'non-sedating' antihistamine, dose-related sedation has been noted. For this reason, it would be prudent to monitor for drowsiness during concurrent use of desloratadine with CNS depressants such as other H1-blockers.
Acrivastine; Pseudoephedrine: (Minor) Although desloratadine is considered a 'non-sedating' antihistamine, dose-related sedation has been noted. For this reason, it would be prudent to monitor for drowsiness during concurrent use of desloratadine with CNS depressants such as other H1-blockers.
Brompheniramine: (Minor) Although desloratadine is considered a 'non-sedating' antihistamine, dose-related sedation has been noted. For this reason, it would be prudent to monitor for drowsiness during concurrent use of desloratadine with CNS depressants such as other H1-blockers.
Brompheniramine; Dextromethorphan; Phenylephrine: (Minor) Although desloratadine is considered a 'non-sedating' antihistamine, dose-related sedation has been noted. For this reason, it would be prudent to monitor for drowsiness during concurrent use of desloratadine with CNS depressants such as other H1-blockers.
Brompheniramine; Phenylephrine: (Minor) Although desloratadine is considered a 'non-sedating' antihistamine, dose-related sedation has been noted. For this reason, it would be prudent to monitor for drowsiness during concurrent use of desloratadine with CNS depressants such as other H1-blockers.
Brompheniramine; Pseudoephedrine: (Minor) Although desloratadine is considered a 'non-sedating' antihistamine, dose-related sedation has been noted. For this reason, it would be prudent to monitor for drowsiness during concurrent use of desloratadine with CNS depressants such as other H1-blockers.
Brompheniramine; Pseudoephedrine; Dextromethorphan: (Minor) Although desloratadine is considered a 'non-sedating' antihistamine, dose-related sedation has been noted. For this reason, it would be prudent to monitor for drowsiness during concurrent use of desloratadine with CNS depressants such as other H1-blockers.
Carbinoxamine: (Minor) Although desloratadine is considered a 'non-sedating' antihistamine, dose-related sedation has been noted. For this reason, it would be prudent to monitor for drowsiness during concurrent use of desloratadine with CNS depressants such as other H1-blockers.
Cetirizine: (Minor) Although desloratadine is considered a 'non-sedating' antihistamine, dose-related sedation has been noted. For this reason, it would be prudent to monitor for drowsiness during concurrent use of desloratadine with CNS depressants such as other H1-blockers.
Cetirizine; Pseudoephedrine: (Minor) Although desloratadine is considered a 'non-sedating' antihistamine, dose-related sedation has been noted. For this reason, it would be prudent to monitor for drowsiness during concurrent use of desloratadine with CNS depressants such as other H1-blockers.
Chlophedianol; Dexbrompheniramine: (Minor) Although desloratadine is considered a 'non-sedating' antihistamine, dose-related sedation has been noted. For this reason, it would be prudent to monitor for drowsiness during concurrent use of desloratadine with CNS depressants such as other H1-blockers.
Chlophedianol; Dexchlorpheniramine; Pseudoephedrine: (Minor) Although desloratadine is considered a 'non-sedating' antihistamine, dose-related sedation has been noted. For this reason, it would be prudent to monitor for drowsiness during concurrent use of desloratadine with CNS depressants such as other H1-blockers.
Chlorcyclizine: (Minor) Although desloratadine is considered a 'non-sedating' antihistamine, dose-related sedation has been noted. For this reason, it would be prudent to monitor for drowsiness during concurrent use of desloratadine with CNS depressants such as other H1-blockers.
Chlorpheniramine: (Minor) Although desloratadine is considered a 'non-sedating' antihistamine, dose-related sedation has been noted. For this reason, it would be prudent to monitor for drowsiness during concurrent use of desloratadine with CNS depressants such as other H1-blockers.
Chlorpheniramine; Codeine: (Minor) Although desloratadine is considered a 'non-sedating' antihistamine, dose-related sedation has been noted. For this reason, it would be prudent to monitor for drowsiness during concurrent use of desloratadine with CNS depressants such as other H1-blockers.
Chlorpheniramine; Dextromethorphan: (Minor) Although desloratadine is considered a 'non-sedating' antihistamine, dose-related sedation has been noted. For this reason, it would be prudent to monitor for drowsiness during concurrent use of desloratadine with CNS depressants such as other H1-blockers.
Chlorpheniramine; Dextromethorphan; Phenylephrine: (Minor) Although desloratadine is considered a 'non-sedating' antihistamine, dose-related sedation has been noted. For this reason, it would be prudent to monitor for drowsiness during concurrent use of desloratadine with CNS depressants such as other H1-blockers.
Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Minor) Although desloratadine is considered a 'non-sedating' antihistamine, dose-related sedation has been noted. For this reason, it would be prudent to monitor for drowsiness during concurrent use of desloratadine with CNS depressants such as other H1-blockers.
Chlorpheniramine; Hydrocodone: (Minor) Although desloratadine is considered a 'non-sedating' antihistamine, dose-related sedation has been noted. For this reason, it would be prudent to monitor for drowsiness during concurrent use of desloratadine with CNS depressants such as other H1-blockers.
Chlorpheniramine; Ibuprofen; Pseudoephedrine: (Minor) Although desloratadine is considered a 'non-sedating' antihistamine, dose-related sedation has been noted. For this reason, it would be prudent to monitor for drowsiness during concurrent use of desloratadine with CNS depressants such as other H1-blockers.
Chlorpheniramine; Phenylephrine: (Minor) Although desloratadine is considered a 'non-sedating' antihistamine, dose-related sedation has been noted. For this reason, it would be prudent to monitor for drowsiness during concurrent use of desloratadine with CNS depressants such as other H1-blockers.
Chlorpheniramine; Pseudoephedrine: (Minor) Although desloratadine is considered a 'non-sedating' antihistamine, dose-related sedation has been noted. For this reason, it would be prudent to monitor for drowsiness during concurrent use of desloratadine with CNS depressants such as other H1-blockers.
Clemastine: (Minor) Although desloratadine is considered a 'non-sedating' antihistamine, dose-related sedation has been noted. For this reason, it would be prudent to monitor for drowsiness during concurrent use of desloratadine with CNS depressants such as other H1-blockers.
Cyproheptadine: (Minor) Although desloratadine is considered a 'non-sedating' antihistamine, dose-related sedation has been noted. For this reason, it would be prudent to monitor for drowsiness during concurrent use of desloratadine with CNS depressants such as other H1-blockers.
Dexbrompheniramine: (Minor) Although desloratadine is considered a 'non-sedating' antihistamine, dose-related sedation has been noted. For this reason, it would be prudent to monitor for drowsiness during concurrent use of desloratadine with CNS depressants such as other H1-blockers.
Dexbrompheniramine; Pseudoephedrine: (Minor) Although desloratadine is considered a 'non-sedating' antihistamine, dose-related sedation has been noted. For this reason, it would be prudent to monitor for drowsiness during concurrent use of desloratadine with CNS depressants such as other H1-blockers.
Dexchlorpheniramine: (Minor) Although desloratadine is considered a 'non-sedating' antihistamine, dose-related sedation has been noted. For this reason, it would be prudent to monitor for drowsiness during concurrent use of desloratadine with CNS depressants such as other H1-blockers.
Dexchlorpheniramine; Dextromethorphan; Pseudoephedrine: (Minor) Although desloratadine is considered a 'non-sedating' antihistamine, dose-related sedation has been noted. For this reason, it would be prudent to monitor for drowsiness during concurrent use of desloratadine with CNS depressants such as other H1-blockers.
Dextromethorphan; Diphenhydramine; Phenylephrine: (Minor) Although desloratadine is considered a 'non-sedating' antihistamine, dose-related sedation has been noted. For this reason, it would be prudent to monitor for drowsiness during concurrent use of desloratadine with CNS depressants such as other H1-blockers.
Dimenhydrinate: (Minor) Although desloratadine is considered a 'non-sedating' antihistamine, dose-related sedation has been noted. For this reason, it would be prudent to monitor for drowsiness during concurrent use of desloratadine with CNS depressants such as other H1-blockers.
Diphenhydramine: (Minor) Although desloratadine is considered a 'non-sedating' antihistamine, dose-related sedation has been noted. For this reason, it would be prudent to monitor for drowsiness during concurrent use of desloratadine with CNS depressants such as other H1-blockers.
Diphenhydramine; Ibuprofen: (Minor) Although desloratadine is considered a 'non-sedating' antihistamine, dose-related sedation has been noted. For this reason, it would be prudent to monitor for drowsiness during concurrent use of desloratadine with CNS depressants such as other H1-blockers.
Diphenhydramine; Naproxen: (Minor) Although desloratadine is considered a 'non-sedating' antihistamine, dose-related sedation has been noted. For this reason, it would be prudent to monitor for drowsiness during concurrent use of desloratadine with CNS depressants such as other H1-blockers.
Diphenhydramine; Phenylephrine: (Minor) Although desloratadine is considered a 'non-sedating' antihistamine, dose-related sedation has been noted. For this reason, it would be prudent to monitor for drowsiness during concurrent use of desloratadine with CNS depressants such as other H1-blockers.
Doxylamine: (Minor) Although desloratadine is considered a 'non-sedating' antihistamine, dose-related sedation has been noted. For this reason, it would be prudent to monitor for drowsiness during concurrent use of desloratadine with CNS depressants such as other H1-blockers.
Doxylamine; Pyridoxine: (Minor) Although desloratadine is considered a 'non-sedating' antihistamine, dose-related sedation has been noted. For this reason, it would be prudent to monitor for drowsiness during concurrent use of desloratadine with CNS depressants such as other H1-blockers.
Fexofenadine: (Minor) Although desloratadine is considered a 'non-sedating' antihistamine, dose-related sedation has been noted. For this reason, it would be prudent to monitor for drowsiness during concurrent use of desloratadine with CNS depressants such as other H1-blockers.
Fexofenadine; Pseudoephedrine: (Minor) Although desloratadine is considered a 'non-sedating' antihistamine, dose-related sedation has been noted. For this reason, it would be prudent to monitor for drowsiness during concurrent use of desloratadine with CNS depressants such as other H1-blockers.
Heparin: (Minor) Antihistamines may partially counteract the anticoagulant actions of heparin, according to the product labels. However, this interaction is not likely of clinical significance since heparin therapy is adjusted to the partial thromboplastin time (aPTT) and other clinical parameters of the patient.
Hydroxyzine: (Minor) Although desloratadine is considered a 'non-sedating' antihistamine, dose-related sedation has been noted. For this reason, it would be prudent to monitor for drowsiness during concurrent use of desloratadine with CNS depressants such as other H1-blockers.
Levocetirizine: (Minor) Although desloratadine is considered a 'non-sedating' antihistamine, dose-related sedation has been noted. For this reason, it would be prudent to monitor for drowsiness during concurrent use of desloratadine with CNS depressants such as other H1-blockers.
Loratadine: (Major) Desloratadine is the active metabolite of Loratadine. These 2 drugs should not be given at the same time due to the duplication of therapy and the resultant increase in desloratadine concentrations, which may lead to increased CNS or anticholinergic effects.
Loratadine; Pseudoephedrine: (Major) Desloratadine is the active metabolite of Loratadine. These 2 drugs should not be given at the same time due to the duplication of therapy and the resultant increase in desloratadine concentrations, which may lead to increased CNS or anticholinergic effects.
Meclizine: (Minor) Although desloratadine is considered a 'non-sedating' antihistamine, dose-related sedation has been noted. For this reason, it would be prudent to monitor for drowsiness during concurrent use of desloratadine with CNS depressants such as other H1-blockers.
Pseudoephedrine; Triprolidine: (Minor) Although desloratadine is considered a 'non-sedating' antihistamine, dose-related sedation has been noted. For this reason, it would be prudent to monitor for drowsiness during concurrent use of desloratadine with CNS depressants such as other H1-blockers.
Sedating H1-blockers: (Minor) Although desloratadine is considered a 'non-sedating' antihistamine, dose-related sedation has been noted. For this reason, it would be prudent to monitor for drowsiness during concurrent use of desloratadine with CNS depressants such as other H1-blockers.
Sincalide: (Moderate) Sincalide-induced gallbladder ejection fraction may be affected by concurrent medications, including H1-blockers. False study results are possible; thorough patient history is important in the interpretation of procedure results.
Triprolidine: (Minor) Although desloratadine is considered a 'non-sedating' antihistamine, dose-related sedation has been noted. For this reason, it would be prudent to monitor for drowsiness during concurrent use of desloratadine with CNS depressants such as other H1-blockers.
Desloratadine is highly selective for histamine H1-receptors. Unlike cromolyn and nedocromil which block histamine release, H1-antagonists compete with free histamine for binding at H1-receptor sites. This competitive antagonism blocks the effects of histamine on H1-receptors in the GI tract, uterus, large blood vessels, and bronchial smooth muscle. Blockade of H1-receptors also suppresses the formation of edema, flare, and pruritus that result from histaminic activity. At higher concentrations, H1-receptor antagonism becomes relatively irreversible. In vitro studies have demonstrated that desloratadine has a 15-fold higher affinity for the H1-receptor than does the parent compound, loratadine.
Desloratadine does not readily cross the blood-brain barrier, and it preferentially binds at H1-receptors in the periphery rather than within the brain, which probably accounts for some of its nonsedating character. H1-blockers are similar in structure to anticholinergics, local anesthetics, antispasmodics, and ganglionic- and adrenergic-blocking agents, sharing some of their properties. H1-blockers possess anticholinergic properties in varying degrees; however, desloratadine does not exert significant anticholinergic effects at therapeutic concentrations.
In patients with allergic rhinitis, the inflammatory response plays a prominent role in the development of nasal obstruction and involves a number of mediators. Initial release of histamine from mast cells is followed by late-phase reactions involving a number of other cells, such as fibroblasts, epithelial cells, neutrophils, eosinophils (especially in conditions with raised IgE levels), macrophages, platelets, and lymphocytes. Cell adhesion can also be part of the inflammatory process. Desloratadine has demonstrated anti-inflammatory effects in both in vitro and in vivo studies. The anti-inflammatory action appears to be related to a reduction in eosinophils, neutrophils, interleukin-4 and interleukin-8.
Desloratadine is administered orally. It is extensively metabolized and only minimal amounts of the orally administered dose are recovered in the urine (less than 2%) and feces (less than 7%). The major metabolic pathway is hydroxylation to form 3-OH-desloratadine that is glucoronidated and the glucuronide conjugate is excreted in the urine and bile. The elimination plasma half-life is approximately 20 to 30 hours. Steady state plasma concentrations are attained in 4 to 6 days.
Affected cytochrome P450 (CYP450) isoenzymes and drug transporters: None
Clinically relevant drug interactions related to inhibition of CYP450 system enzymes, such as CYP3A4, or drug transporters (such as P-glycoprotein) with desloratadine have not been noted in drug-drug interaction studies. Desloratadine is a CYP3A4 and P-gp substrate. Increased plasma concentrations (Cmax and AUC) of desloratadine and 3-hydroxydesloratadine were observed with some potent CYP3A4 inhibitors in studies. However, there were no clinically relevant changes in the safety profile of desloratadine, as assessed by electrocardiographic parameters (including the corrected QT interval), clinical laboratory tests, vital signs and adverse events.
-Route-Specific Pharmacokinetics
Oral Route
Peak plasma concentrations are obtained 3 hours after a 5 mg oral dose of the conventional tablets. Food has no effect on the extent of desloratadine absorption. The conventional tablet, disintegrating tablet, and oral solution are bioequivalent.
-Special Populations
Hepatic Impairment
Patients with hepatic impairment, regardless of severity, have demonstrated mean desloratadine AUC values 2.4 times greater than the normal patient population. An increase in the mean elimination half-life of desloratadine is observed in these patients. Dosage adjustments for patients with hepatic impairment are recommended.
Renal Impairment
In adult patients with mild (CrCl 51 to 69 mL/minute/1.73 m2) or moderate (CrCl 34 to 43 mL/minute/1.73 m2) renal impairment, the median Cmax and AUC values increased 1.2- and 1.9-fold, respectively relative to subjects with normal renal function. In adult patients with severe renal impairment or who were hemodialysis dependent, median Cmax and AUC values increase by approximately 1.7- and 2.5-fold, respectively. Minimal changes in 3-OH-desloratadine were observed. Dosage adjustments of desloratadine are recommended for patients with renal impairment.
Pediatrics
Children 2 to 11 years
In a pharmacokinetic study, children (6 to 11 years of age) receiving a single dose of desloratadine 2.5 mg PO had plasma concentrations similar to those achieved in adults receiving 5 mg PO. In children (2 to 5 years of age), a single dose of desloratadine 1.25 mg resulted in desloratadine plasma concentrations similar to those achieved in adults receiving 5 mg PO. However, the Cmax and AUC of the metabolite (3-hydroxydesloratadine) were 1.27 and 1.61 times higher for adults compared to the Cmax and AUC obtained in children 2 to 11 years of age.
Infants and Children less than 2 years
In a pharmacokinetic study, children (6 to 23 months of age) were given a single dose of either 1.25 mg or 0.625 mg desloratadine PO. The results indicated that a dose of 1 mg for subjects aged 6-11 months and 1.25 mg for subjects 12-23 months of age is required to obtain desloratadine plasma concentrations similar to those achieved in adults administered a single 5 mg oral dose.
Geriatric
Elderly patients over 65 years old have shown mean AUC and Cmax values which were 20% greater than those of younger adults. The mean plasma elimination half-life was prolonged by approximately 30%. Dosage adjustment of desloratadine does not appear to be warranted in the elderly population.
Gender Differences
AUC and Cmax values are not significantly different among gender, so no dosage adjustment among this group is necessary with desloratadine use.
Ethnic Differences
AUC and Cmax values are not significantly different among race, so no dosage adjustment among this group is necessary with desloratadine use.
Other
Slow metabolizers
Slow metabolizers of desloratadine have been identified. In this patient population (which is estimated at 4%), half-lives are much longer (up to 60 hours), and median AUC values are approximately 6-fold higher. However, major differences in safety have not been observed between slow and normal metabolizers; however, an increased risk of exposure-related adverse events in patients who are poor metabolizers cannot be ruled out. The major elimination pathway for slow metabolizers is via excretion of unchanged drug in the urine and feces.