DESLORATADINE (Generic for CLARINEX)

General Administration Information
For storage information, see the specific product information within the How Supplied section.

Route-Specific Administration

Oral Administration
May administer desloratadine with or without food.
Oral Solid Formulations
-Tablets: Swallow tablets whole; do not chew.
-Disintegrating Tablets: Place tablet on the tongue and allow to disintegrate before swallowing. May be taken with or without water. Administer immediately after opening the blister.

Oral Liquid Formulations
-Oral syrup: Administer using an oral syringe, or other calibrated oral measuring device to ensure accurate dosing.

Due to poor penetration into the central nervous system (CNS) and a low affinity for CNS H1-receptors, CNS effects are less with desloratadine, a non-sedating antihistamine, as compared to the traditional H1-blockers, such as diphenhydramine. Somnolence/drowsiness was reported in 9.1% of infants age 6 to 11 months and in 2.1% of pediatric patients age 12 years or older receiving desloratadine. Irritability (12.1%) and insomnia (4.5%) were reported in infants age 6 to 11 months. Emotional lability (3.1%) was reported in young children age 12 to 23 months. Headache (14%), fatigue (2.1% to 5%), dizziness (4%), and myalgia (2.1% to 3%) have been reported during multiple-dose placebo-controlled trials of desloratadine in pediatric patients 12 years or older.

Erythema (3%) was reported in infants age 6 to 11 months and maculopapular rash (3.1%) was reported in pediatric patients 12 to 23 months of age; both side effects occurred at higher rates than with placebo. Rare cases of hypersensitivity reactions, such as rash (unspecified), pruritus, urticaria, edema, dyspnea, and anaphylactoid reactions have been reported postmarketing with desloratadine (patient ages unspecified).

Respiratory and infectious adverse reactions can occur in pediatric patients receiving desloratadine. Pharyngitis (3.1% to 4.5%) was reported in pediatric patients age 6 months to 5 years. Fever was reported in 12.1% of infants age 6 to 11 months, 16.9% of young children age 12 to 23 months, and 5.5% of patients age 2 to 5 years. Upper respiratory tract infection was reported in 21.2% of infants age 6 to 11 months and 10.8% of young children age 12 to 23 months. Bronchitis (6.1%), otitis media (6.1%), and rhinorrhea (4.5%) were reported in infants age 6 to 11 months. Cough (10.6% to 10.8%) was reported in pediatric patients age 6 to 23 months. Epistaxis (3.1%) and parasitic infection (3.1%) were reported in young children age 12 to 23 months. Urinary tract infection (3.6%) and varicella (3.6%) were reported in young children age 2 to 5 years.

Gastrointestinal adverse reactions have been reported in pediatric patients receiving desloratadine. Vomiting (6.1%) and anorexia (4.5% were reported in infants age 6 to 11 months. Diarrhea (15.4% to 19.7%) was reported infants/young children age 6 to 23 months. Nausea was reported in 3% of infants 6 to 11 months of age and 5% of pediatric patients 12 years or older. Appetite stimulation (3.1%) was reported in young children age 12 to 23 months. Xerostomia (3%) and dyspepsia (3%) were reported in pediatric patients 12 years and older.

Dysmenorrhea has been reported in 2.1% of adolescent pediatric patients 12 years and older receiving desloratadine.

Palpitations and sinus tachycardia were reported during postmarketing with desloratadine (patient ages unspecified).

Elevated hepatic enzymes including hyperbilirubinemia, and very rarely, hepatitis have all been reported during postmarketing experience with desloratadine (patient ages unspecified).

Seizures, psychomotor hyperactivity (restlessness), and involuntary movements including dystonic reaction, tics, and extrapyramidal symptoms have been reported during postmarketing use of desloratadine.

Desloratadine is contraindicated in patients who are hypersensitive to desloratadine, loratadine, or to any of the desloratadine product ingredients.

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. Due to lack of data in pediatric patients with hepatic or renal impairment, specific dosage adjustments are not available.

The safety and effectiveness of desloratadine in infants < 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 effects.

While desloratadine is generally non-sedating, the drug may cause drowsiness or somnolence in individual patients; therefore, patients receiving desloratadine should be advised to avoid activities requiring coordination and concentration 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 pediatric patients with phenylketonuria.

Description: Desloratadine is a non-sedating, potent, long-acting antihistamine, with selective H1 receptor histamine antagonist activity. Desloratadine is effective in the once daily treatment of seasonal allergic rhinitis, perennial allergic rhinitis, and chronic spontaneous urticaria. Due to poor penetration into the central nervous system (CNS) and a low affinity for CNS H1-receptors, CNS effects are less with desloratadine as compared to the traditional H1-antagonists, such as diphenhydramine. 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 when given in doses 4 to 9 times the recommended dose in adults. Desloratadine is FDA approved in infants and children as young as 6 months of age.

For the management of symptoms of seasonal allergies or perennial allergies, including allergic rhinitis:
Oral dosage (oral solution):
Infants 6 to 11 months: 1 mg PO once daily. NOTE: Desloratadine is not FDA-approved for the treatment of seasonal allergic rhinitis in infants.
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.
Children 6 to 11 years: 2.5 mg PO once daily.
Children and Adolescents 12 years and older: 5 mg PO once daily.
Oral dosage (orally disintegrating tablet):
Children 6 to 11 years: 2.5 mg PO once daily.
Children and Adolescents 12 years and older: 5 mg PO once daily.
Oral dosage (tablet):
Children and Adolescents 12 years and older: 5 mg PO once daily.

For the treatment of symptoms of chronic spontaneous urticaria (e.g., relief of pruritus, reduction in the size and number of hives):
Oral dosage (oral solution):
Infants 6 months and older: 1 mg PO once daily.
Children 1 to 5 years: 1.25 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.
Oral dosage (orally disintegrating tablet):
Children 6 to 11 years: 2.5 mg PO once daily.
Children and Adolescents 12 years and older: 5 mg PO once daily.
Oral dosage (tablet):
Children and Adolescents 12 years and older: 5 mg PO once daily.

Maximum Dosage Limits:
-Neonates
Safety and efficacy have not been established.
-Infants
Less than 6 months: Safety and efficacy have not been established.
6 to 11 months: 1 mg/day PO.
-Children
1 to 5 years: 1.25 mg/day PO.
6 to 11 years: 2.5 mg/day PO.
12 years: 5 mg/day PO.
-Adolescents
5 mg/day PO.

Patients with Hepatic Impairment Dosing
Recommendations for dosage adjustments in pediatric patients with hepatic impairment are not available, but dosage interval adjustment may be necessary. Adults with hepatic impairment receive an adjusted starting dose of 5 mg PO every other day.

Patients with Renal Impairment Dosing
CrCl greater than 50 mL/minute: No dosage adjustments are necessary.
CrCl 50 mL/minute or less: Recommendations for pediatric patients with renal impairment are not available, but dosage interval adjustment may be necessary. Adult dosages are adjusted to 5 mg PO every other day.

Intermittent hemodialysis
See dosage for CrCl 50 mL/minute or less. Desloratadine and its metabolite are not removed by hemodialysis.

*non-FDA-approved indication

Monograph content under development

Mechanism of Action: 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.

Pharmacokinetics: Desloratadine is administered orally. Desloratadine 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 of desloratadine 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
Pediatrics
Infants and Children < 2 years
In a pharmacokinetic study, children (6-23 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 to 11 months and 1.25 mg for subjects 12 to 23 months of age is required to obtain desloratadine plasma concentrations similar to those achieved in adults administered a single 5 mg dose.

Children 2-5 years
In children (2- 5 years of age), a single dose of desloratadine 1.25 mg resulted in desloratadine plasma concentrations similar to those achieved in adults administered a single 5 mg dose. 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 2-11 years of age.

Children 6-11 years
In a pharmacokinetic study, children (6-11 years of age) receiving a single dose of desloratadine 2.5 mg PO had plasma concentrations similar to those achieved in adults receiving a single 5 mg dose. 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 2-11 years of age.

Hepatic Impairment
Adult 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. Dosage adjustments for adult patients with hepatic impairment are recommended; specific recommendations for pediatrics are not available.

Renal Impairment
In adult patients with mild (creatinine clearance 51-69 ml/min/1.73 m2) or moderate (creatinine clearance 34-43 ml/min/1.73 m2) renal impairment, the median Cmax and AUC values increased 1.2- and 1.9-fold, respectively relative to adult subjects with normal renal function. In adults 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 for adult patients are recommended; specific recommendations for pediatrics are not available.

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. The major elimination pathway for slow metabolizers is via excretion of unchanged drug in the urine and feces.