5 Loratadine and Desloratadine Use in Children
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PEDIATRIC PHARMACOTHERAPY A Monthly Newsletter for Health Care Professionals from the University of Virginia Children’s Hospital Volume 17 Number 5 May 2011 Loratadine and Desloratadine Use in Children Marcia L. Buck, Pharm.D., FCCP, FPPAG oratadine is one of the most widely used does not significantly alter absorption. Both L antihistamines in the United States. compounds are highly protein bound (80-90%). Introduced on April 12, 1993 as a prescription medication for the treatment of perennial or Loratadine is metabolized via cytochrome P450 seasonal allergic rhinitis and chronic idiopathic 3A4 (CYP3A4) and to a lesser extent by urticaria, it is now available without a CYP2D6. The major metabolite of loratadine, prescription or “over the counter” (OTC) in a desloratadine, is metabolized to 3- wide variety of formulations.1,2 Desloratadine, hydroxydesloratadine. This compound then the single active isomer of loratadine, was undergoes glucuronidation prior to excretion. approved by the Food and Drug Administration The mean elimination half-lives of both (FDA) on December 21, 2001 and still requires a loratadine and desloratadine are approximately prescription.3,4 Both versions are approved for 27-28 hours in healthy adults. It has been pediatric use: loratadine for children as young as estimated that up to 6% of the population are 2 years of age and desloratadine for infants 6 poor metabolizers of desloratadine, having a months of age and older. This issue of Pediatric half-life of more than 50 hours. Hepatic Pharmacotherapy will provide a brief review of dysfunction also extends the half-lives of both loratadine and desloratadine, focusing on studies drugs in adults.2-4 supporting their use in the pediatric population. The pharmacokinetic profiles of both loratadine Mechanism of Action and desloratadine have been studied in children Loratadine is a long-acting tricyclic second- and appear similar to values found in adults. In generation antihistamine. It is an antagonist at 1995, Lin and colleagues studied the peripheral histamine (H1) receptors. pharmacokinetics of loratadine in 14 children Desloratadine (descarboethoxyloratadine) is the between 8 and 12 years of age.5 The children active metabolite of loratadine and produces the weighing less than 30 kg received a single dose same pharmacologic effect as the parent of 5 mg loratadine syrup and those weighing compound. An oral dose of loratadine or more than 30 kg were given a 10 mg dose. The desloratadine typically begins to inhibit the mean loratadine peak concentration of 4.38 wheal and flare reaction after intradermal ng/mL occurred at an average of 1 hour after histamine injection within 1-3 hours, reaches a administration. The average peak desloratadine peak effect within 8-12, and lasts for concentration, 3.79 ng/mL, was reached at 1.69 approximately 24 hours. As with other second- hours. While the elimination half-life for generation antihistamines, neither drug crosses loratadine was not evaluated, the average half- the blood-brain barrier in significant quantities to life for desloratadine was 13.8 hours. produce central nervous system (CNS) effects. While up to 100% of central H1 receptors may be In 2000, Salmun and colleagues studied occupied by first-generation antihistamines, the loratadine pharmacokinetics in children between second-generation agents typically occupy only 2 and 5 years of age.6 In their open-label study, 20% of these receptors.1-4 18 children received a single 5 mg dose of loratadine syrup. The maximum serum Pharmacokinetics concentrations of loratadine and desloratadine Both loratadine and desloratadine are rapidly were 7.8 ng/mL and 5.1 ng/mL, respectively. absorbed after oral administration. Loratadine The peak concentration of loratadine occurred at reaches maximum concentrations in 1-1.5 hours, 1.2 hours, with a desloratadine peak at 2.3 hours, compared to 3 hours for desloratadine. Food similar to the results observed in older children. The pharmacokinetic profile of desloratadine has Significant improvement in allergy symptoms been studied by Gupta and colleagues in both was reported in both groups, with a response of infants and children. In their 2006 paper excellent or good in 83.3% of the loratadine published in the British Journal of Clinical patients and 58.8% of the astemizole group. Pharmacology, the authors described the results of two open-label single-dose studies, one in 18 Lutsky and colleagues compared loratadine and children 2-5 years of age and one in 18 children terfenadine in an international study of 96 3-6 6-11 years of age.7 The younger children year old children with allergic rhinitis.11 Patients received 1.25 mg of desloratadine syrup and the were randomized to receive loratadine (5 or 10 older subjects were given 2.5 mg. In both mg once daily) or terfenadine (15 mg twice groups, maximum desloratadine concentrations daily) for 14 days. Mean scores for nasal and occurred at 2 hours after dosing. The average non-nasal allergy symptoms were significantly elimination half-life was 16.4 + 13.9 in the reduced from baseline in both groups (p < 0.05) younger children and 19.4 + 15.8 hours for the at days 3, 7, and 14. Non-nasal symptoms were older group. more likely to improve with loratadine (p < 0.05). Therapeutic response was rated as In a separate study, Gupta and colleagues used a excellent or good in 82% of the loratadine population pharmacokinetic analysis to evaluate patients and 60% of the terfenadine group. desloratadine in 58 infants and children between 6 months to 2 years of age.8 Subjects were The first published report of desloratadine in randomly assigned to either a 0.625 mg or 1.25 children was a tolerability study conducted by the mg dose of desloratadine syrup. The mean peak manufacturer. Bloom and colleagues performed desloratadine concentrations were 1.69 ng/mL in a double-blind, placebo-controlled trial in 111 the patients less than 1 year of age and 1.56 children between 2 and 5 years of age and 129 ng/mL in the patients 1-2 years of age. The time children 6 to 11 years of age.12 Desloratadine to reach maximum concentration was similar in doses were 1.25 mg in the younger group and 2.5 the two groups: 3.16 hours in the infants and 3.1 mg in the older children. There were no hours in the 1-2 year olds). The estimated significant differences in the incidence of minor elimination half-life was 14.6 hours in the infants adverse effects between active drug and placebo and 12.4 hours in the 1-2 year old group. The in either age group. No serious or severe adverse results of these three studies establish the event were reported. Electrocardiogram (ECG) similarity in pharmacokinetic characteristics of results showed no significant changes. desloratadine in infants, children, and adults. In 2005, Rossi and coworkers described the first Clinical Trials clinical efficacy trial of desloratadine in In 1989, Boner and colleagues compared the children.13 A total of 54 children (6-12 years of efficacy and safety of loratadine to standard age) were enrolled in their 4-week open-label therapy with a first-generation antihistamine in trial. The patients received 2.5 mg desloratadine 40 children with allergic rhinitis.9 Patients were syrup once daily. Rhinorrhea, sneezing, nasal randomized to receive either loratadine (2.5 or 5 congestion, cough, ocular symptoms, and itching mg once daily, equivalent to 0.11-0.24 mg/kg, were significantly reduced during the study. In once daily) or dexchlorpheniramine (0.1-0.23 the children with underlying asthma, the use of mg/kg every 8 hours) for 14 days. Nasal short-acting beta2-adrengergic agonists was also discharge, congestion, and nasal itching, as well reduced. There only adverse effects reported as itching, burning, or watery eyes and itching of were one case each of insomnia and diarrhea. the ears or palate were evaluated at days 3, 7, and 14. Both drugs significantly reduced nasal and The safety of desloratadine was evaluated in ocular symptoms compared to baseline children 6 months to 2 years of age by Prenner throughout the duration of the study (p < 0.01). and colleagues in 2006.14 Two hundred fifty-five While both drugs were well tolerated overall, children were randomized to either desloratadine only the children in the dexchlorpheniramine (1 or 1.25 mg once daily, depending on age) or group experienced drowsiness. placebo for 15 days. The most commonly reported adverse effects were somnolence (in These investigators published another pediatric 5.3% of desloratadine and 7.3% of controls), loratadine study in 1992, comparing loratadine (5 diarrhea (6.1% and 2.4%, respectively), and or 10 mg once daily) and astemizole (0.2 mg/kg irritability (6.9% and 5.6%, respectively). There once daily).10 Forty-one children (6-14 years of were no significant changes in ECG parameters age) were enrolled in the 14-day blinded study. and no serious or severe adverse effects. In 2007, Dizdar and colleagues compared regular The adverse effects of desloratadine were studied and intermittent “as needed” desloratadine by the manufacturer in three placebo-controlled administration in 37 adolescents (ages 12-18 clinical trials of 246 children between 6 months years) with allergic rhinitis.15 Patients were and 11 years of age. In the oldest children (those randomized to a regimen of 10 mg desloratadine between 6 and 11 years of age), there were no each morning for 4 weeks or 10 mg daily on an adverse effects reported in more than 2% of as needed basis. There were no differences patients. In the 2-5 year old group, the most between the groups in symptom control.