LORATADINE (Generic for CHILDRENS CLARITIN)

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

Route-Specific Administration

Oral Administration
-Loratadine may be administered without regard to meals.
Oral Solid Formulations
Rapidly-disintegrating oral tablets
-Open blister package with dry hands; use tablet immediately after removing from package.
-Place tablet on patient's tongue; patient must allow to dissolve and then swallow. May be administered with or without water.

Oral Liquid Formulations
-Oral syrup or solution: Measure dosage using a calibrated measuring device, such as an oral syringe, to ensure accurate dosing.

Similar to other low-sedating antihistamines, side effects from loratadine reported in placebo-controlled trials in adults and children aged 12 years and older include headache (12% vs. 11% placebo), somnolence/drowsiness (8% vs. 6% placebo) and fatigue (4% vs. 3% placebo). Dizziness, hypoesthesia, hyperhidrosis, tremor, vertigo, asthenia, dysphonia, hypertonia, malaise, migraine, muscle cramps (legs), back pain, paresthesias, arthralgia, and myalgia have been reported in at least one adult or pediatric patient receiving loratadine during clinical trials. Nervousness (4% vs. 2% placebo), dysphonia (2% vs. < 1% placebo), fatigue (3% vs. 2% placebo), malaise (2% vs. 0% placebo) and hyperkinesis (3% vs. 1% placebo) have been reported in placebo-controlled trials in children 6 to 12 years old. Fatigue also occurred in 2% to 3% of young children (2 to 5 years old) treated with loratadine during the placebo-controlled trial. Seizures have been reported rarely during post-marketing experience (patient ages unspecified). Patients should be warned about undertaking hazardous tasks while taking loratadine, although the risk of sedation is relatively low.

Gastrointestinal adverse reactions have been reported in pediatric patients receiving loratadine. Diarrhea occurred in 2-3% of young children (2 to 5 years old) treated with loratadine during the placebo-controlled trial. In placebo-controlled trials, abdominal pain (2% vs. 0% placebo) was reported in children 6 to 12 years old. In addition, the following adverse events have been reported in at least one adult or pediatric patient receiving loratadine during clinical trials: dysgeusia, anorexia, constipation, diarrhea, dyspepsia, flatulence, gastritis, hiccups, appetite stimulation, loose stools, weight gain, polydipsia, nausea, vomiting.

Adverse effects of the mouth, nose, and throat may occur during loratadine therapy. Pharyngitis, epistaxis, otalgia, stomatitis, influenza-like symptoms, and tooth disorder occurred in 2% to 3% of young children 2 to 5 years old treated with loratadine. Wheezing (4% vs. 2% placebo) was reported in children 6 to 12 years of age. Xerostomia (3% vs. 2% placebo) was reported patients age 12 years and older. Adverse effects reported in at least one adult or pediatric patient receiving loratadine during clinical trials include altered salivation, bronchitis, bronchospasm, dyspnea, hemoptysis, laryngitis, nasal dryness, sinusitis, otalgia, and tinnitus.

Cardiovascular adverse events may occur during loratadine therapy. Hypertension, hypotension, palpitations, supraventricular tachycardia (SVT), syncope, sinus tachycardia, and chest pain (unspecified) have been reported in at least one adult or pediatric patient receiving loratadine during clinical trials. Peripheral edema has been reported during post-marketing experience (patient ages unspecified). Palpitations have been reported in children with overdoses of greater than 10 mg of loratadine. In a human study in which doses 4 times the clinical dose were administered to adults for up to 90 days, loratadine did not cause clinically significant changes on the QT interval. The manufacturer reports that in a single, rising-dose study in which doses up to 160 mg (16 times the clinical dose) were studied in adults, loratadine did not cause any clinically significant changes on the QTc interval.

Infection and signs and symptoms of infections have been reported in pediatric patients treated with loratadine. Viral infection occurred in 2-3% of young children 2 to 5 years old receiving loratadine. Upper respiratory infection (2% vs. <1% placebo) has been reported in children 6 to 12 years of age. Adverse effects reported in at least one adult or pediatric patient receiving loratadine during clinical trials include cough, chills, fever and sneezing.

The following psychiatric adverse events have been reported in at least one patient in loratadine clinical trials in adult and pediatric patients: amnesia, anxiety, confusion, depression, impaired concentration, insomnia, irritability, paranoia.

The following adverse events have been reported in at least one patient in loratadine clinical trials in adult and pediatric patients: mastalgia, dysmenorrhea, menorrhagia, and vaginitis. In addition, breast enlargement has been reported during post-marketing experience (patient ages unspecified).

Hypersensitivity reactions have been reported with loratadine. During clinical trials, rash (unspecified) was reported in 2% to 3% of children 2 to 5 years of age. The following adverse events have been reported in at least one patient in loratadine clinical trials in adult and pediatric patients: angioedema, dermatitis, dry hair, dry skin (xerosis), flushing, photosensitivity reaction, pruritus, purpura, urticaria. In addition, anaphylactoid reactions, alopecia, and erythema multiforme have been reported rarely during post-marketing experience (patient ages unspecified).

Renal adverse events may occur during loratadine therapy.The following adverse events have been reported in at least one patient in loratadine clinical trials in adult and pediatric patients: altered micturition, urine discoloration, urinary incontinence, urinary retention.

Hepatic adverse events may occur during loratadine therapy. During post-marketing experience, abnormal hepatic function (elevated hepatic enzymes), jaundice, hepatitis, and hepatic necrosis have been reported (patient ages unspecified).

Thrombocytopenia has been reported rarely during post-marketing experience with loratadine (patient ages unspecified).

Visual impairment may occur during loratadine therapy. Conjunctivitis (2% vs. < 1% placebo) was reported in pediatric patients age 6 to 12 years. Altered lacrimation, blurred vision, ocular pain, and blepharospasm have been reported in at least one adult or pediatric patient receiving loratadine during clinical trials.

Loratadine is contraindicated in any individual hypersensitive to the drug or any of the ingredients of the specific drug formulation, or in any patient hypersensitive to desloratadine, due to cross-sensitivity.

Loratadine is extensively metabolized in the liver. Loratadine should be used cautiously in those with hepatic disease and initial dosage adjustments for hepatic impairment should be made according to the manufacturer's guidelines based on age of the pediatric patient.

The AUC and Cmax of loratadine and its metabolite are elevated in the presence of significant renal impairment (CrCl < 30 ml/min) or renal failure. Loratadine should be used cautiously in those with renal failure or impairment and initial dosage adjustments should be made according to the manufacturer's guidelines based on age of the pediatric patient.

Loratadine is generally non-sedating. However, the drug may cause drowsiness or somnolence in individual patients; therefore patients receiving this medication should be advised to avoid activities requiring coordination and concentration until the effects of the drug are known.

Some formulations of loratadine (e.g., Alavert Orally Disintegrating tablets, Dimetapp ND Orally Disintegrating tablets) contain aspartame, a source of phenylalanine. These products should be used cautiously in patients with phenylketonuria.

Safety and efficacy of loratadine have not been established in infants or children <= 2 years of age ; data in infants are extremely limited. Antihistamines generally should not be used in neonates due to the possibility of paradoxical CNS stimulation or other adverse effects.

Description: Loratadine is an oral non-sedating H1-receptor antagonist. Loratadine is effective in the once daily for seasonal allergic rhinitis and chronic spontaneous urticaria. Structurally, loratadine is similar to cyproheptadine and azatadine, but differs from the other non-sedating H1-blockers terfenadine and astemizole. Due to poor penetration into the CNS and a low affinity for CNS H1-receptors, the CNS effects are less with loratadine compared to the traditional H1-blockers. Unlike astemizole and terfenadine, loratadine has not been associated with QT prolongation or torsades de pointes. Loratadine is FDA approved in pediatric patients as young as 2 years of age.

For the management of symptoms of seasonal allergies or perennial allergies, including allergic rhinitis:
Oral dosage (oral syrup or solution):
Children 2 to 5 years: 5 mg PO once daily. Do not exceed 5 mg in 24 hours.
Children and Adolescents 6 to 17 years: 10 mg PO once daily. Do not exceed 10 mg in 24 hours.
Oral dosage (chewable tablets):
Children 2 to 5 years: 5 mg PO once daily. Do not exceed 5 mg in 24 hours.
Children and Adolescents 6 to 17 years: 10 mg PO once daily. Do not exceed 10 mg in 24 hours.
Oral dosage (orally disintegrating tablets):
Children and Adolescents 6 to 17 years: 10 mg/day PO, given as 5 mg PO twice daily or 10 mg PO once daily. Tablet disintegrates on tongue with or without water. Do not exceed 10 mg in 24 hours.
Oral dosage (tablet or capsules):
Children and Adolescents 6 to 17 years: 10 mg PO once daily. Do not exceed 10 mg in 24 hours.

For the management of symptoms of chronic spontaneous urticaria (e.g., relief of pruritus, reduction in the size and number of hives):
Oral dosage (oral syrup or solution):
Children 2 to 5 years: 5 mg PO once daily. Do not exceed 5 mg in 24 hours.
Children and Adolescents 6 to 17 years: 10 mg PO once daily. Do not exceed 10 mg in 24 hours.
Oral dosage (chewable tablets):
Children 2 to 5 years: 5 mg PO once daily. Do not exceed 5 mg in 24 hours.
Children and Adolescents 6 to 17 years: 10 mg PO once daily. Do not exceed 10 mg in 24 hours.
Oral dosage (orally disintegrating tablets):
Children and Adolescents 6 to 17 years: 10 mg/day PO, given as 5 mg PO twice daily or 10 mg PO once daily. Tablet disintegrates on tongue with or without water. Do not exceed 10 mg in 24 hours.
Oral dosage (tablet or capsules):
Children and Adolescents 6 to 17 years: 10 mg PO once daily. Do not exceed 10 mg in 24 hours.

Maximum Dosage Limits:
-Neonates
Safety and efficacy have not been established.
-Infants
Safety and efficacy have not been established.
-Children
1 year: Safety and efficacy have not been established.
2 to 5 years: 5 mg/day PO.
6 to 12 years: 10 mg/day PO.
-Adolescents
10 mg/day PO.

Patients with Hepatic Impairment Dosing
Adjust dose in hepatic impairment as listed.
-children 2-5 years: reduce initial dose to 5 mg PO every other day.
-children >= 6 years and adolescents: reduce initial dosage to 10 mg PO every other day.

Patients with Renal Impairment Dosing
CrCl >= 30 ml/min: No adjustment needed.
CrCl < 30 ml/min: Adjust dosage as listed.
-children 2-5 years: reduce initial dose to 5 mg PO every other day.
-children >= 6 years and adolescents: reduce initial dosage to 10 mg PO every other day.

Intermittent hemodialysis
See dosage for pediatric patients with CrCl < 30 ml/min. Loratadine and its active metabolite are not removed by hemodialysis.

*non-FDA-approved indication

Monograph content under development

Mechanism of Action: Loratadine 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 muscle. Loratadine 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, loratadine does not exert significant anticholinergic effects at therapeutic concentrations. In vitro studies have shown that loratadine has a weak affinity for acetylcholine and alpha-adrenergic receptors.

Pharmacokinetics: Loratadine is administered orally. It is 97% protein-bound. Loratadine has a high first pass effect and is almost completely metabolized in the liver to the minimally active metabolite, descarboethoxyloratadine. In vitro studies indicate that metabolism to descarboethoxyloratadine predominantly by CYP3A4 and, to a lesser extent, by cytochrome CYP2D6. In the presence of a CYP3A4 inhibitor, loratadine is metabolized to descarboethoxyloratadine predominantly by CYP2D6. The normal mean elimination half-lives of loratadine and its metabolite are 8.4 hours (range 3 to 20 hours) and 28 hours, respectively. Elimination occurs through the fecal and renal routes.

Affected cytochrome P450 (CYP450) isoenzymes and drug transporters: CYP3A4, CYP2D6, P-gp
Metabolism of loratadine occurs predominantly by CYP3A4 and to a lesser extent by cytochrome CYP2D6. Concurrent administration with either ketoconazole, erythromycin (both CYP3A4 inhibitors), or cimetidine (CYP2D6 and CYP3A4 inhibitor) to healthy volunteers was associated with increased plasma concentrations of loratadine. However, in drug-drug interaction studies there were no clinically relevant changes in the safety profile of loratadine associated with these increases. Loratadine is also a substrate for P-glycoprotein (P-gp) transport; however, no clinically significant drug-drug interactions have been reported with P-gp inhibitors.


-Route-Specific Pharmacokinetics
Oral Route
After oral administration, the onset of action of loratadine occurs within 1-3 hours, with peak effects in 8-12 hours and a duration of action greater than 24 hours. Administration with food increases absorption and AUC up to 40% for the syrup or tablets and up to 48% for the rapidly-disintegrating tablets. The time to peak concentrations is also delayed by administration with food. However, since the clinical response is unaffected, the manufacturer states that the drug can be administered without regard to meals.


-Special Populations
Pediatrics
Children 2-5 years
The pharmacokinetic profile of loratadine in children (2-5 years of age) is similar to that of adults. The pharmacokinetic parameters (AUC and Cmax) of 18 children (aged 2-5 years) receiving a single-dose of 5 mg loratadine syrup were comparable to those after administration of a 10 mg tablet or syrup to adult volunteers or children >= 8 years of age and older.

Children 6-12 years
The pharmacokinetic profile of loratadine in children ages 6-12 years is similar to that of adults. The pharmacokinetic parameters (AUC and Cmax) of 13 children (aged 8-12 years) receiving a single-dose of 10 mg loratadine syrup were comparable to those following administration of a 10 mg tablet or syrup to adult volunteers.

Hepatic Impairment
Loratadine dosages should be altered in patients with hepatic impairment, based on pharmacokinetic data in adult patients.

Renal Impairment
Loratadine dosages should be altered in adult patients with renal impairment (CrCl < 30 ml/min). Peak serum concentrations of loratadine may increase up to 73% in the presence of renal impairment in adults; although elimination half-lives are similar to those of normal adult controls. Hemodialysis does not alter the pharmacokinetics of loratadine or its metabolite.