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LORATADINE AND RELATED AGENTS

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Classification   |    Detailed evidence-based information

Substances Included Synonyms

Therapeutic Toxic Class

    A) Loratadine and desloratadine (a major metabolite of loratadine) are long acting tricyclic histamine antagonists with selective H1-receptor histamine antagonist activity used in the treatment of allergic rhinitis.

Specific Substances

    A) DESLORATADINE
    1) DCL
    2) Decarboethoxyloratadine
    3) Descarboethoxyloratadine
    4) Molecular formula: C19-H19-CIN2
    LORATADINE
    1) Loratadin
    2) Loratadinum
    3) Sch-29581
    4) CAS 79794-75-5
    5) Molecular formula: C22-H23-CIN2-O2

Available Forms Sources

    A) FORMS
    1) DESLORATADINE
    1) Oral tablet: 5 mg light blue round coated tablet packaged in bottles of 100 and 500 (Prod Info CLARINEX(R) tablets, syrup, 2005)
    2) Oral, disintegrating tablet (reditab): 2.5 mg, 5 mg tablets taken immediately after opening with or without water (Prod Info CLARINEX(R) tablets, syrup, 2005)
    3) Oral Syrup: orange colored liquid containing 0.5 mg/mL desloratadine in a 4 or 16 ounce bottle (Prod Info CLARINEX(R) tablets, syrup, 2005)
    4) Oral, extended release tablet (12 hour formula): contains 2.5 mg desloratadine in an immediate-release layer and 120 mg of pseudoephedrine sulfate in an extended-release layer; supplied in bottles of 100 (Prod Info CLARINEX-D(R) 12 HOUR extended release tablets, 2006)
    5) Oral, extended release tablet (24 hour formula): contains 5 mg desloratadine in an immediate-release layer and 240 mg pseudoephedrine sulfate in an extended-release layer; supplied in bottles of 100 (Prod Info CLARINEX-D(R) 24 hour tablet, 2005)
    2) LORATADINE
    1) Syrup: loratadine 1 mg/mL available by prescription only in 16 ounces, (Prod Info CLARITIN(R) tablets, syrup, disintegrating tablets, 2000) and available OTC in 5 mg/5 mL in 118 mL
    2) Oral tablet: 10 mg loratadine (Prod Info Claritin(R), 2000a; Prod Info ALAVERT(TM) oral tablet, 2005)
    3) Oral tablet, extended release: contains 10 mg loratadine and pseudoephedrine sulfate 240 mg for allergy relief and nasal congestion; 24 hour formulation (Prod Info CLARITIN-D(R) 24 Hour extended-release oral tablets, 2002)
    4) Oral, rapidly disintegrating tablet: 2.5 mg, 5 mg available OTC in counts of 5, 10, 30 and 40 tablets and 10 mg tablets in packages of 30 tablets (Prod Info Claritin Reditabs(R) loratadine rapidly-disintegrating tablets, 2000). Another formulation contains 10 mg loratadine and 8.4 mg phenylalanine per tablet (Prod Info ALAVERT(TM) oral disintegrating tablet, 2004).
    B) USES
    1) Loratadine and desloratadine are used for the relief of allergic rhinitis for both seasonal and perennial symptoms. They are also indicated for the relief of pruritus and hives in patients with chronic idiopathic urticaria (Prod Info CLARINEX(R) tablets, 2002; Prod Info CLARITIN(R) oral disintegrating tablet, syrup, tablet, 2000).

Overview

Life Support

    A) This overview assumes that basic life support measures have been instituted.

Clinical Effects

    0.2.1) SUMMARY OF EXPOSURE
    A) USES: Loratadine and desloratadine are used for the relief of allergic rhinitis for both seasonal and perennial symptoms. They are also indicated for the relief of pruritus and hives in patients with chronic idiopathic urticaria.
    B) PHARMACOLOGY: Loratadine and desloratadine (a major metabolite of loratadine) are long acting tricyclic histamine antagonists with selective H1-receptor histamine antagonist activity.
    C) EPIDEMIOLOGY: Overdose is rare.
    D) WITH THERAPEUTIC USE
    1) COMMON: Xerostomia, headache, somnolence, and fatigue have been reported in adults. Children (6 to 12 years) also developed nervousness, wheezing, hyperkinesia, abdominal pain and conjunctivitis in addition to symptoms reported with adults following therapeutic use. In young children (2 to 5 years), diarrhea, epistaxis, pharyngitis, influenza-like symptoms, stomatitis, earache, fatigue, and rash were observed. RARE: Hepatotoxicity, ventricular dysrhythmias, anaphylaxis, alopecia, erythema multiforme, peripheral edema, and seizures.
    E) WITH POISONING/EXPOSURE
    1) MILD TO MODERATE: ADULT: Somnolence, tachycardia, and headache have been reported in overdose (range 40 to 180 mg). Additional symptoms have included lethargy, syncope, urticaria, and vomiting. Sinus tachycardia (150 bpm) and respiratory alkalosis were reported in an adult following an ingestion of 300 mg; the patient recovered completely. PEDIATRIC: Extrapyramidal signs and palpitations have been reported in children following doses of greater than 10 mg. A 6-year-old child ingested 300 mg of loratadine and developed mild elevations in heart rate and blood pressure with no permanent sequelae.
    2) SEVERE: Prolonged QT interval and Torsdades de Pointes (TDP)and/or Ventricular Tachycardia (VT) have been reported after therapeutic use, and might occur after overdose. Most of thest patients had other risk factors for TDP or VT.
    0.2.20) REPRODUCTIVE
    A) Loratadine is classified as FDA pregnancy category B and desloratadine is classified as FDA pregnancy category C. Clinical trials of loratadine use during pregnancy have shown no association between loratadine use and fetal malformations. Additionally, the small amount of loratadine excreted in breast milk would most likely not seriously affect the exposed infant.

Laboratory Monitoring

    A) Plasma concentrations are not readily available or clinically useful.
    B) No routine laboratory studies are necessary unless otherwise clinically indicated.
    C) Monitor vital signs and mental status.
    D) Obtain an ECG, and institute continuous cardiac monitoring.
    E) Monitor serum electrolytes in patients with significant vomiting and/or diarrhea.

Treatment Overview

    0.4.2) ORAL/PARENTERAL EXPOSURE
    A) MANAGEMENT OF MILD TO MODERATE TOXICITY
    1) Treatment is symptomatic and supportive.
    B) MANAGEMENT OF SEVERE TOXICITY
    1) Treatment is symptomatic and supportive. Sinus tachycardia has been reported in overdose. Sinus tachycardia does not generally require treatment unless hemodynamic compromise develops.
    C) DECONTAMINATION
    1) PREHOSPITAL: Prehospital gastrointestinal decontamination is not routinely required.
    2) HOSPITAL: Consider activated charcoal if the overdose is very large, recent, the patient is not vomiting, and is able to maintain airway.
    D) AIRWAY MANAGEMENT
    1) Maintain open airway and perform orotracheal intubation if necessary.
    E) ANTIDOTE
    1) None.
    F) ENHANCED ELIMINATION
    1) Loratadine or desloratadine are not eliminated by hemodialysis.
    G) PATIENT DISPOSITION
    1) HOME CRITERIA: Although a retrospective review suggested that individuals inadvertently ingesting up to 35 mg of loratadine may be safely managed at home with observation only, 2 published abstracts (a retrospective study and a prospective study) suggested that suspected pediatric ingestions of up to 300 mg may be safely monitored at home, with referral to the ED if significant symptoms develop.
    2) OBSERVATION CRITERIA: Patients with a deliberate overdose and those who are symptomatic should be referred to a healthcare facility for evaluation. Patients that remain asymptomatic can be discharged. Although a retrospective review suggested that individuals with ingestions of more than 35 mg of loratadine should be observed in a healthcare facility, 2 later published abstracts (a retrospective study and a prospective study) suggested that suspected pediatric ingestions of greater than 300 mg should be referred to a healthcare facility for evaluation and observation.
    3) ADMISSION CRITERIA: Patients who remain symptomatic despite treatment should be admitted.
    4) CONSULT CRITERIA: Consult a poison center or medical toxicologist for assistance in managing patients with severe toxicity or in whom a diagnosis is not clear.
    H) PITFALLS
    1) When managing a suspected overdose, the possibility of multidrug involvement should be considered.
    I) PHARMACOKINETICS
    1) Tmax: loratadine: about 2 hours; desloratadine: 3 hours. Protein binding: loratadine: 97%; desloratadine: 82% to 87%. Metabolism: extensively metabolized in liver. Excretion: renal: loratadine: approximately 80% of the total dose administered can be found equally distributed between urine and feces as metabolic products after 10 days; desloratadine: approximately, 40.6% is excreted in the kidneys. Elimination half-life: loratadine: 8.4 hours (range, 3 to 20 hours); desloratadine: 27 hours.
    J) DIFFERENTIAL DIAGNOSIS
    1) Includes overdose ingestions of other antihistamines or substances that produce anticholinergic effects.

Range Of Toxicity

    A) TOXICITY: ADULTS: Somnolence, tachycardia, and headache have been reported in overdose (range 40 to 180 mg). CASE SERIES: In one small study, ingestions of less than 35 mg of loratadine did not result in significant toxicity. In a series of 54 patients with loratadine only overdose (average dose 32.5 mg, range 10 to 70 mg), 9 developed symptoms, including syncope, lethargy, drowsiness, urticaria, vomiting, nausea, and headache. CASE REPORT: An 18-year-old woman developed sinus tachycardia (150 bpm) and respiratory alkalosis following an ingestion of 300 mg; the patient recovered without permanent sequelae following supportive care. PEDIATRIC: Extrapyramidal signs and palpitations have been reported in children at doses of greater than 10 mg. A 6-year-old child ingested 300 mg of loratadine and developed mild elevations in heart rate and blood pressure; recovery was complete following supportive care.
    B) THERAPEUTIC DOSE: LORATADINE: Allergic Rhinitis: ADULTS: 10 mg orally once daily. PEDIATRIC: (2 to 5 years) 1 teaspoonful of syrup (each 5 mL contains 5 mg) orally once daily; (6 years and older) 10 mg tablet orally once daily OR 2 teaspoonfuls of syrup (each 5 mL contains 5 mg) once daily. Asthma: ADULT: 10 to 20 mg orally once daily has been used for up to 8 weeks. DESLORATADINE: Adults and children 12 years of age and over: 5 mg once daily.

Clinical Effects

Summary Of Exposure

    A) USES: Loratadine and desloratadine are used for the relief of allergic rhinitis for both seasonal and perennial symptoms. They are also indicated for the relief of pruritus and hives in patients with chronic idiopathic urticaria.
    B) PHARMACOLOGY: Loratadine and desloratadine (a major metabolite of loratadine) are long acting tricyclic histamine antagonists with selective H1-receptor histamine antagonist activity.
    C) EPIDEMIOLOGY: Overdose is rare.
    D) WITH THERAPEUTIC USE
    1) COMMON: Xerostomia, headache, somnolence, and fatigue have been reported in adults. Children (6 to 12 years) also developed nervousness, wheezing, hyperkinesia, abdominal pain and conjunctivitis in addition to symptoms reported with adults following therapeutic use. In young children (2 to 5 years), diarrhea, epistaxis, pharyngitis, influenza-like symptoms, stomatitis, earache, fatigue, and rash were observed. RARE: Hepatotoxicity, ventricular dysrhythmias, anaphylaxis, alopecia, erythema multiforme, peripheral edema, and seizures.
    E) WITH POISONING/EXPOSURE
    1) MILD TO MODERATE: ADULT: Somnolence, tachycardia, and headache have been reported in overdose (range 40 to 180 mg). Additional symptoms have included lethargy, syncope, urticaria, and vomiting. Sinus tachycardia (150 bpm) and respiratory alkalosis were reported in an adult following an ingestion of 300 mg; the patient recovered completely. PEDIATRIC: Extrapyramidal signs and palpitations have been reported in children following doses of greater than 10 mg. A 6-year-old child ingested 300 mg of loratadine and developed mild elevations in heart rate and blood pressure with no permanent sequelae.
    2) SEVERE: Prolonged QT interval and Torsdades de Pointes (TDP)and/or Ventricular Tachycardia (VT) have been reported after therapeutic use, and might occur after overdose. Most of thest patients had other risk factors for TDP or VT.

Heent

    3.4.3) EYES
    A) WITH THERAPEUTIC USE
    1) During clinical trials, conjunctivitis was reported in 2% of children (6 to 12 years) treated with loratadine as compared to less than 1% in the placebo group (Prod Info Claritin(R), 2000a).
    2) Altered lacrimation, conjunctivitis, blurred vision, eye pain, and blepharospasm have been rarely reported with the use of loratadine (Prod Info Claritin(R), 2000a).

Cardiovascular

    3.5.2) CLINICAL EFFECTS
    A) SINUS TACHYCARDIA
    1) WITH POISONING/EXPOSURE
    a) CASE REPORTS
    1) LORATADINE/ADULT: Sinus tachycardia (150 bpm) with a normal QRS complex duration and QTc interval was reported in an 18-year-old female following an overdose ingestion of loratadine, 300 mg, in a suicide attempt. The patient recovered with supportive care (Gokel et al, 2000).
    2) LORATADINE/PEDIATRIC: A 6-year-old child ingested 300 mg of loratadine (rapidly disintegrating formulation) alone and developed mild elevations in heart rate (138-150/bpm) and blood pressure (121/77). Heart rate remained in the 120s for approximately 33 hours with no hemodynamic instability. No QTc prolongation or ectopy were observed on ECG. Recovery was complete following supportive care (Cobb et al, 2001).
    B) VENTRICULAR TACHYCARDIA
    1) WITH THERAPEUTIC USE
    a) LORATADINE
    1) CASE REPORT: A 43-year-old woman with a history of an identical twin that died suddenly of presumed cardiac dysrhythmias and evidence of mitral valve prolapse had a automatic implantable defibrillator inserted prophylactically . Two years later, the patient had a presyncopal episode which was stopped by a defibrillator shock 90 minutes after taking one 10 mg tablet of loratadine. ECG readings from the device revealed a rapid ventricular tachycardia (VT) (average rate 250 bpm) with changing axis of the intracardiac ventricular electrogram. The authors suggested that the VT observed was likely torsades de pointes, and that the patient's family history may have also predisposed her to develop dysrhythmias (Kuchar et al, 2002).
    2) CASE REPORT: A 69-year-old man experienced 2 near syncopal episodes 24 hours after ingesting loratadine, 10 mg/day in addition to quinidine gluconate 324 mg 3 times daily. Three days later, the patient was admitted to the hospital, where an ECG revealed atrial fibrillation with ventricular tachycardia and prolonged QTc interval. The dysrhythmias and prolonged QTc interval resolved following supportive care and discontinuation of the loratadine (Good et al, 1994).
    C) PROLONGED QT INTERVAL
    1) WITH THERAPEUTIC USE
    a) CASE REPORT: QTc interval prolongation and syncope were reported in a 46-year-old woman after taking a loratadine 5 mg/pseudoephedrine 120 mg tablet for 5 days. The patient's QTc interval returned to normal after cessation of loratadine (Hoffman et al, 2001).
    b) DESLORATADINE
    1) LACK OF EFFECT: In human studies, desloratadine had no effect on the corrected QT interval, including high-dose desloratadine (45 mg/day for 10 days) or desloratadine 7.5 mg co-administered with ketoconazole or erythromycin (Henz, 2001a). Further studies have shown little risk for cardiotoxicity with the therapeutic use of desloratadine (Scheinfeld, 2002).
    2) No significant effect on QTc, PR, or QRS intervals were observed in healthy subjects during administration of high-dose desloratadine (45 mg) (Banfield et al, 2000a).
    D) TORSADES DE POINTES
    1) WITH THERAPEUTIC USE
    a) LORATADINE/AMIODARONE
    1) CASE REPORT: A 73-year-old woman with a history of hypertension and paroxysmal atrial fibrillation maintained on chronic amiodarone therapy, developed a syncopal episode after being administered loratadine 10 mg for several days. The patient presented with frequent long-short QRS cycles proceeded by intermittent episodes of torsades de pointes (TdP) that did not require intervention. Amiodarone and loratadine were stopped. By day 4, the patient was asymptomatic, and the QT interval returned to baseline. The authors suggested that amiodarone may have an effect on sodium and calcium channels that are involved in the production of early after-depolorizations and TdP (Atar et al, 2003).

Respiratory

    3.6.2) CLINICAL EFFECTS
    A) PHARYNGITIS
    1) WITH THERAPEUTIC USE
    a) DESLORATADINE: In clinical trials, patients who received desloratadine (5 mg/day; n=1655), 4.1% reported pharyngitis as compared with 2% in the placebo group (n=1652) (Prod Info Clarinex(R), 2002).

Neurologic

    3.7.2) CLINICAL EFFECTS
    A) HEADACHE
    1) WITH THERAPEUTIC USE
    a) Headache appears to be the most commonly reported side effect with these agents in therapeutic use; however, the incidence of headache appears similar to that observed with placebo (Prod Info Claritin(R), 2000a; Rosenberg et al, 2000a; Salmun et al, 2000; Banfield et al, 2000a; Padhi et al, 2000a).
    b) INCIDENCE
    1) LORATADINE: In a 2-day comparative trial in patients with seasonal allergic rhinitis, headache occurred in 33% of patients on loratadine, 27% of patients on cetirizine, and 28% of patients on placebo. The differences were not considered significant (Day et al, 1998).
    2) DESLORATADINE: In one relatively large clinical study, headache was described by 16% to 24% of patients after desloratadine (5 or 7.5 mg daily) and by 14% to 22% after placebo (Salmun et al, 2000). However, none of these studies have been published in full form, precluding adequate evaluation of adverse effects data.
    B) SEDATION
    1) WITH THERAPEUTIC USE
    a) LORATADINE
    1) In a 2-week trial, the incidence of somnolence for loratadine was 7.3% which was similar to the placebo group (6.5%) (Alexander et al, 1994). In a review of clinical trials involving 55,000 patients being treated for allergic rhinitis or allergic skin disorders, the incidence of somnolence was 1%. Additional clinical trials utilizing high-dose oral loratadine (40 mg) for 14 days demonstrated no sedation among 105 patients (Bruttmann & Pedrali, 1987). Other trials have shown that the incidence of sedation is similar to that observed in patients taking placebo (Nolen, 1997; Adelsberg, 1997; Monroe et al, 1992a; Bruttmann et al, 1989; Kemp et al, 1987).
    2) INCIDENCE: In a review of nonsedating (ie, astemizole, fexofenadine, loratadine, and terfenadine) and sedating antihistamines (ie, cetirizine, chlorpheniramine, clemastine, diphenhydramine, hydroxyzine, promethazine, and triprolidine), loratadine did NOT cause sedation or impaired performance (ie, driving or flight performance) in comparison to placebo (Nolen, 1997).
    b) DESLORATADINE
    1) In clinical trials, somnolence and fatigue were reported by 2.1% of patients (n=1655) who received 5 mg desloratadine daily, and were similar to rates reported in the placebo (n=1652) group (Prod Info CLARINEX(R) tablets, 2002).
    a) The sedation associated with desloratadine was comparable to that of placebo in tests of wakefulness, such as the Stanford Sleepiness Scale, the Digital Symbol Substitution Test, the Psychomotor Vigilance Test, and the Serial Add Subtract Reaction Time test (Henz, 2001a).
    b) The frequency of somnolence was similar with desloratadine (5 or 7.5 mg daily) (2% to 4%) and placebo (2%) in one study (Salmun et al, 2000).
    2) WITH POISONING/EXPOSURE
    a) Somnolence has been reported in adults following loratadine overdoses of greater than 10 mg (range 40 to 180 mg) (Prod Info Claritin(R), 2000a).
    b) In dose escalation studies, somnolence has also been reported with desloratadine at doses of 10 mg and 20 mg/day (Prod Info Clarinex(R), 2002a). Somnolence was found to increase at the highest dose. Approximately 3% of patients receiving 2.5 to 10 mg of desloratadine reported somnolence, as compared to 6% in the 20 mg group (Spangler & Brunton, 2006).
    C) CENTRAL NERVOUS SYSTEM FINDING
    1) WITH THERAPEUTIC USE
    a) SUMMARY
    1) According to a compilation of placebo-controlled trials, side effects (incidence greater than 2%) reported with loratadine are similar to that seen with placebo. The following CNS side effects were reported with loratadine (n=1926): headache (12%), somnolence (8%), and fatigue (4%); as compared with placebo (n=2545): headache (11%), somnolence (6%), and fatigue (3%) (Prod Info Claritin(R), 2000a).
    2) FEWER THAN 2% of patients given loratadine experience anxiety, depression, agitation, insomnia, paranoia, amnesia, impaired concentration, confusion, decreased libido, nervousness, hyperkinesia, paresthesias, migraine, tremor, vertigo, dysphonia, seizures, or hypoesthesia (Prod Info Claritin(R), 2000a).
    b) Patients given the combination product (Claritin-D(R) 24 HOUR) have experienced a slightly higher incidence of dry mouth (8%), somnolence (6%), and insomnia (5%), then patients given loratadine alone (Prod Info Claritin-D(R) 24 HOUR, 1999). The incidence of anticholinergic effects with loratadine was considered comparable to both placebo and oral clemastine (1 mg twice daily) in 1 clinical trial (Dockhorn et al, 1987). Additional clinical trials utilizing oral loratadine 20 mg to 80 mg daily for 14 to 28 days have demonstrated no significant anticholinergic effects with the drug in the patients treated (Bruttmann & Pedrali, 1987; Roman et al, 1986a). At recommended doses, anticholinergic side effects are uncommon with loratadine use.
    c) Using the recommended dosage of 10 mg once daily, there are no differences in CNS effects (ie, sedation, cognition, mood, and psychomotor performance) between placebo-treated and loratadine-treated patients (Kay et al, 1997).
    d) DESLORATADINE: In clinical trials, dizziness was reported in 4% of patients receiving desloratadine (5 mg/day; n=211) and 3% of patients who received placebo (Prod Info Clarinex(R), 2002).
    2) WITH POISONING/EXPOSURE
    a) Extrapyramidal signs and palpitations have been reported in children at doses of greater than 10 mg (Prod Info Claritin(R), 2000a).
    D) COGNITIVE FUNCTION FINDING
    1) WITH THERAPEUTIC USE
    a) LORATADINE: does NOT appear to impact office performance skills (eg, clerical, accounting, and mathematical skills) (Adelsberg, 1997).
    b) DESLORATADINE: A double-blinded, placebo-controlled, crossover study demonstrated that desloratadine did not have any adverse effects on psychomotor performance, daytime sleep latencies, and subjective sleepiness. Each patient (n=9) was tested during 3 test sessions. At each session, subjects were given a dose of desloratadine 5 milligrams (mg), promethazine 25 mg or placebo. Performance was assessed using 7 different tasks developed to study memory, tracking, sustained attention, digit substitution and reaction time. Patients also underwent a multiple sleep latency test and assessed their mood with visual analog scales, the multiple Stanford Sleepiness Scale and the Samn-Perelli fatigue rating. Compared with placebo, desloratadine did not demonstrate any differences in tracking, reaction time, attention, digit symbol substitution or memory. Subjective ratings of sleepiness and fatigue with desloratadine were also similar to placebo (Nicholson et al, 2003).

Gastrointestinal

    3.8.2) CLINICAL EFFECTS
    A) GASTROINTESTINAL TRACT FINDING
    1) WITH THERAPEUTIC USE
    a) LORATADINE: Among 111 patients given oral loratadine 10 mg once daily for 14 days, 2 (1.8%) patients complained of dry mouth (Dockhorn et al, 1987). Patients given the combination product (Claritin-D(R) 24 HOUR) experienced a slightly higher incidence of dry mouth (8%) (Prod Info Claritin-D(R) 24 HOUR, 1999).
    b) DESLORATADINE: Gastrointestinal symptoms (eg, nausea, dyspepsia) have occurred infrequently with desloratadine (Glue et al, 2000).
    B) DIARRHEA
    1) WITH THERAPEUTIC USE
    a) In a placebo-controlled trial in pediatric patients, age 2 to 5 years old, diarrhea was reported in 3% of children given loratadine 5 mg daily for 14 days; no symptoms were reported in the placebo group(Prod Info Claritin(R), 2000a). During clinical trials, abdominal pain was reported in 2% of children (n=188) 6 to 12 years of age receiving 10 mg loratadine daily (Prod Info Claritin(R), 2000a).

Hepatic

    3.9.2) CLINICAL EFFECTS
    A) INJURY OF LIVER
    1) WITH THERAPEUTIC USE
    a) Abnormal hepatic function, jaundice, hepatitis, and hepatic necrosis have been rarely reported with the use of loratadine (Prod Info Claritin(R), 2000a).
    b) LORATADINE
    1) CASE REPORTS: A 42-year-old female had been taking loratadine for 14 months prior to the development of jaundice. Due to progressive liver failure, the patient required an orthotopic liver transplant. Laboratory tests were negative for a viral or autoimmune cause and normal values were reported for ceruloplasmin and alpha-1-antitrypsin. In the second case, a 33-year-old male had a self-limited attack of acute neocroinflammatory liver and cholestatic injury after receiving 2 weeks of loratadine 10 mg/day therapy. Tests ruled out alcohol-induced liver injury or other markers of autoimmune disease (Schiano et al, 1996).
    c) DESLORATADINE
    1) During the marketing of desloratadine, there have been rare reports of elevated liver enzymes including elevated bilirubin (Prod Info CLARINEX(R) tablets, 2002).
    2) CASE REPORT: A 41-year-old woman with asthma and chronic rhinitis developed an episode of acute cholestasis approximately one month after taking desloratadine 5 mg daily. Symptoms included acute right upper quadrant abdominal pain and distension. Liver enzymes were slightly elevated with values of AST 54 IU/L, ALT 170 IU/L, alkaline phosphatase 169 IU/L and gamma-glutamyl-transferase 229 IU/L. Serology testing was negative and diagnostic studies were normal. Clinical symptoms resolved completely within 10 days of drug discontinuation (Perez et al, 2005).

Genitourinary

    3.10.2) CLINICAL EFFECTS
    A) URINARY SYSTEM FINDING
    1) WITH THERAPEUTIC USE
    a) Discolored urine, altered micturition and impotence have been reported rarely with therapeutic use (Prod Info Claritin(R), 2000a).

Acid-Base

    3.11.2) CLINICAL EFFECTS
    A) RESPIRATORY ALKALOSIS
    1) WITH POISONING/EXPOSURE
    a) CASE REPORT: Respiratory alkalosis (pH 7.551; pCO2 16.7 mmHg; pO2 156.8 mmHg; HCO3 14.2 mEq/L {on room air}) was reported in an 18-year-old woman following an overdose ingestion of loratadine, 300 mg, in a suicide attempt. The patient recovered with supportive care and was discharged 48 hours later (Gokel et al, 2000).

Dermatologic

    3.14.2) CLINICAL EFFECTS
    A) ERUPTION
    1) WITH THERAPEUTIC USE
    a) During clinical trials, rash was reported in 2% of young children (2 to 5 years) treated with loratadine syrup; no cases were reported in the placebo group (Prod Info Claritin(R), 2000a).
    b) CASE REPORT: A 19-year-old woman developed a fixed drug eruption after receiving a loratadine-pseudoephedrine containing product (Narine(R)). The patient had been using the product for several years, and complained of three episodes of pruritic lesions within nine months. Each episode was preceded by the ingestion of Narine(R) within several hours. Patch tests to loratadine 10% and pseudoephedrine 1% were negative, but a single oral dose of loratadine 10 mg resulted in erythematous, edematous, and pruritic patches in locations previously reported (Ruiz-Genao et al, 2002).
    B) SKIN FINDING
    1) WITH THERAPEUTIC USE
    a) Dermatitis, dry hair and skin, photosensitivity, pruritus, purpura and erythema multiforme have been reported rarely with loratadine use (Prod Info Claritin(R), 2000a).

Musculoskeletal

    3.15.2) CLINICAL EFFECTS
    A) JOINT PAIN
    1) WITH THERAPEUTIC USE
    a) LORATADINE: Arthralgia, myalgia, back pain and leg cramps have been reported rarely with therapeutic use (Prod Info Claritin(R), 2000a).
    b) DESLORATADINE: In clinical trials, rates of myalgia were similar in patients (n=1655) receiving loratadine 5 mg daily (2.1%), as compared to patients (n=1652) receiving placebo (1.8%) (Prod Info Clarinex(R), 2002a).

Immunologic

    3.19.2) CLINICAL EFFECTS
    A) ANAPHYLAXIS
    1) WITH THERAPEUTIC USE
    a) LORATADINE
    1) CASE REPORT: A 27-year-old woman with seasonal allergic rhinitis had been taking loratadine daily for several months when she developed an episode of moderate dyspnea and edema of the glottis. Symptoms resolved with prednisone therapy. The patient experienced two more similar episodes, which were controlled by prednisone. No new symptoms occurred once loratadine was discontinued. Patch testing with loratadine was positive (Bonanni et al, 2004).
    b) DESLORATADINE
    1) During the marketing of desloratadine, there have been rare reports of hypersensitivity reactions such as rash, pruritus, urticaria, edema, dyspnea and anaphylaxis (Prod Info Clarinex(R), 2002).

Reproductive

    3.20.1) SUMMARY
    A) Loratadine is classified as FDA pregnancy category B and desloratadine is classified as FDA pregnancy category C. Clinical trials of loratadine use during pregnancy have shown no association between loratadine use and fetal malformations. Additionally, the small amount of loratadine excreted in breast milk would most likely not seriously affect the exposed infant.
    3.20.2) TERATOGENICITY
    A) LACK OF EFFECT
    1) No increase in the rate of fetal abnormalities was found in women who took loratadine in pregnancy compared with women who took other antihistamines and a control group with unexposed infants in a prospective, cohort study. The incidence of malformation was 2.3% for the loratadine group; 4% for the other antihistamine group; and 3% for the control group, (p=0.553); there was no difference in risk of malformation with loratadine use compared with control (relative risk (RR), 0.77; 95% confidence interval (CI), 0.27 to 2.19) and compared with other antihistamines (RR, 0.56; 95% CI 0.18 to 1.77). When analyzing only those infants exposed to antihistamines during the first trimester, the malformation rates were similar between all three groups (incidence: loratadine 0.8%; others 4.8%, control 3%, p=0.152. The malformation rates during the first trimester were also similar between loratadine and control (RR, 0.27; 95% CI, 0.04 to 1.94) and between loratadine and other antihistamines (RR, 0.17; 95% CI, 0.02 to 1.33). The loratadine group had a higher incidence of miscarriage (11.4% vs. others: 4.9%, control: 7.2%), but the women using loratadine had a significantly higher maternal age than those in the other groups (31.5 years vs 30 years in other two groups, p=0.005) (Diav-Citrin et al, 2003).
    2) In a multicenter case-controlled study, women exposed to potential teratogenic agents including loratadine were observed postpartum. In a follow-up report of 161 loratadine exposed pregnancies, there were 5 malformations, including kidney defect, aortic valve stenosis, chromosomal abnormalities, bilateral inguinal hernia, and congenital hip dislocation, observed in the exposed group compared with 6 in the control group; a difference that was not significantly different (p=0.9). Additionally, the live birth rate, gestational age at delivery, and birth weights did not differ between the two groups (Moretti et al, 2003).
    3) In an analysis of 17,776 pregnancies in the Swedish Medical Birth Registry, infants born to mothers who used antihistamines during pregnancy had a malformation rate equal to that normally expected (3.17% for antihistamine use vs 3.16% in the general population). A slightly reduced rate of cardiovascular defects was also seen in the offspring of women using antihistamines during pregnancy. Reduced risks of premature births, low birth weight, and small size for gestational age were also seen with use of antihistamines. The most common antihistamines used by women in this study were clemastine, promethazine, cyclizine, meclizine, cetirizine, terfenadine, and loratadine (Kallen, 2002).
    4) In a series of observational cohort studies, it is suggested that loratadine does not cause an increased rate of congenital anomalies when used during pregnancy. Of 67 pregnant women who took the drug, 45 discontinued the drug before the last menstrual period; 18 were exposed during the first trimester, and none during the second or third trimester; exposure for five was unknown. Of the 18 exposed during the first trimester, there were 16 births without congenital anomalies and two pregnancies intentionally terminated (Wilton et al, 1998).
    5) HYPOSPADIAS
    a) In a nested-case control study of women enrolled in the Danish National Birth Cohort from 1998 to 2002 (n=approximately 95,000 women), no increased risk of hypospadias was associated with loratadine use or any other antihistamine. The adjusted odds ratio for hypospadia among women exposed to loratadine during pregnancy as compared to nonusers was 0.9 (95% confidence interval, 0.1 to 6.9) (Pedersen et al, 2006). Another study also found no increased risk of infant hypospadias following maternal use of loratadine during early pregnancy (Kallen & Olausson, 2006).
    b) The National Birth Defects Prevention Study concluded that there is no association between the use of loratadine from 1 month before pregnancy through the first trimester and the development of second- or third-degree hypospadias in male patients. This case control study examined 563 male infants with hypospadias identified through birth defect surveillance systems in 8 states and 1444 male infant controls from the same population. Exposure was ascertained through detailed telephone interviews with the mothers. Of all infants, 1.7% reported the use of loratadine during this time period. Univariate analysis demonstrated no association between the use of loratadine and hypospadias (odds ratio (OR), 1.29; 95% confidence interval, 0.62 to 2.68). Multivariate analyses were similar to univariate estimates. Limitations to this study include recall bias and case selection bias (Anon, 2004).
    3.20.3) EFFECTS IN PREGNANCY
    A) PREGNANCY CATEGORY
    1) Loratadine is classified by the manufacturer as FDA pregnancy category B (Prod Info CLARITIN(R) tablets, syrup, disintegrating tablets, 2000), and desloratadine is classified as FDA pregnancy category C (Prod Info CLARINEX(R) tablets, 2002).
    3.20.4) EFFECTS DURING BREAST-FEEDING
    A) BREAST MILK
    1) LORATADINE
    a) Loratadine and its metabolite, descarboethoxyloratadine, are detectable in breast milk at concentrations equivalent to that of maternal plasma levels. Loratadine achieves concentrations that are equivalent to plasma levels with an AUC (milk)/AUC (plasma) ratio of 1.17. After a single, 40-mg oral dose, both parent drug and metabolite measured 0.03% over 48 hours (Prod Info CLARITIN(R) tablets, syrup, disintegrating tablets, 2000).
    2) DESLORATADINE
    a) Desloratadine is also found in breast milk (Prod Info CLARINEX(R) tablets, 2002).
    B) LACK OF EFFECT
    1) Lactation studies have determined that the dose received by a breast feeding infant (4 kg) would be 0.46% of the dose given to the mother, which is considered unlikely to pose a hazard to the infant (Hilbert et al, 1988).
    3.20.5) FERTILITY
    A) LACK OF EFFECT
    1) LORATADINE
    a) Oral doses of loratadine of 24 mg/kg/day (approximately 20 times the maximum recommended human daily dose) had no effect on male or female fertility or reproduction in rats (Prod Info Claritin(R), 2000a). Doses of 64 mg/kg impaired fertility in rats. The clinical significance of these findings relative to long-term use in humans is not known (Prod Info Claritin(R), 2000a)
    2) DESLORATADINE
    a) Oral doses of 3 mg/kg/day of desloratadine (approximately, 8 times the AUC in humans at the recommended daily oral dose) had no effect on fertility in rats (Prod Info CLARINEX(R) tablets, 2002).

Carcinogenicity

    3.21.4) ANIMAL STUDIES
    A) LORATADINE
    1) Male rats given loratadine at 10 mg/kg had an increased incidence of hepatocellular tumors compared with controls. Most mutagenicity studies were negative, but in the mouse lymphoma assay, a positive finding occurred in the non-activated, but not the activated study (Prod Info Claritin(R), 2000a).
    B) DESLORATADINE
    1) The carcinogenic potential of desloratadine was assessed using loratadine animal studies (Prod Info Clarinex®, 2002).
    2) In 18-month and 2-year studies in mice and rats, loratadine was administered in the diet at doses up to 40 mg/kg/day in mice and 25 mg/kg/day in rats. Male mice given 40 mg/kg/day of loratadine had a significantly higher incidence of hepatocellular tumors (combined adenomas and carcinomas) than concurrent controls. In rats, a significantly higher incidence of hepatocellular tumors (combined adenomas and carcinomas) was observed in males given 10 mg/kg/day and females given 25 mg/kg/day. The estimated desloratadine and desloratadine metabolite exposures of rats given 10 mg/kg of loratadine were approximately 7 times the area under the curve in humans at the recommended daily oral dose (Prod Info Clarinex®, 2002).

Laboratory Monitoring

Monitoring Parameters Levels

    4.1.1) SUMMARY
    A) Plasma concentrations are not readily available or clinically useful.
    B) No routine laboratory studies are necessary unless otherwise clinically indicated.
    C) Monitor vital signs and mental status.
    D) Obtain an ECG, and institute continuous cardiac monitoring.
    E) Monitor serum electrolytes in patients with significant vomiting and/or diarrhea.
    4.1.2) SERUM/BLOOD
    A) Specific laboratory tests are not necessary following inadvertent exposure, unless otherwise clinically indicated.
    4.1.4) OTHER
    A) OTHER
    1) ECG
    a) Monitor heart rate and cardiac rhythm in symptomatic patients. Tachycardia may develop which does not usually require treatment; unless hemodynamic compromise is present. Obtain a baseline ECG in patients with tachycardia or syncope/near-syncope. QT interval prolongation has been reported, very rarely, with these agents when taken alone.

Methods

    A) HPLC/MS
    1) Vlase et al (2006) described a sensitive and selective high performance liquid chromatography with mass spectrometry method for the the quantification of loratadine and its active metabolite descarboethoxyloratadine in human plasma (Vlase et al, 2006).

Treatment

Life Support

    A) Support respiratory and cardiovascular function.

Patient Disposition

    6.3.1) DISPOSITION/ORAL EXPOSURE
    6.3.1.1) ADMISSION CRITERIA/ORAL
    A) Patients who remain symptomatic despite treatment should be admitted.
    6.3.1.2) HOME CRITERIA/ORAL
    A) SUMMARY: Although a retrospective review suggested that individuals inadvertently ingesting up to 35 mg of loratadine may be safely managed at home with observation only, 2 published abstracts (a retrospective study and a prospective study) suggested that suspected pediatric ingestions of up to 300 mg may be safely monitored at home, with referral to the ED if significant symptoms develop.
    1) Based on a retrospective review of 54 loratadine exposures, 83% of patients remained asymptomatic following loratadine exposure. It was suggested that individuals inadvertently ingesting up to 35 mg may be safely managed at home with observation only (Vignogna-Barlas et al, 1998).
    2) ABSTRACT - RETROSPECTIVE STUDY: In a 4-year retrospective review of 547 pediatric (age: 5 years and under) loratadine exposures, 200 patients were referred to an emergency department and 346 patients were managed at home. Fourteen and 136 patients received ipecac and activated charcoal, respectively. Mild transient CNS and cardiovascular effects developed in 23 (4.2%) patients; however, none of the patients required a specific intervention. The average suspected dose ingested by patients with moderate and no or minor effects were 115 mg (with an upper range of 300 mg) and 52 mg (with an upper range of 310 mg), respectively. Overall, suspected doses greater than 120 mg were ingested in 8% of cases with no or minor effects and 35% of cases with moderate effects (Manning et al, 2003).
    3) ABSTRACT - PROSPECTIVE STUDY: In a prospective study of children (n=68; age: 5 years and under) with inadvertent loratadine ingestions (average suspected dose ingested: 85 mg; range 5 to 830 mg) during an 11-month period, no effects, minor effects, and moderate effects were observed in 53 (86%; average suspected dose: 49.5 mg; range: 50 to 200 mg), 7 (11%; average suspected dose: 167.9 mg; range: 20 to 680), and 2 (3%; average suspected dose: 725 mg; range: 620 to 830 mg) patients, respectively. Six of 68 patients were lost to follow-up. Overall, 5 patients were referred to an ED (average dose: 396 mg; range: 70 to 830 mg) and 57 patients were monitored at home (average dose: 57 mg; range 5 to 680 mg). Sedation, agitation, and tachycardia were the most common effects in children. One patient (a 3-year-old; weight: 14 kg) with moderate effects ingested up to 620 mg of loratadine and received activated charcoal within 2 hours of loratadine overdose. He had normal mental status and a heart rate of 144 beats/min, blood pressure of 112/67 mmHg, temperature of 99.4 degrees F, and respiratory rate of 28 breaths/min. A loratadine blood concentration 2.5 hours after ingestion was 310 ng/mL (therapeutic: 4.7 ng/mL). The second patient (a 2-year-old; weight: 7.7 kg) with moderate effects ingested up to 830 mg of loratadine and developed drowsiness, a heart rate of 190 beats/min and a blood pressure of 99/68 mmHg. He also received activated charcoal. It was concluded that the ingestion of loratadine doses up to 620 mg caused only minor symptoms. The authors added that pediatric ingestions of less than 300 mg may be safely monitored at home, with referral to ED if significant symptoms develop (Manning et al, 2006).
    6.3.1.3) CONSULT CRITERIA/ORAL
    A) Consult a poison center or medical toxicologist for assistance in managing patients with severe toxicity or in whom a diagnosis is not clear.
    6.3.1.5) OBSERVATION CRITERIA/ORAL
    A) Patients with a deliberate overdose and those who are symptomatic should be referred to a healthcare facility for evaluation. Patients that remain asymptomatic can be discharged. Although a retrospective review suggested that individuals with ingestions of more than 35 mg of loratadine should be observed in a healthcare facility, 2 later published abstracts (a retrospective study and a prospective study) suggested that suspected pediatric ingestions of greater than 300 mg should be referred to a healthcare facility for evaluation and observation.

Monitoring

    A) Plasma concentrations are not readily available or clinically useful.
    B) No routine laboratory studies are necessary unless otherwise clinically indicated.
    C) Monitor vital signs and mental status.
    D) Obtain an ECG, and institute continuous cardiac monitoring.
    E) Monitor serum electrolytes in patients with significant vomiting and/or diarrhea.

Oral Exposure

    6.5.1) PREVENTION OF ABSORPTION/PREHOSPITAL
    A) Prehospital gastrointestinal decontamination is not routinely required.
    6.5.2) PREVENTION OF ABSORPTION
    A) ACTIVATED CHARCOAL
    1) CHARCOAL ADMINISTRATION
    a) Consider administration of activated charcoal after a potentially toxic ingestion (Chyka et al, 2005). Administer charcoal as an aqueous slurry; most effective when administered within one hour of ingestion.
    2) CHARCOAL DOSE
    a) Use a minimum of 240 milliliters of water per 30 grams charcoal (FDA, 1985). Optimum dose not established; usual dose is 25 to 100 grams in adults and adolescents; 25 to 50 grams in children aged 1 to 12 years (or 0.5 to 1 gram/kilogram body weight) ; and 0.5 to 1 gram/kilogram in infants up to 1 year old (Chyka et al, 2005).
    1) Routine use of a cathartic with activated charcoal is NOT recommended as there is no evidence that cathartics reduce drug absorption and cathartics are known to cause adverse effects such as nausea, vomiting, abdominal cramps, electrolyte imbalances and occasionally hypotension (None Listed, 2004).
    b) ADVERSE EFFECTS/CONTRAINDICATIONS
    1) Complications: emesis, aspiration (Chyka et al, 2005). Aspiration may be complicated by acute respiratory failure, ARDS, bronchiolitis obliterans or chronic lung disease (Golej et al, 2001; Graff et al, 2002; Pollack et al, 1981; Harris & Filandrinos, 1993; Elliot et al, 1989; Rau et al, 1988; Golej et al, 2001; Graff et al, 2002). Refer to the ACTIVATED CHARCOAL/TREATMENT management for further information.
    2) Contraindications: unprotected airway (increases risk/severity of aspiration) , nonfunctioning gastrointestinal tract, uncontrolled vomiting, and ingestion of most hydrocarbons (Chyka et al, 2005).
    6.5.3) TREATMENT
    A) SUPPORT
    1) MANAGEMENT OF MILD TO MODERATE TOXICITY
    a) Treatment is symptomatic and supportive.
    2) MANAGEMENT OF SEVERE TOXICITY
    a) Treatment is symptomatic and supportive. Sinus tachycardia has been reported in overdose. Sinus tachycardia does not generally require treatment unless hemodynamic compromise develops.
    B) MONITORING OF PATIENT
    1) Plasma concentrations are not readily available or clinically useful.
    2) No routine laboratory studies are necessary unless otherwise clinically indicated.
    3) Monitor vital signs and mental status.
    4) Obtain an ECG, and institute continuous cardiac monitoring.
    5) Monitor serum electrolytes in patients with significant vomiting and/or diarrhea.
    C) TACHYCARDIA
    1) Tachycardia has been reported in overdose (Prod Info CLARINEX(R) tablets, 2002; Prod Info Claritin(R), 2000a), but does not usually require intervention unless hemodynamic compromise is present. Monitor heart rate. A baseline ECG may be indicated and repeated as necessary. Institute continuous cardiac monitoring as needed.

Enhanced Elimination

    A) HEMODIALYSIS
    1) Loratadine or desloratadine are not eliminated by hemodialysis (Prod Info CLARINEX(R) tablets, 2002; Prod Info Claritin(R), 2000a).

Range Of Toxicity

Summary

    A) TOXICITY: ADULTS: Somnolence, tachycardia, and headache have been reported in overdose (range 40 to 180 mg). CASE SERIES: In one small study, ingestions of less than 35 mg of loratadine did not result in significant toxicity. In a series of 54 patients with loratadine only overdose (average dose 32.5 mg, range 10 to 70 mg), 9 developed symptoms, including syncope, lethargy, drowsiness, urticaria, vomiting, nausea, and headache. CASE REPORT: An 18-year-old woman developed sinus tachycardia (150 bpm) and respiratory alkalosis following an ingestion of 300 mg; the patient recovered without permanent sequelae following supportive care. PEDIATRIC: Extrapyramidal signs and palpitations have been reported in children at doses of greater than 10 mg. A 6-year-old child ingested 300 mg of loratadine and developed mild elevations in heart rate and blood pressure; recovery was complete following supportive care.
    B) THERAPEUTIC DOSE: LORATADINE: Allergic Rhinitis: ADULTS: 10 mg orally once daily. PEDIATRIC: (2 to 5 years) 1 teaspoonful of syrup (each 5 mL contains 5 mg) orally once daily; (6 years and older) 10 mg tablet orally once daily OR 2 teaspoonfuls of syrup (each 5 mL contains 5 mg) once daily. Asthma: ADULT: 10 to 20 mg orally once daily has been used for up to 8 weeks. DESLORATADINE: Adults and children 12 years of age and over: 5 mg once daily.

Therapeutic Dose

    7.2.1) ADULT
    A) DESLORATADINE
    1) The recommended oral dose of desloratadine is a single 5 milligram (mg) tablet once daily or 2 teaspoonfuls of syrup (5 mg in 10 milliliters (mL)) once daily in the treatment of allergic rhinitis or chronic idiopathic urticaria (Prod Info Clarinex(R), , 2004; Ortonne et al, 2007).
    2) Pharmacokinetic studies have demonstrated that a single 5 milligram (mg) orally disintegrating tablet (Clarinex Reditabs(R)) is bioequivalent to a single 5 mg tablet and that a single dose of 10 milliliters of syrup containing 5 mg of desloratadine (Clarinex(R) syrup) is bioequivalent to a single 5 mg tablet (Prod Info Clarinex(R), , 2004).
    B) LORATADINE
    1) For the treatment of allergic rhinitis or chronic idiopathic urticaria: 10 milligrams orally once daily (Prod Info Claritin(R), 2000).
    7.2.2) PEDIATRIC
    A) DESLORATADINE
    1) The safety and efficacy of desloratadine have not been established in patients less than 6 months old. Pediatric safety and efficacy studies in patients under 12 years of age were conducted using the desloratadine syrup formulation (Prod Info Clarinex(R), , 2004).
    2) For children 12 years of age and older: the recommended oral dose of desloratadine is one 5 milligram (mg) tablet once daily or 2 teaspoonfuls of syrup (5 mg in 10 milliliters (mL)) once daily (Prod Info Clarinex(R), , 2004).
    3) For children 6 years to 11 years of age: the recommended oral dose of desloratadine is 1 teaspoonful of syrup (2.5 mg in 5 mL) once daily (Prod Info Clarinex(R), , 2004).
    4) For children 12 months to 5 years of age: the recommended oral dose is one-half teaspoonful of syrup (1.25 mg in 2.5 mL) once daily (Prod Info Clarinex(R), , 2004).
    5) For children 6 months to 11 months of age: the recommended oral dose is 2 mL of syrup (1 mg) once daily (Prod Info Clarinex(R), , 2004).
    B) LORATADINE
    1) For children 2 to 5 years of age: the recommended dose is 5 milligrams orally once daily (Prod Info Claritin(R), 2000).
    2) For children 6 years to 11 years: the recommended dose is 10 milligrams orally once daily (Prod Info Claritin(R), 2000).

Maximum Tolerated Exposure

    A) LORATADINE
    1) PEDIATRIC - ABSTRACT - RETROSPECTIVE STUDY: In a 4-year retrospective review of 547 pediatric (age: 5 years and under) loratadine exposures, 200 patients were referred to an emergency department and 346 patients were managed at home. Fourteen and 136 patients received ipecac and activated charcoal, respectively. Mild transient CNS and cardiovascular effects developed in 23 (4.2%) patients; however, none of the patients required a specific intervention. The average suspected dose ingested by patients with moderate and no or minor effects were 115 mg (with an upper range of 300 mg) and 52 mg (with an upper range of 310 mg), respectively. Overall, suspected doses greater than 120 mg were ingested in 8% of cases with no or minor effects and 35% of cases with moderate effects (Manning et al, 2003).
    2) PEDIATRIC - ABSTRACT - PROSPECTIVE STUDY: In a prospective study of children (n=68; age: 5 years and under) with inadvertent loratadine ingestions (average suspected dose ingested: 85 mg; range 5 to 830 mg) during an 11-month period, no effects, minor effects, and moderate effects were observed in 53 (86%; average suspected dose: 49.5 mg; range: 50 to 200 mg), 7 (11%; average suspected dose: 167.9 mg; range: 20 to 680), and 2 (3%; average suspected dose: 725 mg; range: 620 to 830 mg) patients, respectively. Six of 68 patients were lost to follow-up. Overall, 5 patients were referred to an ED (average dose: 396 mg; range: 70 to 830 mg) and 57 patients were monitored at home (average dose: 57 mg; range 5 to 680 mg). Sedation, agitation, and tachycardia were the most common effects in children. One patient (a 3-year-old; weight: 14 kg) with moderate effects ingested up to 620 mg of loratadine and received activated charcoal within 2 hours of loratadine overdose. He had normal mental status and a heart rate of 144 beats/min, blood pressure of 112/67 mmHg, temperature of 99.4 degrees F, and respiratory rate of 28 breaths/min. A loratadine blood concentration 2.5 hours after ingestion was 310 ng/mL (therapeutic: 4.7 ng/mL). The second patient (a 2-year-old; weight: 7.7 kg) with moderate effects ingested up to 830 mg of loratadine and developed drowsiness, a heart rate of 190 beats/min and a blood pressure of 99/68 mmHg. He also received activated charcoal. It was concluded that the ingestion of loratadine doses up to 620 mg caused only minor symptoms. The authors added that pediatric ingestions of less than 300 mg may be safely monitored at home, with referral to ED if significant symptoms develop (Manning et al, 2006).
    3) ADULT: Six of 17 patients with multiple drug exposures experienced confusion, mydriasis, vomiting, lethargy, and headache following an average loratadine dose of 220 milligrams (range 40 to 400 milligrams). Nine of 54 patients with single drug ingestions experienced syncope, lethargy, drowsiness, urticaria, vomiting, nausea, and headache following an average loratadine dose of 32.5 milligrams (range 10 to 70 milligrams). Patients ingesting less than 35 milligrams did not develop significant toxicity (Vignogna-Barlas et al, 1998).
    4) ADULT: Sinus tachycardia (150 bpm) with a normal QRS complex duration and QTc interval and respiratory alkalosis (pH 7.551; pCO2 16.7 mmHg; pO2 156.8 mmHg; HCO3 14.2 mEq/L {on room air}) was reported in an 18-year-old female following an overdose ingestion of loratadine, 300 mg, in a suicide attempt. The patient recovered with supportive care and was discharged 48 hours later (Gokel et al, 2000).
    5) PEDIATRIC: A 6-year-old child ingested 300 mg of loratadine alone, and developed mild elevations in heart rate and blood pressure. Recovery was complete following supportive care (Cobb et al, 2001).
    6) Extrapyramidal signs and palpitations have been reported in children at doses of greater than 10 mg (Prod Info Claritin(R), 2000a).
    B) ANIMAL STUDIES
    1) LORATADINE: No deaths were reported in rats or mice given oral doses of up to 5000 mg/kg (greater than 2400 and 1200 times, respectively the maximum recommended human daily oral dose on a mg/m(2) basis) of loratadine. In addition, single doses of loratadine at 10 times the maximum recommended human daily oral dose produced no symptoms in rats, mice, or monkeys (Prod Info Claritin(R), 2000a).
    2) DESLORATADINE: Deaths occurred in rats at oral doses of 250 mg/kg or greater (approximately 120 times the recommended human daily oral dose), and the median lethal dose in mice was 353 mg/kg (approximately 290 times the recommended human daily dose). Oral doses of up to 250 mg/kg (810 times the recommended human daily oral dose) in monkeys resulted in no deaths (Prod Info CLARINEX(R) tablets, 2002).

Serum Plasma Blood Concentrations

    7.5.1) THERAPEUTIC CONCENTRATIONS
    A) THERAPEUTIC CONCENTRATION LEVELS
    1) LORATADINE
    a) Therapeutic levels are 2.5 to 100 ng/mL (Prod Info Claritin-D(R) 12 HOUR, 1999), and therapeutic levels for loratadine's active metabolite (descarboethoxyloratadine) ranges from 0.5 to 100 ng/mL (Prod Info Claritin(R), 2000b).

Pharmacology Toxicology

Pharmacologic Mechanism

    A) LORATADINE
    1) Loratadine is a selective peripheral histamine H1 receptor antagonist that is devoid of significant central and autonomic nervous system activity (Roman et al, 1986). Animal and human studies have shown that loratadine inhibits the release of several different allergic mediators including histamine, leukotrienes, and prostaglandins (Bousquet et al, 1995). One in vivo study found that loratadine has a dose-dependent, inhibitory effect on IgE mediated and IgE independent histamine release from human basophils (Miadonna et al, 1994).
    2) ANIMAL STUDIES
    a) Loratadine, as well as its active metabolite descarboethoxyloratadine (DCL), exhibit significant antiallergic activity in an experimental animal model. Animal studies have shown that loratadine and DCL inhibits histamine release from IgE-sensitive leukemia cell following antigenic challenge. Other important animal study findings regarding the activity of loratadine include: (a) inhibition of leukotriene synthesis; (b) inhibition of cytosolic calcium uptake; (c) inhibition of histamine and LTD (4) release from lung tissue; and (d) limits the increases in airway resistance following allergic anaphylaxis. All of these physiologic responses to loratadine are important to its clinical use in the treatment of allergic bronchial asthma (Menardo et al, 1997).
    b) Original animal studies have shown that loratadine prevented the bronchospasm that is normally observed when animals are injected with PAF (1-0-alkyl-2-0-acetyl phosphatidylcholine), which is a potent mediator of systemic anaphylactoid reactions (Kreutner et al, 1987; Archer et al, 1985). Additionally, loratadine has been shown to possess antiserotonin activity and will stabilize mast cells. If mast cells are stabilized then histamine and other chemical mediators of the allergic response are not released (Kreutner et al, 1987). All of these physiologic processes are affected by loratadine without compromising the central nervous system (Barnett et al, 1984).
    3) CLINICAL STUDIES
    a) In patients with seasonal allergic rhinitis (SAR), loratadine has demonstrated the following effects (Bousquet et al, 1995; Greiff et al, 1995): (1) Decreases allergen-induced histamine release into the nasal cavity; (2) decreases TAME-esterase activity, which is a marker of mast cell degranulation; (3) improves nasal peak expiratory flow; (4) decreases sneezing; (5) decreases nasal blockage; (6) improves nasal secretion scores; (7) reduces number of activated lymphocytes. Skin tests in patients with SAR demonstrated that loratadine decreases skin-test response to allergen, and it also inhibits basophil degranulation.
    b) In patients with seasonal allergic rhinoconjunctivitis, loratadine reduces (Bousquet et al, 1995; Ciprandi et al, 1991): (1) The number of inflammatory cells; (2) hyperemia and eyelid swelling; and (3) the total number of neutrophils, eosinophils, lymphocytes, and monocytes.
    c) Loratadine is protective against early- and late-phase reactions with the allergen-specific conjunctival provocation test (Baroody et al, 1996).
    d) Following nasal allergen challenge with methacholine chloride, oral loratadine 10 milligrams once daily dosing, significantly (p less than 0.05) reduced sneezing and plasma concentrations of histamine, kinins, albumin, and N-alpha- tosyl-L-arginine methyl ester-esterase activity (Baroody et al, 1996).
    B) DESLORATADINE
    1) Systemic: Desloratadine is a long-acting tricyclic histamine antagonist with selective H1-receptor histamine antagonist activity. Receptor binding data indicates that at a concentration of 2 to 3 ng/mL (7 nanomolar), desloratadine shows significant interaction with the human histamine H1-receptor. Desloratadine inhibited histamine release from human mast cells in vitro (Prod Info CLARINEX(R) tablets, 2002).
    2) Desloratadine exhibits selective peripheral histamine-1 (H1)-receptor blocking activity and antiallergic effects (Prod Info Clarinex(R), 2002; Vignola et al, 1995; Handley et al, 1996; Anthes et al, 2000). In preclinical studies, desloratadine was more potent than loratadine or terfenadine as a functional antagonist at H1 receptors (histamine antagonism on isolated guinea pig ileum), but less potent than levocabastine in a guinea pig nasal histamine-challenge model (Kreutner et al, 2000). Desloratadine was more potent than loratadine with respect to in vivo inhibition of histamine-induced wheal and flare (Handley et al, 1996).
    3) In vitro, desloratadine has a strong affinity for H-1 receptors and 15 to 50 times less affinity for H-2 and muscarinic receptors. The drug reduced human mast cell release of the inflammatory cytokines interleukin-3 (IL-3, -32.1%), interleukin-6 (IL-6, -32.6%), tumor necrosis factor-alfa (TNF-a, -64.5%), and granulocyte-macrophage colony- stimulating factor (GM-CSF, -27.8%). In vitro, it down-regulates histamine, tryptase, cysteinyl leukotriene, and prostaglandin release from mast cells and basophils. Desloratadine is apparently free of anti-cholinergic effects (Henz, 2001).
    4) EFFECTS ON CARDIAC POTASSIUM CHANNELS
    a) Loratadine and desloratadine lacked significant effects on cardiac potassium channels in animal myocyte preparations (DuBuske, 1999; Hey et al, 2000). However, both agents have been reported to block the human cardiac potassium channel Kv1.5; although desloratadine was less potent in this regard (Caballero et al, 1997). The clinical relevance of these findings is unclear.
    b) The general consensus from available studies is that loratadine and desloratadine, in contrast to astemizole and terfenadine, do not pose a significant risk for ventricular dysrhythmias (DuBuske, 1999; Brannan et al, 1995). No significant effect on the QT-interval or heart rate or blood pressure have been reported with oral desloratadine in animal studies or studies involving healthy human subjects (Banfield et al, 2000; Hey et al, 2000).

Toxicologic Mechanism

    A) Based on there pharmacokinetic profile, it is not anticipated that these agents when taken alone can produce significant alterations in cardiac function. Inadvertent exposures with desloratadine may require a longer observation period, due to its prolonged half-life (27 hours) as compared to loratadine (8.4 hours).
    B) HUMAN
    1) DESLORATADINE
    a) It has been observed that some individuals may be slow metabolizers of desloratadine; approximately 7% of the general population and 20% of the African-American population. For these individuals it may be more difficult to convert desloratadine to its active metabolite and can produce higher blood concentrations. Further study is suggested to determine the potential risk of prolonged desloratadine exposure (Spangler & Brunton, 2006).

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