Background:  Terfenadine, astemizole, cetirizine, and loratadine are compared in their abilities to produce relief of symptoms of allergic rhinitis (running nose). 

Objective:  The aim of this study was to compare the onset of action and efficacy of the study medications.

Methods:  111 ragweed-sensitive subjects were primed with pollen in the Environmental Exposure Unit—300 grains of ragweed pollen per meter for 3 hours.  On the test day, subjects were given a single dose of either terfenadine (60 mg, astemizole 10 mg, cetirizine 10 mg, loratadine 10 mg, or placebo when sufficiently symptomatic after 60-minute exposure Allergen levels were maintained and symptoms were recorded every 30 minutes. 

Results:  Subjects realizing definitive relief were cetirizine 65.2%, terfenadine, 45.5% loratadine, 31.8%, placebo 27.3%, and astemizole 22.7%

{Is Claritin, which lessen runny nose in 4.5% of the users, worth taking???  Astenizole, which did worse than placebo, has been taken off the market, not because it doesn’t work, but because of ventricular arrhythmias and cardiac arrest.}

QT PROLONGATION/ VENTRICULAR ARRHYTHMIAS

RARE CASES OF SERIOUS CARDIOVASCULAR ADVERSE EVENTS INCLUDING DEATH, CARDIAC ARREST, QT PROLONGATION, TORSADES DE POINTES, AND OTHER VENTRICULAR ARRHYTHMIAS HAVE BEEN OBSERVED IN PATIENTS EXCEEDING RECOMMENDED DOSES OF ASTEMIZOLE. WHILE THE MAJORITY OF SUCH EVENTS HAVE OCCURRED FOLLOWING SUBSTANTIAL OVERDOSES OF ASTEMIZOLE, TORSADES DE POINTES (ARRHYTHMIAS) HAVE VERY RARELY OCCURRED AT REPORTED DOSES AS LOW AS 20- 30 MG DAILY (2- 3 TIMES THE RECOMMENDED DAILY DOSE).

DATA SUGGEST THAT THESE EVENTS ARE ASSOCIATED WITH ELEVATION OF ASTEMIZOLE AND/ OR ASTEMIZOLE METABOLITE LEVELS, RESULTING IN ELECTROCARDIOGRAPHIC QT PROLONGATION. THESE EVENTS HAVE ALSO OCCURRED AT 10 MG DAILY IN A FEW PATIENTS WITH POSSIBLE AUGMENTING CIRCUMSTANCES (SEE CONTRAINDICATIONS AND WARNINGS). IN VIEW OF THE POTENTIAL FOR CARDIAC ARRHYTHMIAS, ADHERENCE TO THE RECOMMENDED DOSE SHOULD BE EMPHASIZED. DO NOT EXCEED THE RECOMMENDED DOSE OF 10 MG (ONE TABLET) DAILY. SOME PATIENTS APPEAR TO INCREASE THE DOSE OF HISMANAL (ASTEMIZOLE) TABLETS IN AN ATTEMPT TO ACCELERATE THE ONSET OF ACTION. PATIENTS SHOULD BE ADVISED NOT TO DO THIS AND NOT TO USE HISMANAL® ON AN AS- NEEDED BASIS (I. E., P R N) FOR IMMEDIATE RELIEF OF SYMPTOMS.

CONCOMITANT ADMINISTRATION OF ASTEMIZOLE WITH SYSTEMIC KETOCONAZOLE, TRACONAZOLE, ERYTHROMYCIN, CLARITHROMYCIN, TROLEANDOMYCIN, MIBEFRADIL OR QUININE IS CONTRAINDICATED (SEE CONTRAINDICATIONS AND PRECAUTIONS: DRUG INTERACTIONS). SINCE ASTEMIZOLE IS EXTENSIVELY METABOLIZED BY THE LIVER, THE USE OF ASTEMIZOLE IN PATIENTS WITH HEPATIC DYSFUNCTION IS CONTRAINDICATED. IN SOME CASES, SEVERE ARRHYTHMIAS HAVE BEEN PRECEDED BY EPISODES OF SYNCOPE. SYNCOPE IN PATIENTS RECEIVING ASTEMIZOLE SHOULD LEAD TOIMMEDIATE DISCONTINUATION OF TREATMENT AND APPROPRIATE CLINICAL EVALUATION, INCLUDING ELECTRO- CARDIOGRAPHIC TESTING (LOOKING FOR QTPROLONGATION AND VENTRICULAR ARRHYTHMIA). (SEE CLINICAL PHARMACOLOGY, CONTRAINDICATIONS, WARNINGS, PRECAUTIONS, OVERDOSAGE, AND DOSAGE AND ADMINISTRATION.)

A double-blind, single-dose, crossover comparison of cetirizine, terfenadine, loratadine, astemizole, and chlorpheniramine versus placebo: suppressive effects on histamine-induced wheals and flares during 24 hours in normal subjects.

Simons FE, McMillan JL, Simons KJ.

University of Manitoba, Health Sciences Clinical Research Center, Winnipeg, Canada.

We objectively tested the relative antihistaminic effects of cetirizine, 10 mg; terfenadine, 120 mg; terfenadine, 60 mg; loratadine, 10 mg; astemizole, 10 mg; chlorpheniramine, 4 mg; and placebo in healthy, male volunteers, mean age 25 +/- 4 years, and mean weight, 73 +/- 9 kg. The wheal areas and flare areas produced by epicutaneous tests with histamine phosphate, 1 mg/ml, before ingestion of the H1-receptor antagonist or placebo, and afterward, at 0.3 and 0.7 hours, then hourly from 1 to 12 hours and at 24 hours, were traced at 10 minutes and measured with an IBM-PC digitizer and stereometric software. In this experimental model, the H1-receptor antagonists differed significantly with regard to time of onset of action, amount of suppression of the histamine-induced wheal and flare, and duration of action. The rank order was, from most effective to least effective, cetirizine, 10 mg; terfenadine, 120 mg; terfenadine, 60 mg; loratadine, 10 mg; astemizole, 10 mg; chlorpheniramine, 4 mg; and placebo.

NEGATIVE RESULTS FOR CLARATIN

Comparison of the effects of levocetirizine and loratadine on histamine-induced wheal, flare, and itch in human skin

Authors: Clough G.F.; Boutsiouki P.; Church M.K.

Source: Allergy, Volume 56, Number 10, October 2001, pp. 985-988(4)

Publisher:Blackwell Publishing

Abstract:

Background: This randomized, double-blind, crossover study compared the effects of the R-enantiomer of cetirizine, levocetirizine, with those of loratadine on the wheal, flare, and itch response to histamine in human skin.

Methods: Levocetirizine (5 mg), loratadine (10 mg), or placebo was taken orally 4 h before the intradermal injection of histamine (20 µl, 100 µM) or the control vehicle into the forearm skin of healthy volunteers. Flare areas were assessed by scanning laser Doppler imaging before and at 30-s intervals for a period of 9 min. Wheal areas were measured by planimetry at 10 min. Itch was scored every 30 s with a visual analogue scale.

Results: After placebo administration, the mean peak flare area was 23.01±1.94 cm², the wheal area 248±27 mm², and the cumulative itch score 28.8±4.6% (mean±SEM). Levocetirizine reduced the flare, wheal, and itch by 60%, 68%, and 91%, respectively (all P<0.001, Student's t-test for paired data). The effects of loratadine were variable and not statistically significant.

Conclusions: Levocetirizine (5 mg) is a potent inhibitor of the effects of histamine in human skin with an efficacy that exceeded that of loratadine (10 mg) when single doses of the drugs were administered 4 h before the test.

Affiliations: Dermatopharmacology Unit, Allergy and Inflammation Sciences, School of Medicine, University of Southampton, Southampton, UK : *

A double-blind, randomized, single-dose, crossover comparison of levocetirizine with ebastine, fexofenadine, loratadine, mizolastine, and placebo: suppression of histamine-induced wheal-and-flare response during 24 hours in healthy male subjects

Authors: Grant, Andrew J.¹; Riethuisen, Jean-Michel²; Moulaert, Béatrice²; DeVos, Christine³

Source: Annals of Allergy, Asthma and Immunology, Volume 88, Number 2, February 2002, pp. 190-197(8)

Publisher:American College of Allergy, Asthma, & Immunology

Abstract:

Objective: This study compares the potency, consistency, onset, and duration of action of levocetirizine with other popular antihistamines.

Methods: Levocetirizine 5 mg, ebastine 10 mg, fexofenadine 180 mg, loratadine 10 mg, mizolastine 10 mg, or placebo in single doses were given to 18 healthy male volunteers in a double-blind, crossover, randomized fashion. Wheal-and-flare responses to epicutaneous histamine dihydrochloride (100 mg/mL) challenge were measured at 0, 0.5, 1, 2, 4, 6, 8, 10, 12, and 24 hours after each dose.

Results: The overall effect of each drug was evaluated by the area under the curve (0 to 24 hours). Levocetirizine was the most potent and consistently effective drug for inhibiting the histamine-induced wheal-and-flare surface areas. Ebastine, fexofenadine, and mizolastine ranked next and had almost identical effects for inhibiting the wheal. Loratadine was the least potent drug. Levocetirizine, fexofenadine, and mizolastine inhibited the wheal-and-flare response after 1 hour and reached their peak for inhibition after 4 hours. Ebastine and loratadine could be distinguished from placebo only after 4 hours. After treatment with levocetirizine, all 18 subjects had >95% inhibition of the wheal response at one timepoint. Fexofenadine, mizolastine, and ebastine were inhibitory in declining order. All treatments were considered safe and well tolerated.

Conclusions: Levocetirizine, the active enantiomer of cetirizine, is more potent and consistent than other popular H₁ antihistamines for blocking the cutaneous response to histamine. These findings may predict the efficacy of this drug in treating allergic disorders.

Document Type: Original article

Affiliations: 1: University of Texas Medical Branch, Galveston, Texas. 2: UCB Pharma, Braine-l’Alleud, Belgium. 3: UCB Pharma, Brussels, Belgium.