|Year : 2002 | Volume
| Issue : 2 | Page : 73-76
Evaluation of the efficacy and safety of fexofenadine in the management of chronic idiopathic urticaria: A prospective study with 512 patients
Sandipan Dhar , Debasis Basu , Goutam Mistri , Prakash K Hazra , Subrata Malakar , Ajit K Dutta
Divisions of Dermatology and Cardiology, AMRI Goenka Hospital and Duncan Gleneagles Clinic, Calcutta, India
H.No.6, S.P D. Block Baghajatin, Calcutta - 700 086, India
Five hundred and twelve patients with chronic idiopathic urticaria (CIU) were treated with fexofenadine at a dose on 180mg/day. Maximum number of patients were between 20 to 40 years of age and female to male ratio was 1.45:1. The severity of itching was calculated on a scale of 0 to 4 and was recorded by the patients. The mean daily total symptom score (TSS) was measured as sum of the patients' pruritus and number of wheal scores (0 to 7). A mean TSS was determined for each week. Baseline TSS came down to '0' by 4 weeks in all groups except those with TSS 4. There was no correlation between the baseline TSS and degree of improvement. Of 512, 14 (2.73%) patients did not complete the study. The commonest adverse effect was headache (9.04%). There was no report of drowsiness or cardiac arrythmia. In no patient fexofenadine had to be withdrawn because of its adverse effects.
|How to cite this article:|
Dhar S, Basu D, Mistri G, Hazra PK, Malakar S, Dutta AK. Evaluation of the efficacy and safety of fexofenadine in the management of chronic idiopathic urticaria: A prospective study with 512 patients. Indian J Dermatol Venereol Leprol 2002;68:73-6
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Dhar S, Basu D, Mistri G, Hazra PK, Malakar S, Dutta AK. Evaluation of the efficacy and safety of fexofenadine in the management of chronic idiopathic urticaria: A prospective study with 512 patients. Indian J Dermatol Venereol Leprol [serial online] 2002 [cited 2019 May 24];68:73-6. Available from: http://www.ijdvl.com/text.asp?2002/68/2/73/12594
| Introduction|| |
Chronic idiopathic urticaria (CIU) is defined as occurrence of urticarial wheals or hives daily or almost everyday lasting for more than 6 weeks. It affects at least 0.1% of the population. The entity covers 75% of the cases of chronic urticaria where the aetiology remains unknown. About 50% of the patients with CIU have concurrent angioedema. The disease occurs most often in the adults and is about twice as common in women as in men. Although the itching/discomfort associated with CIU is not life threatening, it can be incapacitating and may reduce the quality of life for the sufferers resulting in considerable anxiety and depression. Recent research has suggested that patients with CIU finds the outcome of the disease as devastating as those experienced by patients with coronary heart disease.
The pathogenesis of CIU in most of the cases remains unknown. However, recently there have been significant developments in understanding of the disease. At least 25% of the patients with CIU (type 1 urticaria) have circulating IgG autoantibodies against the ? - sub unit of the affinity IgE receptor (FcE Rl?) which is located on the outer surface of mast cells and basophils. These IgG autoantibodies crosslink with Fc8Rla receptors which trigger the release of histamine and other inflammatory mediators resulting in wheals. There is also a small minority of patients with CIU who have IgG anti IgE autoantibodies (type 1A urticaria). It has been found that nearly 60% of the patients with CIU have functional IgG anti FcaRIE autoantibodies. A further subgroup of patients with CIU (approx. 12%) have a mast cell specific circulating factor (type 2 urticaria) which is currently been characterized by Prof Malcom W Greaves' group. This is a protein, not an immunoglobulin, that does not react with the FcE Rla receptor but promotes the release of histamine from the mast cells. Therefore, the treatment with antihistamines has been the mainstay for patients with mild to moderately severe CIU..,, It has been proposed that in CIU larger doses of antihistamines may be required than those for the treatment of seasonal allergic rhinitis (SAR).
Fexofenadine, a metabolite of terfenadine, is a recently approved second generation antihistamine with selective peripheral H1 receptor antagonist activity. The drug appears to be quite promising one among the newer antihistamines since it fulfills almost all the criteria for an ideal H1 antagonist viz., rapid onset of action, 24 hour duration of action, rapid onset of action and absence of tachyphylaxis., Moreover, the drug does not cross the blood brain barrier and is devoid of any CNS toxicity. It does not impair cognitive and psychomotor functions. The drug has shown an excellent cardiological safety in clinical trials., This has been in keeping with the result of in vitro studies using the ventricular myocyte model where it did not affect the delayed rectifier potassium channel. Fexofenadine can be taken with ketoconazole or erythromycin without any increase in QTC period.
The present prospective study was undertaken to evaluate the efficacy and safety of fexofenadine in the treatment of CIU at a single daily dosage of 180mg for 6 weeks.
| Materials and Methods|| |
The study included 512 patients in whom the diagnosis of CIU was made on the basis of urticarial lesions on at least 3 days a week for the previous 6 consecutive weeks immediately prior to the study. Patients with predominantly physical urticarias and urticarial vasculitis were excluded from the study. Patients known to be hypersensitive to terfenadine were also excluded from the study. Each patient was given fexofenadine 180 mg in a single daily oral dose 1 hour before food at a consistent time each day for a period of 6 weeks. No other systemic or topical medication likely to influence CIU was permitted. The assessment of efficacy and safety was undertaken daily by the patients and the results were recorded in a diary. The investigators (SD, SM, AD) performed the evaluation at 2,4 and 6 weeks. In all patients through cardiological check up and electrocardiogram (ECG) were carried out by the cardiologists (DB, PKH, GM). The patients were asked to record severity of itching experienced in previous 24 hours of medication using rating scale commonly used for the evaluation of CIU viz., a scale of 0 to 4 (where 0= none, 1 = 1-5, 2=6-15,3= 16-25and4= 17-25)., The mean daily total symptom score (TSS) was measured as sum of the patients pruritus and number of wheal scores (rating 0-7). A mean TSS was also determined for each week. A patient was considered to have improved if the mean TSS on treatment was less than the mean baseline TSS. The number of patients with 'O' TSS at every week were recorded. The patients were asked to note the adverse effects if any and report those to the corresponding investigator. Routine haematological examination and urinalysis were performed in each patient.
| Results|| |
Of 512, 14 (2.73%) patients dropped out from the follow -up. [Table - 1] highlights the age and sex distributions of the patients. Maximum number of patients were between 20 to 40 year of age and females outnumbered males with a female to male ratio I. 46:1.
[Table - 2] depicts the baseline TSS and weekly reduction of TSS with fexofenadine. The baseline TSS came down to 'O' by 4 weeks in all groups except those with TSS 4, where in 6 and 2 patients baseline TSS came down to '0' after 5 weeks and 6 weeks respectively. However, there was no correlation between the baseline TSS and degree of improvement. While in some patients baseline TSS came down to 0 quickly, in others it took several weeks to respond. There was no report of fexofenadine induced drowsiness or cardiac arrhythmia. The commonest adverse effect was headache (9.04%). Other minor side effects have been listed in [Table - 3]. However, in none of the patients fexofenadine had to be withdrawn because of its toxicity.
| Discussion|| |
In the study majority of the patients were between 20 to 40 years of age and females outnumbered males. This was in corroboration with the earlier observations that CIU mostly affects adults and females. There was improvement in TSS in all the patients. The baseline TSS came down to '0' by the end of 4 weeks. However, there was no correlation between the baseline TSS and degree of improvement.
The most distressing symptom of CIU is pruritus. It is generally recognized that H1 receptor antagonists are more effective in controlling the pruritus than the whealing. In the present study the drug controlled the pruritus effectively in 50% of the patients within 4 weeks and in 8 patients by 6 weeks. This was in corroboration with the study by Paul et al. Fexofenadine was well tolerated throughout the study period. Adverse effects were analysed in 498 patients. Among the side effects, headache was a common complaint experienced by 45 (9.04%) patients. No patient receiving the medicine complained of drowsiness. Intake of the drug was not associated with palpitation and/ or ECG evidence of QT prolongation in any patient. The observations were in corroboration with the study by Paul et al. The safety profile has been found to remain unaltered with differential dosing schedule for the treatment of different conditions viz. seasonal allergic rhinitis (SAR) or CIU. However, for the treatment of CIU, fexofenadine HC1 180 mg/day dose has been recommended.
Recently the issue of cardiological safety of fexofenadine has been blown out of proportion on the basis of a single case report from the Netherlands. However, we as well as others have failed to appreciate any such adverse effect of the drug in large number of patients, even when the drug was given for longterm and in doses 10 - fold than the recommended one. This has been substantiated by experimental work on the effect of fexofenadine on isolated myocyte preparation.
The study, therefore, demonstrates that fexofenadine HC1 at a single daily oral dose of 180mg is an effective nonsedating antihistamine for the treatment of CIU and is devoid of any significant adverse effect including cardiotoxicity. So far there is not much published data available on 180mg fexofenadine molecule. Most of the studies address the efficacy and safety parameters of 120 mg fexofenadine in seasonal allergic rhinitis (SAR). Therefore, inspite of the fact that the present study is an uncontrolled one, it appears to be worthwhile because of its large sample size.
| References|| |
|1.||Greaves MW, Sabroe RA. Allergy and the skin I - urticaria. Br Med J 1998;316:1147-1150. |
|2.||Warin RP. Food and factors in urticaris. J Hum Nutr 1976;30:179-186. |
|3.||Sibbald RG, Cheema AS, Lozinski A, et al. Chronic urticaria evaluation of the role of physical, immunologic and other contributory factors. Int J Dermatol 1991;30:381-386. |
|4.||O' Donnell BF, Lawlor F, Simpson J, et al. The impact of chronic urticaria on the quality of life. Br J Dermatol 1997;136:197-201. |
|5.||Nimmi N, Francis DM, Kermani F, et al. Dermal mast cell activation by autoantibodies against the high affinity IgE receptor in chronic urticaria. J Invest Dermatol 1996;106:1001-1006. |
|6.||Tong U, Balakrishnan G, Kochan JP, et al. Assessment of autoimmunity in patients with chronic urticaria. J Allergy Clin Immunol 1997;99:461-465. |
|7.||Mathews KR. The urticarias. Current concepts of pathogenesis and treatment. Drugs 1985;30:552-560. |
|8.||Soter NA. Urticaria: current therapy. J Allergy Clin Immunol 1990;86:1009-1014. |
|9.||Simons PER, Simons KJ. The pharmacology and use of H, receptor antagonist drugs. N Eng J Med 1994;330:1663-1670. |
|10.||Markham A, Wagstaff AJ. Fexofenadine. Drugs 1998;55:269-274. |
|11.||Day JH, Briscoe MR Welsh A, et al. Onset of action, efficacy and safety of a single dose of fexofenadine hydrochloride for ragweed allergy using an environmental exposure unit. Ann Allergy Asthma Immunol 1997;79:533-540. |
|12.||Rampe D, Wible B, Brown AM, et al. Effects of terfenadine and its metabolites on delayed rectifier K+ channel cloned from human heart. Mol Pharmacol 1995;123:1240-1245. |
|13.||Dhar S, Hazra PK, Malakar S, et al. Fexofenadine induced QT prolongation - a myth or fact? Br J Dermatol 2000;142:1-3. |
|14.||Woosley RL, Chen Y, Freiman JP, et al. Mechanism of the cardiotoxic actions of terfenadine, JAMA 1993;269:1532-1536. |
|15.||Pratt CM, Mason J, Russell T, et al. Effect of fexofenadine on corrected QT interval (QTc). Allergy 1997;52:67. |
|16.||Greares MW. Antihistamine treatment, a patient self assessment method in chronic urticaria. Br Med J 1981;283:1435-1436. |
|17.||Bllehen SS, Thomas SE, Greaves MW, et al. Cimetidine and chlorpheniramine in the treatment of chronic idiopathic urticaria: a multicentre randomized double blind study. Br J Dermatol 1987;117:81-88. |