Pharmacological properties of the drug Fexofenadine
Antiallergic agent, H1 receptor blocker. Fexofenadine is a pharmacologically active metabolite of terfenadine. Does not have a sedative effect. The antihistamine effect appears 1 hour after oral administration, reaches a maximum after 6 hours and continues for 24 hours. After 28 days of administration, no addiction was observed. When taken orally in doses up to 130 mg, the effectiveness of fexofenadine is dose-dependent. The effect after taking a dose of 120 mg lasts for 24 hours. After oral administration, fexofenadine hydrochloride is rapidly absorbed in the digestive tract, reaching a maximum concentration in the blood plasma after approximately 1–3 hours. The average maximum concentration after taking a dose of 180 mg 1 time per day day is approximately 494 ng/ml, and after taking a dose of 120 mg - 427 ng/ml. The pharmacokinetics of fexofenadine when taken orally at a dose of up to 120 g 2 times a day is linear. Administration at a dose of 240 mg 2 times a day causes a slightly greater than proportional increase (8.8%) in AUC, indicating that when fexofenadine is taken daily in doses of 40-240 mg, its pharmacokinetics are almost linear. Plasma protein binding is 60–70%. Fexofenadine undergoes little metabolism (hepatic or extrahepatic) as it is found primarily unchanged in urine. Fexofenadine plasma concentrations decrease biexponentially with an elimination half-life ranging from 11 to 15 hours after multiple doses. Excreted primarily in bile, up to 10% of the dose is excreted unchanged in the urine.
FEXADINE (tablets)
Since I inherited allergies to food, household, seasonal and to animals, at first I tried many tablets, drops, sprays, syrups and before undergoing complex treatment I settled on Fexadin.
Of course, I was examined by an allergist, and not only did skin tests (which are not always accurate), but I also took a blood test to determine the spectrum of allergens and reactions to them. The allergist prescribed many medications that do not cause drowsiness, but some of them either did not help, or I suffered from lethargy and poor concentration, although the symptoms were relieved. In this regard, allergy sufferers differ from allergy sufferers - there are those who do not experience drowsiness at all, or those for whom the best medicine does not help. For me, I found the ideal option - a combination of price and effect.
RELEASE
Ten tablets are packaged in a very positive and bright box.
Now the medicine has become more expensive, before it was cheaper, but the price is far from exorbitant. On the reverse side there is brief information with dosage, composition and manufacturer. But we won’t limit ourselves to it - let’s look inside and be sure to read the instructions.
The expiration date, as often happens, is printed on the side and is duplicated on the package of tablets.
There are only ten tablets, but this is enough to remove the allergen from the blood (take the medicine in a course), and quickly relieve the symptoms of any allergic reaction.
You can see some curious black markings on the tablet. I won’t dare to lie and won’t say that it is this that confirms the authenticity of the drug - but it is a mark on the weight of the release. “Fexadin” is available in 120 and 180 g. Tablets of 120 g are quite enough in my case. For severe allergies, 180 g tablets are needed.
It is, of course, important to read the instructions, although taking Fexadin is not much different from taking other allergy pills - once a day.
The shelf life is quite long - 3 years. During this time, the medicine will not disappear and will have time to help, unless, of course, side effects occur.
There is one very important point. Allergy sufferers are often interested in whether the medicine is “sleepy or not.” In this case, the instructions say that it is either not recommended or you can get behind the wheel. In this case, they emphasize that the reaction is individual. This means that, in most cases, you will not feel any change in your well-being, but I did, but more on that below.
EFFECT
The effect is immediate. Within 5-8 minutes I already felt relief from the most unpleasant symptoms (the last reaction I got from interacting with dust during repairs) - the runny nose and itching went away, the cough subsided, which there was little that could be done to calm it down. If an allergic cough provokes difficulty breathing, then breathing can still be eased with an aerosol, but only tablets can relieve swelling, which is what Fexadin did.
SIDE EFFECTS
There were and still are, unfortunately. But, I must say, these are the weakest side effects that I have ever experienced. All medicines are known by comparison. For example, when taking Zodak, I suffered terribly from difficulty concentrating, drowsiness, and weakness, as when using Suprastinex (a new generation of tablets, not Suprastin). “Fexadin” causes such mild drowsiness that it is not difficult to fight. Because of this drug drowsiness, my eyes become slightly photosensitive, but I am quite functional and I do not fall off my feet, I can play sports and work at the computer. Again, if you compare it with Zodak, I was literally dying at work from a heavy cloudy head and inability to concentrate. Everything taken together (and Zodak lasts for two days) made me even more irritable and inadequate, because simple things seemed unbearably heavy.
RESULT
With Fexadin I’m not just a person, I completely forget that a few minutes ago I was suffering from a reaction to something, and now I’ve finally switched from Zodak to it. If some other medications do not allow you to work normally (you want to sleep) or simply do not work, then you should definitely try taking Fexadin, because allergies, unfortunately, are not a rare phenomenon now, and there is no ideal drug for all occasions came up with it.
Special instructions for the use of the drug Fexofenadine
There is no data on the safety of fexofenadine during pregnancy, so it should be prescribed only when the expected therapeutic effect for the expectant mother outweighs the potential risk to the fetus. If it is necessary to use fexofenadine during breastfeeding, the issue of stopping breastfeeding should be considered, since fexofenadine passes into breast milk. The effectiveness and safety of fexofenadine in children under 12 years of age have not been studied. Fexofenadine should be used with caution in the elderly, patients with renal or hepatic insufficiency, since at present there is not enough clinical experience with the use of fexofenadine in patients in these groups. Based on the pharmacodynamic profile and known side effects, it can be assumed that the effect of taking fexofenadine on the ability to drive vehicles and perform tasks requiring concentration is unlikely. However, it is recommended to assess individual response to fexofenadine before driving or performing other demanding activities.
Fexofenadine - new opportunities in the treatment of seasonal allergic rhinitis
Professor A.S.
Lopatin Central Clinical Hospital MC UD of the President of the Russian Federation
A
Allergic rhinitis (AR) is one of the most common human diseases, which now affects more than 20% of the adult population (N.I. Ilyina, 1997). AR is a classic example of an IgE-mediated process. The main participants in allergic inflammation in the nasal mucosa are mast cells, which secrete the main mediator of allergic inflammation - histamine. The activity of these cells determines the characteristics of the early and, to some extent, late phases of allergic inflammation (I.S. Gushchin, 1998). The effect of histamine on H1 receptors after contact with an allergen in the case of AR is manifested by nasal congestion, rhinorrhea, sneezing and itching.
Antihistamines have long been used in the treatment of AR. In connection with this significant event in the treatment of allergic diseases was the creation in the early 1980s of a new antihistamine that does not have a sedative effect - terfenadine. However, a significant drawback of terfenadine, like some other non-sedating antihistamines, was the presence of a cardiotoxic effect, which sometimes led to the development of severe arrhythmias.
Clinical trials have established that, unlike other H1 blockers, the new drug fexofenadine does not have a negative effect on the cardiovascular system (MH Terrien et al., 1999). in vitro studies
It has been proven that fexofenadine has twice the affinity for H1 receptors than terfenadine and at the same time lacks anticholinergic and calcium channel blocking effects, which determines the complete absence of cardiotoxic effect. Fexofenadine has been extensively studied for possible cardiotoxicity. Heart rate monitoring, blood pressure and left ventricular pressure were monitored. No abnormalities were reported for any of these measures (C. Pratt et al., 1997). Fexofenadine does not penetrate the blood-brain barrier, does not undergo biotransformation and is quickly eliminated from the body mainly through biliary excretion.
To study the pharmacological action and safety of fexofenadine, clinical studies were conducted in more than 4,000 patients with allergies, 500 healthy volunteers, as well as in patients with liver and kidney failure. More than 470 people took part in a long-term study to study the safety of the drug. These studies showed that fexofenadine at a dose of 60 and 120 mg relieves symptoms of seasonal AR within 60 minutes. In placebo-controlled studies, it was found that a single administration of fexofenadine at a dose of up to 800 mg or repeated doses of up to 690 mg did not cause adverse reactions such as drowsiness, dry mucous membranes, changes in heart rate and blood pressure. Taking fexofenadine at a dose of up to 1380 mg per day had no effect on ECG parameters.
It has now been proven that fexofenadine inhibits the expression of adhesion molecules ICAM-1, as well as the eosinophil-induced release of ICAM-1 and other inflammatory mediators in cultured nasal epithelial cells, that is, it has not only an antiallergic, but also an anti-inflammatory effect (M. Muntasir et al., 1998). In in vivo
fexofenadine at a dose of 1.6 mg/kg inhibited the formation of a skin blister in guinea pigs during a provocative histamine test, which indicates purely competitive antagonism.
The effects of fexofenadine on driving ability and effects on psychomotor responses were assessed in a double-blind crossover study compared with placebo and clemastine (a sedative drug). Regardless of this, the effect of the drug on psychomotor state and daytime activity was studied by the British Defense Development Agency in a double-blind, placebo-controlled study in 6 groups of patients. Promethazine, which has a pronounced sedative effect, was used as an active control. The results of these independent studies were identical. They showed that fexofenadine does not affect psychomotor reactions and does not cause drowsiness, so it was found suitable for the treatment of allergies in people employed in automated manufacturing and in vehicle drivers (AN Nicholson, C. Turner, 1998), and the dose of fexofenadine was not requires correction in patients with renal and liver failure (A.Markham, AJWagstaff, 1998). A 1997 US multicenter, placebo-controlled study found that fexofenadine 120 mg once daily was equally effective and more convenient for patients (TB Casale et al., 1999).
Material and research methods
We studied the effectiveness of fexofenadine (Telfast) in patients suffering from seasonal allergic rhinitis (SAR). The study involved 20 people aged from 22 to 63 years (average age - 33.5 years), among whom there were 14 women and 6 men. The duration of the disease is from 2 to 40 years (on average 10.5 years). Among the concomitant diseases, allergic conjunctivitis was noted in 9, migraine – in 4, bronchial asthma – in 6, urticaria – in 7, allergic dermatitis – in 2 patients.
Skin testing with non-bacterial allergens revealed an allergy to tree pollen in 15 patients, an allergy to cereal pollen in 11, and a weed pollen in 14 patients. In 13 patients, a positive reaction to epidermal allergens was noted.
Fexofenadine was prescribed at a dose of 120 mg once a day against the background of maximum clinical manifestations of SAR during the flowering season of trees and cereal grasses. The duration of treatment was 28 days. The severity of standard symptoms of the disease (nasal discharge, sneezing, nasal congestion, itchy eyes, watery eyes, red eyes and sore throat) was assessed on a 4-point scale: 0 – no symptoms, 1 – mild, 2 – moderate, 3 - intense.
To objectively assess the effectiveness and safety of the drug, the following research methods were used:
- anterior active rhinomanometry (APR);
- endoscopy and photography of the nasal cavity;
- general blood analysis;
- counting the number of eosinophils in fingerprint smears from the nasal mucosa;
- ECG;
- measurement of blood pressure and heart rate (HR).
The treatment results were assessed by the doctor and the patient on a five-point scale:
4 – excellent result – all symptoms of SAD disappeared;
3 – good – almost all symptoms have disappeared, but 1-2 of them persist, although they have become significantly less pronounced;
2 – satisfactory – disappearance or regression of most of the symptoms of SAD;
1 – no effect;
0 – deterioration.
Clinical and laboratory parameters were assessed by a doctor at the patient’s first visit, on the 14th and 28th day of taking the drug.
Research results
As can be seen from Table 1, during treatment with fexofenadine, a clear positive dynamics in the severity of all SAD symptoms was observed.
During the initial examination, all patients had severe symptoms of SAD. Thus, all 20 patients complained of nasal discharge, and in 15 of them the severity of this symptom was maximum, in 4 it was of moderate intensity, and in only 1 it was mild. Nasal congestion was noted by 19 subjects, of which 17 characterized difficulty in nasal breathing as intense. Itching in the eyes was noted in 20 patients (including intense in 15), itching in the nose in 19 (intensive in 15), sore throat in 18 (intensive in 13). Eye redness and lacrimation were observed in 19 and 18 subjects, respectively.
Two weeks after starting the drug, a sharp decrease in the intensity of clinical manifestations of SAD was recorded. During the last visit, slight nasal discharge bothered only 2 and sneezing in 4 patients, mild nasal congestion and tickling in the nose were noted in 1 and 2 patients, respectively. The remaining symptoms of SAD were completely relieved by taking fexofenadine (Fig. 1, 2).
Fig.1. Dynamics of the severity of rhinitis symptoms during treatment with fexofenadine
Fig.2. Dynamics of the severity of concomitant symptoms during treatment with fexofenadine
Using the method of anterior active rhinomanometry, the indicators of total volume flow (SVF) and total airflow resistance (ARF) were studied. Normal values of SOP (682.6±35.8 cm3/s) and SS (0.22±0.01 Pa/cm3/s) for comparison were derived from an examination of a control group of 14 healthy individuals without any nasal diseases .
At the first visit, the average SOP value in patients with SAR was 260.8±46.2 cm3/s, at the second – 425.7±58.2 cm3/s, and at the third – 643.6±47.7 cm3/s , that is, close to normal. The average SS value changed from 1.2±0.27 Pa/cm3/s (first visit), to 0.54±0.12 Pa/cm3/s (second visit) and 0.26±0.05 Pa/cm3 /s at the end of treatment with the drug. According to the paired t-test, the average value of SOP significantly increased from the first to the third visit (p<0.0001), respectively, the average value of SS significantly decreased (p<0.0001).
Thus, despite the widespread belief that difficulty in nasal breathing is not the main symptom of SAD, anterior active rhinomanometry data indicate a statistically significant significant improvement in nasal breathing in patients taking fexofenadine.
The dynamics of the size of the nasal turbinates and the width of the nasal passages during endoscopy of the nasal cavity also indicated the restoration of nasal breathing in patients with SAR during treatment.
When examining fingerprint smears from the nasal mucosa before treatment, eosinophils were found in 19 (95%) patients, and at the end of the course of treatment - in only 2 (10%). Before starting the drug, 12 (60%) patients had blood eosinophilia; by the end of the study, it persisted in only 1 patient, however, in this case, the number of eosinophils decreased from 14% to 8%.
ECG in all patients was recorded before, after and during treatment. Negative dynamics were not noted in any of the examined people. Blood pressure and heart rate remained within normal limits. It should be noted that while taking fexofenadine at the indicated dosage, the manifestations of allergic dermatitis disappeared in one patient, and another patient was able to refuse insufflations of the corticosteroid drug flixonase during treatment with fexofenadine.
Thus, fexofenadine was effective in all 20 patients.
The general assessment of the treatment results made by the doctor and the patients coincided. An excellent result was observed in 15 (75%), and a good result in 5 patients (25%). There was no lack of effect and no increase in the severity of symptoms of the disease in this group of patients. The results obtained allow us to conclude that fexofenadine is a highly effective and safe drug for the treatment of SAD. Literature:
1. Gushchin I.S. Allergic inflammation and its pharmacological control. – M.: Farmus print, 1998.
2. Ilyina N.I. Allergic rhinitis // Information collection. News of science and technology. Series: Medicine. Issue: Allergy, asthma and clinical immunology. – 1997. – No. 4 – pp. 20–24.
3. Abdelaziz MM, Devalia JL, Khair OA, et al. Effect of fexofenadine on eosinofil–induced changes in epithelial permeability and cytokine release from nasal epithelial cells of patients with seasonal allergic rhinitis // J. Allergy Clin. Immunol. – 1998. – Vol.101, N.3. – P.410–420.
4. Casale TB, Andrade C., Qu R. Safety and efficacy of once-daily fexofenadine HCI in the treatment of autumn seasonal allergic rhinitis // Allergy and Asthma Proc. – 1999. – Vol.20, N.3. – P.194–198.
5. Markham A., Wagstaff AJ Fexofenadine. Adis new drug profile // Drug. – 1998. – Vol.55. – P.269–274.
6. Nicholson AN, Turner C. Central effects of the H1–antihistamin, cetirizin // Aviation Space Environ. Med. – 1998. – Vol.69. – P.166–171.
7. Pratt C., Mason J., Russell T., Ahlbrandt R. Effect of fexofenadine HCI on corrected QT interval (QTc) // Paper presented at the Congress of European Academy Of Allergology and Clinical Immunology. –, Rhodos, Greece, June 1997.
8. Terrien MH, Rahm F., Fellrath JM, Spertini F. Comparison of the effects of terfenadine on nasal provocation tests with allergen // J. Allergy Clin. Immunol. – 1999.– Vol.103, N.6. – P.1025–1030.
Drug interactions Fexofenadine
fexofenadine is not biotransformed in the liver and therefore does not interact with other drugs metabolized by microsomal liver enzymes. When fexofenadine is co-administered with erythromycin or ketoconazole, the concentration of fexofenadine in the blood plasma increases 2-3 times, which is apparently due to increased absorption in the digestive tract and decreased elimination in the bile. These changes are not accompanied by a change in the QT and are not associated with an increase in the severity of side effects compared to the effects of drugs administered separately. No interaction between fexofenadine and omeprazole was observed. When using antacids containing aluminum or magnesium 15 minutes before taking fexofenadine, bioavailability is reduced, probably due to binding in the digestive tract. The recommended interval between taking fexofenadine and antacids containing aluminum or magnesium hydroxide is 2 hours.
Fexofenadine
- In animal experiments, fexofenadine suppressed allergic reactions and did not cause prolongation of the QI interval (QIc)
in dogs and rabbits at plasma concentrations that were many times higher than therapeutic levels. - Compared with placebo, fexofenadine had no effect on the mean duration of the QTc interval in patients receiving the drug at a dose of up to 480 mg/day for 2 weeks, and in volunteers receiving fexofenadine at a dose of up to 800 mg/day for 6 days or 240 mg/day. days for 12 months.
- In a double-blind clinical study, fexofenadine 120 or 180 mg orally once daily reduced symptoms of seasonal allergic rhinitis as effectively as cetirizine. In other double-blind clinical studies, fexofenadine at a dose of 40–240 mg 2 times a day was significantly more effective than placebo. In patients with chronic idiopathic urticaria, fexofenadine 180 or 210 mg once daily was also significantly more effective than placebo.
- In clinical studies, the drug was well tolerated; the nature of adverse reactions did not differ from those of placebo. The most common side effects were headache, throat irritation, viral infections, nausea, dysmenorrhea, somnolence, dyspepsia and fatigue.
Fexofenadine is an active metabolite of the H1-histamine receptor antagonist terfenadine, which does not have sedative activity and does not affect the QT interval on the ECG.
Pharmacodynamics
*According to experimental studies in rats, labeled fexofenadine did not penetrate the blood-brain barrier *Fexofenadine suppressed antigen-induced bronchospasm in sensitized guinea pigs, as well as histamine release from peritoneal mast cells in rats *One of the characteristic features of allergic inflammation is increased expression of adhesion molecules on endothelial/epithelial cells, which leads to the migration of leukocytes to the site of inflammation. In vitro, fexofenadine significantly reduced the basal expression of the adhesion molecule ICAM-1 on human conjunctival epithelial cells and the spontaneous release of interleukin-6 from fibroblasts. The latter effect depended on the concentration of the drug. Fexofenadine at concentrations ranging from 10-4 to 10-3 mol/L in vitro significantly suppressed the eosinophil-induced release of interleukin-8, granulocyte-macrophage colony-stimulating factor and soluble ICAM-1 from nasal epithelial cells obtained from patients with seasonal allergic rhinitis. *In experiments on mice, oral administration of fexofenadine at a dose of 5 mg before and during the inhalation test with methacholine prevented the development of airway hyperresponsiveness, but did not affect eosinophilic inflammation. *Fexofenadine did not cause prolongation of the QTc interval in dogs when administered orally at a dose of 10 mg/kg/day for 5 days and in rabbits when administered intravenously at a dose of 10 mg/kg, although its plasma concentrations were 28 and 63 times higher than drug levels, respectively in patients receiving it in therapeutic doses (60 mg 2 times a day). *Average QTc interval in 714 patients receiving fexofenadine capsules 60-240 mg twice daily for 2 weeks, and 40 volunteers receiving the drug as an oral solution in doses up to 400 mg twice daily for 6 days was not significantly different from that in patients receiving placebo. *The lack of effect of fexofenadine on the QTc interval was confirmed in 2 long-term studies in volunteers. Fexofenadine, which was used at 60 mg 2 times a day for 6 months or 240 mg 1 time a day for 12 months, did not cause significant changes in the QTc interval compared with placebo (Fig. 1). *In sensitized volunteers who were exposed to controlled exposure to the allergen (ragweed pollen) in a special chamber, the median time to the onset of a clinically significant effect after a single dose of fexofenadine at a dose of 60 (n=33) or 120 mg (n=33) was 60 minutes. and after taking placebo (n=33) - 100 min. Fexofenadine reduced the total symptom index to a significantly greater extent than placebo (30 or 28% versus 14%). The rate of onset of effect and efficacy were similar when using fexofenadine in two doses. *In a randomized, double-blind, crossover study in volunteers (n=20), fexofenadine 60 mg twice daily (two doses) or 120 mg (one dose) suppressed histamine-induced wheals and flushing significantly more rapidly than loratadine (10 mg once daily). ). Compared with loratadine, fexofenadine at a dose of 120 mg 1 time per day more effectively inhibited the development of blisters in the intervals from 2 to 6 hours and from 8 to 10 hours. At the indicated dose, fexofenadine in the interval from 2 to 5 hours more actively suppressed hyperemia than loratadine at dose 10 mg. Fexofenadine and loratidine were significantly more effective than placebo at 2 hours (fexofenadine 120 mg) or 3 hours (loratadine 10 mg and fexofenadine 60 mg twice daily) after dosing and throughout the remainder of the 24-hour study period. *In 20 volunteers, a single dose of fexofenadine (60 mg) reduced the formation of blisters with subcutaneous histamine injection significantly more effectively than a single dose of loratadine (10 mg) 5, 6 and 7 hours after application. Terfenadine 60 mg was also superior to loratadine (but not fexofenadine) at certain time points after administration. All three drugs were significantly more effective than placebo. *In 9 patients with an allergy to ragweed, skin tests (hives and flushing with subcutaneous administration of pollen from this plant) returned to baseline within 2 days after stopping treatment with fexofenadine (60 mg twice daily).
Pharmacokinetics
*In 24 healthy male volunteers who received fexofenadine at a dose of 60 mg 2 times a day for 5 days, the maximum plasma concentration (Cmax) at steady state was 286 mcg/l and was reached 1.3 hours after administration (t max ). The area under the plasma concentration curve (AUC) at steady state was 1521 mcg/L/h. *In volunteers receiving fexofenadine at doses of 20, 60, 120, or 240 mg twice daily, steady-state Cmax and AUC increased dose-proportionally, while Tmax and steady-state oral clearance remained relatively constant. *The effect of gender on the pharmacokinetic properties of fexofenadine was studied in volunteers. In women (n=20), oral clearance of the drug was 33% lower than in men (n=20). However, renal clearance was similar (3.49 and 3.42 L/h), and fexofenadine was equally well tolerated in doses of 80 to 800 mg/day. *In elderly volunteers aged 65-80 years (n=20), who received fexofenadine once orally at a dose of 80 mg, clearance was lower, and Cmax and AUC were higher than in younger people (19-45 years old; n=110 ). However, AUC values in elderly patients were within acceptable limits. *In patients with renal failure of varying severity (from mild to severe), the Cmax and half-life of fexofenadine were significantly higher (by 87 III and 59 - 72%, respectively) than in healthy volunteers. In the United States, fexofenadine is recommended to be prescribed at a lower starting dose (60 mg/day) in patients with impaired renal function. Impaired liver function did not significantly affect the pharmacokinetics of the drug. *In male volunteers (n=6) who received [14C] fexofenadine at a dose of 60 mg, 80% of the drug was excreted in feces and 12% in urine. More than 85% of the dose was excreted unchanged, indicating the absence of significant systemic metabolism.
Clinical researches
*In a 2-week randomized, double-blind study in 570 patients with seasonal allergic rhinitis, fexofenadine at a dose of 60 to 240 mg twice daily was significantly more effective than placebo. Efficacy was determined in all patients included in the study (intention-to-treat), based on patients' assessment of the severity of symptoms on a 5-point scale. *According to a multicenter, 2-week, double-blind study in 588 patients with confirmed seasonal allergic rhinitis, fexofenadine at a dose of 49 to 120 mg 2 times a day was also more effective than placebo. In this study, efficacy was determined in the intention-to-treat population using the same scale as in the previous study. In a double-blind, placebo-controlled study in patients with seasonal allergic rhinitis (n=821), the effectiveness of fexofenadine 120 or 180 mg once daily and cetirizine 10 mg once daily was not significantly different. In patients receiving active treatment, the total symptom index at 24 hours decreased significantly more than in patients assigned to placebo (n = 0.0001). The dynamics of nasal congestion, which was not taken into account when determining the total symptom index, were also more pronounced during treatment with fexofenadine and cetirizine than when taking placebo. In a placebo-controlled study in patients with chronic idiopathic urticaria (n=224), treatment with fexofenadine at doses of 180 and 240 mg (but not at doses of 60 or 120 mg) once daily for 14 days led to a significant reduction in the total symptom index ( their severity was assessed by the patients themselves using scales). Compared with placebo, fexofenadine at all doses significantly reduced itching and the impact of allergy on sleep and normal functioning. In 1948 patients with seasonal allergic rhinitis, treatment with fexofenadine 60 mg twice daily resulted in a greater improvement in quality of life (assessed using a special questionnaire designed for patients with rhinoconjunctivitis - Rhino-conjunctivitis Quality of Life Questionnaire) than placebo. In patients receiving fexofenadine, impairments in performance and activity decreased to a greater extent than in the placebo group.
Portability
*In clinical studies of fexofenadine in doses ranging from 20 to 240 mg twice daily (n=2461), the incidence of adverse events in the fexofenadine and placebo groups was similar. In Fig. Table 2 shows adverse events that occurred with a frequency of more than 1% when using fexofenadine at a dose of 60 mg 2 times a day (n=679) and placebo (n=672). Although the frequency of headaches and pharyngeal irritation are not indicated in Fig. 2, they exceeded 1% and were more common in the placebo group. The incidence of adverse events was not dose dependent. Due to adverse events, 2.2% of patients in the fexofenadine group and 3.3% of patients in the placebo group were excluded from the studies. *In patients receiving fexofenadine and placebo, laboratory abnormalities were observed with the same frequency and severity. *In an acute test (single 10-800 mg) and with repeated use of fexofenadine (20-690 mg 2 times a day for 28.5 days) in male volunteers, there was no dependence of the frequency of adverse events or laboratory abnormalities on the dose identified; There were also no significant differences with the placebo group. *The use of fexofenadine at a dose of 60 mg 2 times a day for 6 months or 240 mg 1 time a day for 12 months did not lead to a significant increase in the QTc interval compared with placebo. *In volunteers, taking fexofenadine at a dose of 120 mg 2 times a day in combination with erythromycin 500 mg every 8 hours or ketoconazole 400 mg 1 time a day was accompanied by an increase in the equilibrium Cmax and AUC0 12 hours of fexofenadine. However, their values remained lower than those in tolerability studies in which fexofenadine was used at higher doses (400 mg twice daily). Fexofenadine had no effect on plasma concentrations of erythromycin and ketoconazole. In addition, with its simultaneous use with these drugs, no increase in the incidence of side effects or deviations in the QTc interval was observed compared with that with fexofenadine monotherapy. There is no need to change the dosage of fexofenadine when used in combination with erythromycin or ketoconazole.
Fexofenadine: summary
Clinical studies have demonstrated the effectiveness of the H1-histamine receptor antagonist fexofenadine in the treatment of seasonal allergic rhinitis and chronic idiopathic urticaria. These studies are registered indications for the use of the drug. It should be noted that fexofenadine did not cause QT prolongation, which has sometimes been observed with terfenadyl (fexofenadine is an active metabolite of the latter). E. Markham and E. J. Wagstaff Actiz international Limited, Auckland, New Zealand From Drugs, 1998, Feb;55(2)
