Telfast

Telfast

fexofenadine

Manufacturer:

sanofi-aventis

Distributor:

DKSH
Full Prescribing Info
Contents
Fexofenadine hydrochloride.
Description
Each tablet contains fexofenadine 112 and 168 mg as fexofenadine HCl 120 and 180 mg, respectively. It also contains the following inactive ingredients: Microcrystalline cellulose, pregelatinised maize starch, croscarmellose sodium, magnesium stearate, hypromellose, povidone, titanium dioxide (E171), colloidal anhydrous silica, macrogol 400 and iron oxide (E172).
Fexofenadine HCl is a histamine H1- receptor antagonist with chemical name (±)-4-[1-hydroxy-4-[4-(hydroxydiphenylmethyl)-1-piperidinyl]-butyl]-α, α-dimethyl benzeneacetic acid HCl. The molecular weight is 538.13 and the empirical formula is C32H39NO4·HCl.
Fexofenadine HCl is a white to off-white crystalline powder. It is freely soluble in methanol and ethanol, slightly soluble in chloroform and water, and insoluble in hexane.
Fexofenadine HCl is a racemate and exists as a zwitterion in aqueous media at physiological pH.
Action
Pharmacology: Pharmacodynamics: Fexofenadine HCl is a nonsedating H1-antihistamine. It is a pharmacologically active metabolite of terfenadine.
Wheal and Flare: Human histamine skin wheal and flare studies conducted in adults following single- and twice-daily doses of fexofenadine HCl 20 mg and 40 mg, respectively, demonstrated that the drug exhibits an antihistamine effect by 1 hr, achieves maximum effect at 2-3 hrs and their effect is still seen at 12 hrs. There was no evidence of tolerance to these effects after 28 days of dosing. The clinical significance of these observations is unknown.
Histamine skin wheal and flare studies in 7-12 years subjects showed that following a single-dose of 30 mg or 60 mg, antihistamine effect was observed at 1 hr and reached a maximum by 3 hrs. Greater than 49% inhibition of wheal area and 74% inhibition of flare area were maintained for 8 hrs following the 30-mg and 60-mg dose.
No statistically significant increase in mean QTc interval compared to placebo was observed in 714 adult subjects with seasonal allergic rhinitis given fexofenadine HCl capsules in doses of 60-240 mg twice daily for 2 weeks. Pediatric subjects from 2 placebo controlled trials (n=855) treated with up to fexofenadine HCl 60 mg twice daily demonstrated no significant treatment- or dose-related increases in QTc. In addition, no statistically significant increase in mean QTc interval compared to placebo was observed in 40 healthy adult subjects given fexofenadine HCl as an oral solution at doses up to 400 mg twice daily for 6 days or in 230 healthy adult subjects given fexofenadine HCl 240 mg once daily for 1 year. In subjects with chronic idiopathic urticaria, there were no clinically relevant differences for any ECG intervals, including QTc, between those treated with fexofenadine HCl 180 mg once daily (n=163) and those treated with placebo (n=91) for 4 weeks.
Mechanism of Action: Fexofenadine HCl, the major active metabolite of terfenadine, is an antihistamine with selective H1-receptor antagonist activity. Both enantiomers of fexofenadine HCl displayed approximately equipotent antihistaminic effects. Fexofenadine HCl inhibited antigen-induced bronchospasm in sensitized guinea pigs and histamine release from peritoneal mast cells in rats. The clinical significance of these findings is unknown. In laboratory animals, no anticholinergic or α1-adrenergic blocking effects were observed. Moreover, no sedative or other central nervous system effects were observed. Radiolabeled tissue distribution studies in rats indicated that fexofenadine does not cross the blood-brain barrier.
Clinical Studies: Seasonal Allergic Rhinitis: Adults: In three 2-week, multicenter, randomized, double-blind, placebo-controlled trials in subjects 12-68 years with seasonal allergic rhinitis (n=1634), fexofenadine HCl 60 mg twice daily significantly reduced total symptom scores (the sum of the individual scores for sneezing, rhinorrhea, itchy nose/palate/throat, itchy/watery/red eyes) compared to placebo. Statistically significant reductions in symptom scores were observed following the 1st 60-mg dose, with the effect maintained throughout the 12-hr interval. In these studies, there was no additional reduction in total symptom scores with higher doses of fexofenadine HCl up to 240 mg twice daily.
In one 2-week, multicenter, randomized, double-blind clinical trial in subjects 12-65 years with seasonal allergic rhinitis (n=863), fexofenadine HCl 180 mg once daily significantly reduced total symptom scores (the sum of the individual scores for sneezing, rhinorrhea, itchy nose/palate/throat, itchy/watery/red eyes) compared to placebo. Although the number of subjects in some of the subgroups was small, there were no significant differences in the effect of fexofenadine HCl across subgroups of subjects defined by gender, age and race. Onset of action for reduction in total symptom scores, excluding nasal congestion, was observed at 60 min compared to placebo following a single 60 mg fexofenadine HCl dose administered to subjects with seasonal allergic rhinitis who were exposed to ragweed pollen in an environmental exposure unit. In 1 clinical trial conducted with Telfast 60 mg capsules, and in 1 clinical trial conducted with Telfast-D 12-hr extended-release tablets, onset of action was seen within 1-3 hrs.
Pediatrics: Two 2-week, multicenter, randomized, placebo-controlled, double-blind trials in 877 pediatric subjects 6-11 years with seasonal allergic rhinitis were conducted at doses of 15 mg, 30 mg and 60 mg (tablets) twice daily. In 1 of these 2 studies, conducted in 411 pediatric subjects, all 3 doses of fexofenadine HCl significantly reduced total symptom scores (the sum of the individual scores for sneezing, rhinorrhea, itchy nose/palate/throat, itchy/watery/red eyes) compared to placebo, however, a dose-response relationship was not seen. The 60-mg twice daily dose did not provide any additional benefit over the 30 mg twice daily dose in pediatric subjects 6-11 years. Administration of a 30-mg dose to pediatric subjects 2-11 years produced exposures comparable to those seen with a dose of 60-mg administered to adults.
Chronic Idiopathic Urticaria: Two 4-week, multicenter, randomized, double-blind, placebo-controlled clinical trials compared 4 different doses of fexofenadine HCl tablet (20 mg, 60 mg, 120 mg and 240 mg twice daily) to placebo in subjects 12-70 years with chronic idiopathic urticaria (n=726). Efficacy was demonstrated by a significant reduction in mean pruritus scores (MPS), mean number of wheals (MNW), and mean total symptom scores (MTSS, the sum of the MPS and MNW score). Although all 4 doses were significantly superior to placebo, symptom reduction was greater and efficacy was maintained over the entire 4-week treatment period with fexofenadine HCl doses of ≥60 mg twice daily. However, no additional benefit of the fexofenadine HCl 120 mg or 240 mg twice daily dose was seen over the 60-mg twice daily dose in reducing symptom scores. There were no significant differences in the effect of fexofenadine HCl across subgroups of subjects defined by gender, age, weight and race.
In one 4-week, multicenter, randomized, double-blind, placebo-controlled clinical trial in subjects ≥12 years with chronic idiopathic urticaria (n=259), fexofenadine HCl 180 mg once daily significantly reduced the mean number of wheals (MNW), the mean pruritus score (MPS), and the mean total symptom score (MTSS, the sum of the MPS and MNW scores). Similar reductions were observed for MNW and MPS at the end of the 24-hr dosing interval. Symptom reduction was greater with fexofenadine HCl 180 mg than with placebo. Improvement was demonstrated within 1 day of treatment with fexofenadine HCl 180 mg and was maintained over the entire 4-week treatment period. There were no significant differences in the effect of fexofenadine HCl across subgroups of subjects defined by gender, age and race.
Pharmacokinetics: The pharmacokinetics of fexofenadine HCl in subjects with seasonal allergic rhinitis and subjects with chronic urticaria were similar to those in healthy subjects.
Absorption: Fexofenadine HCl was absorbed following oral administration of a single dose of two 60 mg capsules to healthy male subjects with a mean time to maximum plasma concentration occuring at 2.6 hrs post-dose. After administration of a single 60 mg capsule to healthy adult subjects, the mean maximum plasma concentration (Cmax) was 131 ng/mL. Following single oral administrations of either the 60 and 180 mg tablet to healthy adult male subjects, mean Cmax were 142 ng/mL and 494 ng/mL, respectively. The tablet formulations are bioequivalent to the capsule when administered at equal doses. Fexofenadine HCl pharmacokinetics are linear for oral doses up to a total daily dose of 240 mg (120 mg twice daily). The administration of the 60-mg capsule contents mixed with applesauce did not have significant effect on the pharmacokinetics of fexofenadine in adults. Co-administration of fexofenadine HCl 180 mg tablet with a high-fat meal decreased the mean area under the curve (AUC) and Cmax of fexofenadine by 21% and 20%, respectively.
Distribution: Fexofenadine HCl is 60-70% bound to plasma proteins, primarily albumin and α1-acid glycoprotein.
Metabolism: Approximately, 5% of the total dose of fexofenadine HCl was eliminated by hepatic metabolism.
Elimination: The mean elimination half-life of fexofenadine was 14.4 hrs following administration of 60-mg twice daily in healthy adult subjects. Human mass balance studies documented a recovery of approximately 80% and 11%, respectively of the [14C] fexofenadine HCl dose in the feces and urine, respectively. Because the absolute bioavailability of fexofenadine HCl has not been established, it is unknown if the fecal component represents primarily unabsorbed drug or is the result of biliary excretion.
Special Populations: Pharmacokinetics in renally and hepatically impaired subjects and geriatric subjects, obtained after a single dose of fexofenadine HCl 80 mg, were compared to those from healthy subjects in a separate study of similar design.
Renal Impairment: In subjects with mild to moderate [creatinine clearance (CrCl) 41-80 mL/min] and severe (CrCl 11-40 mL/min) renal impairment, peak plasma concentrations of fexofenadine were 87% and 111% greater, respectively and mean elimination half-lives were 59% and 72% longer, respectively, than observed in healthy subjects. Peak plasma concentrations in subjects on dialysis (CrCl ≤10 mL/min) were 82% greater and half-life was 31% longer than observed in healthy subjects. Based on increases in bioavailability and half-life, a dose of 60-mg once daily is recommended as the starting dose in adult patients with decreased renal function. For pediatric patients with decreased renal function, the recommended starting dose of fexofenadine is 30-mg once daily for patients 2-11 years and 15 mg once daily for patients 6 months to <2 years (see Dosage & Administration).
Hepatic Impairment: The pharmacokinetics of fexofenadine HCl in subjects with hepatic impairment did not differ substantially from that observed in healthy subjects.
Geriatric Subjects: In older subjects (≥65 years), peak plasma levels of fexofenadine were 99% greater than those observed in younger subjects (<65 years). Mean fexofenadine elimination half-lives were similar to those observed in younger subjects.
Pediatric Subjects: A population pharmacokinetic analysis was performed with data from 77 pediatric subjects (6 months to 12 years) with allergic rhinitis and 136 adult subjects. The individual apparent oral clearance estimates of fexofenadine were on average 44% and 36% lower in pediatric subjects 6-12 years (n=14) and 2-5 years (n=21), respectively, compared to adult subjects. Administration of fexofenadine HCl 15 mg to pediatric subjects 6 months to <2 years of age and a 30 mg dose to pediatric subjects 2-11 years produced exposures comparable to those seen with a dose of 60 mg administered to adults.
Effect of Gender: Across several trials, no clinically significant gender-related differences were observed in the pharmacokinetics of fexofenadine HCl.
Toxicology: Nonclinical: Carcinogenesis, Mutagenesis, Impairment of Fertility: The carcinogenic potential of fexofenadine was assessed using terfenadine studies with adequate fexofenadine exposure (based on plasma area under the concentration versus time [AUC) values]. No evidence of carcinogenicity was observed in an 18-month study in mice and in a 24-month study in rats at oral doses up to terfenadine 150 mg/kg [which led to fexofenadine exposures that were approximately 3 and 5 times the exposure at the maximum recommended daily oral dose of fexofenadine HCl in adults (180 mg) and children (60 mg), respectively].
In in vitro (Bacterial Reverse Mutation, CHO/HGPRT Forward Mutation and Rat Lymphocyte Chromosomal Aberration assays) and in vivo Mouse Bone Marrow Micronucleus assay) tests, fexofenadine HCl revealed no evidence of mutagenicity.
In rat fertility studies, dose-related reductions in implants and increases in post-implantation losses were observed at an oral dose of terfenadine 150 mg/kg (which led to fexofenadine exposures that were approximately 3 times the exposure at the maximum recommended human daily oral dose of fexofenadine HCl 180 mg/kg based on comparison of AUCs). In mice, fexofenadine HCl produced no effect on male or female fertility at average oral doses up to 4438 mg/kg (which led to fexofenadine exposures that were approximately 13 times the exposure at the maximum recommended human daily oral dose of fexofenadine HCl 180 mg based on comparison of AUCs).
Animal Toxicology and/or Pharmacology: In dogs (30 mg/kg/orally twice daily for 5 days) and rabbits (10 mg/kg, IV over 1 hr), fexofenadine HCl did not prolong QTc. In dogs, the plasma fexofenadine concentration was approximately 9 times the therapeutic plasma concentrations in adults receiving the maximum recommended human daily oral dose of 180 mg. In rabbits, the plasma fexofenadine concentration was approximately 20 times the therapeutic plasma concentration in adults receiving the maximum recommended human daily oral dose of 180 mg. No effect was observed on calcium channel current, delayed K+ channel current, or action potential duration in guinea pig myocytes, or on the delayed rectifier K+ channel cloned from human heart at concentrations up to 1 x 10-5 M of fexofenadine.
Indications/Uses
Telfast 120 mg: To relieve the symptoms of allergic rhinitis eg, sneezing, itchy, red eyes and runny nose for adults and children ≥12 years.
Telfast 180 mg: For the relief of symptoms associated with seasonal allergic rhinitis and chronic idiopathic urticaria in adults and children ≥12 years.
Dosage/Direction for Use
Adults and Children ≥12 years: Recommended Dose: 1 tab once daily.
Overdosage
No deaths occurred at oral doses of fexofenadine HCl up to 5000 mg/kg in mice (110 times the maximum recommended daily oral dose in adults and children based on mg/m2) and up to 5000 mg/kg in rats (230 times the maximum recommended daily oral dose in adults and 210 times the maximum recommended daily oral dose in children based on mg/m2).
Additionally, no clinical signs of toxicity or gross pathological findings were observed. In dogs, no evidence of toxicity was observed at oral doses up to 2000 mg/kg (300 times the maximum recommended daily oral dose in adults and 280 times the maximum recommended daily oral dose in children based on mg/m2).
Symptoms: Most reports of fexofenadine HCl overdose contain limited information. However, dizziness, drowsiness and dry mouth have been reported. Single doses of fexofenadine HCl up to 800 mg (6 healthy subjects at this dose level) and doses up to 690 mg twice daily for 1 month (3 healthy subjects at this dose level) or 240 mg once daily for 1 year (234 healthy subjects at this dose level) were administered without the development of clinically significant adverse events as compared to placebo. In the event of overdose, consider standard measures to remove any unabsorbed drug.
Treatment: Symptomatic and supportive treatment is recommended. Hemodialysis did not effectively remove fexofenadine from blood (up to 1.7% removed) following terfenadine administration.
Contraindications
Known hypersensitivity to fexofenadine or to any of the ingredients of Telfast. Rare cases of hypersensitivity reactions with manifestations eg, angioedema, chest tightness, dyspnea, flushing and systemic anaphylaxis have been reported.
Special Precautions
As with most new drugs, there is only limited data in the elderly and renally or hepatically impaired patients. Fexofenadine HCl should be administered with care in these special groups.
Renal Impairment: Based on increases in bioavailability and half-life, a dose of 60-mg once daily is recommended as the starting dose in adult patients with decreased renal function (mild, moderate or severe renal impairment). For pediatric patients with decreased renal function (mild, moderate or severe renal impairment), the recommended starting dose of fexofenadine is 30 mg once daily for patients 2-11 years and 15 mg once daily for patients 6 months to <2 years. (See Pharmacology: Pharmacodynamics under Actions and Dosage & Administration).
Hepatic Impairment: The pharmacokinetics of fexofenadine HCl in subjects with hepatic impairment did not differ substantially from that observed in healthy subjects.
Effects on the Ability to Drive or Operate Machinery: On the basis of the pharmacodynamic profile and reported adverse events, it is unlikely that fexofenadine HCl will produce an effect on the ability to drive or use machines. In objective tests, Telfast has been shown to have no significant effects on central nervous system function. This means that patients may drive or perform tasks that require concentration. However, in order to identify sensitive people who have an unusual reaction to drugs, it is advisable to check the individual response before driving or performing complicated tasks.
Use in pregnancy: Teratogenic Effects: Pregnancy Category C. There was no evidence of teratogenicity in rats or rabbits at oral doses of terfenadine up to 300 mg/kg (which led to fexofenadine exposures that were approximately 4 and 30 times, respectively, the exposure at the maximum recommended human daily oral dose of fexofenadine HCl 180 mg based on comparison of AUCs).
In mice, no adverse effects and no teratogenic effects during gestation were observed with fexofenadine HCl at oral doses up to 3730 mg/kg (which led to fexofenadine exposures that were approximately 15 times the exposure at the maximum recommended human daily oral dose of fexofenadine HCl 180 mg based on comparison of AUCs).
There are no adequate and well controlled studies in pregnant women. Fexofenadine HCl should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Nonteratogenic Effects: Dose-related decreases in pup weight gain and survival were observed in rats exposed to an oral dose of terfenadine 150 mg/kg (which led to fexofenadine exposures that were approximately 3 times the exposure at the maximum recommended human daily oral dose of fexofenadine HCl 180 mg based on comparison of AUCs).
Use in lactation: It is not known if fexofenadine is excreted in human milk. There are no adequate and well controlled studies in women during lactation. Because many drugs are excreted in human milk, caution should be exercised when fexofenadine HCl is administered to a nursing woman.
Use in children: The recommended dose of fexofenadine HCl in pediatric patients 6 months to 11 years are based on cross-study comparison of the pharmacokinetics of fexofenadine in adults and pediatric subjects and on the safety profile of fexofenadine HCl in both adult and pediatric subjects at doses equal to or higher than the recommended doses. The safety and effectiveness of fexofenadine HCl in pediatric patients <6 months have not been established.
The safety of fexofenadine HCl is based on the administration of Telfast tablets at a dose of 30 mg twice daily demonstrated in 438 pediatric subjects 6-11 years in 2 placebo-controlled 2-week seasonal allergic rhinitis trials. The safety of fexofenadine HCl at doses of 15 mg and 30 mg given once and twice a day has been demonstrated in 969 pediatric subjects (6 months to 5 years) with allergic rhinitis in 3 pharmacokinetic studies and 3 safety studies. The safety of fexofenadine HCl for the treatment of chronic idiopathic urticaria in subjects 6 months to 11 years is based on cross-study comparison of the pharmacokinetics of Telfast in adult and pediatric subjects and on the safety profile of fexofenadine in both adult and pediatric subjects at doses equal to or higher than the recommended dose.
The effectiveness of fexofenadine HCl for the treatment of seasonal allergic rhinitis in subjects 6-11 years was demonstrated in 1 trial (n=411) in which Telfast tablets 30 mg twice daily significantly reduced total symptom scores compared to placebo, along with extrapolation of demonstrated efficacy in subjects ≥12 years and the pharmacokinetic comparisons in adults and children. The effectiveness of fexofenadine HCl 30 mg twice daily for the treatment of seasonal allergic rhinitis in patients 2-5 years is based on the pharmacokinetic comparisons in adult and pediatric subjects and an extrapolation of the demonstrated efficacy of fexofenadine HCl in adult subjects with this condition and the likelihood that the disease course, pathophysiology and the drug’s effect are substantially similar in pediatric patients to those in adult patients. The effectiveness of fexofenadine HCl for the treatment of chronic idiopathic urticaria in patients 6 months to 11 years is based on the pharmacokinetic comparisons in adults and children and an extrapolation of the demonstrated efficacy of Telfast in adults with this condition and the likelihood that the disease course, pathophysiology and the drug’s effect are substantially similar in children to that of adult patients. Administration of fexofenadine HCl 15 mg to pediatric subjects 6 months to <2 years and a 30 mg dose to pediatric subjects 2-11 years produced exposures comparable to those seen with a dose of 60 mg administered to adults.
Use in the elderly: Clinical studies of Telfast tablets and capsules did not include sufficient numbers of subjects ≥65 years to determine whether this population responds differently from younger subjects. Other reported clinical experience has not identified differences in responses between the geriatric and younger subjects. Telfast is known to be substantially excreted by the kidney and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function (see Pharmacology: Pharmacodynamics under Actions).
Use In Pregnancy & Lactation
Use in pregnancy: Teratogenic Effects: Pregnancy Category C. There was no evidence of teratogenicity in rats or rabbits at oral doses of terfenadine up to 300 mg/kg (which led to fexofenadine exposures that were approximately 4 and 30 times, respectively, the exposure at the maximum recommended human daily oral dose of fexofenadine HCl 180 mg based on comparison of AUCs).
In mice, no adverse effects and no teratogenic effects during gestation were observed with fexofenadine HCl at oral doses up to 3730 mg/kg (which led to fexofenadine exposures that were approximately 15 times the exposure at the maximum recommended human daily oral dose of fexofenadine HCl 180 mg based on comparison of AUCs).
There are no adequate and well controlled studies in pregnant women. Fexofenadine HCl should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Nonteratogenic Effects: Dose-related decreases in pup weight gain and survival were observed in rats exposed to an oral dose of terfenadine 150 mg/kg (which led to fexofenadine exposures that were approximately 3 times the exposure at the maximum recommended human daily oral dose of fexofenadine HCl 180 mg based on comparison of AUCs).
Use in lactation: It is not known if fexofenadine is excreted in human milk. There are no adequate and well controlled studies in women during lactation. Because many drugs are excreted in human milk, caution should be exercised when fexofenadine HCl is administered to a nursing woman.
Adverse Reactions
Clinical Studies Experience: Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
The safety data described as follows reflect exposure to fexofenadine HCl in 5083 patients in trials for allergic rhinitis and chronic idiopathic urticaria. In these trials, 3010 patients ≥12 years with seasonal allergic rhinitis were exposed to fexofenadine HCl at doses of 20-240 mg twice daily or 120-180 mg once daily. A total of 646 patients 6-11 years with seasonal allergic rhinitis were exposed to fexofenadine HCl at doses of 15-60 mg twice daily. The duration of treatment in these trials was 2 weeks. A total of 534 patients 6 months to 5 years with allergic rhinitis were exposed to fexofenadine HCl at doses of 15-30 mg twice daily. The duration of treatment in these trials ranged from 1 day to 2 weeks. There were 893 patients ≥12 years with chronic idiopathic urticaria exposed to fexofenadine HCl at doses of 20-240 mg twice daily or 180 mg once daily. The duration of treatment in these trials was 4 weeks.
Seasonal Allergic Rhinitis: Adults and Adolescents: In placebo-controlled seasonal allergic rhinitis clinical trials in subjects ≥12 years, 2439 subjects received fexofenadine HCl capsules at doses of 20-240 mg twice daily. All adverse reactions that were reported by >1% of subjects who received the recommended daily dose of fexofenadine HCl (60-mg capsules twice daily) are listed in Table 1.
In another placebo-controlled clinical study in the United States, 571 subjects ≥12 years received fexofenadine HCl tablets at doses of 120 or 180 mg once daily. Table 1 also lists adverse reactions that were reported by >2% of subjects treated with fexofenadine HCl tablets at doses of 180 mg once daily. The incidence of adverse reactions, including somnolence/fatigue, was not dose-related and was similar across subgroups defined by age, gender and race. (See Table 1.)

Click on icon to see table/diagram/image

The frequency and magnitude of laboratory abnormalities were similar in fexofenadine HCl- and placebo-treated subjects.
Pediatrics: Table 2 lists adverse reactions in subjects 6-11 years which were reported by >2% of subjects treated with fexofenadine HCl tablets at a dose of 30 mg twice daily in placebo-controlled seasonal allergic rhinitis studies in the United States and Canada. (See Table 2.)

Click on icon to see table/diagram/image

Table 3 lists adverse reactions in subjects 6 months to 5 years which were reported by >2% of subjects treated with fexofenadine HCl in 3 open single- and multiple-dose pharmacokinetic studies and 3 placebo-controlled safety studies with fexofenadine HCl capsule content (484 subjects) and suspension (50 subjects) at doses of 15 mg (108 subjects) and 30 mg (426 subjects) given twice a day. (See Table 3.)

Click on icon to see table/diagram/image

Chronic Idiopathic Urticaria: Adverse reactions reported by subjects ≥12 years in placebo-controlled chronic idiopathic urticaria studies were similar to those reported in placebo-controlled seasonal allergic rhinitis studies.
In placebo-controlled chronic idiopathic urticaria clinical trials, 726 subjects ≥12 years received fexofenadine HCl tablets at doses of 20-240 mg twice daily.
Table 4 lists adverse reactions in subjects ≥12 years which were reported by >2% of subjects treated with fexofenadine HCl 60 mg tablets twice daily in controlled clinical studies in the United States and Canada.
In a placebo-controlled clinical study in the United States, 167 subjects ≥12 years received fexofenadine HCl 180 mg tablets. Table 4 also lists adverse reactions that were reported by >2% of subjects treated with fexofenadine HCl tablets at doses of 180 mg once daily. (See Table 4.)

Click on icon to see table/diagram/image

The safety of fexofenadine HCl in the treatment of chronic idiopathic urticarial in pediatric patients 6 months to 11 years is based on the safety profile of fexofenadine HCl in adults and pediatric patients at doses equal to or higher than the recommended dose (see Precautions).
Post-Marketing Experience: In addition to the adverse reactions reported during clinical studies and listed in the tables previously mentioned, the following adverse events have been identified during post-approval use of Telfast. Because these events are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Events that have been reported rarely during post-marketing experience include: Insomnia, nervousness, sleep disorders or paranoia, and hypersensitivity reactions (including anaphylaxis, urticaria, angioedema, chest tightness, dyspnea, flushing, pruritus and rash).
Drug Interactions
Antacids: Fexofenadine HCl should not be taken closely in time with aluminum- and magnesium-containing antacids. In healthy adult subjects, administration of fexofenadine HCl 120 mg (2 x 60-mg cap) within 15 min of an aluminum- and magnesium-containing antacid (Maalox) decreased fexofenadine AUC by 41% and Cmax by 43%.
Erythromycin and Ketoconazole: Fexofenadine has been shown to exhibit minimal (ca. 5%) metabolism. However, co-administration of fexofenadine HCl with either ketoconazole or erythromycin led to increased plasma concentrations of fexofenadine in healthy adult subjects. Fexofenadine had no effect on the pharmacokinetics of either erythromycin or ketoconazole. In 2 separate studies in healthy adult subjects, fexofenadine HCl 120 mg twice daily (240 mg total daily dose) was co-administered with either erythromycin 500 mg every 8 hrs or ketoconazole 400 mg once daily under steady-state conditions to healthy adult subjects (n=24, each study). No differences in adverse events or QTc interval were observed when subjects were administered fexofenadine HCl alone or in combination with either erythromycin or ketoconazole.
The findings of these studies are summarized in the following table: (See Table 5.)

Click on icon to see table/diagram/image

The changes in plasma levels were within the range of plasma levels achieved in adequate and well-controlled clinical trials.
The mechanism of these interactions has been evaluated in in vitro, in situ and in vivo animal models. These studies indicate that ketoconazole or erythromycin co-administration enhances fexofenadine gastrointestinal absorption. This observed increase in the bioavailability of fexofenadine may be due to transport-related effects eg, p-glycoprotein. In vivo animal studies also suggest that in addition to enhancing absorption, ketoconazole decreases fexofenadine gastrointestinal secretion, while erythromycin may also decrease biliary excretion.
Fruit Juices: Fruit juices eg, grapefruit, orange and apple may reduce the bioavailability and exposure of fexofenadine. This is based on the results from 3 clinical studies using histamine induced skin wheals and flares coupled with population pharmacokinetic analysis. The size of wheal and flare were significantly larger when fexofenadine HCl was administered with either grapefruit or orange juices compared to water. Based on the literature reports, the same effects may be extrapolated to other fruit juices eg, apple juice. The clinical significance of these observations is unknown. In addition, based on the population pharmacokinetics analysis of the combined data from grapefruit and orange juices studies with the data from a bioequivalence study, the bioavailability of fexofenadine was reduced by 36%. Therefore, to maximize the effects of fexofenadine, it is recommended that Telfast tablets should be taken with water (see Pharmacology under Actions and Dosage & Administration).
Caution For Usage
Instructions for Handling: Discard any remaining contents 60 days after 1st opening the bottle.
Storage
Store below 30°C.
ATC Classification
R06AX26 - fexofenadine ; Belongs to the class of other antihistamines for systemic use.
120 mg tab: G; 180 mg tab: POM
Presentation/Packing
Tab 120 mg x 10's. 180 mg x 50's.
Exclusive offer for doctors
Register for a MIMS account and receive free medical publications worth $139 a year.
Sign up for free
Already a member? Sign in