Telfast

Fexofenadine hydrochloride.

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 hydrochloride. 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.
Oral suspension: Each mL contains fexofenadine hydrochloride (equivalent to 5.6 mg of fexofenadine) 6 mg.
Excipients/Inactive Ingredients: Tablet: Croscarmellose sodium, magnesium stearate, microcrystalline cellulose, pregelatinized maize starch. The aqueous tablet film coating is made from hydroxypropyl methylcellulose, iron oxide, polyethylene glycol, povidone, silicon dioxide and titanium dioxide.
Oral suspension: Propylene glycol, disodium EDTA, propylparaben, butylparaben, xanthan gum, poloxamer, titanium dioxide, monobasic monohydrate sodium phosphate, dibasic heptahydrate sodium phosphate, artificial raspberry flavoring cream, sucrose, xylitol and purified water.

Pharmacology: Pharmacodynamics: Tablet: Wheal and Flare: Human histamine skin wheal and flare studies conducted in adults following single- and twice-daily doses of fexofenadine HCl 20 and 40 mg 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 not known.
In children (6-11 years), fexofenadine HCl suppressed histamine-induced wheal and flare to a similar extent to that observed in adults. Histamine skin wheal and flare studies in pediatric patients showed that following a single dose of 30 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- and 60-mg dose.
Effects on QTc: In dogs (10 mg/kg/day, orally for 5 days) and rabbits (10 mg/kg IV over 1 hr), fexofenadine did not prolong QTc at plasma concentrations that were at least 28 and 63 times, respectively, the therapeutic plasma concentrations in man (based on a 60-mg twice-daily fexofenadine HCl dose). No effect was observed on calcium channel current, delayed K⁺ channel current or action potential duration in guinea pig myocytes, Na⁺ current in rat neonatal myocytes, or on the delayed rectifier K⁺ channel cloned from human heart at concentrations up to 1 x 10^-5 M of fexofenadine. This concentration was at least 32 times the therapeutic plasma concentration in man (based on a 60-mg twice-daily fexofenadine HCl dose).
No statistically significant increase in mean QTc interval compared to placebo was observed in 714 seasonal allergic rhinitis patients given fexofenadine HCl capsules in doses of 60-240 mg twice daily for 2 weeks or in 40 healthy volunteers given fexofenadine HCl as an oral solution at doses up to 400 mg twice daily for 6 days. Pediatric patients from 2 placebo controlled trials (n=855) treated with up to 60 mg fexofenadine HCl twice daily demonstrated no significant treatment or dose-related increases in QTc.
A 1 year study designed to evaluate safety and tolerability of 240 mg of fexofenadine HCl (n=240) compared to placebo (n=237) in healthy subjects, did not reveal a statistically significant increase in the mean QTc interval for the fexofenadine HCl treated group when evaluated pretreatment and after 1, 2, 3, 6, 9 and 12 months of treatment.
Mechanism of Action: Fexofenadine HCl, the major active metabolite of terfenadine, is an antihistamine with selective peripheral H₁-receptor antagonist activity. It inhibited antigen-induced bronchospasm in sensitized guinea pigs and histamine release from peritoneal mast cells in rats. In laboratory animals, no anticholinergic or α₁-adrenergic receptor-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.
Oral suspension: Fexofenadine hydrochloride is an anti-histaminic with peripheral H1-receptors selective antagonistic activity. Fexofenadine inhibited antigen-induced bronchospasm in sensitized guinea pigs and the release of histamine from the peritoneal mast cells in rats. In laboratory animals, no anticholinergic effects or blockage of alpha1-adrenergic receptors were observed. In addition, no sedative or other effects on the central nervous system were observed. Tissue distribution studies conducted with radio-labeled fexofenadine hydrochloride in rats demonstrated that fexofenadine does not cross the hematoencephalic barrier.
Pharmacokinetics: Tablet: Absorption: Fexofenadine HCl was rapidly absorbed following oral administration of a single dose of two 60-mg cap to healthy male volunteers with a mean time to maximum plasma concentration occurring at 2.6 hrs post-dose. After administration of a single 60-mg dose as an oral solution to healthy subjects, the mean plasma concentration was 209 ng/mL. Mean steady-state peak plasma concentrations of 286 ng/mL were observed when healthy volunteers were administered with multiple doses of fexofenadine HCl (60 mg oral solution every 12 hrs for 10 doses). Although the absolute bioavailability of fexofenadine HCl capsules is unknown, the capsules are bioequivalent to an oral solution. In addition, tablets are also bioequivalent to capsules. Fexofenadine HCl pharmacokinetics were linear for oral doses up to a total daily dose of 240 mg (120 mg twice daily).
Distribution: Fexofenadine is 60-70% bound to plasma proteins, primarily albumin and α₁-acid glycoprotein.
Elimination: The mean elimination half-life of fexofenadine was 14.4 hrs following administration of 60 mg, twice daily in normal volunteers.
Human mass balance studies documented a recovery of approximately 80% and 11% 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 unabsorbed drug or the result of biliary excretion.
Fexofenadine clearance in children (6-11 years) is approximately 40% slower than in adults. Therefore, a dose of 30 mg twice daily was determined to provide plasma levels (AUC and C_max) in children which were comparable to plasma levels achieved in adults following 120 mg once daily.
Metabolism: Approximately 5% of the total dose was metabolized.
The pharmacokinetics of fexofenadine HCl in seasonal allergic rhinitis and chronic idiopathic urticaria patients were similar to those in healthy subjects. Peak fexofenadine plasma concentrations were similar between adolescent (12-16 years) and adult patients.
Special Populations: Special population pharmacokinetics (for geriatric subjects, renal and hepatic impairment), obtained after a single dose of fexofenadine HCl 80 mg, were compared to those for normal subjects from a separate study of similar design. While subject weights were relatively uniform between studies, these adult special population patients were substantially older than the healthy, young volunteers. Thus, an age effect may be confounding the pharmacokinetic differences observed in some of the special populations.
Geriatric Subjects: In older subjects (≥65 years), peak plasma levels of fexofenadine were 99% greater than those observed in normal volunteers (<65 years). Mean elimination half-lives were similar to those observed in normal volunteers.
Pediatrics Patients: Cross study comparisons indicated that fexofenadine HCl area under the curve (AUC) following oral administration of a 60-mg dose to 7- to 12-year old pediatric allergic rhinitis patients was 56% greater compared to healthy adult subjects given the same dose. Plasma exposure in pediatric patients given fexofenadine HCl 30 mg is comparable to adults given 60 mg.
Renal Impairment: In patients with mild to moderate (Cl_cr 41-80 mL/min) and severe (Cl_cr 11-40 mL/min) renal impairment, peak plasma levels of fexofenadine were 87% and 111% greater, respectively, and mean elimination half-lives were 59% and 72% longer, respectively, than observed in normal volunteers. Peak plasma levels in patients on dialysis (Cl_cr ≤10 mL/min) were 82% greater and half-life was 31% longer than observed in normal volunteers. Based on increases in bioavailability and half-life, a dose of 60 mg once daily is recommended as the starting dose in patients with decreased renal function. (See Dosage & Administration.)
Hepatic Impairment: The pharmacokinetics of fexofenadine HCl in patients with hepatic disease did not differ substantially from that observed in healthy subjects.
Effect of Gender: Across several trials, no clinically significant gender-related differences were observed in the pharmacokinetics of fexofenadine HCl.
Oral suspension: Fexofenadine hydrochloride is rapidly absorbed after oral administration, with its T_max occurring within approximately 1-3 hours from dose administration. The mean C_max value was approximately 142 ng/mL after the administration of a single dose of 60 mg, approximately 289 ng/mL after a single dose of 120 mg and approximately 494 ng/mL after a 180 mg-single dose.
Plasma exposures resulting from single doses of 15, 30 and 60 mg in children from 2-11 years of age are dose-proportional and can be compared to those produced by the corresponding single doses of 30 mg, 60 mg and 120 mg in adults, respectively. The dose of 30 mg, twice a day, was determined to provide plasma levels area under the curve (AUC) in pediatric patients, which are comparable to those reached in adults after a dose of 120 mg. A 5 mL oral dose of the suspension containing fexofenadine hydrochloride 30 mg is bioequivalent to a dose of 30 mg of fexofenadine hydrochloride tablets. After a single 30 mg dose of TELFAST (ORAL SUSPENSION) was administered to healthy adults, the average C_max was 118 ng/mL and occurred within 1 hour. The administration of 30 mg of TELFAST (ORAL SUSPENSION) with a meal rich in fat reduced the AUC and mean C_max approximately 30 and 47%, respectively, in healthy adults.
Fexofenadine binds to the plasma proteins at a rate of approximately 60-70%. Insignificant amounts of fexofenadine are metabolized. After the administration of a 60 mg single dose of fexofenadine hydrochloride, 80% of the total dose was recovered in the feces and 11% in the urine. After multiple doses, the average elimination half-life of fexofenadine was 11-16 hours. The main route of elimination is believed to be through biliary excretion, whereas up to 10% of the dose taken is excreted unchanged in the urine.
The pharmacokinetics of fexofenadine hydrochloride, in single and multiple doses, is linear within a dose from 20 mg and a dose of 120 mg. One dose of 240 mg, twice a day, caused a slightly greater than proportional increase (8.8%) in the area under the curve, at steady state.
Toxicology: Pre-clinical safety data: Oral suspension: The carcinogenic potential of fexofenadine hydrochloride was assessed through studies with terfenadine and supporting pharmacokinetic studies which demonstrated the proper exposure to fexofenadine hydrochloride (through the area under the curve concentration plasma values - AUC). No evidence of carcinogenicity was observed in rats and mice with terfenadine (up to 150 mg/kg/day), resulting in a plasma exposure to fexofenadine of up to 4 times the therapeutic value in humans (based on 60 mg fexofenadine hydrochloride, twice a day).
Several in vitro and in vivo studies conducted with fexofenadine hydrochloride did not demonstrate mutagenicity. When fexofenadine hydrochloride was administered as 2000 mg/kg oral doses in acute toxicity studies conducted with several animal species, no clinical signs of toxicity and no effect on body weight or food intake were observed. No relevant treatment-related effects were observed in rodents after necropsy. Dogs tolerated 450 mg/kg, administered twice a day, for 6 months and did not exhibit any toxicity other than occasional vomit.
Clinical Studies: Tablet: Adults: In three 2-week multicenter, randomized, double-blind, placebo-controlled trials in patients 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 first 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. 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 patients 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 patients with seasonal allergic rhinitis who were exposed to ragweed pollen in an environmental exposure unit.
Pediatrics: Two 2-week multicenter, randomized, placebo-controlled, double-blind trials in 877 pediatric patients (6-11 years) with seasonal allergic rhinitis were conducted at doses of 15, 30 and 60 mg twice daily. In 1 of these 2 studies, conducted in 411 pediatric patients, 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. Furthermore, exposure in pediatric patients given fexofenadine HCl 30 mg is comparable to adults given 60 mg.
Oral suspension: Efficacy results: Fexofenadine hydrochloride inhibited the formation of papule and erythema caused by histamine. After single dose and 2x/day oral doses of fexofenadine hydrochloride it was demonstrated that the drug exhibits an anti-histaminic effect, starting within one hour and achieving maximum effect within 2 to 3 hours, and the effect is still observed at least 12 hours. More than 80% maximum inhibition was achieved in the areas of formation of the papule and erythema. No tolerance to these effects was observed after 28 days. Clinical studies conducted on allergic rhinitis demonstrated that one 120 mg dose is sufficient for 24 hours efficacy, using total symptom score assessment as the primary end-point. In children from 6 to 11 years of age, the suppressive effect of fexofenadine hydrochloride on the histamine-induced papule and erythema were comparable to those in adults with similar exposure.
In the integrated analysis of a phase III double-blind placebo-controlled study involving 1369 children from 6 to 11 years of age with allergic rhinitis, the 30 mg-fexofenadine hydrochloride twice a day was significantly better than placebo in reducing the total symptom score (p = 0.0001). All individual symptoms components including rhinorrhea, sneezing, cough, itchy/red/watery eyes, itchy nose/palate/throat and nasal congestion showed significant improvement (p = 0.0334 to p = 0.0001) with fexofenadine hydrochloride.
The effectiveness of fexofenadine hydrochloride 30 mg twice a day in the treatment of seasonal allergic rhinitis in patients from 2 to 5 years of age is based on pharmacokinetic comparisons in adult and pediatric subjects and an extrapolation which demonstrated the efficacy of fexofenadine hydrochloride in adult and older pediatric individuals in these conditions and the progress of the disease, the physiopathology, and the effects of the drug are substantially similar in pediatric and adult subjects. The effectiveness of TELFAST (ORAL SUSPENSION) in treating chronic idiopathic urticaria in patients from 6 months to 11 years of age is based on pharmacokinetic comparisons of adults and children and an extrapolation of demonstrated efficacy of TELFAST (ORAL SUSPENSION) in adults in these conditions and the progress of this disease, the physiopathology and the effects of the drug are substantially similar in pediatric and adult patients. The administration of a 15 mg dose of fexofenadine hydrochloride to pediatrics individuals from 6 months to less than 2 years of age and a 30 mg dose for pediatric individuals from 2 to 11 years of age resulted in an exposure comparable to that of adults receiving a 60 mg dose.
The onset of reduction in total symptom scores was observed at 60 minutes as compared to placebo following a 60 mg single dose of fexofenadine hydrochloride administered to subjects with seasonal rhinitis who were exposed to ragweed pollen in an environmental exposure unit.
In patients with allergic rhinitis who received doses of up to 240 mg of fexofenadine hydrochloride, twice a day, for 2 weeks, no significant differences in QTc were observed when compared to placebo. Likewise, no alterations in the QTc interval were observed in healthy patients after the intake of up to 400 mg of fexofenadine hydrochloride, twice a day, for 6.5 days and 240 mg, once a day for 1 year, when compared to placebo. In children from 6 to 11 years of age, no significant differences in QTc were observed after the administration of up to 60 mg of fexofenadine hydrochloride, twice a day, for 2 weeks when compared to placebo. Fexofenadine, at concentrations 32 times higher than the therapeutic concentration in men, did not have any effect on the delayed rectifier K⁺ channel cloned from human heart.

Tablet: For the relief of symptoms associated with seasonal allergic rhinitis and chronic idiopathic urticaria in adults and children ≥6 years. Symptoms treated effectively include sneezing, rhinorrhea, itchy nose/palate/throat, itchy/watery/red eyes and symptoms associated with the non-complicated cutaneous manifestations of the chronic idiopathic urticaria.
Oral suspension: TELFAST (ORAL SUSPENSION) is indicated for the relief of the symptoms associated with seasonal allergic rhinitis and of the symptoms associated with the non-complicated cutaneous manifestations of the chronic idiopathic urticaria.

Tablet: Adults and Children ≥12 years: Recommended Dose: 60 mg twice daily or 180 mg once daily. A dose of 60 mg once daily is recommended as the starting dose in patients with decreased renal function. (See Pharmacology under Actions.)
Children 6-11 years: Recommended Dose: 30 mg twice daily. A dose of 30 mg once daily is recommended as the starting dose in pediatric patients with decreased renal function. (See Pharmacology under Actions.)
Oral suspension: Seasonal allergic rhinitis: For seasonal allergic rhinitis, TELFAST (ORAL SUSPENSION) is indicated for pediatric patients from 2 to 11 years of age and the recommended dose is 30 mg (5 mL) twice a day.
Chronic idiopathic urticaria: For chronic idiopathic urticaria, the recommended dose of TELFAST (ORAL SUSPENSION) is 30 mg (5 mL) twice a day for children from 2 to 11 years of age (weighing more than 10.5 kg) and 15 mg (2.5 mL) twice a day for children from 6 months to less than 2 years of age (weighing 10.5 kg or less).
Children: The efficacy and safety of fexofenadine hydrochloride have not been established in children under 2 years of age for seasonal allergic rhinitis and children under 6 months of age for chronic idiopathic urticaria.
Other risk groups: Adjustment of the dose for the elderly or for patients with hepatic impairment is not required.
Administration in special cases: Studies conducted with special risk groups (the elderly, patients with hepatic impairment) have indicated that dose adjustment of fexofenadine hydrochloride in these patients is not required.
In case of renal failure, the recommended starting dose of fexofenadine hydrochloride in pediatric patients from 2 to 11 years of age (weighing more than 10.5 kg) is 30 mg once a day and in pediatric patients from 6 months to under 2 years of age (weighing 10.5 kg or less) the recommended starting dose of fexofenadine hydrochloride is 15 mg once a day.
Necessary conduct when a dose is missed: When a dose is missed, use it as soon as the patient remembers; however, if it is near the time to take the next dose, skip the missed dose and resume the usual dosing schedule, always observing the interval indicated in administration. Never double a dose.

Information regarding acute overdosage is limited to experience from clinical trials conducted during the development of Telfast. Single doses of fexofenadine HCl up to 800 mg (6 normal volunteers at this dose level) and doses up to 690 mg twice daily for 1 month (3 normal volunteers at this dose level) were administered without the development of clinically significant adverse events.
No deaths occurred in mature mice and rats at oral doses of fexofenadine HCl up to 5000 mg/kg (approximately 170 and 340 times, respectively, the maximum recommended daily oral dose in adults on a mg/m² basis). The median oral lethal dose in newborn rats was 438 mg/kg (approximately 30 times the maximum recommended daily oral dose in adults on a mg/m² basis). In dogs, no evidence of toxicity was observed at oral doses up to 2000 mg/kg (approximately 450 times the maximum recommended daily oral dose on a mg/m² basis).
Symptoms: Tablet: In large doses, sympathomimetics may give rise to giddiness, headache, nausea, vomiting, sweating, thirst, tachycardia, precordial pain, palpitations, difficulty in micturition, muscular weakness and tenseness, anxiety, restlessness and insomnia. Many patients can present a toxic psychosis with delusions and hallucinations. Some may develop cardiac arrhythmias, circulatory collapse, convulsions, coma and respiratory failure.
Oral suspension: Most of the fexofenadine hydrochloride overdose reports presented restricted information. However, dizziness, drowsiness and dry mouth were reported. In adults a single dose of up to 800 mg and doses of up to 690 mg, twice a day for one month or 240 mg daily, for 1 year, were studied in healthy volunteers without the emergence of any clinically significant adverse events compared to the placebo. The maximum tolerated dose of TELFAST (ORAL SUSPENSION) has not been established.
There were no deaths of mice that received oral doses of fexofenadine hydrochloride of up to 5000 mg/kg (110 times the maximum daily oral dose for adults and children on a mg/m² basis) and in rats with oral doses of up to 5000 mg/kg (230 times the maximum recommended daily oral dose for adults and 210 times the maximum recommended daily oral dose for children on a mg/m² base). Additionally, no clinical signals of toxicity were observed; nor were there any significant pathologic findings. In dogs, no evidence of toxicity was observed with oral doses of up to 2000 mg/kg (300 times the maximum daily oral dose for adults and 280 times the maximum oral dose for children on a mg/m² basis).
Treatment: In the event of overdose, consider standard measures to remove any unabsorbed drug. Symptomatic and supportive treatment is recommended. Hemodialysis did not effectively remove fexofenadine from blood (up to 1.7% removed) following terfenadine administration.
Oral suspension: In case of overdose, it is recommended that the usual symptomatic and support measures be taken to remove the non-absorbed drug from the body.
Hemodialysis does not effectively remove fexofenadine hydrochloride from the blood.

TELFAST is contraindicated for use in patients with hypersensitivity to any of its components.
This medicine is contraindicated for children under 2 years of age for seasonal allergic rhinitis and younger than 6 months of age for chronic idiopathic urticaria.

Oral suspension: Studies conducted with fexofenadine hydrochloride did not associate the use of the product with reduced attention when operating motor vehicles or machinery, alteration in sleep quality or other effects on the central nervous system.
Always check the expiration date indicated on the product package, and confirm the name of the medication to avoid mistakes. Do not use TELFAST (ORAL SUSPENSION) if there are signs that the package has been tampered or damaged.

Tablet: Carcinogenicity, Mutagenicity & Impairment of Fertility: The carcinogenic potential and reproductive toxicity of fexofenadine HCl were assessed using terfenadine studies with adequate fexofenadine exposure [based on plasma area-under-the-curve (AUC) values]. No evidence of carcinogenicity was observed when mice and rats were given daily oral doses of 50 and 150 mg/kg of terfenadine for 18 and 24 months, respectively; these doses resulted in plasma AUC values of fexofenadine that were up to 4 times the human therapeutic value (based on a 60-mg twice-daily fexofenadine HCl dose).
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 oral doses ≥150 mg/kg of terfenadine; these doses produced plasma AUC values of fexofenadine that were ≥3 times the human therapeutic value (based on a 60-mg twice-daily fexofenadine HCl dose).
Reproduction and fertility studies with terfenadine in rats produced no effect on male or female fertility at oral doses up to 300 mg/kg/day. However, reduced implants and post implantation losses were reported at 300 mg/kg. A reduction in implants was also observed at an oral dose of 150 mg/kg/day. Oral doses of 150 and 300 mg/kg of terfenadine produced AUC values of fexofenadine that were approximately 3 and 4 times, respectively, the human AUC at the maximum recommended daily oral dose in adults.
Oral suspension: Do not exceed the recommended dose.
In case of an adverse event during the treatment with TELFAST (ORAL SUSPENSION), discontinue the medication and seek medical assistance.
Avoid taking TELFAST (ORAL SUSPENSION), with food rich in fat.
It is recommended that the medicine be taken with water. Avoid taking it with fruit juice.
Use in Pregnancy: Teratogenic Effects: Pregnancy Category C: There was no evidence of teratogenicity in rats or rabbits at oral terfenadine doses up to 300 mg/kg; these doses produced fexofenadine plasma AUC values that were up to 4, 30 and 37 times the human therapeutic value (based on a 60-mg twice-daily fexofenadine HCl dose), respectively. There are no adequate and well-controlled studies in pregnant women. Telfast 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 oral doses ≥150 mg/kg of terfenadine; at these doses, the plasma AUC values of fexofenadine were ≥3 times the human therapeutic values (based on a 60-mg twice-daily fexofenadine HCl dose).
Use in Lactation: It is not known if fexofenadine is excreted in human milk. Because many drugs are excreted in human milk, caution should be used when fexofenadine HCl is administered to a nursing woman.
Use in Children: Tablet: The recommended dose in patients 6-11 years is based on cross-study comparison of the pharmacokinetics of Telfast in adults and pediatric patients and on the safety profile of fexofenadine HCl in both adult and pediatric patients at dose equal to or higher than the recommended doses.
The safety of Telfast tablets at a dose of 30 mg twice daily has been demonstrated in 438 pediatric patients (6-11 years) in 2 placebo-controlled 2-week seasonal allergic rhinitis trials. The safety of Telfast for the treatment of chronic idiopathic urticaria in patients (6-11 years) is based on cross-study comparison of the pharmacokinetics of Telfast in adult and pediatric patients and on the safety profile of fexofenadine in both adult and pediatric patients at doses equal to or higher than the recommended dose.
The effectiveness of Telfast for the treatment of seasonal allergic rhinitis in patients (6-11 years) was demonstrated in 1 trial (n=411) in which Telfast 30-mg tablets twice daily significantly reduced total symptom scores compared to placebo, along with extrapolation of demonstrated efficacy in patients ≥12 years, and the pharmacokinetic comparisons in adults and children. The effectiveness of Telfast for the treatment of chronic idiopathic urticaria in patients (6-11 years) is based on 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.
The safety and effectiveness of Telfast in pediatric patients <6 years have not been established.
Use in the Elderly: Tablet: Clinical studies of Telfast did not include sufficient numbers of subjects ≥65 years to determine whether this population responds differently from younger patients. Other reported clinical experience has not identified differences in responses between the geriatric and younger patients. This drug 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 may be useful to monitor renal function. (See Pharmacology under Actions).
In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

Pregnancy: Teratogenic Effects: Pregnancy Category C: There was no evidence of teratogenicity in rats or rabbits at oral terfenadine doses up to 300 mg/kg; these doses produced fexofenadine plasma AUC values that were up to 4, 30 and 37 times the human therapeutic value (based on a 60-mg twice-daily fexofenadine HCl dose), respectively.
There are no adequate and well-controlled studies in pregnant women. Telfast 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 oral doses ≥150 mg/kg of terfenadine; at these doses, the plasma AUC values of fexofenadine were ≥3 times the human therapeutic values (based on a 60-mg twice-daily fexofenadine HCl dose).
Oral suspension: Risk category in pregnancy: category C.
This medication must not be used by pregnant women without a physician or surgeon dentist's advice.
No studies of TELFAST (ORAL SUSPENSION) have been conducted in pregnant women.
TELFAST (ORAL SUSPENSION) should not be used during pregnancy unless the potential benefits exceed the potential risks to the fetus.
In studies that assessed reproductive toxicity conducted in mice, fexofenadine did not impair fertility, was not teratogenic and did not impair pre- or postnatal development.
Lactation: It is not known if fexofenadine is excreted in human milk. Because many drugs are excreted in human milk, caution should be used when fexofenadine HCl is administered to a nursing woman.
Oral suspension: No studies of TELFAST (ORAL SUSPENSION) have been conducted in breast feeding women.
TELFAST (ORAL SUSPENSION) must only be used by lactating women if the potential benefits exceed the potential risks to the child.

Tablet: Seasonal Allergic Rhinitis: Adults: In placebo-controlled seasonal allergic rhinitis clinical trials in patients ≥12 years, which included 2461 patients receiving fexofenadine HCl capsules at doses of 20-240 mg twice daily, adverse events were similar in fexofenadine HCl and placebo-treated patients. All adverse events that were reported by >1% of patients who received the recommended daily dose of fexofenadine HCl (60-mg cap twice daily), and that were more common with fexofenadine HCl than placebo, are listed in Table 1.
In a placebo-controlled clinical study in the United States, which included 570 patients ≥12 years receiving fexofenadine HCl tablets at doses of 120 or 180 mg once daily, adverse events were similar in fexofenadine HCl and placebo-treated patients. Table 1 also lists adverse experiences that were reported by >2% of patients treated with fexofenadine HCl tablets at doses of 180 mg once daily and that were more common with fexofenadine HCl than placebo.
The incidence of adverse events, including drowsiness, was not dose-related and was similar across subgroups defined by age, gender and race. (See Table 1.)

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The frequency and magnitude of laboratory abnormalities were similar in fexofenadine HCl and placebo-treated patients.
Pediatric: Table 2 lists adverse experiences in patients (6-11 years) which were reported by >2% of patients 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 that were more common with fexofenadine HCl than placebo. (See Table 2.)

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Chronic Idiopathic Urticaria: Adverse events reported by patients ≥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, which included 726 patients ≥12 years receiving fexofenadine HCl tablets at doses of 20-240 mg twice daily, adverse events were similar in fexofenadine HCl and placebo-treated patients.
Table 3 lists adverse experiences in patients aged ≥12 years which were reported by >2% of patients treated with fexofenadine HCl 60 mg tab twice daily in controlled clinical studies in the United States and Canada and that were more common with fexofenadine HCl than placebo. The safety of fexofenadine HCl in the treatment of chronic idiopathic urticaria in pediatric patients (6-11 years) is based on the safety profile of fexofenadine HCl in adults and adolescent patients at doses equal to or higher than the recommended dose (see Use in children under Precautions). (See Table 3.)

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Events that have been reported during controlled clinical trials involving seasonal allergic rhinitis and chronic idiopathic urticaria patients with incidences <1% and similar to placebo and have been rarely reported during post-marketing surveillance include: Insomnia, nervousness and sleep disorders or paroniria. In rare cases, rash, urticaria, pruritus and hypersensitivity reactions with manifestations eg, angioedema, chest tightness, dyspnea, flushing and systemic anaphylaxis have been reported.
Oral suspension: In placebo-controlled studies involving patients with seasonal allergic rhinitis and chronic idiopathic urticaria, adverse events were similar to those of patients treated with placebo or fexofenadine.
Most frequently reported adverse events by adults include: headache (>3%), drowsiness, dizziness and nausea (1-3%). The adverse events reported during the controlled studies involving patients with seasonal allergic rhinitis and chronic idiopathic urticaria, with an incidence lower than 1% and similar to those of the placebo group and that were rarely reported during post-marketing experience include: fatigue, insomnia, nervousness, sleep disorders or paroniria. Patients also reported rare cases of rash, urticaria, pruritus and hypersensitivity reactions such as: angioedema, chest tightness, dyspnea, flushing and systemic anaphylaxis.
The adverse events reported in placebo-controlled studies of chronic idiopathic urticaria were similar to those reported in placebo-controlled studies of allergic rhinitis.
In placebo-controlled studies in children from 6 to 11 years of age with seasonal allergic rhinitis, adverse events were similar to those observed in clinical studies involving adults and children 12 years of age or older with seasonal allergic rhinitis.
In controlled clinical studies involving pediatric patients from 6 months to 5 years of age, no unexpected adverse events were observed in patients treated with fexofenadine hydrochloride.

Erythromycin and Ketoconazole: Fexofenadine HCl has been shown to exhibit minimal (ca. 5%) metabolism. However, co-administration of fexofenadine HCl with ketoconazole and erythromycin led to increased plasma levels of fexofenadine HCl. Fexofenadine HCl had no effect on the pharmacokinetics of erythromycin and ketoconazole. In 2 separate studies, fexofenadine HCl 120 mg twice daily (2 times the recommended twice-daily dose) was co-administered with erythromycin 500 mg every 8 hrs or ketoconazole 400 mg once daily under steady-state conditions to normal, healthy volunteers (n=24, each study). No differences in adverse events or QTc interval were observed when patients were administered fexofenadine HCl alone or in combination with erythromycin or ketoconazole. The findings of these studies are summarized in Table 4. (See Table 4.)

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. In vivo animal studies also suggest that in addition to increasing absorption, ketoconazole decreases fexofenadine HCl gastrointestinal secretion, while erythromycin may also decrease biliary excretion.
Omeprazole: No fexofenadine-omeprazole interaction was observed.
Antacids: 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 C_max by 43%. Telfast should not be taken closely in time with aluminum- and magnesium-containing antacids. A period of approximately 2 hrs between the administration of fenofexadine HCl and antacid should be maintained.
Oral suspension: The concomitant administration of TELFAST (ORAL SUSPENSION) with erythromycin or ketoconazole did not demonstrate any significant increase in the QTc interval. No difference in adverse effects was reported when these agents were administered alone or combined.
No fexofenadine-omeprazole interaction was observed. However, the administration of an antacid containing aluminum hydroxide and magnesium, approximately 15 minutes before taking fexofenadine hydrochloride reduced bioavailability. A period of approximately two hours between the administration of fexofenadine hydrochloride and antacids that contain aluminum hydroxide and magnesium should be maintained.

Incompatibilities: Not applicable.
Oral suspension: USAGE INSTRUCTIONS FOR TELFAST SUSPENSION: 1^st step: Remove the external cap and put the bung (internal cap) that is provided with the dosing syringe and the bottle of TELFAST (ORAL SUSPENSION).
2^nd step: Recap the bottle using the external cap and shake well.
3^rd step: Remove the external cap and insert the dosing syringe into the hole of the bottle bung (internal cap). Turn the bottle upside down and pull the plunger up to the mark that corresponds to the necessary dose.
4^th step: Administer the content of the syringe directly into the child's mouth.
5^th step: After administering the drug, wash the syringe with water and put it back in the corresponding box to reuse it.
The syringe was exclusively developed for administering TELFAST (ORAL SUSPENSION). It must not be used with other medications.
FOLLOW THE PHYSICIAN'S INSTRUCTIONS, THE SCHEDULE, THE DOSES AND TREATMENT DURATION.
DO NOT DISCONTINUE TREATMENT WITHOUT INFORMING THE PHYSICIAN.
DO NOT USE THE MEDICATION AFTER THE EXPIRATION DATE. OBSERVE THE APPEARANCE OF THE DRUG BEFORE TAKING IT.

Tablet: Store at room temperature (below 30°C).
Oral suspension: Shake the bottle well before administering TELFAST (ORAL SUSPENSION).
It is recommended that the dosing syringe included in the carton be used.
Store below 30°C.
After opening the package, TELFAST (ORAL SUSPENSION) must be stored in its original package at room temperature (between 15 and 30°C).
Shelf-life: Oral suspension: 24 months.

Antihistamines & Antiallergics

R06AX26 - fexofenadine ; Belongs to the class of other antihistamines for systemic use.

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