Tuesday, November 6, 2007

OVERDOSAGE

Dizziness, drowsiness, dry mouth, and have been reported with fexofenadine hydrochloride overdose. Single doses of fexofenadine hydrochloride up to 800 mg (6 healthy subjects at this dose level), and doses up to 690 mg twice daily for 1 months (3 healthy subjects at this dose level ) or 240 mg once daily for 1 year (234 healthy subjects at this level of dose) were administered without the development of clinically significant adverse events compared to placebo. In case of overdose, examine the conventional methods to remove any unabsorbed drug. Symptomatic treatment and support is recommended. Following administration of terfenadine, hemodialysis did not have the effect of eliminating fexofenadine, the primary active metabolite of terfenadine, blood (up 1.7% withdrew). No deaths occurred at oral doses of fexofenadine hydrochloride 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 timesthe maximum recommended daily oral dose in adults and 210 times the maximum recommended daily oral dose in children based on mg/m2). Furthermore, no clinical signs of toxicity or gross pathological were observed. In dogs, no evidence of oral toxicity was observed at 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 at the child is based on mg/m2). 11 DESCRIPTION Fexofenadine hydrochloride, the active ingredient pill Allegra, Allegra and Allegra ODT oral suspension, is a receptor of histamine H1-antagonist with the chemical name (±) -4-[1 hydroxy-4-[4 - (hydroxydiphenylmethyl) - 1-piperidinyl] Butyle] - α, α - dimethyl benzeneacetic acid hydrochloride. He has more of the chemical structure The molecular weight is 538.13 and the empirical formula is C32H39NO4 • HCl. Fexofenadine hydrochloride is a white to off-white crystalline powder. It is readily soluble in methanol and ethanol, sparingly soluble in chloroform and water, and insoluble in hexane. Fexofenadine hydrochloride is a racemate and exists as a zwitterion aqueous at physiological pH. Allegra is formulated as a tablet for oral administration. Each tablet contains 30, 60 or 180 mg of fexofenadine hydrochloride (depending on the dose strength) and excipients: croscarmellose sodium, magnesium stearate, microcrystalline cellulose, pregelatinized starch. The tablet aqueous film coating is made of hypromellose, iron oxide blends, polyethylene glycol, povidone, silicon dioxide, titanium dioxide. Allegra ODT is formulated decay in the mouth immediately after dosing. , Cream artificial flavor, and anhydrous alcohol; Alcohol is largely removed during the manufacturing process. Allegra oral suspension, a white uniform suspension, contains 6 mg of fexofenadine hydrochloride per mL and excipients: propylene glycol, edetate disodium, propylparaben, butylparaben, xanthan gum, poloxamer 407, titanium dioxide, sodium phosphate monobasic monohydrate, sodium phosphate dibasic heptahydrate, artificial raspberry cream flavor, sucrose, xylitol and purified water. 12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Fexofenadine hydrochloride, the primary active metabolite of terfenadine, an antihistamine is selective H1-receptor antagonist activity. Both enantiomers of fexofenadine hydrochloride posted approximately equipotent antihistamine effects. Fexofenadine hydrochloride inhibited antigen-induced bronchospasm in sensitized guinea pigs and release of histamine peritoneal mast cells in rats. The clinical significance of these findings is unknown. In laboratory animals, no anticholinergic or alpha1-adrenergic blocking effects were observed. Furthermore, no sedation or other effects on the central nervous system was observed. Radiomarqué tissue distribution studies in rats indicate that fexofenadine not to cross the blood-brain barrier. 12.2 Pharmacodynamics Wheal and Flare. Human histamine skin wheal and flare following studies in adults are single and twice daily doses of 20 and 40 mg of fexofenadine hydrochloride demonstrated that the drug presents an antihistamine effect by 1 hour, reaching a maximum effect at 2 to 3 hours, and the effect is still observed at 12 hours. There was no evidence of tolerance to the effects, after 28 days of treatment. The clinical significance of these findings is unknown. Histamine skin wheal and flare studies in 7 to 12 years has demonstrated that subjects following a single dose of 30 or 60 mg, the effects of antihistamines was observed at 1 hour and reached a maximum of 3 hours. Over 49% inhibition of wheal area, and 74% inhibition of the area have been maintained flare for 8 hours of the 30 and 60 mg. No statistically significant increase in the QTc interval on average compared to placebo was observed in 714 adult subjects with seasonal allergic rhinitis given fexofenadine hydrochloride capsules in doses of 60 to 240 mg twice daily for 2 weeks. Pediatric subjects of 2 placebo-controlled trials (N = 855) treated with a maximum of 60 mg of fexofenadine hydrochloride twice daily, no evidence of treatment or dose-related increases in QTc. In addition, no statistically significant increase in the QTc interval on average compared to placebo was observed in 40 healthy adult subjects given fexofenadine hydrochloride as an oral solution at doses up to 400 mg twice daily for 6 days, or in 230 healthy adult subjects given fexofenadine hydrochloride 240 Mg once a day for 1 year. In subjects with chronic idiopathic urticaria, there were no differences in any clinically relevant QTc intervals ECG including, among those treated with fexofenadine hydrochloride 180 mg once daily (n = 163) and those treated with a placebo (n = 91) during 4 weeks. 12.3 Pharmacokinetics The pharmacokinetics of fexofenadine hydrochloride in patients with seasonal allergic rhinitis and subjects with chronic urticaria were similar to those of healthy subjects. Absorption: Allegra tablets: Fexofenadine hydrochloride was absorbed after oral administration of a single dose of two 60 mg to healthy subjects male, with a mean time of maximum plasma concentration occurring at 2.6 hours after dosing. After administration of a single 60 mg capsules subjects healthy adults, the average maximum plasma concentration (Cmax) was 131 ng / mL. Following single dose oral administrations one of the 60 and 180 mg / day for adult males in good health, mean Cmax were 142 and 494 ng / mL, respectively. The tablets are bioequivalent to the capsule when administered at doses equal. Fexofenadine hydrochloride is linear pharmacokinetics of oral doses up to a total daily dose of 240 mg (120 mg twice daily). The administration of 60 mg capsule contents mixed with applesauce had no significant effect on the pharmacokinetics of fexofenadine in adults. The administration of 180 mg of fexofenadine hydrochloride tablets with a high fat meal reduced the average area under the curve (AUC) and (Cmax) of fexofenadine by 21 and 20% respectively. Allegra ODT: Fexofenadine hydrochloride was absorbed following a single dose of oral administration of Allegra ODT 30 mg in healthy subjects adults with a mean time to maximum plasma concentration occurring at approximately 2.0 hours after the dose. After a single dose administration of Allegra 30 mg ODT subjects healthy adults, the average maximum plasma concentration (Cmax) was 88.0 ng / mL. Allegra ODT 30 mg tablets are bioequivalent to the 30 mg Allegra tablets. The administration of Allegra ODT 30 mg with a high-fat meal has decreased the AUC and Cmax by approximately 40% and 60%, respectively, and 2 hours late in the exposure time peak (Tmax) been observed. Allegra ODT should be taken on an empty stomach. The bioavailability of Allegra ODT was comparable whether given with or without water [see Dosage and administration (2.2)] Allegra oral suspension: A dose of 5 mL of Allegra oral suspension containing 30 mg of fexofenadine hydrochloride is bioequivalent to 30 mg tablets Allegra. After oral administration of 30 mg of oral suspension for Allegra subjects healthy adults, the mean Cmax was 118 ng / mL and occurred at approximately 1 hour. The administration of 30 mg of Allegra oral suspension with a high fat meal reduced AUC and Cmax average of approximately 30 and 47%, respectively in healthy adult subjects. Distribution: Fexofenadine hydrochloride is 60% to 70% bound to plasma proteins, primarily albumin and α1-acid glycoprotein. Metabolism: Approximately 5% of the total dose of fexofenadine hydrochloride was eliminated by hepatic metabolism. Elimination: The mean elimination half-life of fexofenadine was 14.4 hours after administration of 60 mg twice daily to healthy subjects adults. Human mass balance studies documented a recovery of approximately 80% and 11% of the [14C] fexofenadine hydrochloride dose in the feces and urine, respectively. Because the absolute bioavailability of fexofenadine hydrochloride has not been established, it is not known if the fecal component primarily represents unabsorbed drug or is the result of biliary excretion. Special Populations: Pharmacokinetics in the liver and renal impaired geriatric topics and themes, obtained after a single dose of 80 mg of fexofenadine hydrochloride, were compared with those of healthy subjects in a separate study of similar design. Impaired renal: In subjects with mild to moderate (creatinine clearance 41-80 mL / min) and severe (creatinine clearance 11-40 mL / min) renal, peak plasma concentration of fexofenadine were 87% and 111% more, respectively, and the mean elimination half-life-were 59% Vies and 72% higher, respectively, than observed in healthy subjects. Peak plasma concentrations dialysis patients (creatinine clearance <10 n =" 14)" n =" 21)," n =" 1634)," n =" 863)," n =" 726)." n =" 259),">

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