Fexofenadine dosing

Grant JA, Riethuisen JM, Moulaert B, DeVos C A double-blind, randomized, single-dose, crossover comparison of levocetirizine with ebastine, fexofenadine, loratadine, mizolastine, and placebo sup- 59 pression of histamine-induced wheal-and-flare response during 24 hours in healthy male subjects. 

Antagonists. Most of the so-called Hi-antihistamines also block other receptors, including M-cholinoceptors and D-receptors. Hi-antihistamines are used for the symptomatic relief of allergies (e.g., bamipine, chlorpheniramine, clemastine, dimethindene, mebhydroline pheniramine) as antiemetics (meclizine, dimenhydrinate, p. 330), as over-the-counter hypnotics (e.g., diphenhydramine, p. 222). Promethazine represents the transition to the neuroleptic phenothiazines (p. 236). Unwanted effects of most Hi-antihistamines are lassitude (impaired driving skills) and atropine-like reactions (e.g., dry mouth, constipation). At the usual therapeutic doses, astemizole, cetrizine, fexofenadine, and loratidine are practically devoid of sedative and anticholinergic effects. Hj-antihistamines (cimetidine, ranitidine, famotidine, nizatidine) inhibit gastric acid secretion, and thus are useful in the treatment of peptic ulcers. 

Geriatric Considerations - Summary Clearance and half-life are altered in older adults therefore reduce starting dose. More sedating than fexofenadine and lorata-dine consider an alternate second-generation antihistamine. 

Fexofenadine hydrochloride is rapidly absorbed into the body following oral administration, with Tmax occurring at approximately 1-3 hours post dose. It is 60-70% plasma protein bound. 

In a recent example, a sensitive LC-MS/MS method was successfully applied to assay for fexofenadine in plasma following a single oral administration of a microdose (100-pg solution) and a clinical dose (60-mg dose) to eight healthy volunteers (Yamane et al., 2007). Fexofenadine and terfenadine (IS) eluted at 0.95 and 2.07 min, respectively, and the correct m/z for the protonated precursor ions were observed at m/z 502.2 and 472.2. For SRM (or MRM) experiments, both precursor ions were fragmented separately in the collision cell and the fragment ions of m/z 466 and 436, respectively, were monitored for fexofenadine and terfenadine. The details of the fexofenadine assay are given in the following ... 

Figure 1.6. Fexofenadine calibration curves and mean plasma concentration-time profiles following a single oral administration of (a) 100 pug (microdosing) or (b) 60 mg (clinical dosing) fexofenadine to healthy volunteers. (Reprinted with pemnission from Yamane et al., 2007.)...

Uno T, Shimizu M, Sugawara K, et al. Lack of dose-dependent effects of itraconazole on the pharmacokinetic interaction with fexofenadine. Drug Metab Dispos 2006 34 1875-1879. 

Q7 What is the daily dose of fexofenadine and are there any potential side effects when using this agent ... 

In a double-blind, placebo-controlled, crossover study of the acute effects of single doses of fexofenadine 120 mg, olopatadine 10 mg, and chlorphenamine 4 mg on cognitive and psychomotor performance in 11 healthy Japanese volunteers, both chlorphenamine and olopatadine reduced behavioral activity while fexofenadine was similar to placebo (61). 

In a randomized, double blind, six-way, crossover study of the cognitive effects of fexofenadine 180 mg, both alone and in combination with alcohol, fexofenadine had no disruptive effects on objective measures related to driving a car and aspects of psychomotor and cognitive function, even when combined with a dose of alcohol equivalent to 0.3 g/kg (62). 

Even in a high dose (360 mg bd versus the recommended dose of 60 mg bd) fexofenadine had no disruptive effects on psychomotor performance and cognitive function in healthy volunteers (269). 

Bower EA, Moore JL, Moss M, Selby KA, Austin M, Meeves S. The effects of single-dose fexofenadine, diphenhydramine, and placebo on cognitive performance in flight personnel. Aviat Space Environ Med. 2003 74 145-52. 

Kamei H, Noda Y, Ishikawa K, Senzaki K, Muraoka I, Hasegawa Y, Hindmarch I, Nabeshima T. Comparative study of acute effects of single doses of fexofenadine, olopatadine, d-chlorpheniramine and placebo on psychomotor function in healthy volunteers. Hum Psychopharmacol 2003 18 611-8. 

Hindmarch I, Shamsi Z, Kimber S. An evaluation of the effects of high-dose fexofenadine on the central nervous system a double-blind, placebo-controlled study in healthy volunteers. Clin Exp Allergy 2002 32(l) 133-9. 

Adverse effects. Terfenadine can prolong the QTc interval on the surface ECG. This is especially likely to occur when the recommended dose is exceeded or the drug is administered with substances that block hepatic metabolism. Since this is dependent solely on the 3A4 isoform of cytochrome P450, offending drugs include erythromycin, ketoconazole and even grapefruit juice. Fexofenadine is the active metabolite of terfenadine and appears safe in this respect. 

The effects of azithromycin 250 mg/day on the pharmacokinetics of desloratadine 5 mg/day and fexofenadine 60 mg bd have been studied in a parallel-group, third-party-blind, multiple-dose, randomized, placebo-controlled study (46). There were small increases (under 15%) in the mean plasma concentrations of desloratadine. In contrast, peak fexofenadine concentrations were increased by 69% and the AUC by 67%. There were no changes in the electrocardiogram. 

The effect of co-administration of azithromycin on plasma concentrations of fexofenadine 60 mg bd has been examined in a randomized third-party-blind, placebo-controlled, parallel-group study in 98 healthy volunteers (5). An initial loading dose of azithromycin (500 mg) was given on day 3, followed by 250 mg od for 4 days. Concomitant azithromycin caused increases in the Cmax and AUC of fexofenadine (69 and 67% respectively). However, there were no statistically significant increases in the PR, QT, QTc interval, QRS complex duration, or ventricular rate after administration of fexofenadine with or without azithromycin. 

Unlike its parent drug, only 5% of the total dose of fexofenadine is metabolized. The remainder is excreted in the bile and urine the mean elimination half-life is about 14 hours. 

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