Fexofenadine is a metabolite of terfenadine and is a second-generation antihistamine. It is FDA approved to treat both seasonal allergic rhinitis and chronic idiopathic urticaria.
Fexofenadine has approval for use in both children and adults. Children should be six months old or older, dependent upon the indication for use. Specific dosing is discussed below in the administration section.
The mechanism of action of fexofenadine is to selectively antagonize H1 receptors on the surface of cells on multiple different organ systems. It is a second-generation H1 receptor blocker and is non-sedating. Fexofenadine also affects inflammatory mediators. Fexofenadine does not cross the blood-brain barrier and thus does not cause drowsiness like other H1 blockers. Second-generation antihistamines such as fexofenadine have less affinity for cholinergic and alpha-adrenergic receptors and therefore do not display the anticholinergic side effects that other antihistamines do. Fexofenadine is also able to inhibit other mechanisms such as mast cell, basophilic histamine, and inflammatory cell release.
The onset of action is about 2 hours and is long-acting, which allows for once a day administration. While the metabolism of other antihistamines occurs in the liver, fexofenadine is hepatically cleared to a lesser degree than others and excreted in the stool.
Fexofenadine comes in multiple different forms. It may be administered orally as a tablet, oral suspension (syrup), or branded oral disintegrating tablets. Fexofenadine may be used in adults and children, though the dose for children is lower than that of an adult (up to 60 mg vs. 180 mg daily PO).
ODT tablets are branded and should be placed on the tongue, allowed to dissolve (with or without water) then swallowed. Patients should not chew them, and patients should take the medication before eating or drinking anything.
No matter the route of administration, it is important to note that taking the drug with grapefruit, apple, or orange juice decreases bioavailability. This reduced bioavailability is because of the inhibition of P-glycoprotein transporter (P-gp). Patients should separate the administration of fexofenadine and any of these juices by at least 4 hours.
Reported side effects in a meta-analysis of other random, double-blind, placebo-controlled study versus placebo are as follows:
The most frequently occurring side effects of these are drowsiness, fatigue, and dry mouth, which may occur at larger doses.
Hypersensitivity to fexofenadine or any of its components is the only true contraindication to use of this medication. There is little hepatic involvement in the clearance of this medication, so it is safe for use in patients with liver pathology. Caution is necessary when treating patients with renal disease, and renal dosing, as noted above, should be followed.
There is no significant interaction with fexofenadine and concomitant use of alcohol or food. However, bioavailability decreases when used with grapefruit, apple, or orange juices.
In animal models, fexofenadine has been shown to cause low birth weight and is currently a category C medication in pregnancy. Alternatives for symptom relief of allergic rhinitis include loratadine and cetirizine.
Monitoring fexofenadine involves monitoring for improvement or worsening of symptoms with use. Because of fexofenadine's close relationship with cardiotoxic terfenadine, patients with underlying cardiac conditions may need to be monitored with periodic EKG to watch for QT-prolongation and arrhythmias.
A study out of Vietnam compared fexofenadine and levocetirizine for chronic urticaria. The study found that at doses that were two times the recommended dosing showed improvement of urticarial symptoms without increasing negative side effects. The most common side effects noted were fatigue and drowsiness, which occurred at the same rates in patients taking the recommended dose rather than the higher dose. This same study mentions a European study in which dosing was quadrupled and still had similar side effects outcomes.
As previously mentioned, fexofenadine is a metabolite of terfenadine, which proved to have cardiotoxic effects. Terfenadine blocked cardiac potassium channels, which, when taken in large doses or with other medications such as ketoconazole, caused prolonged QT-interval. Prolonged QT-interval can lead to fatal arrhythmias. Fexofenadine has replaced terfenadine in the United States per FDA guidelines because it does not block potassium channels and, in multiple studies, did not cause any arrhythmias or significant prolonged QT-intervals.
Despite the findings of these studies, other case reports have found a relationship between fexofenadine and QT-interval elongation and ventricular arrhythmia though it is very rare. It bears mentioning that the use of fexofenadine with hepatic CYP3A4 blockers (such as erythromycin, ketoconazole) can increase its concentration in the blood and combined use with drugs such as rifampin and troglitazone will decrease the concentration. These effects are likely due to the interaction between these compounds and the P-glycoprotein transporter, which removes fexofenadine from the blood.
Fexofenadine is a commonly used medication for seasonal allergic rhinitis and chronic urticaria and is an overall safe and effective therapy when used properly. While it is available to patients without a prescription, care id necessary when starting any new medication. Patients should discuss the use of fexofenadine with their primary care physician and pharmacist to educate themselves on side effects, recommended dosing and possible interactions with commonly ingested items such as fruit juices. Care should be taken by providers to ensure that renal and pediatric patients are taking the appropriate adjusted dosage of fexofenadine. [Level V]
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