Products
Fexofenadine is commercially available in tablet form (Telfast, Telfastin Allergo, generic). It was approved in many countries in 1997 and has been available without a doctor’s prescription since 2010. Telfastin Allergo 120 for self-medication went on sale in February 2011. Fexofenadine is the successor product to terfenadine (Teldane), which had to be withdrawn from the market due to prolongation of the QT interval and its metabolism via CYP3A4. Fexofenadine is free of these side effects and is excreted almost completely unchanged.
Structure and properties
Fexofenadine (C32H39NO4, Mr = 501.66 g/mol) is a piperidine derivative and the active carboxylate metabolite of terfenadine. In drugs, it is present as fexofenadine hydrochloride, a white crystalline powder that is somewhat soluble in water. The hydrophilic zwitterion is a racemate consisting of – and -fexofenadine. Both enantiomers are involved in the effect and differ in pharmacokinetics.
Effects
Fexofenadine (ATC R06AX26) has antihistamine, antiallergic, antiinflammatory, and mast cell stabilizing properties. It does not cross the blood–brain barrier into the brain because it is hydrophilic and a substrate of P-glycoprotein. Therefore, it is less depressant than 1st generation antihistamines. Fexofenadine is not anticholinergic or cardiotoxic like its precursor terfenadine. It is an inverse and selective antagonist at the H1 receptor, abolishes histamine effects and thus relieves symptoms such as pruritus, sneezing, runny nose, redness, swelling, and eye tearing.
Indications
For symptomatic treatment of seasonal allergic rhinitis (hay fever) and chronic idiopathic urticaria (hives of unknown cause).
Dosage
According to the package insert. Tablets may be taken once daily due to the long half-life of 14.4 hours. The usual dose for allergic rhinitis is 120 mg (adults). For hives, the higher dose of 180 mg is recommended.
Contraindications
- Hypersensitivity
For complete precautions, see the drug label.
Interactions
Fexofenadine is not metabolized in the liver via CYP450 isozymes like its precursor terfenadine, but is excreted almost completely unchanged primarily in feces (80%) and urine (10%). Only 5% of the dose is biotransformed. It therefore has a reduced interaction potential. However, fexofenadine is a substrate of the transporters P-glycoprotein and OATP. Enhancement or attenuation of the effect is possible via both mechanisms. For example, an increase in concentrations has been observed with the P-gp inhibitors erythromycin and ketoconazole. Fexofenadine should not be taken with magnesium– or aluminum-containing antacids because absorption is reduced.
Adverse Effects
Side effects are rare. Possible adverse effects include hypersensitivity reactions, headache, drowsiness, dizziness, fatigue, sleep disturbances, nightmares, nervousness, nausea, and skin rashes.
