Fexofenadine
 | |
| Clinical data | |
|---|---|
| Pregnancy category | |
| Routes of administration | Oral |
| ATC code | |
| Legal status | |
| Legal status | |
| Pharmacokinetic data | |
| Bioavailability | Not yet established |
| Protein binding | 60-70% |
| Metabolism | Hepatic (5% of dose) |
| Elimination half-life | 14.4 hours |
| Excretion | Feces (~80%) and urine (~11%) as unchanged drug |
| Identifiers | |
| |
| CAS Number | |
| ChemSpider | |
| CompTox Dashboard (EPA) | |
| ECHA InfoCard | 100.228.648 |
| Chemical and physical data | |
| Formula | C32H39NO4 |
| Molar mass | 501.656 g·mol−1 |
| 3D model (JSmol) | |
| |
| (verify) | |
Fexofenadine (Allegra, Telfast, Fastofen, Tilfur) is an antihistamine drug used in the treatment of hayfever and similar allergy symptoms. It was developed as a successor of and alternative to terfenadine (brand names include Triludan and Seldane), an antihistamine with potentially serious contraindications. Fexofenadine, like other second and third-generation antihistamines, does not readily cross the blood-brain barrier, and so causes less drowsiness than first-generation histamine-receptor antagonists. It works by being an antagonist to the H1 receptor.[1]
It has been described as both second-generation[2] and third-generation.[3]
Indications
Fexofenadine is indicated for the relief from physical symptoms associated with seasonal allergic rhinitis and treatment of chronic idiopathic urticaria. It is not a therapeutic drug and does not cure but rather prevents the aggravation of rhinitis and urticaria and reduces the severity of the symptoms providing much relief from repeated sneezing, runny nose, itchy eyes and general body fatigue caused by rhinitis and urticaria. It is a safe and easy to use drug available in doses as indicated below.
Dosage
- Chronic idiopathic urticaria: Children 6 months to < 2 years: 15 mg twice daily
- Chronic idiopathic urticaria, seasonal allergic rhinitis:
- Children 2–11 years: 30 mg twice daily
- Children ≥ 12 years and Adult: 60 mg twice daily or 180 mg once daily
- Elderly: Starting dose: 60 mg once daily;
Administration
Administer with water only; do not administer with fruit juices. Shake suspension well before use.
Dosage forms
- Suspension: 6 mg/mL (30 mL, 300 mL) [raspberry cream]
- Tablet: 30 mg, 60 mg, 180 mg
Common side effects
- Nausea
- Dizziness
- Vomiting
- Weakness
- Drowsiness, sleepiness
- Fatigue
- Diarrhea
- Unusual bowel movements
- Headache
- Aggression
- Fever
Overdose
Reports of fexofenadine overdose are infrequent, and because of this, the effects are not well established. No deaths occurred in testing on mice, at 5000 mg/kg, which is 110 times the maximum recommended dose for an adult human. Further research shows no deaths in rats at the same concentration, which equates four hundred times the recommended dose in an adult human. Research on humans ranges from a single 800 mg dose, to a twice-daily 690 mg dose for a month, with no clinically significant adverse effects, when compared to a placebo.
History
The older antihistaminic agent terfenadine was found to metabolize into the related carboxylic acid, fexofenadine. Fexofenadine was found to retain all of the biological activity of its parent while giving fewer adverse reactions in patients, so terfenadine was replaced in the market by its metabolite.[4] Fexofenadine was originally synthesized in 1993 by Massachusetts-based biotechnology company Sepracor, which then sold the development rights to Hoechst Marion Roussel (now part of Sanofi-Aventis), and was later approved by the Food and Drug Administration (FDA) in 1996. AMRI holds the patents to the intermediates and production of fexofenadine HCl along with Roussel. Since that time, it has achieved blockbuster drug status with global sales of $1.87B USD in 2004 (with $1.49B USD coming from the United States). AMRI received royalty payments from Aventis that enabled the growth of AMRI.
Synthesis
Fexofenadine may be synthesized as shown from piperidine-4-carboxylate ester and 4-bromophenylacetonitrile.[4]
To produce the piperidine piece, two phenyl groups are first introduced using a Grignard reaction on the ester, giving a tertiary alcohol. The amine group is then alkylated with a protected aldehyde, then the aldehyde is recovered by deprotection with acid. The remaining piece of the molecule is produced by a double alkylation by iodomethane of the carbanion derived from the nitrile. The nitrile group is then hydrolyzed to a carboxylic acid. The aryl bromide is then lithiated to produce the organolithium compound, which can be coupled with the aldehyde piece to give (after workup) fexofenadine.
Notes
- ^ IngentaConnect - Fexofenadine, an H1-receptor antagonist, partially ...
- ^ Dicpinigaitis PV, Gayle YE (2003). "Effect of the second-generation antihistamine, fexofenadine, on cough reflex sensitivity and pulmonary function". British journal of clinical pharmacology. 56 (5): 501–4. PMC 1884387. PMID 14651723.
{{cite journal}}: Unknown parameter|month=ignored (help) - ^ Vena GA, Cassano N, Filieri M, Filotico R, D'Argento V, Coviello C (2002). "Fexofenadine in chronic idiopathic urticaria: a clinical and immunohistochemical evaluation". International journal of immunopathology and pharmacology. 15 (3): 217–224. PMID 12575922.
{{cite journal}}: Cite has empty unknown parameter:|month=(help)CS1 maint: multiple names: authors list (link) - ^ a b Daniel Lednicer (1999). The Organic Chemistry of Drug Synthesis. Vol. 6. New York: Wiley Interscience. pp. 38–40. ISBN 0-471-24510-0. Cite error: The named reference "Lednicer1999" was defined multiple times with different content (see the help page).
References
- Synthesis: J. Org. Chem. 1994, 59, 2620.
- Biological effects: Mol. Pharmacol. 1993, 44, 1240.
External links
- Fexofenadine (UK patient information leaflet)
- Allegra (Fexofenadine Hydrochloride) label and research information
- Sanofi-aventis (Home page)
- Fexofenadine (MedicineNet) (Written by Pharmacists; Reviewed by Doctors)