Fexofenadine

R06A - Antihistamines for systemic use ATC R06AX26 Small molecule approved 1996 Oral Natural product

JFDA label: Fenadex 120 mg F.C Tab

Mechanism of Action

Fexofenadine is an active metabolite of terfenadine and like terfenadine it competes with histamine for H1-receptor sites on effector cells in the gastrointestinal tract, blood vessels and respiratory tract; it appears that fexofenadine does not cross the blood-brain barrier to any appreciable degree, resulting in a reduced potential for sedation

Indications

Approved

Upper respiratory allergies

Off-label

Chronic idiopathic urticaria

Contraindications

Source: Lexicomp

OTC labeling: When used for self-medication do not use if you ever had an allergic reaction to fexofenadine or any component of the formulation. Documentation of allergenic cross-reactivity for antihistamines is limited. However, because of similarities in chemical structure and/or pharmacologic actions, the possibility of cross-sensitivity can not be ruled out with certainty Absolute

Adverse Reactions

Very Common >10%Common 1–10%Uncommon 0.1–1% Rare 0.01–0.1%Very Rare <0.01%Not Known

Nervous system disorders (5)

Very Common Headache

Common dizziness · Drowsiness · fatigue · pain

Renal and urinary disorders (1)

Common Dysmenorrhea

Gastrointestinal disorders (4)

Very Common Vomiting

Common Diarrhea · dyspepsia · nausea

Musculoskeletal and connective tissue disorders (3)

Common back pain · limb pain · Myalgia

Ear and labyrinth disorders (1)

Common Otitis media

Infections and infestations (1)

Common Viral infection

General disorders and administration site conditions (1)

Common Fever

Respiratory, thoracic and mediastinal disorders (3)

Common cough · rhinorrhea · Upper respiratory tract infection

Dosing

Source: Lexicomp

Upper respiratory allergies: Oral: Twice daily formulations: 60 mg every 12 hours (maximum: 120 mg/day) Once daily formulations: 180 mg once daily (maximum: 180 mg/day) Chronic idiopathic urticaria (off-label use): Oral: 180 mg once daily (Kaplan 2005) or 60 mg twice daily (range: 20 to 240 mg twice daily (Finn 1999)

(For additional information see "Fexofenadine: Pediatric drug information") Upper respiratory allergies: Oral: Children 2 to 11 years: Suspension: 30 mg every 12 hours; maximum: 60 mg/day Children 6 to 11 years: Orally disintegrating tablet: 30 mg every 12 hours; maximum: 60 mg/day Children ≥12 years and Adolescents: Refer to adult dosing. Chronic idiopathic urticaria (off-label use): Children ≥12 years and Adolescents: Oral: Refer to adult dosing.

Refer to adult dosing.

There are no dosage adjustment provided in the manufacturer's labeling; however, the following adjustments have been recommended (Aronoff 2007): Adults: GFR >50 mL/minute: No dosage adjustment necessary for twice daily dosing (ie, 60 mg every 12 hours). GFR 10 to 50 mL/minute: Recommended dose every 12 to 24 hours. GFR Intermittent hemodialysis or peritoneal dialysis: Recommended dose every 24 hours. Continuous renal replacement therapy (CRRT): 60 mg every 24 hours. Infants, Children, and Adolescents: GFR >50 mL/minute/1.73 m2: No dosage adjustment necessary. GFR 10 to 50 mL/minute/1.73 m2: 60 mg every 24 hours. GFR 2: 30 mg every 24 hours. Intermittent hemodialysis or peritoneal dialysis: 30 mg every 24 hours.

There are no dosage adjustments provided in the manufacturer's labeling.

Warnings & Precautions

Source: Lexicomp

Renal impairment

Use with caution in patients with renal impairment; dosage adjustment may be recommended. Concurrent drug therapy issues:

Drug-drug interactions

Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information. Dosage form specific issues:

Orally disintegrating tablet

Some products may contain phenylalanine. Other warnings/precautions:

OTC labeling

When used for self-medication (OTC), do not exceed recommended dosage or administer at the same time with aluminum or magnesium antacids or with fruit juices.

Pregnancy & Lactation

Pregnancy

Limited information is available related to the use of fexofenadine in pregnancy. When a second generation antihistamine is needed, other agents with more information available regarding their use in pregnancy are currently preferred (Murase 2014; Powell 2015; Scadding 2008; Wallace 2008; Zuberbier 2014).

Lactation

Information specific to fexofenadine and breastfeeding has not been located. Fexofenadine is present in breast milk following administration of its parent compound, terfenadine, to breastfeeding mothers (Lucas 1995). Drowsiness and irritability have been reported in breastfed infants exposed to antihistamines; only irritability was reported in infants exposed to fexofenadine’s parent compound, terfenadine (Ito 1993). In general, second generation antihistamines are less sedating as compared

Monitoring

Clinical pearl	Relief of symptoms

Chemistry & Properties

Formula	C32H39NO4
Molecular weight	501.67 g/mol
IUPAC name	2-[4-[1-hydroxy-4-[4-[hydroxy(diphenyl)methyl]piperidin-1-yl]butyl]phenyl]-2-methylpropanoic acid
CAS	83799-24-0
PubChem CID	3348
InChIKey	`RWTNPBWLLIMQHL-UHFFFAOYSA-N`
logP	5.51 (XLogP 3.0)
Polar surface area	81.0 Å²
H-bond acceptors / donors	4 / 3
Drug-likeness (QED)	0.34
Lipinski violations	2

SMILES

CC(C)(C(=O)O)c1ccc(C(O)CCCN2CCC(C(O)(c3ccccc3)c3ccccc3)CC2)cc1

Biology & Pharmacokinetics

Pharmacokinetics

BBB penetrant	Yes (logBB -1.0)

Enzyme interactions

Enzyme	Role	Detail
CYP3A4	Substrate	—

Receptor binding (top 1)

Target	Action	Affinity
H1 receptor (HRH1)	Antagonist	pKi 7.6

Transporters

BCRP (Inhibitor)BCRP (Inhibitor)BSEP (Inhibitor)MDR1 (Inhibitor)MRP1 (Inhibitor)MRP2 (Inhibitor)OATP1B1 (Inhibitor)OATP1B1 (Inhibitor)OATP1B3 (Inhibitor)OATP1B3 (Inhibitor)OATP2B1 (Inhibitor)OCT1 (Inhibitor)OCTN1 (Inhibitor)OCTN2 (Inhibitor)P-gp (Inhibitor)MDR1 (Substrate)MRP2 (Substrate)MRP3 (Substrate)OAT (Substrate)OAT1 (Substrate)OAT2 (Substrate)OAT3 (Substrate)OATP (Substrate)OATP1A2 (Substrate)OATP1B1 (Substrate)OATP1B3 (Substrate)OATP2B1 (Substrate)P-gp (Substrate)

Drug–drug interactions (71, DDInter)

Interacting drug	Severity	Management
Aluminum hydroxide	moderate
Apalutamide	moderate
Bempedoic acid	moderate
Berotralstat	moderate
Brigatinib	moderate
Cabozantinib	moderate
Candida albicans	moderate
Capmatinib	moderate
Coccidioides immitis spherule	moderate
Daclatasvir	moderate
Darolutamide	moderate
Dronedarone	moderate
Elagolix	moderate
Eliglustat	moderate
Eltrombopag	moderate
Eluxadoline	moderate
Enasidenib	moderate
Encorafenib	moderate
Entrectinib	moderate
Enzalutamide	moderate
Erdafitinib	moderate
Flibanserin	moderate
Fostamatinib	moderate
Fostemsavir	moderate
Gilteritinib	moderate
Glasdegib	moderate
Histamine	moderate
Ibrutinib	moderate
Iodide I-123	moderate
Iodide I-131	moderate
Isavuconazonium	moderate
Istradefylline	moderate
Ivacaftor	moderate
Lasmiditan	moderate
Ledipasvir	moderate
Letermovir	moderate
Lomitapide	moderate
Lonafarnib	moderate
Lorlatinib	moderate
Magaldrate	moderate

Showing 40 of 71.

Registered Products (10)

Brand	Form / strength	Pack	Agent	Citizen (JOD)
Feksine	Tablet 180 mg	20 tab	eastward drugstore	1.620
Feksine	Tablet 120 mg	20 tab	eastward drugstore	1.620
Exofen Tablet	Tablet 180 mg	15 tab	UNITED PHARM.MFG.CO.LTD(UPM)/JORDAN	2.140
Exofen Tablet	Tablet 120 mg	15 tab	UNITED PHARM.MFG.CO.LTD(UPM)/JORDAN	2.140
Fenadex	Tablet 180 mg	15 tab	THE JORDANIAN PHARMACEUTICAL MANUFACTURING COMPANY/JORDAN	2.140
Fenadex 120 mg F.C Tab	Film-Coated Tablet 120 mg	15 tab	THE JORDANIAN PHARMACEUTICAL MANUFACTURING COMPANY/JORDAN	2.140
Telfast Tabs	Tablet 180 mg	15 tab	THE ARAB DRUG STORE P.S.C	2.480
Telfast Tabs	Tablet 120 mg	15 tab	THE ARAB DRUG STORE P.S.C	2.480
Fenadex	Tablet 60 mg	30 tab	THE JORDANIAN PHARMACEUTICAL MANUFACTURING COMPANY/JORDAN	2.700
Fexadine	Tablet 120 mg	100 tab	Al Saleem Drug Store	13.150