Fexofenadine

Pharmacologic Category

Histamine H1 Antagonist; Histamine H1 Antagonist, Second Generation; Piperidine Derivative

Dosing: Adult

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).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

* See Dosage and Administration in AHFS Essentials for additional information.

Dosing: Geriatric

Refer to adult dosing.

Dosing: Renal Impairment: Adult

There are no dosage adjustment provided in the manufacturer's labeling; however, the following adjustments have been recommended (Aronoff 2007):

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 <10 mL/minute: Recommended dose every 24 hours.

Intermittent hemodialysis or peritoneal dialysis: Recommended dose every 24 hours.

Continuous renal replacement therapy (CRRT): 60 mg every 24 hours.

Dosing: Hepatic Impairment: Adult

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

Dosing: Pediatric

Allergic symptoms/rhinitis: Product-specific dosing:

Twice-daily formulations (eg, oral suspension, oral disintegrating tablet, regular tablet):

Oral suspension:

Infants ≥6 months and Children <2 years: Limited data available (Hampel 2007):

<10.5 kg: Oral: 15 mg every 12 hours.

≥10.5 kg: Oral: 30 mg every 12 hours.

Dosing based on a safety and tolerability study on patients with allergic rhinitis receiving fexofenadine 15 mg twice daily (weight <10.5 kg, n=85) and fexofenadine 30 mg twice daily (weight ≥10.5 kg, n=108) compared to placebo (n=199); adverse events were similar between fexofenadine and placebo (Hampel 2007).

Children ≥2 to <12 years: Oral: 30 mg every 12 hours; maximum daily dose: 60 mg/day.

Children ≥12 years and Adolescents: Oral: 60 mg every 12 hours; maximum daily dose: 120 mg/day.

Orally-disintegrating tablet (ODT):

Children ≥6 years to <12 years: Oral: 30 mg every 12 hours; maximum daily dose: 60 mg/day.

Children ≥12 years and Adolescents: Oral: 60 mg every 12 hours; maximum daily dose: 120 mg/day.

12-hour tablet: Children ≥12 years and Adolescents: Oral: 60 mg every 12 hours; maximum daily dose: 120 mg/day.

Once-daily formulation:

Children ≥12 years and Adolescents: Oral: 180 mg once daily.

Urticaria, acute: Limited data available (Kliegman 2020):

Children ≥6 to 11 years: Twice-daily formulations (eg, oral suspension, oral disintegrating tablet, regular tablet): Oral: 30 mg every 12 hours.

Children ≥12 years and Adolescents: Twice-daily formulations (eg, oral suspension, oral disintegrating tablet, regular tablet): Oral: 60 mg every 12 hours.

Urticaria, chronic spontaneous: Limited data available: Note: Considered first-line therapy for management of chronic urticaria; if response inadequate after 2 to 4 weeks of therapy or symptoms intolerable, consider increasing the dose of fexofenadine (as age and weight permits) as second-line treatment rather than changing therapy (Zuberbier 2018).

Infants ≥6 months to Children <2 years: Twice-daily formulations (eg, oral suspension): Oral: 15 mg every 12 hours (Lee 2016).

Children ≥2 to <12 years: Twice-daily formulations (eg, oral suspension, orally-disintegrating tablet, regular tablet): Oral: 30 mg twice daily (Pozzo-Magaña 2017).

Children ≥12 years and Adolescents:

Twice-daily formulations (eg, oral suspension, orally-disintegrating tablet, regular tablet): Oral: 60 mg every 12 hours (Finn 1999).

Once-daily formulation: Oral: 180 mg once daily (Kaplan 2005).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Renal Impairment: Pediatric

Twice-daily formulations (eg, oral suspension, oral disintegrating tablet, regular tablet):

There are no dosage adjustments provided in the OTC manufacturer's labeling; previous prescribing information (Allegra prescribing information 2007) suggested the following:

Infants ≥6 months to Children <2 years: Any degree of kidney impairment: Initial: 15 mg once daily.

Children 2 to 11 years: Any degree of kidney impairment: 30 mg once daily.

Children ≥12 years and Adolescents: Any degree of kidney impairment: 60 mg once daily.

Others have suggested the following: Children ≥12 years and Adolescents (Aronoff 2007):

CrCl 10 to 50 mL/minute: 60 mg once daily.

CrCl <10 mL/minute: 30 mg once daily.

Hemodialysis: Not effectively removed by hemodialysis: 30 mg once daily.

Peritoneal dialysis: 30 mg once daily.

Once-daily formulation: There are no dosage adjustments provided in the manufacturer's labeling.

Dosing: Hepatic Impairment: Pediatric

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

Calculations

• Creatinine Clearance by Cockcroft-Gault
• Creatinine Clearance by Cockcroft-Gault (SI units)
• Creatinine Clearance by Cockcroft-Gault with IBW
• Creatinine Clearance by Cockcroft-Gault with IBW (SI units)
• Creatinine Clearance by Jelliffe
• Creatinine Clearance by Sanaka
• Glomerular Filtration Rate by Abbreviated MDRD
• Glomerular Filtration Rate by Abbreviated MDRD (SI units)
• Glomerular Filtration Rate by MDRD
• Glomerular Filtration Rate by MDRD (IDMS-Traceable SCr)
• Glomerular Filtration Rate by MDRD (SI units)
• Glomerular Filtration Rate by Schwartz
• Glomerular Filtration Rate Estimate in African Americans by AASK Equation

Use: Labeled Indications

Upper respiratory allergies: Temporary relief of runny nose, sneezing, itching of the nose or throat, and/or itchy, watery eyes due to hay fever or other upper respiratory allergies.

* See Uses in AHFS Essentials for additional information.

Use: Off-Label: Adult

​Chronic idiopathic urticariaLevel of Evidence [A, G]

Data from a multicenter, randomized, double-blind, placebo-controlled study suggest that fexofenadine is effective in the treatment of chronic idiopathic urticaria Ref.

A joint guideline published by the American Academy of Allergy, Asthma, & Immunology (AAAAI) and American College of Allergy, Asthma, and Immunology (ACAAI) recommend second-generation antihistamines as first-line therapy in the treatment of patients with chronic urticaria Ref.

Level of Evidence Definitions

​Level of Evidence Scale

Class and Related Monographs

Antihistamines

Clinical Practice Guidelines

Allergic Rhinitis:

AAO-HNS, “Clinical Practice Guideline: Allergic Rhinitis,” 2015

Urticaria:

AAAAI, “The Diagnosis and Management of Acute and Chronic Urticaria: 2014 update

EAACI/GA²LEN/EDF/WAO, “Guideline for the Definition, Classification, Diagnosis and Management of Urticaria - 2017 Update,” April 2018

Administration: Oral

Orally disintegrating tablet: Administer on an empty stomach. Remove tablet from individual blister and place immediately on tongue; tablet will disintegrate with or without water (do not administer with fruit juices).

Suspension, tablet: Administer with water only; do not administer with fruit juices. Shake suspension well before use. Use suspension only with enclosed dosing cup.

Administration: Pediatric

Oral:

Twice-daily formulations:

Suspension, regular tablet: May administer without respect to food. Take with water; avoid administration with fruit juices; shake suspension well before use. Administer suspension with an accurate measuring device; do not use a household teaspoon.

Orally-disintegrating tablet: Administer on an empty stomach. Do not remove from blister pack until ready to administer. Using dry hands, place immediately on tongue. Tablet will dissolve within seconds and may be swallowed with or without liquid; avoid administering with fruit juices.

Once-daily formulation: Swallow whole with water; do not take with fruit juices.

Dietary Considerations

Some products may contain phenylalanine and/or sodium. Take suspension and tablets preferably with water; separate administration with grapefruit or other fruit juices by at least 4 hours.

Storage/Stability

Store at 20°C to 25°C (68°F to 77°F). Use orally disintegrating tablet immediately after opening individual blister.

Medication Patient Education with HCAHPS Considerations

What is this drug used for?

• It is used to ease allergy signs.

• It is used to treat hives.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Headache

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a limited summary of general information about the medicine's uses from the patient education leaflet and is not intended to be comprehensive. This limited summary does NOT include all information available about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not intended to provide medical advice, diagnosis or treatment and does not replace information you receive from the healthcare provider. For a more detailed summary of information about the risks and benefits of using this medicine, please speak with your healthcare provider and review the entire patient education leaflet.

Medication Safety Issues

​Sound-alike/look-alike issues:

​International issues:

Contraindications

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.

Warnings/Precautions

Disease-related concerns:

• Renal impairment: Use with caution in patients with renal impairment; dosage adjustment may be recommended.

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.

* See Cautions in AHFS Essentials for additional information.

Geriatric Considerations

Plasma levels in the elderly are generally higher than those observed in other age groups. Once daily dosing is recommended when starting therapy in elderly patients or patients with decreased renal function.

Warnings: Additional Pediatric Considerations

Safety and efficacy for the use of cough and cold products in pediatric patients <4 years of age is limited; the AAP warns against the use of these products for respiratory illnesses in young children. Serious adverse effects including death have been reported. Many of these products contain multiple active ingredients, increasing the risk of accidental overdose when used with other products. The FDA does not recommend OTC uses for these products in pediatric patients <2 years of age and recommends to use with caution in pediatric patients ≥2 years of age. Health care providers are reminded to ask caregivers about the use of OTC cough and cold products in order to avoid exposure to multiple medications containing the same ingredient (AAP 2018; CDC 2007; FDA 2017; FDA 2018).

Some dosage forms may contain propylene glycol; in neonates, large amounts of propylene glycol delivered orally, intravenously (eg, >3,000 mg/day), or topically have been associated with potentially fatal toxicities which can include metabolic acidosis, seizures, renal failure, and CNS depression; toxicities have also been reported in children and adults including hyperosmolality, lactic acidosis, seizures, and respiratory depression; use caution (AAP 1997; Shehab 2009).

Pregnancy Considerations

Agents other than fexofenadine are preferred for the treatment of allergic conditions, such as rhinitis, pruritus, and urticaria, in pregnant women (BSACI [Powell 2015]; BSACI [Scadding 2017]; Murase 2014; Zuberbier 2018).

Breast-Feeding Considerations

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 to their first generation counterparts. If a breastfed infant is exposed to a second generation antihistamine via breast milk, they should be monitored for irritability, jitteriness, or drowsiness (Butler 2014).

When treatment with an antihistamine is needed in breastfeeding women, other second generation antihistamines with more information available regarding their use in this patient population are preferred (BSACI [Powell 2015]; BSACI [Scadding 2017]; Butler 2014; Zuberier 2018).

Lexicomp Pregnancy & Lactation, In-Depth

• Fexofenadine

Briggs' Drugs in Pregnancy & Lactation

• Fexofenadine

Adverse Reactions

>10%:

Central nervous system: Headache (5% to 11%)

Gastrointestinal: Vomiting (children 6 months to 5 years: 4% to 12%)

1% to 10%:

Central nervous system: Drowsiness (1% to 3%), fatigue (1% to 3%), dizziness (2%), pain (2%)

Gastrointestinal: Diarrhea (3% to 4%), nausea (2%), dyspepsia (1% to 2%)

Genitourinary: Dysmenorrhea (2%)

Infection: Viral infection (3%)

Neuromuscular & skeletal: Myalgia (3%), back pain (2% to 3%), limb pain (2%)

Otic: Otitis media (2% to 4%)

Respiratory: Upper respiratory tract infection (3% to 4%), cough (2% to 4%), rhinorrhea (1% to 2%)

Miscellaneous: Fever (2%)

<1%, postmarketing, and/or case reports: Hypersensitivity reaction (including anaphylaxis, angioedema, chest tightness, dyspnea, flushing, pruritus, skin rash, urticaria), insomnia, nervousness, nightmares, sleep disorder

* See Cautions in AHFS Essentials for additional information.

Allergy and Idiosyncratic Reactions

• H1 Antihistamine Allergy

Toxicology

• Histamine H1 Antagonists, Second Generation

Metabolism/Transport Effects

Substrate of CYP3A4 (minor), OATP1B1/1B3 (SLCO1B1/1B3), P-glycoprotein/ABCB1 (minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential

Drug Interactions Open Interactions

Acetylcholinesterase Inhibitors: Anticholinergic Agents may diminish the therapeutic effect of Acetylcholinesterase Inhibitors. Acetylcholinesterase Inhibitors may diminish the therapeutic effect of Anticholinergic Agents. Risk C: Monitor therapy

Aclidinium: May enhance the anticholinergic effect of Anticholinergic Agents. Risk X: Avoid combination

Alcohol (Ethyl): CNS Depressants may enhance the CNS depressant effect of Alcohol (Ethyl). Risk C: Monitor therapy

Alizapride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Amantadine: May enhance the anticholinergic effect of Anticholinergic Agents. Risk C: Monitor therapy

Amezinium: Antihistamines may enhance the stimulatory effect of Amezinium. Risk C: Monitor therapy

Amphetamines: May diminish the sedative effect of Antihistamines. Risk C: Monitor therapy

Antacids: May decrease the serum concentration of Fexofenadine. Management: Separate the administration of fexofenadine and aluminum- or magnesium-containing antacids. Exceptions: Calcium Carbonate; Magaldrate; Sodium Bicarbonate. Risk D: Consider therapy modification

Anticholinergic Agents: May enhance the adverse/toxic effect of other Anticholinergic Agents. Risk C: Monitor therapy

Azelastine (Nasal): May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination

Benzylpenicilloyl Polylysine: Antihistamines may diminish the diagnostic effect of Benzylpenicilloyl Polylysine. Management: Suspend systemic H1 antagonists for benzylpenicilloyl-polylysine skin testing and delay testing until systemic antihistaminic effects have dissipated. A histamine skin test may be used to assess persistent antihistaminic effects. Risk D: Consider therapy modification

Betahistine: Antihistamines may diminish the therapeutic effect of Betahistine. Risk C: Monitor therapy

Blonanserin: CNS Depressants may enhance the CNS depressant effect of Blonanserin. Management: Use caution if coadministering blonanserin and CNS depressants; dose reduction of the other CNS depressant may be required. Strong CNS depressants should not be coadministered with blonanserin. Risk D: Consider therapy modification

Botulinum Toxin-Containing Products: May enhance the anticholinergic effect of Anticholinergic Agents. Risk C: Monitor therapy

Brexanolone: CNS Depressants may enhance the CNS depressant effect of Brexanolone. Risk C: Monitor therapy

Brimonidine (Topical): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Bromopride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Bromperidol: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination

Buprenorphine: CNS Depressants may enhance the CNS depressant effect of Buprenorphine. Management: Consider reduced doses of other CNS depressants, and avoiding such drugs in patients at high risk of buprenorphine overuse/self-injection. Initiate buprenorphine at lower doses in patients already receiving CNS depressants. Risk D: Consider therapy modification

Cannabidiol: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Cannabis: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Chloral Betaine: May enhance the adverse/toxic effect of Anticholinergic Agents. Risk C: Monitor therapy

Chlormethiazole: May enhance the CNS depressant effect of CNS Depressants. Management: Monitor closely for evidence of excessive CNS depression. The chlormethiazole labeling states that an appropriately reduced dose should be used if such a combination must be used. Risk D: Consider therapy modification

Chlorphenesin Carbamate: May enhance the adverse/toxic effect of CNS Depressants. Risk C: Monitor therapy

Cimetropium: Anticholinergic Agents may enhance the anticholinergic effect of Cimetropium. Risk X: Avoid combination

CloZAPine: Anticholinergic Agents may enhance the constipating effect of CloZAPine. Management: Consider alternatives to this combination whenever possible. If combined, monitor closely for signs and symptoms of gastrointestinal hypomotility and consider prophylactic laxative treatment. Risk D: Consider therapy modification

CNS Depressants: May enhance the adverse/toxic effect of other CNS Depressants. Risk C: Monitor therapy

Dimethindene (Topical): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Doxylamine: May enhance the CNS depressant effect of CNS Depressants. Management: The manufacturer of Diclegis (doxylamine/pyridoxine), intended for use in pregnancy, specifically states that use with other CNS depressants is not recommended. Risk C: Monitor therapy

Dronabinol: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Droperidol: May enhance the CNS depressant effect of CNS Depressants. Management: Consider dose reductions of droperidol or of other CNS agents (eg, opioids, barbiturates) with concomitant use. Exceptions to this monograph are discussed in further detail in separate drug interaction monographs. Risk D: Consider therapy modification

Eltrombopag: May increase the serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates. Risk C: Monitor therapy

Eluxadoline: Anticholinergic Agents may enhance the constipating effect of Eluxadoline. Risk X: Avoid combination

Esketamine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Flunitrazepam: CNS Depressants may enhance the CNS depressant effect of Flunitrazepam. Management: Reduce the dose of CNS depressants when combined with flunitrazepam and monitor patients for evidence of CNS depression (eg, sedation, respiratory depression). Use non-CNS depressant alternatives when available. Risk D: Consider therapy modification

Gastrointestinal Agents (Prokinetic): Anticholinergic Agents may diminish the therapeutic effect of Gastrointestinal Agents (Prokinetic). Risk C: Monitor therapy

Gemfibrozil: May increase the serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates. See separate drug interaction monographs for agents listed as exceptions. Risk C: Monitor therapy

Glucagon: Anticholinergic Agents may enhance the adverse/toxic effect of Glucagon. Specifically, the risk of gastrointestinal adverse effects may be increased. Risk C: Monitor therapy

Glycopyrrolate (Oral Inhalation): Anticholinergic Agents may enhance the anticholinergic effect of Glycopyrrolate (Oral Inhalation). Risk X: Avoid combination

Glycopyrronium (Topical): May enhance the anticholinergic effect of Anticholinergic Agents. Risk X: Avoid combination

Grapefruit Juice: May decrease the serum concentration of Fexofenadine. Risk C: Monitor therapy

Hyaluronidase: Antihistamines may diminish the therapeutic effect of Hyaluronidase. Risk D: Consider therapy modification

HydrOXYzine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Ipratropium (Oral Inhalation): May enhance the anticholinergic effect of Anticholinergic Agents. Risk X: Avoid combination

Itopride: Anticholinergic Agents may diminish the therapeutic effect of Itopride. Risk C: Monitor therapy

Kava Kava: May enhance the adverse/toxic effect of CNS Depressants. Risk C: Monitor therapy

Lemborexant: May enhance the CNS depressant effect of CNS Depressants. Management: Dosage adjustments of lemborexant and of concomitant CNS depressants may be necessary when administered together because of potentially additive CNS depressant effects. Close monitoring for CNS depressant effects is necessary. Risk D: Consider therapy modification

Levosulpiride: Anticholinergic Agents may diminish the therapeutic effect of Levosulpiride. Risk X: Avoid combination

Lisuride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Lofexidine: May enhance the CNS depressant effect of CNS Depressants. Management: Drugs listed as exceptions to this monograph are discussed in further detail in separate drug interaction monographs. Risk C: Monitor therapy

Magnesium Sulfate: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Methotrimeprazine: May enhance the CNS depressant effect of CNS Depressants. CNS Depressants may enhance the CNS depressant effect of Methotrimeprazine. Management: Reduce the usual dose of CNS depressants by 50% if starting methotrimeprazine until the dose of methotrimeprazine is stable. Monitor patient closely for evidence of CNS depression. Risk D: Consider therapy modification

Metoclopramide: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

MetyroSINE: CNS Depressants may enhance the sedative effect of MetyroSINE. Risk C: Monitor therapy

Mianserin: May enhance the anticholinergic effect of Anticholinergic Agents. Risk C: Monitor therapy

Minocycline (Systemic): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Mirabegron: Anticholinergic Agents may enhance the adverse/toxic effect of Mirabegron. Risk C: Monitor therapy

Nabilone: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Nitroglycerin: Anticholinergic Agents may decrease the absorption of Nitroglycerin. Specifically, anticholinergic agents may decrease the dissolution of sublingual nitroglycerin tablets, possibly impairing or slowing nitroglycerin absorption. Risk C: Monitor therapy

Opioid Agonists: CNS Depressants may enhance the CNS depressant effect of Opioid Agonists. Management: Avoid concomitant use of opioid agonists and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Risk D: Consider therapy modification

Orphenadrine: CNS Depressants may enhance the CNS depressant effect of Orphenadrine. Risk X: Avoid combination

Oxatomide: May enhance the anticholinergic effect of Anticholinergic Agents. Risk X: Avoid combination

Oxomemazine: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination

Oxybate Salt Products: CNS Depressants may enhance the CNS depressant effect of Oxybate Salt Products. Management: Consider alternatives to this combination when possible. If combined, dose reduction or discontinuation of one or more CNS depressants (including the oxybate salt product) should be considered. Interupt oxybate salt treatment during short-term opioid use. Risk D: Consider therapy modification

OxyCODONE: CNS Depressants may enhance the CNS depressant effect of OxyCODONE. Management: Avoid concomitant use of oxycodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Risk D: Consider therapy modification

Paraldehyde: CNS Depressants may enhance the CNS depressant effect of Paraldehyde. Risk X: Avoid combination

Perampanel: May enhance the CNS depressant effect of CNS Depressants. Management: Patients taking perampanel with any other drug that has CNS depressant activities should avoid complex and high-risk activities, particularly those such as driving that require alertness and coordination, until they have experience using the combination. Risk D: Consider therapy modification

P-glycoprotein/ABCB1 Inducers: May decrease the serum concentration of Fexofenadine. Risk C: Monitor therapy

Piribedil: CNS Depressants may enhance the CNS depressant effect of Piribedil. Risk C: Monitor therapy

Pitolisant: Antihistamines may diminish the therapeutic effect of Pitolisant. Risk X: Avoid combination

Potassium Chloride: Anticholinergic Agents may enhance the ulcerogenic effect of Potassium Chloride. Management: Patients on drugs with substantial anticholinergic effects should avoid using any solid oral dosage form of potassium chloride. Risk X: Avoid combination

Potassium Citrate: Anticholinergic Agents may enhance the ulcerogenic effect of Potassium Citrate. Risk X: Avoid combination

Pramipexole: CNS Depressants may enhance the sedative effect of Pramipexole. Risk C: Monitor therapy

Pramlintide: May enhance the anticholinergic effect of Anticholinergic Agents. These effects are specific to the GI tract. Risk X: Avoid combination

Ramosetron: Anticholinergic Agents may enhance the constipating effect of Ramosetron. Risk C: Monitor therapy

Revefenacin: Anticholinergic Agents may enhance the anticholinergic effect of Revefenacin. Risk X: Avoid combination

RifAMPin: May decrease the serum concentration of Fexofenadine. RifAMPin may increase the serum concentration of Fexofenadine. Risk C: Monitor therapy

ROPINIRole: CNS Depressants may enhance the sedative effect of ROPINIRole. Risk C: Monitor therapy

Rotigotine: CNS Depressants may enhance the sedative effect of Rotigotine. Risk C: Monitor therapy

Rufinamide: May enhance the adverse/toxic effect of CNS Depressants. Specifically, sleepiness and dizziness may be enhanced. Risk C: Monitor therapy

Secretin: Anticholinergic Agents may diminish the therapeutic effect of Secretin. Management: Avoid concomitant use of anticholinergic agents and secretin. Discontinue anticholinergic agents at least 5 half-lives prior to administration of secretin. Risk D: Consider therapy modification

Suvorexant: CNS Depressants may enhance the CNS depressant effect of Suvorexant. Management: Dose reduction of suvorexant and/or any other CNS depressant may be necessary. Use of suvorexant with alcohol is not recommended, and the use of suvorexant with any other drug to treat insomnia is not recommended. Risk D: Consider therapy modification

Teriflunomide: May increase the serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates. Risk C: Monitor therapy

Tetrahydrocannabinol: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Tetrahydrocannabinol and Cannabidiol: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Thalidomide: CNS Depressants may enhance the CNS depressant effect of Thalidomide. Risk X: Avoid combination

Thiazide and Thiazide-Like Diuretics: Anticholinergic Agents may increase the serum concentration of Thiazide and Thiazide-Like Diuretics. Risk C: Monitor therapy

Tiotropium: Anticholinergic Agents may enhance the anticholinergic effect of Tiotropium. Risk X: Avoid combination

Tolvaptan: May increase the serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates. Management: Avoid concomitant use of OATP1B1/1B3 substrates in patients receiving the Jynarque brand of tolvaptant. Concentrations and effects of the OATP1B1/1B3 substrate would be expected to increase with combined use. Risk D: Consider therapy modification

Topiramate: Anticholinergic Agents may enhance the adverse/toxic effect of Topiramate. Risk C: Monitor therapy

Trimeprazine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Umeclidinium: May enhance the anticholinergic effect of Anticholinergic Agents. Risk X: Avoid combination

Zolpidem: CNS Depressants may enhance the CNS depressant effect of Zolpidem. Management: Reduce the Intermezzo brand sublingual zolpidem adult dose to 1.75 mg for men who are also receiving other CNS depressants. No such dose change is recommended for women. Avoid use with other CNS depressants at bedtime; avoid use with alcohol. Risk D: Consider therapy modification

Food Interactions

High-fat meals decrease the bioavailability of fexofenadine by ~50%. Fruit juice (apple, grapefruit, orange) may decrease bioavailability of fexofenadine by ~36%. Management: Separating fexofenadine administration and fruit juice consumption by at least 4 hours may decrease the significance of this possible interaction.

Test Interactions

May suppress the wheal and flare reactions to skin test antigens.

Genes of Interest

• P-Glycoprotein

Monitoring Parameters

Relief of symptoms

Advanced Practitioners Physical Assessment/Monitoring

Obtain baseline renal function tests; dosage adjustment may be needed. Assess for relief of symptoms.

Nursing Physical Assessment/Monitoring

Check ordered labs and report abnormalities. Monitor if relief of symptoms.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Suspension, Oral, as hydrochloride:

Allegra Allergy Childrens: 30 mg/5 mL (240 mL) [alcohol free, dye free; contains butylparaben, edetate disodium, propylene glycol, propylparaben; berry flavor]

Allegra Allergy Childrens: 30 mg/5 mL (120 mL) [alcohol free, dye free; contains butylparaben, edetate disodium, propylene glycol, propylparaben; raspberry creme flavor]

Fexofenadine HCl Childrens: 30 mg/5 mL (118 mL [DSC]) [alcohol free, dye free; contains butylparaben, edetate disodium, propylene glycol, propylparaben]

Fexofenadine HCl Childrens: 30 mg/5 mL (118 mL [DSC]) [alcohol free, dye free; contains butylparaben, edetate disodium, propylene glycol, propylparaben; berry flavor]

Tablet, Oral, as hydrochloride:

Allegra Allergy: 60 mg, 180 mg

Allegra Allergy: 180 mg [contains brilliant blue fcf (fd&c blue #1)]

Allergy 24-HR: 180 mg

Allergy Relief: 180 mg

Allergy Relief: 180 mg [contains corn starch]

Allergy Relief/Indoor/Outdoor: 180 mg [contains corn starch]

Mucinex Allergy: 180 mg [DSC] [contains fd&c red #40]

Generic: 60 mg, 180 mg

Tablet Disintegrating, Oral, as hydrochloride:

Allegra Allergy Childrens: 30 mg [contains aspartame; orange cream flavor]

Anatomic Therapeutic Chemical (ATC) Classification

• R06AX26

Generic Available (US)

May be product dependent

Pricing: US

Suspension (Allegra Allergy Childrens Oral)

30 mg/5 mL (per mL): $0.09

Tablet, orally-disintegrating (Allegra Allergy Childrens Oral)

30 mg (per each): $0.91

Tablets (Allegra Allergy Oral)

60 mg (per each): $1.32

180 mg (per each): $0.41

Tablets (Fexofenadine HCl Oral)

60 mg (per each): $0.16 - $1.51

180 mg (per each): $0.16 - $2.43

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

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

Pharmacodynamics/Kinetics

Onset of action: 2 hours (Simons 2004)

Duration of action: 24 hours (Simons 2004)

Absorption: Rapid

Protein binding: 60% to 70% (Markham 1998); primarily albumin and alpha1-acid glycoprotein

Metabolism: Minimal (Hepatic: ~5%); 3.6% transformed into methylester metabolite found only in feces

Bioavailability: ~33%

Half-life elimination: 14.4 hours (59% longer in patients with mild to moderate renal impairment [CrCl 41 to 80 mL/minute]; 72% longer in patients with severe renal impairment [CrCl 11 to 40 mL/minute]) (Markham 1998; Simons 2004)

Time to peak, serum: ODT: 2 hours (4 hours with high-fat meal); Tablet: ~2.6 hours (Simons 2004); Suspension: ~1 hour

Excretion: Feces (80%) and urine (12%) as unchanged drug (Simons 2004)

Pharmacodynamics/Kinetics: Additional Considerations

Renal function impairment: Mild to moderate impairment with CrCl 41 to 80 mL/minute has an 87% increase in Cmax. Severe impairment with CrCl 11 to 40 mL/minute has a 111% increase in Cmax.

Geriatric: Cmax is increased 99%.

Local Anesthetic/Vasoconstrictor Precautions

No information available to require special precautions

Effects on Dental Treatment

No significant effects or complications reported

Effects on Bleeding

No information available to require special precautions

Index Terms

Fexofenadine Hydrochloride

FDA Approval Date

July 25, 1996

References

Allegra (fexofenadine) [prescribing information]. Bridgewater, NJ: sanofi-aventis U.S. LLC; July 2007.

Allegra (fexofenadine) [product monograph]. Laval, Quebec, Canada: sanofi-aventis Canada; September 2006.

Allegra Allergy 12 Hour (fexofenadine) [prescribing information]. Chatanooga, TN: Chattam; received April 2020.

Allegra Allergy 24 Hour (fexofenadine) [prescribing information]. Chatanooga, TN: Chattam; received April 2020.

American Academy of Pediatrics (AAP). Cough and cold medicines should not be prescribed, recommended or used for respiratory illnesses in young children. Updated June 12, 2018. Available at http://www.choosingwisely.org/clinician-lists/american-academy-pediatrics-cough-and-cold-medicines-for-children-under-four/

American Academy of Pediatrics Committee on Drugs. "Inactive" ingredients in pharmaceutical products: update (subject review). Pediatrics. 1997;99(2):268-278.[PubMed 9024461]

Aronoff GR, Bennett WM, Berns JS, et al. Drug Prescribing in Renal Failure: Dosing Guidelines for Adults and Children. 5th ed. Philadelphia, PA: American College of Physicians; 2007, p 94.

Bernstein JA, Lang DM, Khan DA, et al; American Academy of Allergy, Asthma & Immunology (AAAAI); the American College of Allergy, Asthma & Immunology (ACAAI); Joint Council of Allergy, Asthma & Immunology. The diagnosis and management of acute and chronic urticaria: 2014 update. J Allergy Clin Immunol. 2014;133(5):1270-1277. doi: 10.1016/j.jaci.2014.02.036.[PubMed 24766875]

Brunton LL, Chabner BA, Knollmann BC, eds. Goodman & Gilman's The Pharmacological Basis of Therapeutics. 12th ed. New York, NY: McGraw-Hill Medical; 2011.

Butler DC, Heller MM, Murase JE. Safety of dermatologic medications in pregnancy and lactation: Part II. Lactation. J Am Acad Dermatol. 2014;70(3):417.[PubMed 24528912]

Centers for Disease Control and Prevention (CDC). Infant deaths associated with cough and cold medications--two states, 2005. MMWR Morb Mortal Wkly Rep. 2007;56(1):1-4.[PubMed 17218934]

Childrens Allegra Allergy (fexofenadine oral suspension) [prescribing information]. Chatanooga, TN: Chattam; received April 2020.

Childrens Allegra Allergy (fexofenadine orally disintegrating tablets) [prescribing information]. Chatanooga, TN: Chattam; received April 2020.

Day JH, Briscoe M, Welsh A, et al, “Onset of Action, Efficacy and Safety of a Single Dose of 60 mg and 120 mg Fexofenadine HCl for Ragweed Allergy Using Controlled Antigen Exposure in an Environmental Exposure Unit (EEU),” J Allergy Clin Immunol, 1996, 97(1 Pt 3):434.

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Finn AF Jr, Kaplan AP, Fretwell R, Qu R, Long J. A double-blind, placebo-controlled trial of fexofenadine HCl in the treatment of chronic idiopathic urticaria. J Allergy Clin Immunol. 1999;104(5):1071-1078.[PubMed 10550755]

Food and Drug Administration (FDA). Most young children with a cough or cold don't need medicines. July 18, 2017. Available at https://www.fda.gov/ForConsumers/ConsumerUpdates/ucm422465.htm. Last accessed November 2, 2018.

Food and Drug Administration (FDA). Use caution when giving cough and cold products to kids. Updated February 8, 2018. Available at https://www.fda.gov/drugs/resourcesforyou/specialfeatures/ucm263948.htm. Last accessed November 2, 2018.

Hampel FC, Kittner B, van Bavel JH. Safety and tolerability of fexofenadine hydrochloride, 15 and 30 mg, twice daily in children aged 6 months to 2 years with allergic rhinitis. Ann Allergy Asthma Immunol. 2007;99(6):549-554.[PubMed 18219837]

Ito S, Blajchman A, Stephenson M, et al. Prospective follow-up of adverse reactions in breast-fed infants exposed to maternal medication. Am J Obstet Gynecol. 1993;168(5):1393-1399.[PubMed 8498418]

Kaplan AP, Spector SL, Meeves S, Liao Y, Varghese ST, Georges G. Once-daily fexofenadine treatment for chronic idiopathic urticaria: a multicenter, randomized, double-blind, placebo-controlled study. Ann Allergy Asthma Immunol. 2005;94(6):662-669.[PubMed 15984599]

Kliegman RM and St. Geme J, eds. Nelson Textbook of Pediatrics. 21st ed. Philadelphia, PA: Saunders Elsevier; 2020.

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Lucas BD Jr, Purdy CY, Scarim SK, et al. Terfenadine pharmacokinetics in breast milk in lactating women. Clin Pharmacol Ther. 1995;57(4):398-402.[PubMed 7712667]

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Murase JE, Heller MM, Butler DC. Safety of dermatologic medications in pregnancy and lactation: part I. Pregnancy. J Am Acad Dermatol. 2014;70(3):401.[PubMed 24528911]

Powell RJ, Leech SC, Till S, et al; British Society for Allergy and Clinical Immunology. BSACI guideline for the management of chronic urticaria and angioedema.Clin Exp Allergy. 2015;45(3):547-565.[PubMed 25711134]

Pozzo-Magaña BR. Chronic urticaria in children: a review. EMJ Dermatol. 2017;5(1):74-82.

Scadding GK, Kariyawasam HH, Scadding G, et al. BSACI guideline for the diagnosis and management of allergic and non-allergic rhinitis (Revised edition 2017; First edition 2007). Clin Exp Allergy. 2017;47(7):856-889. doi:10.1111/cea.12953[PubMed 30239057]

Shehab N, Lewis CL, Streetman DD, Donn SM. Exposure to the pharmaceutical excipients benzyl alcohol and propylene glycol among critically ill neonates. Pediatr Crit Care Med. 2009;10(2):256-259.[PubMed 19188870]

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Zuberbier T, Aberer W, Asero R, et al. The EAACI/GA²LEN/EDF/WAO guideline for the definition, classification, diagnosis and management of urticaria. Allergy. 2018;73(7):1393-1414. doi:10.1111/all.13397[PubMed 29336054]

Brand Names: International

Alagra (BD); Alanil (BD); Alerfedine (AR); Alertam (EG); Alexia (EC, PY); Allegra (BM, BR, BS, BZ, CO, CR, CU, DO, EC, GT, GY, HN, IN, JM, JP, KR, LK, MX, NI, NL, PA, PE, PR, PY, SR, SV, TT, TW, UY, VE); Allegra 180 (CL); Allegra Allergy (BB); Allegratab (MT); Allemax (PE); Allerex (EG); Altifex (NO); Altiva (LK); Avafast (TH); Biostafex (CR, DO, GT, HN, NI, PA, SV); Bosnum (HK, TH); Bosnum 180 (HK); Delaxin (PY); Ewofex (RO); Exofen (BH, JO, LB); Fastel (EG); Fe Min (TW); Fenadex (LB, QA, SA); Fenadin (LK); Fenafex (TH); Fexet (VN); Fexodex (JO); Fexodine (AE, BH, HK, KW, QA, SA); Fexofast (TH); Fexofen (IN); Fexon (EG, KR); Fexoral (PH); Fexostad (HK); Fexotabs (AU); Fexotene (TH); Fexovid (MY); Fynadin (TW); Inflex (VN); Kofixir (HK); Nasaga (TW); Neofex (PH); Raltiva (CN); Rhinogan (PH); Ritch (BD); Sizzle (PK); Sky-Fexo (ZW); Tefodine (AU); Telfast (AE, AT, AU, BE, BF, BG, BH, BJ, CH, CI, CY, CZ, DE, DK, EE, EG, ES, ET, FI, FR, GB, GH, GM, GN, HK, HR, ID, IE, IL, IS, IT, JO, KE, KW, LB, LR, LU, MA, ML, MR, MT, MU, MW, MY, NE, NG, NO, NZ, PL, PT, QA, RO, RU, SA, SC, SD, SE, SG, SI, SK, SL, SN, TH, TN, TR, TZ, UG, VN, ZA, ZM, ZW); Telfast HD (ID); Telfast OD (ID); Telfast Oral Solution (MY); Telfast Oral Suspension (SG); Telfor (VN); Ternafast (VN); Tocimat (VN); Tofexo (TH); Vifas (TH); Xadine (LK); Xergic (AU, NZ); Xofast (BD)

Last Updated 10/22/20