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  • CLASSES

    Second generation (non-sedating) Antihistamines

    DEA CLASS

    Rx, OTC

    DESCRIPTION

    Non-sedating antihistamine (H1-receptor antagonist)
    Used for seasonal allergic rhinitis and chronic idiopathic urticaria
    Active metabolite of terfenadine; fexofenadine does not typically prolong the QT interval

    COMMON BRAND NAMES

    Allegra, Allegra Allergy 12 Hour, Allegra Allergy 24 Hour, Allegra Children's Allergy, Allegra Children's Allergy ODT, Allegra ODT, Allergy Relief, Children's Allergy Fexofenadine

    HOW SUPPLIED

    Allegra Children's Allergy ODT/Allegra ODT Oral Tab Orally Dis: 30mg
    Allegra/Allegra Allergy 12 Hour/Allegra Allergy 24 Hour/Allegra Children's Allergy/Allergy Relief/Fexofenadine/Fexofenadine Hydrochloride Oral Tab: 30mg, 60mg, 180mg
    Allegra/Allegra Children's Allergy/Children's Allergy Fexofenadine/Fexofenadine/Fexofenadine Hydrochloride Oral Susp: 5mL, 30mg

    DOSAGE & INDICATIONS

    For the management of symptoms of perennial allergies and seasonal allergies, including allergic rhinitis.
    Oral dosage (tablets or capsules)
    Adults, Adolescents, and Children 12 years and older

    60 mg PO twice daily. Alternatively, 180 mg PO once daily.

    Children 6 to 11 years

    30 mg PO twice daily. During controlled trials of patients 6 to 11 years of age, 60 mg twice daily was not more beneficial than 30 mg twice daily.

    Oral dosage (orally disintegrating tablets [ODT])
    Adults, Adolescents, and Children 12 years and older

    60 mg PO twice daily; place on the tongue and allow to disintegrate.[42362] [43588]

    Children 6 to 11 years

    30 mg PO twice daily; place on the tongue and allow to disintegrate.

    Oral dosage (oral suspension containing 30 mg fexofenadine per 5 mL)
    Adults, Adolescents, and Children 12 years and older

    60 mg PO twice daily.

    Children 2 to 11 years

    30 mg PO twice daily.

    For the treatment of chronic idiopathic urticaria.
    Oral dosage (tablets or capsules)
    Adults, Adolescents, and Children 12 years and older

    60 mg PO twice daily. Alternatively, 180 mg PO once daily.

    Children 6 to 11 years

    30 mg PO twice daily.

    Oral dosage (orally disintegrating tablets [ODT])
    Children 6 to 11 years

    30 mg PO twice daily; place on tongue and allow to disintegrate.[42362]

    Oral dosage (oral suspension containing fexofenadine 30 mg per 5 mL)
    Children 2 to 11 years

    30 mg PO twice daily.

    Infants and Children 6 months and up to 2 years

    15 mg PO twice daily.

    MAXIMUM DOSAGE

    Adults

    180 mg/day PO if given once daily; 120 mg/day if given in 2 divided doses.

    Geriatric

    180 mg/day PO if given once daily; 120 mg/day if given in 2 divided doses.

    Adolescents

    180 mg/day PO if given once daily; 120 mg/day if given in 2 divided doses.

    Children

    12 years: 180 mg/day PO if given once daily; 120 mg/day if given in 2 divided doses.
    2 to 11 years: 60 mg/day PO.
    Less than 2 years: 30 mg/day PO.

    Infants

    6 months and older: 30 mg/day PO.
    Less than 6 months: Safety and efficacy have not been established.

    Neonates

    Safety and efficacy have not been established.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    No dosage adjustment is recommended. The pharmacokinetics of fexofenadine are not substantially different in patients with hepatic disease.

    Renal Impairment

    CrCl 80 mL/minute/1.73 m2 or more: No adjustment necessary.
    CrCl 11 to 80 mL/minute/1.73 m2: Reduce the starting dose to once daily administration as follows based on age:
    -Adults, Adolescents, and Children 12 years and older: 60 mg PO once daily.
    -Children 2 to 11 years: 30 mg PO once daily.
    -Infants and Children 6 months to less than 2 years: 15 mg PO once daily.
    CrCl  10 mL/minute/1.73 m2 or less:
    -Adults, Adolescents, and Children 12 years and older: Not included in the FDA-approved label, some experts recommend 30 mg PO once daily.
    -Infants and Children less than 12 years: Dosage recommendations are not available.
     
    Intermittent hemodialysis
    Dosing not included in the FDA-approved label, some experts recommend 30 mg PO once daily for patients older than 12 years; dosing for other age groups is not available. The effect of hemodialysis on the removal of fexofenadine is unknown. After terfenadine oral administration, hemodialysis did not effectively remove fexofenadine (the major active metabolite of terfenadine) from blood (up to 1.7% was removed).

    ADMINISTRATION

    Oral Administration

    Avoid grapefruit, orange, and apple juice before or after drug administration to avoid potential reduction bioavailability.

    Oral Solid Formulations

    Tablets or capsules: Administer orally with water. May be administered without regard to meals.
    Orally disintegrating tablets: Dissolve tablets on the tongue then swallow with or without water; do not chew. Administer on an empty stomach. Do not remove from original blister package until the time of administration.

    Oral Liquid Formulations

    Oral suspension: Shake well prior to each use. Measure dosage using a calibrated measuring device. Keep in a tightly closed container away from children.

    STORAGE

    Allegra:
    - Protect from moisture
    - Store between 68 to 77 degrees F
    Allegra Allergy 12 Hour :
    - Protect from moisture
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Allegra Allergy 24 Hour:
    - Protect from moisture
    - Store between 68 to 77 degrees F
    Allegra Children's Allergy :
    - Store between 68 to 77 degrees F
    Allegra Children's Allergy ODT:
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Allegra ODT:
    - Protect from moisture
    - Store at controlled room temperature (between 68 and 77 degrees F)
    - Store in original container
    Allergy Relief:
    - Protect from moisture
    - Store between 68 to 77 degrees F
    Children's Allergy Fexofenadine:
    - Store between 68 to 77 degrees F

    CONTRAINDICATIONS / PRECAUTIONS

    Terfenadine hypersensitivity

    Do not use fexofenadine in patients with a history of fexofenadine hypersensitivity; use with caution in patients with terfenadine hypersensitivity due to the similarity in chemical structure.

    Phenylketonuria

    Fexofenadine Orally Disintegrating Tablets (ODT) contain phenylalanine, a component of aspartame. Each 30 mg tablet contains 5.3 mg of phenylalanine. Allegra ODT should be avoided in patients with phenylketonuria.

    Renal disease, renal failure, renal impairment

    Use fexofenadine cautiously in patients with renal impairment associated with renal disease or renal failure. Peak plasma concentrations were 87% and 111% greater in patients with mild (CrCl 41—80 mL/min) to severe (CrCl 11—40 mL/min) renal impairment, respectively. Mean elimination half-lives were 59% and 72% longer, respectively, than in normal volunteers. Peak plasma concentrations in dialysis patients (CrCl <= 10 mL/min) were 82% greater and half-life was 31% longer than in normal volunteers. Patients with mild to severe renal impairment should be given half the initial dose due to reduced clearance of fexofenadine.

    Geriatric

    It is unknown if geriatric patients respond differently than younger adults to fexofenadine; however, renal function may decline with age. Because of the potential toxicity associated with the use of fexofenadine in those with renal dysfunction, the drug should be used cautiously in geriatric patients. Lower initial dosages may be advisable until the effects of the drug are known. The federal Omnibus Budget Reconciliation Act (OBRA) regulates medication use in residents of long-term care facilities. According to the OBRA guidelines, cough, cold, and allergy medications should be used only for a limited duration (less than 14 days) unless there is documented evidence of enduring symptoms that cannot otherwise be alleviated and for which a cause cannot be identified and corrected.

    Pregnancy

    There have been no adequate and well-controlled studies regarding the use of fexofenadine in human pregnancy. Results of animal studies have revealed an absence of mutagenicity or infertility. Teratogenicity was not observed in rats given approximately 15 times the maximum daily oral dose in humans based on an AUC comparison. Decreased pup weight gain and survival occurred in rats given 3 times the maximum daily oral dose in humans. Fexofenadine should be used during pregnancy only when the benefits of therapy outweigh the risks. Self-medication with non-prescription products is not recommended; pregnant patients should see their health care professional for a proper diagnosis and for treatment recommendations. The American College of Obstetricians and Gynecologists (ACOG) and the American College of Allergy, Asthma, and Immunology consider loratadine an acceptable alternative in pregnancy, preferably after the first trimester, when first generation antihistamines are not tolerated.

    Breast-feeding

    According to the manufacturer, caution should be exercised when fexofenadine is administered to a breast-feeding woman. It is unknown whether fexofenadine is excreted into human breast milk. Fexofenadine has generally been considered to be compatible with breast-feeding due to its low sedative activity; monitor the infant for irritability or for any effects of this antihistamine on lactation. Loratadine may be considered as an alternative for the treatment of allergy symptoms. Because of its lack of sedation and low milk concentrations, maternal use would not be expected to cause adverse effects in breast-fed babies and loratadine is considered usually compatible with breast-feeding. The British Society for Allergy and Clinical Immunology also recommends loratadine at the lowest dose as a preferred antihistamine in breast-feeding women. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally ingested drug, healthcare providers are encouraged to report the adverse effect to the FDA.

    Driving or operating machinery

    The incidence of drowsiness was 1.3% in patients receiving fexofenadine monotherapy (vs placebo 0.9%). Patients should be warned about undertaking hazardous tasks (e.g., driving or operating machinery) while taking fexofenadine, although the risk is relatively low.

    Children, infants, neonates

    The safety and efficacy of fexofenadine for the treatment of allergic rhinitis in neonates, infants, and children younger than 2 years of age has not been established. Safety and efficacy for the treatment of chronic idiopathic urticaria in infants less than 6 months has not been established. Fexofenadine tablets and orally disintegrating tablets (Allegra ODT) are not FDA approved for children less than 6 years of age, while oral suspension is FDA approved for prescription use in those 6 months and older and for over-the-counter use in those 2 years and older. Antihistamines generally should not be used in neonates due to the possibility of paradoxical CNS stimulation.

    ADVERSE REACTIONS

    Severe

    anaphylactoid reactions / Rapid / Incidence not known
    angioedema / Rapid / Incidence not known

    Moderate

    chest pain (unspecified) / Early / Incidence not known
    dyspnea / Early / Incidence not known

    Mild

    vomiting / Early / 4.2-12.0
    headache / Early / 4.8-10.3
    dyspepsia / Early / 4.7-4.7
    fever / Early / 1.9-4.5
    infection / Delayed / 0.9-4.3
    cough / Delayed / 1.9-4.0
    diarrhea / Early / 2.8-3.7
    fatigue / Early / 0.7-2.8
    myalgia / Early / 2.6-2.6
    back pain / Delayed / 2.1-2.5
    pharyngitis / Delayed / 2.4-2.4
    rhinorrhea / Early / 0.9-2.1
    dizziness / Early / 2.1-2.1
    dysmenorrhea / Delayed / 1.5-1.5
    paranoia / Early / 0-1.0
    insomnia / Early / 0-1.0
    restlessness / Early / 0-1.0
    rash / Early / Incidence not known
    urticaria / Rapid / Incidence not known
    pruritus / Rapid / Incidence not known
    flushing / Rapid / Incidence not known

    DRUG INTERACTIONS

    Alogliptin; Pioglitazone: (Minor) Concentrations of fexofenadine may be increased with concomitant use of pioglitazone. The effect of pioglitazone capistration on the systemic exposure of fexofenadine was determined in a drug-drug interaction study. Coadministration of pioglitazone 45 mg once daily with fexofenadine 60 mg twice daily for 7 days resulted in a 30% and 37% increase in fexofenadine AUC and Cmax, respectively. Patients should be monitored for increased side effects from fexofenadine.
    Aluminum Hydroxide: (Major) Coadministration with antacids (containing aluminum or magnesium) within 15 minutes decreases the AUC and Cmax of fexofenadine by 41% and 43%, respectively. Separate administration is recommended.
    Aluminum Hydroxide; Magnesium Carbonate: (Major) Coadministration with antacids (containing aluminum or magnesium) within 15 minutes decreases the AUC and Cmax of fexofenadine by 41% and 43%, respectively. Separate administration is recommended.
    Aluminum Hydroxide; Magnesium Hydroxide: (Major) Coadministration with antacids (containing aluminum or magnesium) within 15 minutes decreases the AUC and Cmax of fexofenadine by 41% and 43%, respectively. Separate administration is recommended.
    Aluminum Hydroxide; Magnesium Hydroxide; Simethicone: (Major) Coadministration with antacids (containing aluminum or magnesium) within 15 minutes decreases the AUC and Cmax of fexofenadine by 41% and 43%, respectively. Separate administration is recommended.
    Aluminum Hydroxide; Magnesium Trisilicate: (Major) Coadministration with antacids (containing aluminum or magnesium) within 15 minutes decreases the AUC and Cmax of fexofenadine by 41% and 43%, respectively. Separate administration is recommended.
    Antacids: (Major) Coadministration with antacids (containing aluminum or magnesium) within 15 minutes decreases the AUC and Cmax of fexofenadine by 41% and 43%, respectively. Separate administration is recommended.
    Aspirin, ASA; Citric Acid; Sodium Bicarbonate: (Major) Co-administration with antacids within 15 minutes decreases the AUC and Cmax of fexofenadine. Separate administration is recommended.
    Atazanavir; Cobicistat: (Minor) Plasma concentrations of fexofenadine may be elevated when administered concurrently with cobicistat. Clinical monitoring for adverse effects, such as drowsiness, is recommended during coadministration. Cobicistat is a P-glycoprotein (P-gp) inhibitor, while fexofenadine is a P-gp substrate.
    Boceprevir: (Moderate) Close clinical monitoring is advised when administering fexofenadine with boceprevir due to an increased potential for fexofenadine-related adverse events. If fexofenadine dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of fexofenadine. Fexofenadine is a substrate of the drug efflux transporter P-glycoprotein (P-gp); boceprevir is an inhibitor of this efflux protein. Coadministration may result in elevated fexofenadine plasma concentrations.
    Cabozantinib: (Minor) Monitor for an increase in fexofenadine-related adverse reactions if coadministration with cabozantinib is necessary. Fexofenadine is a P-glycoprotein (P-gp) substrate. Cabozantinib is a P-gp inhibitor and has the potential to increase plasma concentrations of P-gp substrates; however, the clinical relevance of this finding is unknown.
    Calcium Carbonate: (Major) Co-administration with antacids within 15 minutes decreases the AUC and Cmax of fexofenadine. Separate administration is recommended.
    Calcium Carbonate; Magnesium Hydroxide: (Major) Co-administration with antacids within 15 minutes decreases the AUC and Cmax of fexofenadine. Separate administration is recommended. (Major) Coadministration with antacids (containing aluminum or magnesium) within 15 minutes decreases the AUC and Cmax of fexofenadine by 41% and 43%, respectively. Separate administration is recommended.
    Calcium Carbonate; Risedronate: (Major) Co-administration with antacids within 15 minutes decreases the AUC and Cmax of fexofenadine. Separate administration is recommended.
    Calcium Carbonate; Simethicone: (Major) Co-administration with antacids within 15 minutes decreases the AUC and Cmax of fexofenadine. Separate administration is recommended.
    Carvedilol: (Minor) Increased concentrations of fexofenadine may occur if it is coadministered with carvedilol; exercise caution. Carvedilol is a P-glycoprotein (P-gp) inhibitor and fexofenadine is a P-gp substrate.
    Cobicistat: (Minor) Plasma concentrations of fexofenadine may be elevated when administered concurrently with cobicistat. Clinical monitoring for adverse effects, such as drowsiness, is recommended during coadministration. Cobicistat is a P-glycoprotein (P-gp) inhibitor, while fexofenadine is a P-gp substrate.
    Conivaptan: (Minor) Use caution when administering conivaptan and fexofenadine concurrently. Conivaptan is an inhibitor of P-glycoprotein (P-gp). Co-administration of conivaptan with P-gp substrates, such as fexofenadine, can increase fexofenadine exposure leading to increased or prolonged therapeutic effects and adverse events.
    Daclatasvir: (Minor) Systemic exposure of fexofenadine, a P-glycoprotein (P-gp) substrate, may be increased when administered concurrently with daclatasvir, a P-gp inhibitor. Taking these drugs together could increase or prolong the therapeutic effects of fexofenadine; monitor patients for potential adverse effects.
    Darunavir; Cobicistat: (Minor) Plasma concentrations of fexofenadine may be elevated when administered concurrently with cobicistat. Clinical monitoring for adverse effects, such as drowsiness, is recommended during coadministration. Cobicistat is a P-glycoprotein (P-gp) inhibitor, while fexofenadine is a P-gp substrate.
    Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Minor) Plasma concentrations of fexofenadine may be elevated when administered concurrently with cobicistat. Clinical monitoring for adverse effects, such as drowsiness, is recommended during coadministration. Cobicistat is a P-glycoprotein (P-gp) inhibitor, while fexofenadine is a P-gp substrate.
    Dasabuvir; Ombitasvir; Paritaprevir; Ritonavir: (Minor) The plasma concentrations of fexofenadine may be elevated when administered concurrently with dasabuvir; ombitasvir; paritaprevir; ritonavir. Clinical monitoring for adverse effects, such as drowsiness, is recommended during coadministration. Ritonavir and paritaprevir are P-glycoprotein (P-gp) inhibitors, while fexofenadine is a P-gp substrate. (Minor) The plasma concentrations of fexofenadine may be elevated when administered concurrently with ritonavir. Clinical monitoring for adverse effects, such as drowsiness, is recommended during coadministration. Ritonavir is a P-glycoprotein (P-gp) inhibitor, while fexofenadine is a P-gp substrate.
    Desloratadine: (Minor) Although desloratadine is considered a 'non-sedating' antihistamine, dose-related sedation has been noted. For this reason, it would be prudent to monitor for drowsiness during concurrent use of desloratadine with CNS depressants such as other H1-blockers.
    Desloratadine; Pseudoephedrine: (Minor) Although desloratadine is considered a 'non-sedating' antihistamine, dose-related sedation has been noted. For this reason, it would be prudent to monitor for drowsiness during concurrent use of desloratadine with CNS depressants such as other H1-blockers.
    Elexacaftor; tezacaftor; ivacaftor: (Moderate) Monitor for fexofenadine-related adverse reactions during coadministration of elexacaftor; tezacaftor; ivacaftor as concurrent use may increase exposure of fexofenadine. Fexofenadine is a substrate for the transporters OATP1B1 and OATP1B3; elexacaftor; tezacaftor; ivacaftor may inhibit uptake of OATP1B1 and OATP1B3.
    Eltrombopag: (Moderate) Monitor patients for fexofenadine adverse reactions if coadministered with eltrombopag. Eltrombopag is an inhibitor of the transporter OATP1B1. Drugs that are substrates for this transporter, such as fexofenadine, may exhibit an increase in systemic exposure if coadministered with eltrombopag.
    Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Minor) Plasma concentrations of fexofenadine may be elevated when administered concurrently with cobicistat. Clinical monitoring for adverse effects, such as drowsiness, is recommended during coadministration. Cobicistat is a P-glycoprotein (P-gp) inhibitor, while fexofenadine is a P-gp substrate.
    Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Minor) Plasma concentrations of fexofenadine may be elevated when administered concurrently with cobicistat. Clinical monitoring for adverse effects, such as drowsiness, is recommended during coadministration. Cobicistat is a P-glycoprotein (P-gp) inhibitor, while fexofenadine is a P-gp substrate.
    Etravirine: (Moderate) Etravirine is an inhibitor of the efflux transporter P-glycoprotein (PGP). Fexofenadine is a P-glycoprotein substrate. Increased concentrations of fexofenadine may occur if it is coadministered with etravirine; exercise caution.
    Fosamprenavir: (Moderate) Caution is advised when administering fexofenadine with fosamprenavir, as concurrent use may result in reduced fexofenadine plasma concentrations. Fexofenadine is a substrate for the drug transporter P-glycoprotein (P-gp). Amprenavir, the active metabolite of fosamprenavir, is a P-gp inducer.
    Fostamatinib: (Moderate) Monitor for fexofenadine toxicities that may require fexofenadine dose reduction if given concurrently with fostamatinib. Concomitant use of fostamatinib with a P-gp substrate may increase the concentration of the P-gp substrate. Fostamatinib is a P-gp inhibitor; fexofenadine is a substrate for P-gp. Coadministration of fostamatinib with another P-gp substrate increased the substrate AUC by 37% and Cmax by 70%.
    Glecaprevir; Pibrentasvir: (Moderate) Caution is advised with the coadministration of glecaprevir and fexofenadine as coadministration may increase serum concentrations of fexofenadine and increase the risk of adverse effects. Fexofenadine is a substrate of P-glycoprotein (P-gp); glecaprevir is a P-gp inhibitor. (Moderate) Caution is advised with the coadministration of pibrentasvir and fexofenadine as coadministration may increase serum concentrations of fexofenadine and increase the risk of adverse effects. Fexofenadine is a substrate of P-glycoprotein (P-gp); pibrentasvir is an inhibitor of P-gp.
    Glimepiride; Pioglitazone: (Minor) Concentrations of fexofenadine may be increased with concomitant use of pioglitazone. The effect of pioglitazone capistration on the systemic exposure of fexofenadine was determined in a drug-drug interaction study. Coadministration of pioglitazone 45 mg once daily with fexofenadine 60 mg twice daily for 7 days resulted in a 30% and 37% increase in fexofenadine AUC and Cmax, respectively. Patients should be monitored for increased side effects from fexofenadine.
    Grapefruit juice: (Major) Fruit juices such as grapefruit juice, orange juice, and apple juice may reduce the bioavailability, systemic exposure, and clinical efficacy of fexofenadine. Patients should avoid drinking fruit juice within 4 hours before and 1 to 2 hours after taking fexofenadine; tablets and capsules should be consumed with water, not juice. Many fruit juices are organic anion transporting peptide (OATP) 1A2 and/or OATP2B1 inhibitors. OATP-mediated transport facilitates the intestinal absorption of fexofenadine. It is estimated that the bioavailability of fexofenadine is decreased by 36% when coadministered with grapefruit or orange juice. Apple juice, orange juice, and grapefruit juice have been reported to decrease the AUC and Cmax of fexofenadine by up to 70%.
    Heparin: (Minor) Antihistamines may partially counteract the anticoagulant actions of heparin, according to the product labels. However, this interaction is not likely of clinical significance since heparin therapy is adjusted to the partial thromboplastin time (aPTT) and other clinical parameters of the patient.
    Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Minor) Rifampin may decrease plasma concentrations of fexofenadine and potentially reduce its antihistaminic effects. Although the therapeutic range of fexofenadine is broad, monitor for potential decreased therapeutic effects of fexofenadine if rifampin is initiated.
    Isoniazid, INH; Rifampin: (Minor) Rifampin may decrease plasma concentrations of fexofenadine and potentially reduce its antihistaminic effects. Although the therapeutic range of fexofenadine is broad, monitor for potential decreased therapeutic effects of fexofenadine if rifampin is initiated.
    Ixabepilone: (Minor) Ixabepilone is a weak inhibitor of P-glycoprotein (Pgp). Fexofenadine is a Pgp substrate, and concomitant use of ixabepilone with a Pgp substrate may cause an increase in fexofenadine concentrations. Use caution if ixabepilone is coadministered with a Pgp substrate.
    Ketoconazole: (Minor) Ketoconazole may inhibit the metabolism of fexofenadine via its effects on the CYP3A4 isozyme of the cytochrome P-450 microsomal enzyme system.
    Ledipasvir; Sofosbuvir: (Minor) Caution and close monitoring of fexofenadine-associated adverse reactions is advised with concomitant administration of ledipasvir. Fexofenadine is a substrate of the drug transporter P-glycoprotein (P-gp); ledipasvir is a P-gp inhibitor. Taking these drugs together may increase fexofenadine plasma concentrations.
    Lomitapide: (Moderate) Concomitant use of lomitapide and fexofenadine may result in increased serum concentrations of fexofenadine. According to the manufacturer of lomitapide, dose reduction of fexofenadine should be considered during concurrent use. Lomitapide is an inhibitor of P-glycoprotein (P-gp) and fexofenadine is a P-gp substrate.
    Lopinavir; Ritonavir: (Minor) The plasma concentrations of fexofenadine may be elevated when administered concurrently with ritonavir. Clinical monitoring for adverse effects, such as drowsiness, is recommended during coadministration. Ritonavir is a P-glycoprotein (P-gp) inhibitor, while fexofenadine is a P-gp substrate.
    Loratadine: (Minor) Although loratadine is considered a 'non-sedating' antihistamine, dose-related sedation has been noted. For this reason, it would be prudent to monitor for drowsiness during concurrent use of loratadine with CNS depressants such as other H1-blockers.
    Loratadine; Pseudoephedrine: (Minor) Although loratadine is considered a 'non-sedating' antihistamine, dose-related sedation has been noted. For this reason, it would be prudent to monitor for drowsiness during concurrent use of loratadine with CNS depressants such as other H1-blockers.
    Lumacaftor; Ivacaftor: (Minor) Although the clinical significance of this interaction is unknown, concurrent use of fexofenadine and lumacaftor; ivacaftor may alter fexofenadine exposure. Fexofenadine is a substrate of the drug transporter P-glycoprotein (P-gp). In vitro data suggest that lumacaftor; ivacaftor has the potential to both induce and inhibit P-gp. The net effect of lumacaftor; ivacaftor on P-gp transport is not clear, but substrate exposure may be affected leading to decreased efficacy or increased or prolonged therapeutic effects and adverse events.
    Magnesium Hydroxide: (Major) Coadministration with antacids (containing aluminum or magnesium) within 15 minutes decreases the AUC and Cmax of fexofenadine by 41% and 43%, respectively. Separate administration is recommended.
    Metformin; Pioglitazone: (Minor) Concentrations of fexofenadine may be increased with concomitant use of pioglitazone. The effect of pioglitazone capistration on the systemic exposure of fexofenadine was determined in a drug-drug interaction study. Coadministration of pioglitazone 45 mg once daily with fexofenadine 60 mg twice daily for 7 days resulted in a 30% and 37% increase in fexofenadine AUC and Cmax, respectively. Patients should be monitored for increased side effects from fexofenadine.
    Neratinib: (Moderate) Monitor for an increase in fexofenadine-related adverse reactions if coadministration with neratinib is necessary. Fexofenadine is a P-glycoprotein (P-gp) substrate. Neratinib may inhibit the transport of P-gp substrates.
    Ombitasvir; Paritaprevir; Ritonavir: (Minor) The plasma concentrations of fexofenadine may be elevated when administered concurrently with dasabuvir; ombitasvir; paritaprevir; ritonavir. Clinical monitoring for adverse effects, such as drowsiness, is recommended during coadministration. Ritonavir and paritaprevir are P-glycoprotein (P-gp) inhibitors, while fexofenadine is a P-gp substrate. (Minor) The plasma concentrations of fexofenadine may be elevated when administered concurrently with ritonavir. Clinical monitoring for adverse effects, such as drowsiness, is recommended during coadministration. Ritonavir is a P-glycoprotein (P-gp) inhibitor, while fexofenadine is a P-gp substrate.
    Omeprazole; Sodium Bicarbonate: (Major) Co-administration with antacids within 15 minutes decreases the AUC and Cmax of fexofenadine. Separate administration is recommended.
    Pioglitazone: (Minor) Concentrations of fexofenadine may be increased with concomitant use of pioglitazone. The effect of pioglitazone capistration on the systemic exposure of fexofenadine was determined in a drug-drug interaction study. Coadministration of pioglitazone 45 mg once daily with fexofenadine 60 mg twice daily for 7 days resulted in a 30% and 37% increase in fexofenadine AUC and Cmax, respectively. Patients should be monitored for increased side effects from fexofenadine.
    Ponatinib: (Moderate) Concomitant use of ponatinib, a P-glycoprotein (P-gp) inhibitor, and fexofenadine, a P-gp substrate, may increase the exposure of fexofenadine.
    Posaconazole: (Moderate) Posaconazole and fexofenadine should be coadministered with caution due to a potential for altered plasma concentrations of both drugs. Both fexofenadine and posaconazole are substrates of the drug efflux protein, P-glycoprotein, which when administered together may increase the absorption or decrease the clearance of the other drug. This interaction may cause alterations in the plasma concentrations of both posaconazole and fexofenadine, ultimately resulting in an increased risk of adverse events.
    Rifampin: (Minor) Rifampin may decrease plasma concentrations of fexofenadine and potentially reduce its antihistaminic effects. Although the therapeutic range of fexofenadine is broad, monitor for potential decreased therapeutic effects of fexofenadine if rifampin is initiated.
    Ritonavir: (Minor) The plasma concentrations of fexofenadine may be elevated when administered concurrently with ritonavir. Clinical monitoring for adverse effects, such as drowsiness, is recommended during coadministration. Ritonavir is a P-glycoprotein (P-gp) inhibitor, while fexofenadine is a P-gp substrate.
    Sapropterin: (Minor) Caution is advised with the concomitant use of sapropterin and fexofenadine as coadministration may result in increased systemic exposure of fexofenadine. Fexofenadine is a substrate for the drug transporter P-glycoprotein (P-gp); in vitro data show that sapropterin may inhibit P-gp. If these drugs are used together, closely monitor for increased side effects of fexofenadine.
    Sincalide: (Moderate) Sincalide-induced gallbladder ejection fraction may be affected by concurrent medications, including H1-blockers. False study results are possible; thorough patient history is important in the interpretation of procedure results.
    Sodium Bicarbonate: (Major) Co-administration with antacids within 15 minutes decreases the AUC and Cmax of fexofenadine. Separate administration is recommended.
    Sofosbuvir; Velpatasvir; Voxilaprevir: (Moderate) Plasma concentrations of fexofenadine, a P-glycoprotein (P-gp) substrate, may be increased when administered concurrently with voxilaprevir, a P-gp inhibitor. Monitor patients for increased side effects if these drugs are administered concurrently.
    St. John's Wort, Hypericum perforatum: (Minor) St. John's Wort may increase, decrease, or not change the plasma concentrations and AUC of fexofenadine. The mechanisms proposed have included CYP3A4 induction and/or altered P-glycoprotein efflux transport of fexofenadine. The clinical importance of this theoretical interaction has not been established; further study is needed.
    Telaprevir: (Moderate) Close clinical monitoring is advised when administering fexofenadine with telaprevir due to an increased potential for fexofenadine-related adverse events. If fexofenadine dose adjustments are made, re-adjust the dose upon completion of telaprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of fexofenadine. Fexofenadine is a substrate of the drug efflux transporter P-glycoprotein (P-gp); telaprevir is an inhibitor of this efflux protein. Coadministration may result in elevated fexofenadine plasma concentrations.
    Telithromycin: (Minor) Concentrations of fexofenadine may be increased with concomitant use of telithromycin. Fexofenadine is a P-glycoprotein (P-gp) substrate and telithromycin is a potential P-gp inhibitor. Patients should be monitored for increased side effects.
    Ulipristal: (Moderate) It is recommended that administration of ulipristal acetate and fexofenadine should be separated in time by at least 1.5 hours. Fexofenadine is a substrate of P-glycoprotein (P-gp), and ulipristal is an inhibitor of P-gp in the gastrointestinal (GI) wall at the time of its absorption. In studies, administration at the same time increased the exposure (AUC) of fexofenadine. Administration of ulipristal with fexofenadine in vivo showed that an interaction did not occur if administration of ulipristal was separated from fexofenadine administration by at least 1.5 hours.
    Vemurafenib: (Minor) Concomitant use of vemurafenib and fexofenadine may result in increased fexofenadine concentrations. Vemurafenib is a P-glycoprotein (P-gp) inhibitor and fexofenadine is a P-gp substrate. Monitor patients for increased side effects.

    PREGNANCY AND LACTATION

    Pregnancy

    There have been no adequate and well-controlled studies regarding the use of fexofenadine in human pregnancy. Results of animal studies have revealed an absence of mutagenicity or infertility. Teratogenicity was not observed in rats given approximately 15 times the maximum daily oral dose in humans based on an AUC comparison. Decreased pup weight gain and survival occurred in rats given 3 times the maximum daily oral dose in humans. Fexofenadine should be used during pregnancy only when the benefits of therapy outweigh the risks. Self-medication with non-prescription products is not recommended; pregnant patients should see their health care professional for a proper diagnosis and for treatment recommendations. The American College of Obstetricians and Gynecologists (ACOG) and the American College of Allergy, Asthma, and Immunology consider loratadine an acceptable alternative in pregnancy, preferably after the first trimester, when first generation antihistamines are not tolerated.

    According to the manufacturer, caution should be exercised when fexofenadine is administered to a breast-feeding woman. It is unknown whether fexofenadine is excreted into human breast milk. Fexofenadine has generally been considered to be compatible with breast-feeding due to its low sedative activity; monitor the infant for irritability or for any effects of this antihistamine on lactation. Loratadine may be considered as an alternative for the treatment of allergy symptoms. Because of its lack of sedation and low milk concentrations, maternal use would not be expected to cause adverse effects in breast-fed babies and loratadine is considered usually compatible with breast-feeding. The British Society for Allergy and Clinical Immunology also recommends loratadine at the lowest dose as a preferred antihistamine in breast-feeding women. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally ingested drug, healthcare providers are encouraged to report the adverse effect to the FDA.

    MECHANISM OF ACTION

    Fexofenadine is an antihistamine with selective H1-receptor antagonist activity. Similar to other H1-blockers, fexofenadine does not prevent the release of histamine as do cromolyn and nedocromil, but competes with free histamine for binding at the H1-receptor. This competitive antagonism blocks the effects of histamine on H1-receptors in the GI tract, uterus, large blood vessels, and bronchial smooth muscle. Blockade of H1-receptors also suppresses the formation of edema, flare, and pruritus that result from histaminic activity. At higher concentrations, H1-receptor antagonism becomes relatively irreversible. Fexofenadine does not cross the blood-brain barrier and does not exert anticholinergic or alpha-1-antagonist effects in animal studies. In humans, CNS depression is minimal compared with first-generation H1-antagonists. Although fexofenadine is a metabolite of terfenadine which has been associated with QT prolongation and ventricular tachycardias (torsades de pointes), pre-marketing trials with fexofenadine demonstrated no significant prolongation of the QT interval; doses up to 800 mg/day have been studied.

    PHARMACOKINETICS

    Fexofenadine is administered orally. The onset of antihistamine effectiveness (evaluated by wheal and flare studies) is about 1 hour and persists for up to 12 hours. Protein binding ranges from 60% to 70%; fexofenadine is primarily bound to albumin and alpha-1-acid glycoprotein. Based on radiolabeled studies, approximately 80% and 11% of a dose was recovered in the feces and urine, respectively. Approximately 5% of the total administered dose is metabolized. Because the absolute bioavailability has not been determined, it is unknown if the fecal component represents unabsorbed drug or biliary excretion of the drug. Therefore, it is unknown if either renal excretion and/or metabolism plays a significant role in systemic drug elimination. The mean elimination half-life is approximately 14.4 hours in normal volunteers receiving 60 mg twice daily.
     
    Affected Cytochrome P450 (CYP450) enzymes and drug transporters: P-glycoprotein (P-gp) and OATP
    Fexofenadine is a substrate for P-glycoprotein (P-gp) and organic anion transporting peptide (OATP) transport.

    Oral Route

    Fexofenadine is rapidly absorbed. The absolute bioavailability of fexofenadine is unknown. The mean time to maximum plasma concentrations (Tmax) following oral administration with conventional tablets, capsule or oral solution is 2 to 3 hours and 1 hour, respectively. The Tmax of the orally disintegrating tablet (ODT) formulation is 2 hours post-dose. Administration of the ODT formulation with a high fat-meal decreases the AUC and maximum concentration (Cmax) by about 40% and 60%, respectively, and Tmax is delayed by 2 hours. When the conventional tablet or capsule is given with a high fat meal, the AUC and Cmax are decreased by approximately 20%. Mixing capsule contents with applesauce has no significant effect on the pharmacokinetic parameters. Administration of the oral suspension and a high fat meal decreases the exposure (AUC) and Cmax by approximately 30% and 47% respectively. The tablets, capsule, and oral suspension may be given with food. The fexofenadine ODT should be taken on an empty stomach, but it may be taken with water. Fexofenadine oral suspension is bioequivalent to fexofenadine tablets on a mg per mg basis.