Fexofenadine is a non-sedating antihistamine (H1-receptor antagonist). It is the active metabolite of another H1-antagonist, terfenadine. Unlike terfenadine, fexofenadine does not generally cause QT prolongation when given in doses up to 800 mg/day or when administered concomitantly with ketoconazole or erythromycin. However, one case report documented ventricular tachycardia associated with QT prolongation during fexofenadine therapy in a patient with a history of prolonged QT interval. Fexofenadine was first FDA approved in July 1996 for the treatment of seasonal allergic rhinitis; subsequent approval was granted in February 2000 for a once-daily product and for the treatment of chronic spontaneous urticaria. Other formulations were similarly approved including an oral liquid in October 2006 and an orally disintegrating tablet in July 2007. In January 2011, the FDA approved the over-the-counter sale of fexofenadine in the same formulations, strengths, and indications as available by prescription, with the exception that treatment of urticaria in certain pediatric patients.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Route-Specific 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.
Fexofenadine is a metabolite of terfenadine. Terfenadine has been associated with QT prolongation and ventricular tachycardias (torsade de pointes) and was withdrawn from the U.S. market after ten years of post-marketing experience. Pre-marketing trials with fexofenadine in greater than 900 patients demonstrated no significant prolongation of the QT interval at doses of 60-240 mg PO twice daily. One case report documented ventricular tachycardia associated with QT prolongation during therapy with fexofenadine in a patient with a history of prolonged QT interval. No cases of cardiac arrhythmias are reported in the fexofenadine or Allegra-D product information. No QT prolongation was evident with the maximum fexofenadine dosage studied (400 mg PO twice daily for seven days in healthy subjects).
The most common adverse reactions associated with fexofenadine therapy include headache (4.8-10.3%) and vomiting (4.2-12%). Other adverse reactions included back pain (2.1-2.5%), cough (1.9-4%), diarrhea (2.8-3.7%), dizziness (2.1%), dysmenorrhea (1.5%), dyspepsia (4.7%), somnolence or fatigue (0.7-2.8%), fever or pyrexia (1.9-4.5%), myalgia (2.6%), naso-pharyngitis (2.4%), rhinorrhea (0.9-2.1%), accidental injury (2.9%), unspecified pain (2.4%), and extremity pain (2.1%). Infections were also reported during fexofenadine use, including upper respiratory tract infection (0.9-4.3%) and otitis media (2.4-3.8%). Adverse reactions reported in greater than 2% of patients in a placebo controlled pediatric study (age 6-11 years) included headache (7.2%), accidental injury (2.9%), cough (3.8%), fever (2.4%), otitis media (2.4%), pain (unspecified) (2.4%), and upper respiratory tract infection (4.3%). Other adverse events which have been reported in clinical trials of patients 12 years of age and older include dizziness (2.1%), myalgia (2.6%), pharyngitis (nasal) (2.4%), upper respiratory tract infection (2.4%), dyspepsia (4.7%), headache (4.8%), back pain (2.1%) and unspecified pain in extremity (2.1%). Adverse effects reported with oral suspension or capsule content administration in greater than 2% of patients in placebo-controlled pediatric studies (age 6 months to 5 years) included vomiting (5.8%), pyrexia (fever) (3.9%), cough (3.6%), otitis media (3.6%), diarrhea (3%), rhinorrhea (1.9%), upper respiratory tract infections (1.9%), and somnolence or fatigue (1.1%). Pyrexia (fever) and upper respiratory infection occurred less frequently in the fexofenadine groups than the placebo groups. Vomiting was reported in 12% of subjects receiving fexofenadine 30 mg/day and 4.2% of those receiving 60 mg/day, with an incidence of 8.6% in the placebo group.
Events that have been reported during controlled clinical trials involving seasonal allergic rhinitis and chronic spontaneous urticaria patients with frequencies less than 1%, similar to placebo, and have rarely been reported during post-marketing surveillance of fexofenadine include: insomnia, nervousness (restlessness), and sleep disorders or paranoia. In rare cases, rash (unspecified), urticaria, pruritus and hypersensitivity reactions (anaphylactoid reactions) with manifestations such as angioedema, chest tightness/chest pain (unspecified), dyspnea, flushing and systemic anaphylaxis have been reported.
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.
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.
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.
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. One study examining the risk of adverse fetal outcomes associated with fexofenadine use during pregnancy concluded that it does not appear to be associated with an increased risk of adverse fetal outcomes. However, non-pharmacologic methods (e.g., fluids, rest) are recommended to be tried first during pregnancy and individuals should see their health care professional for a proper diagnosis and for treatment recommendations. Loratadine and oral cetirizine are acceptable antihistamine alternatives based on their excellent safety data and recommendation in multiple guidelines for use to treat allergies and urticaria during pregnancy.
Fexofenadine is considered to be compatible with breast-feeding due to its low sedative activity. While it is unknown whether fexofenadine is excreted into human breast milk, monitoring the infant for irritability or for any effects of this antihistamine on lactation is recommended. 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. For this reason, loratadine is also considered to be compatible with breast-feeding. The British Society for Allergy and Clinical Immunology recommends loratadine or cetirizine 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.
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.
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 spontaneous 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.
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.
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 spontaneous 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.
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 Limits:
-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.
Patients with Hepatic Impairment Dosing
No dosage adjustment is recommended. The pharmacokinetics of fexofenadine are not substantially different in patients with hepatic disease.
Patients with Renal Impairment Dosing
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).
*non-FDA-approved indication
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: (Moderate) 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: (Moderate) 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: (Moderate) 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: (Moderate) 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: (Moderate) 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: (Moderate) 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.
Calcium Carbonate: (Moderate) Co-administration with antacids within 15 minutes decreases the AUC and Cmax of fexofenadine. Separate administration is recommended.
Calcium Carbonate; Famotidine; Magnesium Hydroxide: (Moderate) Co-administration with antacids within 15 minutes decreases the AUC and Cmax of fexofenadine. Separate administration is recommended.
Calcium Carbonate; Magnesium Hydroxide: (Moderate) Co-administration with antacids within 15 minutes decreases the AUC and Cmax of fexofenadine. Separate administration is recommended.
Calcium Carbonate; Magnesium Hydroxide; Simethicone: (Moderate) Co-administration with antacids within 15 minutes decreases the AUC and Cmax of fexofenadine. Separate administration is recommended.
Calcium Carbonate; Simethicone: (Moderate) Co-administration with antacids within 15 minutes decreases the AUC and Cmax of fexofenadine. Separate administration is recommended.
Calcium; Vitamin D: (Moderate) Co-administration with antacids within 15 minutes decreases the AUC and Cmax of fexofenadine. Separate administration is recommended.
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.
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.
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.
Ketoconazole: (Minor) Ketoconazole may inhibit the metabolism of fexofenadine via its effects on the CYP3A4 isozyme of the cytochrome P-450 microsomal enzyme system.
Levoketoconazole: (Minor) Ketoconazole may inhibit the metabolism of fexofenadine via its effects on the CYP3A4 isozyme of the cytochrome P-450 microsomal enzyme system.
Lopinavir; Ritonavir: (Moderate) Monitor for fexofenadine-related adverse reactions during concurrent administration with lopinavir as use of these drugs together may increase exposure of fexofenadine. Fexofenadine is a substrate of the organic anion transporting peptide (OATP1B1); lopinavir inhibits OATP1B1.
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.
Magnesium Hydroxide: (Moderate) 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.
Magnesium Salts: (Moderate) 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.
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.
Pioglitazone; Glimepiride: (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.
Pioglitazone; Metformin: (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.
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.
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.
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.
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.
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.
-Route-Specific Pharmacokinetics
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.
-Special Populations
Hepatic Impairment
The pharmacokinetics of fexofenadine are not altered by hepatic disease. The pharmacokinetics of fexofenadine hydrochloride in adult patients with hepatic disease did not differ substantially from that observed in healthy subjects.
Renal Impairment
The pharmacokinetics of fexofenadine are altered by renal disease. Peak plasma concentrations were 87% and 111% greater in patients with mild (CrCl 41 to 80 mL/minute) to severe (CrCl 11 to 40 mL/minute) 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/minute or less) were 82% greater and half-life was 31% longer than in normal volunteers. The effect of hemodialysis on the removal of fexofenadine is unknown. Hemodialysis did not effectively remove fexofenadine from blood (up to 1.7% removed) following terfenadine oral administration.
Pediatrics
Infants and Children
Fexofenadine, when given in age appropriate doses in infants and children, produces comparable plasma exposure to that seen in adults receiving a 60 mg dose. A population pharmacokinetic analysis was performed using data from 90 treatment exposures in children (6 months to 12 years) and 269 treatment exposures from adults. Estimated oral clearances were on average 36% and 44% lower in children 2 to 5 years and 6 to 12 years, respectively, compared to adults. In a double-blind, two-way crossover study, 14 children (mean age 9.8 +/- 1.8 years) received a single dose of fexofenadine 30 mg and 60 mg 1 week apart. The following mean pharmacokinetic parameters were calculated for the 30 mg dose: Volume of distribution (Vd) = 5.4 +/- 0.7 L/kg, clearance (CL) = 14.4 +/- 2 mL/kg/minute, and terminal elimination half-life (T1/2) = 18.3 +/- 2 hours. The following parameters were calculated for the 60 mg dose: Vd = 5.8 +/- 0.7 L/kg, CL = 18.4 +/- 2.4 mL/kg/minute, and terminal elimination half-life (T1/2) = 17.6 +/- 1 hours.
Geriatric
The pharmacokinetics of fexofenadine is altered by age. In older subjects greater than 65 years old, peak plasma levels of fexofenadine were 99% greater than those observed in younger adult subjects less than 65 years old. Mean elimination half-lives were similar to those observed in younger subjects.
Gender Differences
The pharmacokinetics of fexofenadine is not altered by gender. No clinically significant gender-related differences were observed in the pharmacokinetics of fexofenadine.