Fexofenadine

Fexofenadine Orally Disintegrating Tablet (ODT) contains phenylalanine. Patients with phenylketonuria, a rare genetic condition in which the body is unable to process phenylalanine, should talk to their doctor before using fexofenadine. Fexofenadine products other than ODT formulations do not contain phenylalanine.

Fexofenadine can cause dizziness. Do not drive or operate heavy machinery until you know how fexofenadine affects you.

Do not take fexofenadine if you are allergic to fexofenadine or to any of its ingredients.

Fruit juices such as grapefruit, orange, and apple juice may interact with fexofenadine. Discuss the use of fruit juices with your doctor. Fexofenadine should be taken with water instead.

Tell your doctor if you are pregnant or plan to become pregnant.

The FDA categorizes medications based on safety for use during pregnancy. Five categories - A, B, C, D, and X, are used to classify the possible risks to an unborn baby when a medication is taken during pregnancy.

Fexofenadine falls into category C. There are no well-controlled studies that have been done in pregnant women. Fexofenadine should be used during pregnancy only if the possible benefit outweighs the possible risk to the unborn baby.

Tell your doctor if you are breastfeeding or plan to breastfeed.

It is not known if fexofenadine crosses into human milk. Because many medications can cross into human milk and because of the possibility for serious adverse reactions in nursing infants with use of this medication, a choice should be made whether to stop nursing or stop the use of this medication. Your doctor and you will decide if the benefits outweigh the risk of using fexofenadine.

Ask a doctor or pharmacist if it is safe for you to take this medicine if you are allergic to any drugs, or if you have kidney disease.

FDA pregnancy category C. It is not known whether fexofenadine will harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant while using this medication.

It is not known whether fexofenadine passes into breast milk or if it could harm a nursing baby. Do not use this medication without telling your doctor if you are breast-feeding a baby.

Fexofenadine tablets and capsules may be used to treat seasonal allergy symptoms in children who are at least 6 years old. Fexofenadine oral suspension (liquid) may be used in children ages 2 through 11. When treating chronic idiopathic urticaria, the liquid may be used in children as young as 2 months old.

Do not give this medicine to a child without medical advice.

In the U.S.

• Allegra
• Allegra ODT

Available Dosage Forms:

• Tablet
• Tablet, Disintegrating
• Capsule
• Suspension

Therapeutic Class: Respiratory Agent

Pharmacologic Class: Antihistamine, Less-Sedating

Chemical Class: Butyrophenone

Antacids

Fexofenadine hydrochloride should not be taken closely in time with aluminum and magnesium containing antacids. In healthy adult subjects, administration of 120 mg of Fexofenadine hydrochloride (2 x 60 mg capsule) within 15 minutes of an aluminum and magnesium containing antacid (Maalox®) decreased Fexofenadine AUC by 41% and Cmax by 43%.

Erythromycin and Ketoconazole

Fexofenadine has been shown to exhibit minimal (ca. 5%) metabolism. However, coadministration of Fexofenadine hydrochloride with either ketoconazole or erythromycin led to increased plasma concentrations of Fexofenadine in healthy adult subjects. Fexofenadine had no effect on the pharmacokinetics of either erythromycin or ketoconazole. In 2 separate studies in healthy adult subjects, Fexofenadine hydrochloride 120 mg twice daily (240 mg total daily dose) was coadministered with either erythromycin 500 mg every 8 hours or ketoconazole 400 mg once daily under steady-state conditions to healthy adult subjects (n = 24, each study). No differences in adverse events or QTc interval were observed when subjects were administered Fexofenadine hydrochloride alone or in combination with either erythromycin or ketoconazole. The findings of these studies are summarized in the following table:

The changes in plasma levels were within the range of plasma levels achieved in adequate and well-controlled clinical trials.

The mechanism of these interactions has been evaluated in in vitro, in situ, and in vivo animal models. These studies indicate that ketoconazole or erythromycin coadministration enhances Fexofenadine gastrointestinal absorption. This observed increase in the bioavailability of Fexofenadine may be due to transport-related effects, such as p-glycoprotein. In vivo animal studies also suggest that in addition to enhancing absorption, ketoconazole decreases Fexofenadine gastrointestinal secretion, while erythromycin may also decrease biliary excretion.

Fruit Juices

Fruit juices such as grapefruit, orange and apple may reduce the bioavailability and exposure of Fexofenadine. This is based on the results from 3 clinical studies using histamine induced skin wheals and flares coupled with population pharmacokinetic analysis. The size of wheal and flare were significantly larger when Fexofenadine hydrochloride was administered with either grapefruit or orange juices compared to water. Based on the literature reports, the same effects may be extrapolated to other fruit juices such as apple juice. The clinical significance of these observations is unknown. In addition, based on the population pharmacokinetics analysis of the combined data from grapefruit and orange juices studies with the data from a bioequivalence study, the bioavailability of Fexofenadine was reduced by 36%. Therefore, to maximize the effects of Fexofenadine, it is recommended that Fexofenadine hydrochloride tablets should be taken with water [see Clinical Pharmacology (12.3) and Dosage and Administration (2.1)].

Pregnancy

Pregnancy Category C. There was no evidence of teratogenicity in rats or rabbits at oral doses of terfenadine up to 300 mg/kg (which led to Fexofenadine exposures that were approximately 4 and 30 times, respectively, the exposure at the maximum recommended human daily oral dose of 180 mg of Fexofenadine hydrochloride based on comparison of AUCs).

In mice, no adverse effects and no teratogenic effects during gestation were observed with Fexofenadine hydrochloride at oral doses up to 3730 mg/kg (which led to Fexofenadine exposures that were approximately 15 times the exposure at the maximum recommended human daily oral dose of 180 mg of Fexofenadine hydrochloride based on comparison of AUCs).

There are no adequate and well controlled studies in pregnant women. Fexofenadine hydrochloride should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Dose-related decreases in pup weight gain and survival were observed in rats exposed to an oral dose of 150 mg/kg of terfenadine (which led to Fexofenadine exposures that were approximately 3 times the exposure at the maximum recommended human daily oral dose of 180 mg of Fexofenadine hydrochloride based on comparison of AUCs).

Nursing Mothers

It is not known if Fexofenadine is excreted in human milk. There are no adequate and well-controlled studies in women during lactation. Because many drugs are excreted in human milk, caution should be exercised when Fexofenadine hydrochloride is administered to a nursing woman.

Pediatric Use

The recommended doses of Fexofenadine hydrochloride in pediatric patients 6 months to 11 years of age are based on cross-study comparison of the pharmacokinetics of Fexofenadine in adults and pediatric subjects and on the safety profile of Fexofenadine hydrochloride in both adult and pediatric subjects at doses equal to or higher than the recommended doses. The safety and effectiveness of Fexofenadine hydrochloride in pediatric patients under 6 months of age have not been established.

The safety of Fexofenadine hydrochloride is based on the administration of Fexofenadine hydrochloride tablets at a dose of 30 mg twice daily demonstrated in 438 pediatric subjects 6 years to 11 years of age in 2 placebo-controlled 2 week seasonal allergic rhinitis trials. The safety of Fexofenadine hydrochloride at doses of 15 mg and 30 mg given once and twice a day has been demonstrated in 969 pediatric subjects (6 months to 5 years of age) with allergic rhinitis in 3 pharmacokinetic studies and 3 safety studies. The safety of Fexofenadine hydrochloride for the treatment of chronic idiopathic urticaria in subjects 6 months to 11 years of age is based on cross-study comparison of the pharmacokinetics of Fexofenadine hydrochloride in adult and pediatric subjects and on the safety profile of Fexofenadine in both adult and pediatric subjects at doses equal to or higher than the recommended dose.

The effectiveness of Fexofenadine hydrochloride for the treatment of seasonal allergic rhinitis in subjects 6 to 11 years of age was demonstrated in 1 trial (n = 411) in which Fexofenadine hydrochloride tablets 30 mg twice daily significantly reduced total symptom scores compared to placebo, along with extrapolation of demonstrated efficacy in subjects aged 12 years and above, and the pharmacokinetic comparisons in adults and children. The effectiveness of Fexofenadine hydrochloride 30 mg twice daily for the treatment of seasonal allergic rhinitis in patients 2 to 5 years of age is based on the pharmacokinetic comparisons in adult and pediatric subjects and an extrapolation of the demonstrated efficacy of Fexofenadine hydrochloride in adult subjects with this condition and the likelihood that the disease course, pathophysiology, and the drug’s effect are substantially similar in pediatric patients to those in adult patients. The effectiveness of Fexofenadine hydrochloride for the treatment of chronic idiopathic urticaria in patients 6 months to 11 years of age is based on the pharmacokinetic comparisons in adults and children and an extrapolation of the demonstrated efficacy of Fexofenadine hydrochloride in adults with this condition and the likelihood that the disease course, pathophysiology and the drug’s effect are substantially similar in children to that of adult patients. Administration of a 15 mg dose of Fexofenadine hydrochloride to pediatric subjects 6 months to less than 2 years of age and a 30 mg dose to pediatric subjects 2 to 11 years of age produced exposures comparable to those seen with a dose of 60 mg administered to adults.

Geriatric Use

Clinical studies of Fexofenadine hydrochloride tablets and capsules did not include sufficient numbers of subjects aged 65 years and over to determine whether this population responds differently from younger subjects. Other reported clinical experience has not identified differences in responses between the geriatric and younger subjects. This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function [see Clinical Pharmacology (12.3)].

Renal Impairment

Based on increases in bioavailability and half-life, a dose of 60 mg once daily is recommended as the starting dose in adult patients with decreased renal function (mild, moderate or severe renal impairment). For pediatric patients with decreased renal function (mild, moderate or severe renal impairment), the recommended starting dose of Fexofenadine is 30 mg once daily for patients 2 to 11 years of age and 15 mg once daily for patients 6 months to less than 2 years of age [see Clinical Pharmacology (12.3)].

Hepatic Impairment

The pharmacokinetics of Fexofenadine hydrochloride in subjects with hepatic impairment did not differ substantially from that observed in healthy subjects.

Dizziness, drowsiness, and dry mouth have been reported with Fexofenadine hydrochloride overdose. Single doses of Fexofenadine hydrochloride up to 800 mg (6 healthy subjects at this dose level), and doses up to 690 mg twice daily for 1 month (3 healthy subjects at this dose level) or 240 mg once daily for 1 year (234 healthy subjects at this dose level) were administered without the development of clinically significant adverse events as compared to placebo.

In the event of overdose, consider standard measures to remove any unabsorbed drug. Symptomatic and supportive treatment is recommended. Following administration of terfenadine, hemodialysis did not effectively remove Fexofenadine, the major active metabolite of terfenadine, from blood (up to 1.7% removed).

No deaths occurred at oral doses of Fexofenadine hydrochloride up to 5000 mg/kg in mice (110 times the maximum recommended daily oral dose in adults and children based on mg/m2) and up to 5000 mg/kg in rats (230 times the maximum recommended daily oral dose in adults and 210 times the maximum recommended daily oral dose in children based on mg/m2). Additionally, no clinical signs of toxicity or gross pathological findings were observed. In dogs, no evidence of toxicity was observed at oral doses up to 2000 mg/kg (300 times the maximum recommended daily oral dose in adults and 280 times the maximum recommended daily oral dose in children based on mg/m2).

• Fexofenadine Hydrochloride

• Allegra Allergy Childrens [OTC]
• Allegra Allergy [OTC]
• Allergy 24-HR [OTC]
• Fexofenadine HCl Childrens [OTC]
• Mucinex Allergy [OTC]

Refer to adult dosing.

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

Applies to fexofenadine: oral capsule, oral suspension, oral tablet, oral tablet disintegrating

Along with its needed effects, fexofenadine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur while taking fexofenadine:

• Chest tightness
• feeling of warmth, redness of the face, neck, arms and occasionally, upper chest
• large, hive-like swelling on face, eyelids, lips, tongue, throat, hands, legs, feet, or sex organs
• shortness of breath, difficult or labored breathing

Some side effects of fexofenadine may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Vomiting

• Back pain
• body aches or pain
• chills
• coughing
• diarrhea
• difficulty with moving
• dizziness
• ear congestion
• earache
• fever
• headache
• joint pain
• loss of voice
• muscle aching or cramping
• muscle pains or stiffness
• nasal congestion
• nausea
• pain in arms or legs
• pain or tenderness around eyes or cheekbones
• painful menstrual bleeding
• redness or swelling in ear
• ringing or buzzing in ears
• runny or stuffy nose
• sleepiness or unusual drowsiness
• sneezing
• sore throat
• stomach upset
• swollen joints
• unusual feeling of tiredness or weakness
• viral infection (such as cold and flu)

• Nervousness
• rash
• sleeplessness
• terrifying dreams
• trouble sleeping