Consumer medicine information

FEXOTABS

Fexofenadine hydrochloride

BRAND INFORMATION

Brand name

Fexotabs

Active ingredient

Fexofenadine hydrochloride

Schedule

S2

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using FEXOTABS.

WHAT IS FEXOTABS AND WHAT IS IT USED FOR?

FEXOTABS tablets contain an active ingredient called "fexofenadine". It is one of a group of medicines called antihistamines.

FEXOTABS 60 is used to relieve the symptoms of seasonal and perennial allergic rhinitis (including hayfever). FEXOTABS 120 and 180 are used to relieve the symptoms of hayfever (seasonal allergic rhinitis) such as sneezing, itchy, watery or red eyes, and itchy, blocked or runny nose. FEXOTABS 180 is also used to relieve the symptoms of urticaria otherwise known as hives or itchy rash.

FEXOTABS works by blocking the action of histamine which causes these unwanted effects.

FEXOTABS is a non-sedating antihistamine which means it has been shown not to make you drowsy or slow down your reactions.

IS FEXOTABS SUITABLE FOR ME?

Do not take FEXOTABS, and tell your doctor or pharmacist if:

  • you have had an allergic reaction to fexofenadine, terfenadine (Teldane?) or any of the other ingredients in FEXOTABS. These are listed at the end of this leaflet
  • the expiry date on the pack has passed. It may have no effect or an unexpected effect if it is taken after this date
  • the packaging is torn or shows signs of tampering

Before taking FEXOTABS:

You should inform your pharmacist/doctor if:

  • you are, or might be, pregnant
  • you are breast feeding
  • you have any allergies to any other medicines, foods, preservatives or dyes
  • you are taking other medicines

Your pharmacist/doctor will consider these points when recommending FEXOTABS.

Use in children:

There is currently not enough information available to recommend FEXOTABS for use in children under 12 years of age.

HOW DO I TAKE FEXOTABS?

Take FEXOTABS with a glass of water. FEXOTABS may be taken with or without food.

For the relief of the symptoms of seasonal and perennial allergic rhinitis (including hayfever) the usual dosage for adults and children over 12 years is one FEXOTABS 60mg tablet twice daily, when required.

For the relief of the symptoms of hayfever, the usual dosage for adults and children over 12 years of age is one FEXOTABS 120mg tablet daily when required, or one FEXOTABS 180mg tablet daily when required.

For relief of the symptoms of urticaria, the usual dosage for adults and children over 12 years of age is one FEXOTABS 180mg tablet daily when required.

Do not take more than the recommended dose and remember, this medicine is for you. Do not give it to anyone else, even if their symptoms seem to be the same as yours.

If FEXOTABS does not relieve your symptoms, do not take extra tablets. Tell your doctor or pharmacist.

What do I do in case of Overdose?

If you think that you or someone else may have taken too much FEXOTABS - (even if there are no signs of discomfort or poisoning) - contact your doctor or Poisons Information Centre, or go to the Casualty Department at your nearest hospital.

DOES FEXOTABS CAUSE SIDE EFFECTS?

Tell your doctor or pharmacist as soon as possible if you do not feel well while taking FEXOTABS, even if you do not think the problem is connected with the medicine or is not listed in this leaflet.

All medicines can cause side effects. Although most people will not experience any, some of the side effects that may occur with FEXOTABS are:

  • headache
  • tiredness
  • nausea
  • indigestion
  • dizziness
  • drowsiness

These same effects were seen in patients taking dummy or placebo capsules during the clinical studies.

How do I Store FEXOTABS?

Keep your tablets in a safe place out of the reach of children.

Store the tablets at room temperature below 25°C.

Disposal

Return any unwanted tablets to your pharmacist.

WHAT DOES FEXOTABS LOOK LIKE?

FEXOTABS 60mg tablets are peach coloured oval shaped tablets.

FEXOTABS 120mg and 180mg tablets are peach coloured and have a modified capsule shape.

FEXOTABS 60 is available in blister packs of 20 tablets.

FEXOTABS 120 and 180 are available in blister packs of 10 or 50 tablets.

What are the ingredients in FEXOTABS?

Each FEXOTABS 60 tablet contains 60mg of the active ingredient fexofenadine hydrochloride.

Each FEXOTABS 120 tablet contains 120mg of the active ingredient fexofenadine hydrochloride.

Each FEXOTABS 180 tablet contains 180mg of the active ingredient fexofenadine hydrochloride.

The inactive ingredients in FEXOTABS are: croscarmellose sodium, pregelatinised maize starch, microcrystalline cellulose, magnesium stearate, hypromellose, povidone, titanium dioxide, colloidal anhydrous silica, macrogol 400 and iron oxide.

FEXOTABS does not contain any gluten, lactose or preservatives.

DISTRIBUTOR

Aventis Pharma Pty Limited
27 Sirius Road
LANE COVE NSW 2066

FEXOTABS 60mg tablets AUST R 98161
FEXOTABS 120mg tablets AUST R 98208
FEXOTABS 180mg tablets AUST R 98210

Date of Preparation: December 2003

WHERE TO GO FOR FURTHER INFORMATION

Remember this leaflet provides only a summary of some of the important things you need to know about FEXOTABS. Only your doctor or pharmacist are able to weigh up all the relevant facts and you should consult them about all aspects of this medicine as it relates to you.

Published by MIMS August 2004

BRAND INFORMATION

Brand name

Fexotabs

Active ingredient

Fexofenadine hydrochloride

Schedule

S2

 

Name of the medicine

Fexofenadine (as hydrochloride).

Excipients

Croscarmellose sodium, pregelatinised maize starch, microcrystalline cellulose, magnesium stearate, hypromellose, povidone, titanium dioxide, colloidal anhydrous silica, macrogol 400 and iron oxide.

Description

Chemical name: benzeneacetic acid, 4-[1-hydroxy-4- [4-(hydroxydiphenylmethyl) -1-piperidinyl]butyl] -α,α-dimethyl-, hydrochloride. Molecular formula: C32H39NO4.HCl. MW: 538.13. Fexofenadine is the carboxylic acid metabolite of terfenadine, administered as the hydrochloride salt in Fexotabs. Fexofenadine hydrochloride is an equimolar mixture of two enantiomers.
Fexofenadine occurs as a fine white to off white powder. It is freely soluble in methanol, soluble in ethanol, slightly soluble in water (3.6 mg/mL) and only very slightly soluble in chloroform and hexane.

Actions

Fexofenadine is an orally active nonsedating histamine H1-receptor antagonist.

Pharmacology

The antihistaminic effects of fexofenadine have been demonstrated in animal systems in vitro and in vivo. Oral administration of fexofenadine to guinea pigs indicated that fexofenadine antagonised histamine induced skin weals in a dose dependent manner. Fexofenadine and terfenadine antagonised the contractile effects of histamine in the guinea pig ileum in vitro. In this model fexofenadine was found to be a more selective histamine antagonist than terfenadine.
Fexofenadine inhibited antigen induced bronchospasm in sensitised guinea pigs and, at high doses (> 100-fold higher than those required for antihistaminic activity), inhibited histamine release from peritoneal mast cells of the rat. In laboratory animals, no anticholinergic or α1-adrenergic receptor blocking effects were observed. Radiolabelled tissue distribution studies in the rat indicated that fexofenadine does not cross the blood brain barrier.
Fexofenadine is not associated with significant ECG abnormalities. Studies have shown that fexofenadine does not affect the action potential or ion channel currents (IK, ICa, INa) in either guinea pig or neonatal rat myocytes. Fexofenadine was 583 times less potent than terfenadine in blocking a delayed rectifier potassium channel cloned from human heart. Additionally, doses of fexofenadine ten times greater than the dose of terfenadine that produces prolongation of QTc intervals do not prolong QTc intervals in anaesthetised rabbits and conscious dogs.

Pharmacokinetics

Fexofenadine hydrochloride is rapidly absorbed into the body following oral administration, with Tmax occurring approximately one to three hours postdose. Following administration of a single 60 mg oral dose to healthy volunteers, fexofenadine hydrochloride was rapidly absorbed, with a mean Cmax of 209 nanogram/mL. Following the administration of single oral doses of fexofenadine hydrochloride 120 and 180 mg, the mean Cmax values were approximately 427 and 494 nanogram/mL, respectively.
The absolute bioavailability following fexofenadine hydrochloride administration was estimated to be 33%. Coadministration with food has no clinically significant effect on the absorption of fexofenadine hydrochloride.
The single and multiple dose pharmacokinetics of fexofenadine are linear for oral doses up to 120 mg twice daily. A dose of 240 mg twice daily produced a slightly greater than proportional increase (8.8%) in steady state area under the curve, indicating that fexofenadine pharmacokinetics are practically linear at daily doses between 40 and 240 mg. Fexofenadine is 60 to 70% bound to plasma proteins.
Fexofenadine undergoes negligible metabolism. Following a single radiolabelled 60 mg oral dose, approximately 80 and 11% of the total 14C-fexofenadine dose was excreted in faeces and urine respectively.
The plasma concentration versus time profiles of fexofenadine follow a biexponential decline with a mean terminal elimination half-life ranging from 14 to 15 hours following multiple dosing.
The pharmacokinetics of fexofenadine in seasonal allergic rhinitis patients are similar to those in healthy subjects.
Studies indicated that females may be exposed to higher plasma levels than males, however, there was no indication of any difference in efficacy or in the frequency of adverse events reported. Elderly patients, patients with hepatic impairment and patients with cardiac disease exposed to fexofenadine by administration of terfenadine showed no statistically significant differences in pharmacokinetic parameters for fexofenadine compared to healthy individuals. Although peak plasma level and half-life were increased 68 and 15% respectively in elderly patients and 54 and 19% respectively in patients with renal disease, regardless of disease severity, these levels are within the range of plasma levels shown to be tolerated in short-term dose ranging trials.
The pharmacokinetics of fexofenadine in children and adults are similar, including Tmax, clearance (corrected for body surface area), t½ and volume of distribution, because fexofenadine undergoes negligible metabolism, with 80% of the dose being eliminated unchanged in the faeces. In contrast, other H1-receptor antagonists, which are extensively metabolised in the hepatic cytochrome P450 system, usually have shorter half-life values in children than adults.
In children, studies indicate that fexofenadine 30 or 60 mg suppresses the histamine induced weal and flare within one to two hours, with both doses producing similar mean maximal suppression.

Clinical Trials

An escalating acute dose study demonstrated antihistaminic activity via skin weal and flare inhibition at doses ranging from 40 to 800 mg, with maximum inhibition reaching a plateau at a dose of 130 mg. An escalating repeat dose study demonstrated increasing skin flare inhibition at twice daily doses ranging from 20 to 690 mg. During both acute dose and repeat dose studies, an antihistaminic effect was observed within one hour, achieving maximum effect within two to four hours and lasting a minimum of 12 hours. There was no evidence of tolerance to these effects after 28 days of dosing.
In dose ranging studies, fexofenadine hydrochloride was shown to relieve the symptoms of seasonal allergic rhinitis, significantly reducing total symptom scores (including scores for sneezing, rhinorrhoea, itchy nose, palate and/or throat, and itchy, watery, red eyes) over a dosage range of 40 to 240 mg twice daily. In a double blind, placebo controlled trial of 208 patients with chronic idiopathic urticaria, fexofenadine hydrochloride 180 and 240 mg once daily for six weeks were found to significantly reduce total symptom scores (number of weals (hives) and pruritus).
In a double blind, placebo controlled clinical efficacy study involving 821 patients with seasonal allergic rhinitis, fexofenadine hydrochloride 120 and 180 mg once daily were found to be significantly superior to placebo in relieving symptoms of seasonal allergic rhinitis, including sneezing, rhinorrhoea, itchy nose, palate and/or throat, itchy, red or watery eyes and nasal congestion, after 24 hours. There was no statistically significant difference in efficacy between the two doses of fexofenadine, however the 180 mg dose did show a trend toward greater reduction in the mean total symptom score.
In a double blind placebo controlled study, 861 patients aged 12 to 65 years were randomised to receive either fexofenadine 120 or 180 mg or placebo, once daily for a two week period. The primary efficacy measure was change from baseline of average total symptom score. Both doses provided significant (p ≤ 0.05) improvement in symptoms of seasonal allergic rhinitis, compared to placebo. While there was no statistically significant difference in efficacy between the two doses, the 180 mg dose showed a trend toward greater reduction in the average total symptom score.
In a double blind placebo controlled study investigating quality of life, 845 patients aged 12 to 65 years were randomised to receive fexofenadine 120 or 180 mg or placebo once daily for a two week period. The primary efficacy measures were change from baseline in a quality of life score and in a work/ activity impairment score. Patients receiving either 120 or 180 mg dose reported a significant (p ≤ 0.006) improvement in overall quality of life score and a significant (p ≤ 0.004) reduction in work/ activity impairment score, compared to placebo. No statistical comparison was made between the effects of the two doses of fexofenadine.
The incidence of drowsiness in controlled clinical seasonal allergic rhinitis trials was similar when comparing patients treated with fexofenadine and placebo. There was no dose related increase in drowsiness.
The effects of fexofenadine on the QTc interval have been investigated in a variety of studies at doses up to 800 mg/day. There were no statistically significant differences in QTc interval between fexofenadine and placebo treated patients. Similarly, there were no statistically significant differences from placebo or dose related changes in other ECG parameters as a result of fexofenadine treatment.
Also, no statistically significant change in QTc intervals was observed in long-term studies in healthy subjects given fexofenadine hydrochloride 60 mg twice daily for six months and 240 mg once daily for 12 months, when compared to placebo.
Interaction studies in healthy volunteers between fexofenadine and erythromycin or ketoconazole demonstrated that although the plasma AUC for fexofenadine increased approximately two to threefold, there were no significant effects on mean or maximal QTc, nor were there any effects on the incidence of adverse events. Although these plasma levels were above those seen with the recommended dose, they were within the range of plasma levels achieved in controlled dose ranging clinical trials. Fexofenadine had no effect on the pharmacokinetics of erythromycin or ketoconazole (see Interactions).
Across the clinical trials, patients between the ages of 12 and 16 years have received doses ranging from 20 to 240 mg twice daily. Adverse events were similar in this group compared to patients above the age of 16 years.

Indications

30 mg tablets.

Relief of symptoms associated with seasonal allergic rhinitis in children aged 6 to 11 years.

60 mg tablets.

Relief of symptoms associated with allergic rhinitis in adults and children aged 12 years or older.

120 mg tablets.

Relief of symptoms associated with seasonal allergic rhinitis in adults and children aged 12 years or older.

180 mg tablets.

Relief of symptoms associated with seasonal allergic rhinitis or urticaria in adults and children aged 12 years or older.

Contraindications

Patients with a known hypersensitivity to fexofenadine, terfenadine or any excipient.

Precautions

Carcinogenesis, mutagenesis, impairment of fertility

The carcinogenic potential and reproductive toxicity of fexofenadine hydrochloride were assessed using terfenadine studies. No evidence of carcinogenicity was observed when mice and rats were given daily oral doses of terfenadine 50 and 150 mg/kg for 18 and 24 months, respectively; these doses resulted in plasma AUC values of fexofenadine that were two to four times the human therapeutic value (based on a 60 mg twice daily fexofenadine hydrochloride dose).
Fexofenadine showed no genotoxic activity in a series of assays for gene mutations and chromosomal damage.
In rat fertility studies, dose related reductions in implants and increases in postimplantation losses were observed at oral doses equal to or greater than terfenadine 150 mg/kg respectively; these doses produced plasma AUC values of fexofenadine that were equal to or greater than three times the human therapeutic value respectively (based on a 60 mg twice daily fexofenadine hydrochloride dose).

Use in pregnancy.

(Category B2)
Reproductive toxicity of fexofenadine in animals was assessed through terfenadine exposure. No evidence of teratogenicity was observed in animal reproduction studies (rat and rabbit) when terfenadine was given at oral doses of up to 300 mg/kg/day throughout organogenesis, which corresponds to levels of systemic fexofenadine exposure four and 32-fold higher, respectively, than those anticipated in clinical use. Decreased pup weight and survival occurred in rats when terfenadine was given at oral doses of 150 mg/kg/day and above throughout pregnancy and lactation.
There are no studies in pregnant women exposed to fexofenadine alone or through the administration of terfenadine.

Use in lactation.

Fexotabs is not recommended for breastfeeding women unless, in the doctor's judgment, the potential benefit to the patient outweighs the potential risk to the infant. There are no data on the content of human milk after administering fexofenadine. However, when terfenadine was administered to breastfeeding mothers, fexofenadine was found to cross into human breast milk.
Exposure of rats to fexofenadine and terfenadine through the administration of terfenadine at dietary doses of 150 and 300 mg/kg/day throughout pregnancy and lactation (corresponding to systemic exposure at levels (AUC) approximately three and sixfold higher than those anticipated in clinical use) caused decreased pup weight gain and survival. The relative risks of these effects from terfenadine or fexofenadine are unknown. Effects on pups exposed to fexofenadine only during lactation are unknown.

Use in children

Safety and effectiveness of Fexotabs in children below the age of 6 years have not been established.

Interactions

As fexofenadine undergoes negligible hepatic biotransformation, it is unlikely to interact with other drugs through hepatic metabolism.
The pharmacokinetics of fexofenadine hydrochloride and pseudoephedrine are not altered when both drugs are coadministered.
Coadministration of fexofenadine with erythromycin or ketoconazole has been found to result in a two to threefold increase in the level of fexofenadine in plasma. The changes were not accompanied by any effects on the QT interval and were not associated with any increase in adverse events compared to the drugs given singly. Fexofenadine had no effect on the pharmacokinetics of erythromycin or ketoconazole.
Animal studies have shown that the increase in plasma levels of fexofenadine observed after coadministration of erythromycin or ketoconazole appears to be due to an increase in gastrointestinal absorption and either a decrease in biliary excretion or gastrointestinal secretion respectively.
No interaction between fexofenadine and omeprazole has been observed. However, the administration of an antacid containing aluminium and magnesium hydroxide gel 15 minutes prior to fexofenadine hydrochloride causes a reduction in bioavailability, most likely due to binding in the gastrointestinal tract. It is advisable to leave two hours between administration of fexofenadine hydrochloride and aluminium and magnesium hydroxide containing antacids.

Adverse Effects

Fexotabs is generally well tolerated. The most common adverse events reported in controlled clinical trials were headache, fatigue, dizziness or drowsiness and nausea. The incidence of these effects was similar to that observed with placebo. No apparent dose trends were revealed in adverse events.
As with adults, the incidence of adverse events with fexofenadine in paediatric patients was similar to placebo.

Dosage and Administration

Children aged 6 to 11 years.

The recommended dosage of Fexotabs 30 mg tablets is one tablet twice daily, when required.

Adults and children aged 12 years or older.

60 mg tablets.

The recommended dosage of Fexotabs is one 60 mg tablet twice daily, when required.

120 and 180 mg tablets.

The recommended dosage of Fexotabs 120 and 180 mg tablets is one tablet once daily, when required.
Dosage adjustment is not required in the elderly or in patients with hepatic or renal impairment.

Overdosage

There is no clinical experience with a fexofenadine overdose. The maximum single dose tested in clinical trials is 800 mg in six healthy subjects. In a multiple dose study, doses of 690 mg every 12 hours for 28.5 days were given to three healthy subjects and, in another study with 40 subjects, a dose of 400 mg every 12 hours was given for 6.5 days. No clinically significant adverse events were reported in these studies.
In the case of an overdose, standard measures to remove any unabsorbed drug should be employed. Symptomatic and supportive treatment is recommended. Haemodialysis is not an effective means of removing fexofenadine from plasma.

Presentation

Tablets, 30 mg (peach, film coated, marked 03, e on reverse): 20's; 60 mg (peach, oval, film coated): 20's; 120 mg (≡ fexofenadine 112 mg) (peach, capsule shaped, film coated): 10's, 50's; 180 mg (≡ fexofenadine 168 mg) (peach, capsule shaped, film coated): 10's, 50's.

Storage

Store below 25°C.

Poison Schedule

S2.