Consumer medicine information

Tefodine Tablets

Fexofenadine hydrochloride

BRAND INFORMATION

Brand name

Tefodine Tablets

Active ingredient

Fexofenadine hydrochloride

Schedule

S2: 120 mg: 20's, 30's; 180 mg

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Tefodine Tablets.

What is in this leaflet

This leaflet answers some common questions about TEFODINE.

It does not contain all of the available information. It does not take the place of talking to your doctor or pharmacist.

All medicines have benefits and risks. Your doctor has weighed the risks of you taking TEFODINE against the benefits they expect it will have for you.

If you have any concerns about taking this medicine, talk to your doctor or pharmacist.

Keep this leaflet with your medicine.

You may need to read it again.

What TEFODINE is used for

TEFODINE 120 and 180 are used to relieve the symptoms of hayfever (seasonal allergic rhinitis) such as sneezing, runny or itchy nose, and/or watery, red or itchy eyes.

TEFODINE 180 is also used to relieve the symptoms of urticaria, otherwise known as hives or itchy rash.

TEFODINE belongs to a class of medicines known as antihistamines.

Antihistamines help reduce allergic symptoms by preventing the effects of a substance called histamine.

Histamine is produced by the body in response to foreign substances that the body is allergic to.

Your doctor, however, may prescribe TEFODINE for another purpose. Ask your doctor if you have any questions about why TEFODINE has been prescribed for you.

There is no evidence that TEFODINE is addictive.

Before you take TEFODINE

When you must not take it

Do not take TEFODINE if:

  • you have an allergy to fexofenadine, terfenadine (Teldane®) or any of the ingredients listed at the end of this leaflet.

Some of the symptoms of an allergic reaction may include development or worsening of a skin rash, difficulty breathing or faintness.

Do not take TEFODINE if you are pregnant or breastfeeding, unless you and your doctor or pharmacist have discussed the risks and benefits involved.

Do not take TEFODINE after the expiry date (Exp) printed on the pack.

Do not take TEFODINE if the packaging is torn or shows signs of tampering.

Before you start to take it

You must tell your doctor or pharmacist:

  • if you are allergic to any other medicines, foods, dyes or preservatives.

Taking other medicines

Tell your doctor or pharmacist if you are taking any other medicines, including medicines that you buy without a prescription from a pharmacy, supermarket or health food shop.

Use in children

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

How to take TEFODINE

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

How much to take

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

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

TEFODINE can be stopped when you obtain relief from your symptoms, and restarted if symptoms recur.

Do not take more than the recommended dose.

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

If you take too much TEFODINE (overdose)

Immediately telephone your doctor or the Poisons Information Centre on 13 11 26, or go to Accident and Emergency at the nearest hospital, if you think that you or anyone else may have taken too much TEFODINE.

Do this even if there are no signs of discomfort or poisoning. You may need urgent medical attention.

Keep telephone numbers for these places handy.

While you are taking TEFODINE

Things you must do

Tell all doctors, dentists and pharmacists who are treating you that you are taking TEFODINE.

Tell your doctor or pharmacist if you become pregnant while you are taking TEFODINE.

Things you must not do

Do not give TEFODINE to anyone else, even if their symptoms seem similar to yours.

Do not use it to treat any other complaints unless your doctor or pharmacist says to.

Things to be careful of

Make sure you know how you react to TEFODINE before you drive a car or operate machinery.

TEFODINE is unlikely to make you drowsy. If you are drowsy, do not drive a car or work with machinery.

Stop taking TEFODINE 48 hours before you have any skin tests.

Antihistamines may interfere with the results of skin tests.

Try to avoid contact with known substances you are allergic to.

Hives are sometimes caused by allergy to certain foods. You should talk to your doctor for more information or if you are worried about this.

Side effects

Tell your doctor or pharmacist as soon as possible if you do not feel well while taking TEFODINE.

TEFODINE helps most people with allergies, but it may have unwanted effects in a few people.

Like other medicines, TEFODINE can cause some side effects. If the side effects listed below occur, they are most likely to be minor and temporary.

Although most people will not experience any, some of the side effects that may occur with TEFODINE are:

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

Other unwanted effects not listed above may occur in some people taking TEFODINE. Tell your doctor or pharmacist if you notice anything that is making you feel unwell.

After using TEFODINE

Storage

Keep TEFODINE where children cannot reach it.

A locked cupboard at least one-and-a-half metres above the ground is a good place to store medicines.

Keep TEFODINE tablets in their pack until time to take.

Keep your tablets in a cool dry place where the temperature stays below 25°C.

Do not store TEFODINE or any other medicines in the bathroom or near a sink.

Do not leave TEFODINE in the car or on window sills.

Heat and dampness can destroy some medicines.

Disposal

If your doctor or pharmacist tells you to stop taking TEFODINE or the medicine has passed the expiry date, ask your pharmacist what to do with any unused or out of date medicine.

Product description

TEFODINE tablets can be bought without a doctor's prescription.

What it looks like

TEFODINE tablets come in two strengths:

  • TEFODINE 120 - peach coloured, circular, biconvex film-coated tablets, embossed with 'F' on one side and plain on the other side
  • TEFODINE 180 - peach coloured, capsule-shaped, biconvex film-coated tablets, embossed with 'F' on one side and plain on the other side.

TEFODINE is available in blister packs of 10, 20 and 30 tablets.

Ingredients

The active ingredient in TEFODINE is fexofenadine hydrochloride.

  • each TEFODINE 120 contains
    120 mg of fexofenadine hydrochloride
  • each TEFODINE 180 contains
    180 mg of fexofenadine hydrochloride.

The tablets also contain:

  • microcrystalline cellulose
  • lactose
  • povidone
  • croscarmellose sodium
  • maize starch
  • sodium lauryl sulfate
  • purified talc
  • magnesium stearate
  • Opadry II brown 85G86605.

The tablets do not contain gluten, sucrose, tartrazine or any azo dyes.

Supplier

Arrow Pharmaceuticals
24 Rothschild Ave
Rosebery NSW 2018

Australian registration numbers:
TEFODINE 120 - AUST R 129141
TEFODINE 180 - AUST R 129142

Date of preparation
June 2006.

BRAND INFORMATION

Brand name

Tefodine Tablets

Active ingredient

Fexofenadine hydrochloride

Schedule

S2: 120 mg: 20's, 30's; 180 mg

 

Name of the medicine

Fexofenadine hydrochloride.

Excipients.

Microcrystalline cellulose, lactose, povidone, croscarmellose sodium, maize starch, sodium lauryl sulfate, purified talc, magnesium stearate and opadry II brown 85G86605. The tablets are gluten free.

Description

The chemical name is benzene acetic acid, 4-[1-hydroxy-4[4-(hydroxydiphenylmethyl)-1-piperidinyl]butyl]-α,α-dimethyl-, hydrochloride. C32H39NO4.HCl. Molecular weight: 538.13. Cas No.: 153439-40-8. Fexofenadine is the carboxylic acid metabolite of terfenadine administered as the hydrochloride salt in Tefodine. It occurs as a fine white to off-white powder and 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.
Fexofenadine hydrochloride is an equimolar mixture of two enantiomers.
Tefodine tablets come in two strengths and contain either 120 mg or 180 mg of fexofenadine hydrochloride. The tablets also contain the following excipients: microcrystalline cellulose, lactose, povidone, croscarmellose sodium, maize starch, sodium lauryl sulfate, purified talc, magnesium stearate and opadry II brown 85G86605. The tablets are gluten free.

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 times higher than those required for antihistaminic activity) inhibited histamine release from peritoneal mast cells of the rat. In laboratory animals, no anticholinergic or alpha1-adrenergic receptor blocking effects were observed. Radiolabelled tissue distribution studies in rats 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 of potassium, calcium or sodium ions 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 the administration of a single oral dose of fexofenadine hydrochloride 180 mg, the adjusted mean Cmax value was approximately 682.1 nanogram/mL.
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% of the total 14C-fexofenadine dose was excreted in faeces and 11% in urine.
The plasma concentration versus time profiles of fexofenadine follow a bi-exponential 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 the 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), t1/2 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.

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 mg 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 less than or equal to 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 mg 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 mg or 180 mg dose reported a significant (p less than or equal to 0.006) improvement in overall quality of life score and a significant (p less than or equal to 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 with placebo.
Interaction studies in healthy volunteers between fexofenadine and erythromycin or ketoconazole demonstrated that although the plasma area under the curve (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 with Other Medicines).
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

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 and older.

Contraindications

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 dose of fexofenadine hydrochloride 60 mg twice daily).
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 post-implantation 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 dose of fexofenadine hydrochloride 60 mg twice daily).

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.

Fexofenadine 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 AUC levels 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.

There is currently not enough information available to recommend the use of fexofenadine 120 mg or 180 mg in children under the age of 12 years.

Interactions

As fexofenadine undergoes negligible hepatic biotransformation, it is unlikely to interact with 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 three times 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

Fexofenadine is generally well tolerated. The most common adverse events reported in 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.

Dosage and Administration

Adults and children aged 12 years or older.

The recommended dosage of Tefodine 120 mg and 180 mg 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. Immediately telephone your doctor, or the Poisons Information Centre (telephone 131 126), or go to Accident and Emergency at the nearest hospital.
The maximum single dose tested in clinical trials was 800 mg in six healthy subjects. In a multiple dose study, doses of 690 mg every twelve hours for 28.5 days were given to three healthy subjects. In another study with 40 subjects, a dose of 400 mg every twelve hours was given for 6.5 days. No clinically significant adverse events were reported in these studies.

Treatment.

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

Tefodine 120.

Peach coloured, circular, biconvex film coated tablets, embossed with ‘F’ on one side and plain on the other side.
Blister packs of 10, 20 and 30.

Tefodine 180.

Peach coloured, capsule shaped, biconvex film coated tablets, embossed with ‘F’ on one side and plain on the other side.
Blister packs of 10, 20 and 30.

Storage

Store the tablets below 25°C.

Poison Schedule

S2.