Consumer medicine information

Felodur ER

Felodipine

BRAND INFORMATION

Brand name

Felodur ER

Active ingredient

Felodipine

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Felodur ER.

What is in this leaflet

This leaflet answers some of the common questions people ask about FELODUR ER. It does not contain all the information that is known about FELODUR ER.

It does not take the place of talking to your doctor or pharmacist.

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

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

Keep this leaflet with the medicine. You may need to read it again.

What FELODUR ER is for

FELODUR ER is used to treat high blood pressure, also called hypertension. FELODUR ER lowers blood pressure by dilating (expanding) small blood vessels, letting the blood be pumped around the body more easily.

Your doctor will have explained why you are being treated with FELODUR ER and told you what dose to take.

The ER in FELODUR ER stands for Extended Release. This means that the tablets are designed to work over a 24 hour period.

FELODUR ER contains felodipine, which belongs to the family of medicines known as calcium channel blockers. These medicines do not change the way the body takes in calcium from food.

Follow all directions given to you by your doctor carefully. They may differ from the information contained in this leaflet.

Ask your doctor if you have any questions about why this medicine has been prescribed for you. Your doctor may have prescribed this medicine for another reason.

FELODUR ER is only available with a doctor's prescription.

FELODUR ER is not addictive

Before you use FELODUR ER

When you must not use it

Do not take FELODUR ER if you have an allergy to any medicine containing felodipine or any of the ingredients listed at the end of the leaflet.

Some of the symptoms of an allergic reaction may include, tightness of the chest, wheezing, coughing or difficulty breathing; swelling of the face, lips, tongue or other parts of the body; rash, itching or hives.

Do not take FELODUR ER if you have any of the following conditions:

  • uncompensated heart failure
  • acute myocardial infarction
  • cardiac valvular obstruction
  • dynamic cardiac outflow obstruction
  • unstable angina pectoris

If you are not sure whether you have any of these conditions, ask your doctor.

Do not use FELODUR ER if you are pregnant or likely to become pregnant. Ask your doctor about the risks and benefits involved. FELODUR ER should not be used during pregnancy. It may affect your baby if you take it during pregnancy.

Tell your doctor as soon as possible if you become pregnant while using FELODUR ER.

Tell your doctor if you are breastfeeding or intend to breastfeed before you take FELODUR ER. Your baby can take in FELODUR ER from breast milk if you are breastfeeding, but it is unlikely to affect the infant when the mother is taking doses within the normal range for her treatment. Your doctor can discuss the risks and benefits involved.

Do not give FELODUR ER to children. There is no information on its use in children.

Do not use after the use by (expiry) date printed on the pack.

Do not use FELODUR ER if the packaging is torn or shows signs of tampering. If it has expired or is damaged, return it to your pharmacist for disposal.

Do not use it to treat any other complaint unless your doctor tells you to.

Do not give this medicine to anyone else.

Before you start to use it

You must tell your doctor if:

  1. you have any allergies to
  • any ingredients listed at the end of this leaflet
  • any other medicine used to treat high blood pressure
  • any other medicines, foods, preservatives or dyes
If you have an allergic reaction, you may get a skin rash, hayfever, have difficulty breathing or feel faint.
  1. you have any medical conditions such as
  • any heart problem, including angina
  • liver problems
It may not be safe for you to take FELODUR ER if you have any of these conditions.

Tell your doctor if you are lactose intolerant. FELODUR ER tablets contain lactose

Taking other medicines

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

Some medicines and FELODUR ER may interfere with each other. These include:

  • cimetidine - a medicine used to treat stomach ulcers or heartburn
  • medicines used to treat infections such as erythromycin and rifampicin
  • treatment with FELODUR ER may affect the level of tacrolimus (a medicine given to prevent the body from rejecting a transplanted organ, e.g. kidney or liver) in your blood.
  • medicines used to treat fungal infections such as itraconazole and ketoconazole
  • medicines used to treat epilepsy such as phenytoin and carbamazepine
  • medicines used to help you sleep such as barbiturates
  • St John's Wort - a herbal remedy used to treat mood disorders

These medicines may be affected by FELODUR ER or may affect the way FELODUR ER works. You may need different amounts of your medicines, or may need to take different medicines.

Your doctor can tell you what to do if you are taking any of these medicines.

If you are taking other drugs which lower blood pressure, your doctor may need to change the dose of them to obtain the best results for you.

Your doctor and pharmacist have more information on medicines to be careful with or avoid while taking this medicine. If you are unsure about any medicine you are taking you should check with your doctor or pharmacist.

If you have not told your doctor, dentist or pharmacist about any of these things, tell them before you take any FELODUR ER.

Taking FELODUR ER

How much to take

The usual starting dose of FELODUR ER is one 2.5 mg or 5mg tablet taken once daily.

Your doctor will check your progress and if needed, increase your dose of FELODUR ER. Sometimes the dose will be as high as 20mg once a day.

If you have to take more than one tablet, you must take them together.

Swallow FELODUR ER tablets whole and wash them down with a glass of water. They must not be divided, crushed or chewed. If they are broken or crushed they will not work over 24 hours as they are supposed to.

It does not matter if you take FELODUR ER with food or not, but you must not take it with grapefruit juice. Grapefruit juice may increase the effect of FELODUR ER.

If you forget to take it

If you forget a dose, take it as soon as you remember, as long as it is more than 12 hours before the next dose is due.

If it is less than 12 hours until your next dose, skip the dose you missed and take your next dose when you are meant to.

Do not take a double dose to make up for the dose that you missed. If you have trouble remembering when to take your medicine, ask your pharmacist for some hints.

How long to take it

Take FELODUR ER for as long as your doctor tells you to.

FELODUR ER must be taken every day.

FELODUR ER helps control your high blood pressure, but does not cure it.

Treatment of high blood pressure is necessary in most people for the rest of their lives. Ask your doctor to explain the reasons for this.

Overdose

Telephone your doctor, the Poisons Information Centre (13 11 26) or go to Accident and Emergency at your nearest hospital immediately if you think that you or anyone else may have taken too much FELODUR ER even if there are no signs of discomfort or poisoning.

If you take too much FELODUR ER you may experience a headache, a slow heartbeat, very low blood pressure, dizziness, tiredness or feel sick (nausea).

While you are using it

Things you must do

If you are about to be started on any new medicine, remind your doctor and pharmacist that you are taking FELODUR ER.

Tell any other doctors, dentists, and pharmacists who treat you that you are taking this medicine.

If you become pregnant while taking this medicine, tell your doctor immediately.

Keep all of your doctor's appointments so that your progress can be checked.

Things you must not do

Do not take FELODUR ER with grapefruit juice. Grapefruit juice may increase the effect of FELODUR ER.

Do not stop taking FELODUR ER unless you have discussed it with your doctor.

Do not use this medicine to treat any other complaint unless your doctor tells you to.

Do not give this medicine to anyone else, even if they have the same condition as you.

Things to be careful of

Be careful driving or operating machinery until you know how FELODUR ER affects you. When you start taking FELODUR ER, whether you are changing from another medicine for high blood pressure or not, you may feel dizzy or faint due to the drop in your blood pressure.

Be careful when drinking alcohol while you are using FELODUR ER. Please talk to your doctor or pharmacist about these possibilities.

Side effects

Tell your doctor or pharmacist as soon as possible if you do not feel well while you are taking FELODUR ER. FELODUR ER helps most people with high blood pressure, but it may have unwanted side-effects in a few people.

All medicines can have side effects. Sometimes they are serious, most of the time they are not. You may need medical treatment if you get some of the side effects.

Ask your doctor or pharmacist to answer any questions you may have.

Tell your doctor if you notice any of the following and they worry you:

  • headache
  • swelling of the ankles
  • dizziness
  • flushing
  • palpitations (feeling of heart pounding)
  • fatigue (tiredness)

These side effects usually go away or get less with time. If they do occur, it mostly happens at the beginning of treatment, or when the dose is increased.

Other side effects you should tell your doctor about if they worry you include:

  • nausea (feeling sick)
  • frequent urination
  • impotence / sexual dysfunction
  • stomach pain
  • pain, swelling or redness in your gums
  • fever
  • increased sensitivity of the skin to sunlight
  • sensation of burning, prickling, numbness, "pins and needles"
  • pain in joints or muscular pain

These side effects are usually mild.

Tell your doctor immediately or go to Accident and Emergency at your nearest hospital if you notice any of the following:

  • skin rash
  • fainting
  • chest pain
  • rapid heart beat

These are serious side effects. You may need urgent medical attention.

If any of the following happen, stop taking FELODUR ER and tell your doctor immediately or go to Accident and Emergency at your nearest hospital.

  • swelling of the face, tongue or back of the throat,
  • harsh sounds or difficulty when breathing

These are very serious side effects. If you have them, you may have had a serious (allergic) reaction to FELODUR ER. You may need urgent medical attention or hospitalisation.

Tell your doctor if you notice anything else that is making you feel unwell. Some people may get other side effects while taking FELODUR ER.

After using it

Storage

Keep your tablets in the blister pack until it is time to take them. If you take FELODUR ER out of the blister pack it will not keep well.

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

Do not store FELODUR ER or any other medicine in the bathroom or near a sink.

Do not leave it in the car on hot days. Heat and dampness can destroy some medicines.

Keep it where young children cannot reach it. A locked cupboard at least one-and-a-half metres above the ground is a good place to store medicines.

Disposal

Ask your pharmacist what to do with any tablets you have left over if your doctor tells you to stop taking them, or you find that the expiry date has passed.

Product description

What FELODUR ER looks like

FELODUR ER tablets are available in 3 strengths:

  • FELODUR ER 2.5 mg tablet - round, yellow, marked "A" over "FL" on one side and "2.5" on the other.
  • FELODUR ER 5 mg tablet - round, pink, marked "A" over "Fm" on one side and "5" on the other.
  • FELODUR ER 10 mg tablet - round, reddish-brown, marked "A" over "FE" on one side and "10" on the other.

All strengths are available in blister packs of 30 tablets.

Ingredients

FELODUR ER tablets contain felodipine 2.5 mg, 5 mg or 10 mg as the active ingredient,

plus

  • Hydrogenated castor oil
  • Propyl gallate (E 310)
  • Hypromellose
  • Sodium aluminium silicate
  • Microcrystalline cellulose (E 460)
  • Lactose
  • Sodium stearyl fumarate
  • Hyprolose

The coating on each tablet contains:

  • Macrogol 6000
  • Titanium dioxide (E 171)
  • Iron oxide yellow (E 172)
  • Iron oxide red (E 172) (not in 2.5 mg tablet)
  • Carnauba wax (E 903).

Sponsor

AstraZeneca Pty Ltd
ABN 54 009 682 311
66 Talavera Road
MACQUARIE PARK NSW 2113

Telephone: 1800 805 342

Australian Registration Number:
FELODUR ER

2.5 mg - AUST R 60980
5 mg - AUST R 60981
10 mg - AUST R 60982

This leaflet was prepared in May 2017.

FELODUR ER is a trade mark of the AstraZeneca group of companies.

Doc ID-001688487 v4.0

Published by MIMS September 2017

BRAND INFORMATION

Brand name

Felodur ER

Active ingredient

Felodipine

Schedule

S4

 

1 Name of Medicine

Felodipine.

2 Qualitative and Quantitative Composition

Felodur ER tablets contain 2.5 mg, 5 mg or 10 mg felodipine.

Excipient with known effect.

Lactose.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Felodur ER tablets 2.5 mg.

Yellow, circular, biconvex, film-coated, engraved A/FL on one side and 2.5 on the other. Diameter 8.5 mm.

Felodur ER tablets 5 mg.

Pink, circular, biconvex, film-coated, engraved A/Fm on one side and 5 on the other. Diameter 9 mm.

Felodur ER tablets 10 mg.

Red-brown, circular, biconvex, film-coated, engraved A/FE on one side and 10 on the other. Diameter 9 mm.

4 Clinical Particulars

4.1 Therapeutic Indications

Hypertension.

4.2 Dose and Method of Administration

Adults.

Hypertension.

The dose should be adjusted individually.
Treatment should be started with 5 mg once daily. In elderly patients a starting dose of 2.5 mg once daily should be considered.
If necessary, the dose can be increased in 2.5 or 5 mg/day increments. The usual maintenance dose is 5 mg to 10 mg daily. Doses higher than 20 mg daily of Felodur ER are not recommended.

Special patient populations.

Renal impairment.

Impaired renal function does not influence felodipine peak plasma concentrations or AUC, and a dosage reduction is not necessary for patients with renal impairment.

Hepatic impairment.

The dose of felodipine should be reduced in patients with severely impaired liver function. Patients with impaired hepatic function may have elevated plasma concentrations of felodipine and may respond to lower doses.

Use in the elderly.

The dose should be adjusted individually, taking patient age into consideration (see Section 4.4 Special Warnings and Precautions for Use). An initial dose of 2.5 mg once daily should be considered.

Paediatric use.

Due to limited clinical trial experience, felodipine should not be used in paediatric patients.

Method of administration.

Felodur ER tablets should be swallowed whole and taken with water and must not be divided, crushed or chewed.

4.3 Contraindications

Pregnancy, including the early stages. Women who are likely to become pregnant should not be treated with felodipine.
Known hypersensitivity to felodipine or any other component of the product (see Section 6.1 List of Excipients).
Uncompensated heart failure.
Acute myocardial infarction.
Unstable angina pectoris.
Haemodynamically significant cardiac valvular obstruction.
Dynamic cardiac outflow obstruction.

4.4 Special Warnings and Precautions for Use

Excessive hypotension.

Because felodipine decreases peripheral vascular resistance, careful monitoring of blood pressure during the initial administration and titration of felodipine is suggested. Close observation is especially recommended for patients already taking medications that are known to lower blood pressure. Felodipine, like other vasodilators, can cause significant hypotension which, in susceptible individuals, may result in myocardial ischaemia.

Exacerbation of angina.

Rarely, too great a reduction in blood pressure with an initial reflexogenic increase in heart rate may lead to increased frequency, duration and/or severity of angina, particularly in patients who have severe obstructive coronary artery disease. Therefore, the possibility of precipitation of myocardial ischaemia exists. This may occur in the initial stages of felodipine treatment or following a dosage increase.

Combination with beta-blockers in patients with congestive heart failure.

Beta-blockers are contraindicated in patients with uncompensated heart failure. Although felodipine may appear safe in these patients, combination with a beta-blocker is not recommended.

Leydig cell tumours in rats.

An increased incidence of benign interstitial cell testicular tumours has been observed in rats but not in mice following dosing with felodipine. The relevance of this finding in man is not known, although clinical studies have demonstrated that felodipine has no influence on testosterone formation or on luteinising hormone secretion.

Outflow obstruction.

Calcium antagonists should be used with caution in the presence of fixed left ventricular outflow obstruction. In animal and in vitro studies, felodipine was 6 times more potent than nifedipine in inhibiting vascular, relative to myocardial, contractility. Therefore, in patients with raised left ventricular end diastolic pressure, felodipine is less likely to precipitate pulmonary oedema.

Peripheral oedema.

Mild to moderate peripheral oedema resulting from precapillary vasodilation may occur in about 20% of patients treated with felodipine. This oedema appears to be dose related. The effect of a diuretic on this oedema has not been investigated.

Gingival enlargement.

Mild gingival enlargement has been reported in patients with pronounced gingivitis/ peridontitis. The enlargement can be avoided or reversed by careful dental hygiene.

Lactose.

Felodur ER contains lactose and should not be given to patients with hereditary galactose intolerance or glucose-galactose malabsorption.

Use in the elderly.

Felodipine plasma levels are higher on average in elderly patients than in young and middle aged patients due to reduced first-pass effect, reduced clearance capacity or both. It appears, however, that age per se has relatively little impact on the pharmacokinetics of felodipine. However, an initiation dose of 2.5 mg once daily in the elderly may be appropriate.

Paediatric use.

Due to limited clinical trial experience, felodipine should not be used in paediatric patients.

Effects on laboratory tests.

Slight increases in thrombocyte count, and rare, usually transient, elevations of enzymes such as alkaline phosphatase, ASAT and ALAT have occasionally been noted during felodipine treatment. These laboratory abnormalities have not been associated with clinical symptoms and their relationship to felodipine is uncertain.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Enzyme P450 inducers and inhibitors.

Concomitant administration of substances which interfere with the cytochrome P450 3A4 system may affect plasma concentrations of felodipine.
Enzyme inducers of the cytochrome P450 3A4 system (e.g. phenytoin, carbamazepine, rifampicin, barbiturates, Hypericum perforatum [St John's wort]) will cause a decrease in plasma levels of felodipine.
Enzyme inhibitors of the cytochrome P450 3A4 system (e.g. cimetidine, erythromycin, itraconazole, ketoconazole and certain flavonoids present in grapefruit juice) have been shown to cause an increase in felodipine plasma levels.

Digoxin.

No increase in digoxin levels was observed during concomitant treatment with felodipine extended release (Felodur ER) tablets.

Food.

No significant effect on absorption of felodipine was observed when Felodur ER was given with food.

Grapefruit juice.

An increase in the bioavailability of dihydropyridines has been shown when they have been taken with grapefruit juice. The interaction is thought to be due to a bioflavonoid present in grapefruit juice which is not found in other citrus fruits. The interaction is more pronounced with immediate release formulations.

Tacrolimus.

Felodipine may increase the concentrations of tacrolimus. When used together, the tacrolimus serum concentrations should be followed and the tacrolimus dose may need to be adjusted.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

Data on male and female fertility in patients are missing.
(Category C)
Felodur ER should not be given to pregnant women or those likely to become pregnant. Calcium channel blockers carry the potential to produce foetal hypoxia associated with maternal hypotension.
Following administration of felodipine to pregnant dams during the period of organogenesis, morphological abnormalities of the phalanges were observed in the rabbit foetus.
In rats, oral doses of felodipine 3.8 mg/kg or higher caused prolongation of labour.
 Felodipine is detected in breast milk. When taken in therapeutic doses by the nursing mother, however, it is unlikely to affect the infant.

4.7 Effects on Ability to Drive and Use Machines

The effects of this medicine on a person's ability to drive and use machines were not assessed as part of its registration.

4.8 Adverse Effects (Undesirable Effects)

Felodur ER has been extensively studied in Australia and overseas, both as monotherapy and in combination with other hypotensives such as beta-blockers and/or diuretics.
Felodur ER can, like other vasodilators, cause flushing, peripheral oedema, headache, palpitations, dizziness and fatigue. Most of these reactions are dose dependent and appear at the start of treatment or after a dose increase. Should such reactions occur, they are usually transient and diminish in intensity with time.
As with other dihydropyridines, dose dependent ankle swelling, resulting from precapillary vasodilation, can occur in patients treated with felodipine.
As with other calcium antagonists, gingival enlargement has been reported in patients with pronounced gingivitis or periodontitis. The enlargement can be avoided or reversed by attention to dental hygiene.
The following adverse events have been reported from clinical trials and from postmarketing surveillance. In the great majority of the less common reactions, a causal relationship and treatment with felodipine has not been established.

Very common.

(≥ 10%).

Cardiovascular.

Peripheral oedema.

More common.

(> 1%).

Cardiovascular.

Flushing (feeling of warmth).

Gastrointestinal.

Nausea, vomiting, gum hyperplasia.

CNS.

Headache, dizziness/ vertigo.

Less common.

(≤ 1%).

Cardiovascular.

Hypotension, palpitations, tachycardia, syncope, chest pain. In isolated cases, sensation of cold.

Respiratory.

Dyspnoea, respiratory infection.

Gastrointestinal.

Dyspepsia, flatulence, abdominal pain, gingivitis, constipation.

CNS.

Paraesthesia. In isolated cases, depression.

Hepatic.

Increased liver enzymes, e.g. alkaline phosphatase, ASAT and ALAT.

General.

Hypersensitivity reactions, e.g. skin rashes (including on rare occasions photosensitivity reactions), pruritus, urticaria, angioedema, fever, arthralgia, myalgia, fatigue. In rare cases, impotence/ sexual dysfunction, pollakisuria (urinary frequency) and leucocytoclastic vasculitis.

Serious adverse events.

The following serious adverse events were reported rarely in patients receiving felodipine in placebo controlled studies: myocardial infarction (nonfatal), second degree atrioventricular block, stroke and chest pain. However, a causal relationship with drug therapy has not been established.

Reporting suspected adverse effects.

Reporting suspected adverse reactions after registration of the medicinal product is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions at www.tga.gov.au/reporting-problems.

4.9 Overdose

Symptoms.

Overdosage may cause excessive peripheral vasodilation with marked hypotension and sometimes bradycardia.
Symptoms and signs of overdose may be delayed due to the controlled release properties of Felodur ER, so patients should be kept under observation for at least 24 hours.

Management.

If severe hypotension occurs, symptomatic treatment should be instituted. The patient should be placed supine with the legs elevated. In cases of accompanying bradycardia, atropine 0.5-1.0 mg should be administered intravenously. If this is not sufficient, plasma volume should be increased by electrolyte infusion (e.g. glucose, saline or dextran). Sympathomimetic drugs with predominant effect on the α1-adrenoreceptor may be given if the above mentioned measures are insufficient.
For information on the management of overdose, contact the Poison Information Centre on 131126 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Felodipine is a calcium antagonist which lowers arterial blood pressure by decreasing peripheral vascular resistance. Felodipine exhibits a high degree of selectivity for smooth muscle in the arterioles and in therapeutic doses has no direct effect on cardiac contractility or conduction. Because of its lack of effect on venous smooth muscle and on adrenergic vasomotor control, felodipine does not cause orthostatic hypotension.
Felodipine possesses a mild natriuretic/ diuretic effect and therefore does not produce any general fluid retention. In various studies in which bodyweight was monitored, mean values did not generally increase during felodipine therapy.
Felodipine is effective in all grades of hypertension. It can be combined with other antihypertensives, such as β-receptor blockers, diuretics or ACE inhibitors, in order to achieve an increased antihypertensive effect.
Felodipine has antianginal and anti-ischaemic effects due to the improved oxygen supply/ demand balance of the myocardium. Coronary vascular resistance is decreased and coronary blood flow as well as myocardial oxygen supply are increased by felodipine. The reduction in systemic blood pressure caused by felodipine leads to decreased left ventricular afterload and myocardial oxygen demand.
Felodipine improves exercise tolerance and reduces anginal attacks in patients with stable effort induced angina pectoris. It can be used as monotherapy or in combination with β-receptor blockers in these patients.

Site and mechanism of action.

The predominant pharmacodynamic feature of felodipine is its pronounced vascular vs. myocardial selectivity. Smooth muscles in arterial resistance vessels which exhibit myogenic activity are particularly sensitive to calcium antagonists such as felodipine. Felodipine inhibits electrical and contractile activity of vascular smooth muscle cells via an action at the cell membrane.

Haemodynamic effects.

The acute haemodynamic effect of felodipine is to reduce total peripheral resistance which leads to a decrease in blood pressure and a slight and transient reflex increase in heart rate and cardiac output. A reduction in blood pressure is usually evident 2 hours after an initial oral dose of Felodur ER tablets. The effect lasts for at least 24 hours at steady state.
Plasma concentrations of felodipine and change in total peripheral resistance and blood pressure respectively, are correlated.

Electrophysiological and other cardiac effects.

Felodipine in therapeutic doses has no effect on conduction in the specialised conducting system of the heart and no effect on the AV nodal refractoriness. In therapeutic doses felodipine has no negative effect on cardiac contractility. Antihypertensive treatment with felodipine is associated with significant regression of pre-existing left ventricular hypertrophy.

Renal effects.

Felodipine has a natriuretic and diuretic effect. Studies in rats have shown that the reabsorption of filtered sodium is reduced in the distal tubules and collecting ducts in the kidney. The salt and water retention observed with other vasodilators is not observed with felodipine. Felodipine does not affect daily potassium excretion.
Renal vascular resistance is decreased by felodipine. In normal renal function, glomerular filtration rate is unchanged.
In patients with impaired renal function, the glomerular filtration rate may increase.

Clinical trials.

No data available.

5.2 Pharmacokinetic Properties

Absorption.

Felodipine is completely absorbed from the gastrointestinal tract after administration of Felodur ER tablets.
Peak plasma concentrations following Felodur ER tablets are usually reached within 3-5 hours.
The systemic availability of felodipine is independent of dose in the therapeutic dose range. Due to presystemic metabolism of felodipine the bioavailability of the extended release dosage form (Felodur ER) is approximately 20%.
Felodur ER produces a relatively flat plasma concentration versus time curve, minimising the postabsorption peak seen with conventional tablets and maintaining therapeutic levels over the 24 hours following dosing. This permits single daily dosing of Felodur ER.

Distribution.

The plasma protein binding of felodipine in man is approximately 99%. It is bound predominantly to the albumin fraction.
In man, felodipine has a volume of distribution at steady state of approximately 10 L/kg.

Metabolism.

Felodipine is extensively metabolised in the liver by cytochrome P450 3A4 (CYP3A4). All identified metabolites are inactive. Approximately 70% of a given dose is excreted as metabolites in the urine; the remaining fraction is excreted in the faeces. Less than 0.5% of a dose is recovered unchanged in urine.

Excretion.

The elimination of felodipine from plasma follows a biphasic pattern, with the mean half-life of the α phase approximately 4 hours and that of the β phase approximately 24 hours. There is no significant accumulation during long-term treatment.
Average peak plasma concentrations of felodipine tend to be higher in elderly patients than in young healthy individuals. This can be attributed to reduced systemic clearance of felodipine and a corresponding increase in plasma half-life.
The systemic availability, time to peak plasma concentration and volume of distribution do not appear to be significantly affected by age.
In some patients administered a single dose of 5 mg Felodur ER, there was no detectable blood level of felodipine, indicating a significant interindividual variation in pharmacokinetic response. Therefore, the dosage of Felodur ER for all patients should be individually adjusted rather than based solely on patient age.

5.3 Preclinical Safety Data

Genotoxicity.

No data available.

Carcinogenicity.

No data available.

6 Pharmaceutical Particulars

6.1 List of Excipients

Inactive ingredients: PEG-40 hydrogenated castor oil, hyprolose, propyl gallate, hypromellose, aluminium sodium silicate, microcrystalline cellulose, lactose, sodium stearylfumarate, macrogol 6000, titanium dioxide, carnauba wax, iron oxide yellow (CI77492), iron oxide red (CI77491) (5 mg and 10 mg tablets only).

6.2 Incompatibilities

Incompatibilities were either not assessed or not identified as part of the registration of this medicine.

6.3 Shelf Life

In Australia, information on the shelf life can be found on the public summary of the Australian Register of Therapeutic Goods (ARTG). The expiry date can be found on the packaging.

6.4 Special Precautions for Storage

Stored below 25°C. Protect from moisture.

6.5 Nature and Contents of Container

Packs of 7 and 30 tablets. PVC/PVDC/Al blisters.
*Not all pack sizes may be available in Australia.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of in accordance with local requirements.

6.7 Physicochemical Properties

Felodipine is insoluble in water (0.00012%) at 37°C and is moderately light-sensitive.
Felodur ER tablets contain felodipine, a racemic mixture of ethyl methyl 4-(2,3dichlorophenyl)-1,4-dihydro 2, 6-dimethyl-3,5 pyridine dicarboxylate.

Chemical structure.


MW 384.26.

CAS number.

CAS number: 72509-76-3.

7 Medicine Schedule (Poisons Standard)

Prescription Only Medicine (Schedule 4).

Summary Table of Changes