Neofel Xl 5mg Prolonged Release Tablets
Out of date information, search anotherSUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Neofel XL 5 mg Prolonged Release Tablets
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Neofel XL 5 mg Prolonged Release Tablets contain 5mg of felodipine.
3 PHARMACEUTICAL FORM
Light pink, round, biconvex, film coated prolonged-release tablets with imprint 5.
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
In the management of hypertension and prophylaxis of chronic stable angina pectoris.
4.2 Posology and method of administration
For oral administration
Hypertension:
Adults (including elderly): The dose should be adjusted to the individual requirements of the patient. The recommended starting dose is 5 mg once daily. If necessary the dose may be further increased or another antihypertensive agent added. The usual maintenance dose is 5-10 mg once daily. Doses higher than 20 mg daily are not usually needed. For dose titration purposes a 2.5 mg tablet is available. In elderly patients an initial treatment with 2.5 mg daily should be considered.
Angina pectoris:
Adults: The dose should be adjusted individually. Treatment should be started with 5 mg once daily and if needed be increased to 10 mg once daily.
Administration: The tablets should regularly be taken in the morning without food or with a light meal. Neofel XL 5 mg Prolonged Release Tablets must not be chewed or crushed. They should be swallowed whole with half a glass of water.
Children: The safety and efficacy of Neofel XL 5 mg Prolonged Release Tablets in children has not been established.
Neofel XL 5 mg Prolonged Release Tablets can be used in combination with P-blockers, ACE inhibitors or diuretics. The effects on blood pressure are likely to be additive and combination therapy will usually enhance the antihypertensive effect. Care should be taken to avoid hypotension. In patients with severely impaired liver function the dose of felodipine should be low. The pharmacokinetics are not significantly affected in patients with impaired renal function.
4.3 Contraindications
Unstable angina pectoris.
Pregnancy.
Patient with a previous allergic reaction to Neofel XL 5 mg Prolonged Release Tablets or other dihydropyridines because of the theoretical risk of cross-reactivity.
Neofel XL 5 mg Prolonged Release Tablets should not be used in patients with clinically significant aortic stenosis, and during or within one month of a myocardial infarction.
As with other calcium channel blockers, Neofel XL 5 mg Prolonged Release Tablets should be discontinued in patients who develop cardiogenic shock.
4.4 Special warnings and precautions for use
As with other vasodilators, Neofel XL 5 mg Prolonged Release Tablets may, in rare cases, precipitate significant hypotension with tachycardia which in susceptible individuals may result in myocardial ischaemia.
There is no evidence that Neofel XL 5 mg Prolonged Release Tablets are useful for secondary prevention of myocardial infarction.
The efficacy and safety of Neofel XL 5 mg Prolonged Release Tablets in the treatment of malignant hypertension has not been studied.
Neofel XL 5 mg Prolonged Release Tablets should be used with caution in patients with severe left ventricular dysfunction.
Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
4.5 Interaction with other medicinal products and other forms of interaction
Concomitant administration of substances which interfere with the cytochrome P450 3A4 system may affect plasma concentrations of felodipine. Enzyme inhibitors such as cimetidine, macrolide antibiotics (e.g. erythromycin, clarithromycin), azole
antifungals (e.g. ketoconazole, itraconazole) and protease inhibitors (e.g. nelfinavir, ritonavir, indinavir) impair the elimination of felodipine, and Neofel XL 5 mg Prolonged Release Tablets dosage may need to be reduced when drugs are given concomitantly. Conversely, powerful enzyme inducing agents such as some anticonvulsants (phenytoin, carbamazepine, phenobarbitone) can increase felodipine elimination and higher than normal Neofel XL 5 mg Prolonged Release Tablets doses may be required in patients taking the drugs.
No dosage adjustment is required when Neofel XL 5 mg Prolonged Release Tablets are given concomitantly with digoxin.
Felodipine does not appear to affect the unbound fraction of other extensively plasma protein bound drugs such as warfarin.
Grapefruit juice results in increased peak plasma levels and bioavailability possibly due to an interaction with flavonoids in the fruit juice. This interaction has been seen with other dihydropyridine calcium antagonists and represents a class effect.
Therefore grapefruit juice should not be taken together with Neofel XL 5 mg Prolonged Release Tablets.
Felodipine may increase the plasma concentration of tacrolimus. When used together, the tacrolimus serum concentration should be monitored and the tacrolimus dose adjusted when necessary.
4.6 Fertility, pregnancy and lactation
Felodipine should not be given during pregnancy.
In a study on fertility and general reproductive performance in rats, a prolongation of parturition resulting in difficult labour, increased foetal deaths and early postnatal deaths were observed in the medium- and high-dose groups. Reproductive studies in rabbits have shown a dose-related reversible enlargement of the mammary glands of the parent animals and dose-related digital abnormalities in the foetuses when felodipine was administered during stages of early foetal development.
Felodipine has been detected in breast milk, but it is unknown whether it has harmful effects on the new-born.
4.7 Effects on ability to drive and use machines
None.
4.8 Undesirable effects
As with other calcium antagonists, flushing, headache, palpitations, dizziness and fatigue may occur. These reactions are usually transient and are most likely to occur at the start of treatment or after an increase in dosage. Ankle swelling, resulting from precapillary vasodilatation, may occur. The degree of ankle swelling is dose related.
As with other dihydropyridines, aggravation of angina has been reported in a small number of individuals especially after starting treatment. This is more likely to happen in patients with symptomatic ischaemic heart disease.
In patients with gingivitis/periodontitis, mild gingival enlargement has been reported with Neofel XL Prolonged Release Tablets, as with other calcium antagonists. The enlargement can be avoided or reversed by careful dental hygiene.
The following adverse events have been reported from clinical trials and from Post Marketing Surveillance.
Frequency: very common (>1/10); common (>1/100, <1/10); uncommon (>1/1,000, <1/100); rare (>1/10,000, <1/1,000), very rare (<1/10,000)
|
Frequencies/Organ System |
Very Common (> 1/10) |
Common (> 1/100, <1/10 ) |
Uncommon >1/1,000, <1/100 |
Rare (>1/10,000, <1/1,000) |
Very Rare (<1/10,000) |
|
Cardiac disorders |
Tachycardia, palpitations | ||||
|
Nervous system disorders |
Headache |
Dizziness, paraesthesiae |
Syncope | ||
|
Gastrointestinal disorders |
Nausea, abdominal pain |
Vomiting |
Gum hyperplasia, gingivitis | ||
|
Renal and urinary disorders |
Polyuria | ||||
|
Skin and subcutaneous tissue disorders |
Rash, pruritus |
Urticaria |
Angioedema, photosensitivity, | ||
|
Musculoskeletal and connective tissue disorders |
Athralgia, myalgia | ||||
|
Vascular disorders |
Flushing |
Peripheral oedema (dose related) |
Hypotension, myocardial ischaemia |
Leucocytoclastic vasculitis | |
|
General disorders and administration site conditions |
Fatigue |
Fever | |||
|
Immune system disorders |
Hypersensitivity reactions | ||||
|
Hepatobiliary disorders |
Increased liver enzymes | ||||
|
Psychiatric |
Impotence, |
|
Frequencies/Organ System |
Very Common (> 1/10) |
Common (> 1/100, <1/10 ) |
Uncommon >1/1,000, <1/100 |
Rare (>1/10,000, <1/1,000) |
Very Rare (<1/10,000) |
|
disorders |
sexual dysfunction |
4.9 Overdose
Symptoms: Overdosage may cause excessive peripheral vasodilatation with marked hypotension which may sometimes be accompanied by bradycardia.
Management: Severe hypotension should be treated symptomatically, with the patient placed supine and the legs elevated. Bradycardia, if present, should be treated with atropine 0.5-1 mg i.v. If this is not sufficient, plasma volume should be increased by infusion of e.g. glucose, saline or dextran. Sympathomimetic drugs with predominant effect on the (a1-adrenoceptor may be given e.g. metaraminol or phenylephrine.
5 PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Felodipine is a vascular selective calcium antagonist, which lowers arterial blood pressure by decreasing peripheral vascular residence. Due to the high degree of selectivity for smooth muscle in the arterioles, felodipine in therapeutic doses has no direct effect on cardiac contractility or conduction.
It can be used as monotherapy or in combination with other antihypertensive drugs, e.g. ^-receptor blockers, diuretics or ACE-inhibitors, in order to achieve an increased antihypertensive effect. Felodipine reduces both systolic and diastolic blood pressure and can be used in isolated systolic hypertension. In a study of 12 patients, felodipine maintained its antihypertensive effect during concomitant therapy with indomethacin.
Because there is no effect on venous smooth muscle or adrenergic vasomotor control, felodipine is not associated with orthostatic hypotension.
Felodipine has anti-anginal and anti-ischaemic effects due to improved myocardial oxygen supply/ demand balance. Coronary vascular resistance is decreased and coronary blood flow as well as myocardial oxygen supply are increased by felodipine due to dilation of both epicardial arteries and arterioles. Felodipine effectively counteracts coronary vasospasm. The reduction in systemic blood pressure caused by felodipine leads to decreased left ventricular afterload.
Felodipine improves exercise tolerance and reduces anginal attacks in patients with stable effort induced angina pectoris. Both symptomatic and silent myocardial ischaemia are reduced by felodipine in patients with vasospastic angina. Felodipine can be used as monotherapy or in combination with ^-receptor blockers in patients with stable angina pectoris.
Felodipine possesses a mild natriuretic/diuretic effect and generalised fluid retention does not occur.
Felodipine is well tolerated in patients with concomitant disease such as congestive heart failure well controlled on appropriate therapy, asthma and other obstructive pulmonary diseases, diabetes, gout, hyperlipidemia impaired renal function, renal transplant recipients and Raynaud's disease. Felodipine has no significant effect on bland glucose levels or lipid profiles.
Haemodynamic effects: The primary haemodynamic effect of felodipine is a reduction of total peripheral vascular resistance which leads to a decrease in blood pressure. These effects are dose- dependent. In patients with mild to moderate essential hypertension, a reduction in blood pressure usually occurs 2 hours after the first oral dose and lasts for at least 24 hours with a trough/peak ratio usually above 50%.
Plasma concentration of felodipine and decrease in total peripheral resistance and blood pressure are positively correlated.
Electrophysiological and other cardiac effects: Felodipine in therapeutic doses has no effect on cardiac contractility or atrioventricular conduction or refractoriness.
Renal effects: Felodipine has a natriuretic and diuretic effect. Studies have shown that the tubular reabsorption of filtered sodium is reduced. This counteracts the salt and water retention observed for other vasodilators. Felodipine does not affect the daily potassium excretion. The renal vascular resistance is decreased by felodipine. Normal glomerular filtration rate is unchanged. In patients with impaired renal function glomerular filtration rate may increase.
Felodipine is well tolerated in renal transplant recipients.
Site and mechanism of action: The predominant pharmacodynamic feature of felodipine is its pronounced vascular versus myocardial selectivity. Myogenically active smooth muscles in arterial resistance vessels are particularly sensitive to felodipine.
Felodipine inhibits electrical and contractile activity of vascular smooth muscle cells via an effect on the calcium channels in the cell membrane.
There is limited clinical trial experience of the use of felodipine in hypertensive paediatric patients. In a randomised, double-blind, 3-week, parallel group study in children aged 6-16 years with primary hypertension, the antihypertensive effects of once daily felodipine 2.5 mg (n=33), 5 mg (n=33) and 10 mg (n=31) were compared with placebo (n=35). The study failed to demonstrate the efficacy of felodipine in lowering blood pressure in children aged 6-16 years.
The long-term effects of felodipine on growth, puberty and general development have
not been studied. The long-term efficacy of antihypertensive therapy as therapy in childhood to reduce cardiovascular morbidity and mortality in adulthood has also not been established.
5.2 Pharmacokinetic properties
Absorption and distribution: Felodipine is completely absorbed from the gastrointestinal tract after administration of felodipine extended release tablets.
The systemic availability of felodipine is approximately 15% in man and is independent of dose in the therapeutic dose range.
With the extended-release tablets the absorption phase is prolonged. This results in even felodipine plasma concentrations within the therapeutic range for 24 hours.
The plasma protein binding of felodipine is approximately 99%. It is bound predominantly to the albumin fraction.
Elimination and metabolism: The average half-life of felodipine in the terminal phase is 25 hours. There is no significant accumulation during long-term treatment. Felodipine is extensively metabolised by the liver and all identified metabolites are inactive. Elderly patients and patients with reduced liver function have an average higher plasma concentration of felodipine than younger patients.
About 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 the urine.
The kinetics of felodipine are not changed in patients with renal impairment.
In a single dose (felodipine prolonged release 5 mg) pharmacokinetic study with a limited number of children aged between 6 and 16 years (n=12) there was no apparent relationship between the age and AUC, Cmax or half-life of felodipine.
5.3 Preclinical safety data
Felodipine is a calcium antagonist and lowers arterial blood pressure by decreasing vascular resistance. In general a reduction in blood pressure is evident 2 hours after the first oral dose and at steady state lasts for at least 24 hours after dose.
Felodipine exhibits a high degree of selectivity for smooth muscles in the arterioles and in therapeutic doses has no direct effect on cardiac contractility. Felodipine does not affect venous smooth muscle and adrenergic vasomotor control.
Electrophysiological studies have shown that felodipine has no direct effect on conduction in the specialised conducting system of the heart and no effect on the AV nodal refractories.
Neofel XL 5 mg Prolonged Release Tablets possess a mild natriuretic/diuretic effect and does not produce general fluid retention, nor affect daily potassium excretion. Neofel XL 5 mg Prolonged Release Tablets are well tolerated in patients with congestive heart failure.
6 PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Lactose monohydrate, Cellulose microcristalline, Hypromellose, Povidone, Propyl gallate, Silica colloidal anhydrous, Magnesium stearate, Ferric oxide yellow (E172), Ferric oxide red (E172), Titanium dioxide (E171), Talc, Propylene glycol.
6.2 Incompatibilities
None stated.
6.3 Shelf life
48 months.
6.4 Special precautions for storage
Do not store above 25°C. Store in the original package.
6.5 Nature and contents of container
PVC/PE/PVDC Aluminium Blisters.
A single pack contains 10, 20, 28, 30, 50, 56 or 100 tablets.
6.6 Special precautions for disposal
None stated.
7 MARKETING AUTHORISATION HOLDER
Fannin (UK) Limited
42-46 Booth Drive Park Farm South Wellingborough Northamptonshire NN8 6GT UK
8 MARKETING AUTHORISATION NUMBER(S)
PL 20417/0057
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
23/02/2009
10 DATE OF REVISION OF THE TEXT
02/08/2011