Felodipin Stada 5/10 Retard

Felodipine.

Film-coated tablet: Each film-coated tablet contains 5 mg of felodipine.
Excipients/Inactive Ingredients: Lactose monohydrate, Microcrystalline cellulose, Hypromellose, Povidone K25, Propyl gallate, Anhydrous colloidal silica, Magnesium stearate, Red ferric oxide, Yellow ferric oxide, Titanium dioxide, Talc, Propylene glycol.

Pharmacology: Pharmacodynamics: Felodipine is a vascular selective calcium antagonist, which lowers arterial blood pressure by decreasing peripheral vascular resistance. 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., beta-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.
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 beta-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 diseases 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 blood glucose levels or lipid profiles.
Haemodynamic effects: The effects of felodipine 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%.
Cardiac effects: Felodipine in therapeutic doses has no effect on cardiac contractility or atrioventricular conduction or refractoriness. Antihypertensive treatment with felodipine is associated with significant regression of pre-existing left ventricular hypertrophy.
Renal effects: Felodipine has a natriuretic and diuretic effect. Felodipine does not affect the daily potassium excretion. In patients with impaired renal function glomerular filtration rate may increase.
Pharmacokinetics: 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 in the liver by cytochrome P450 3A4 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 is not changed in patients with renal impairment.

In the management of hypertension and prophylaxis of chronic stable angina pectoris.

Recommended Dose: Adults: Hypertension: The dose should be adjusted to the individual requirements of the patient. The recommended starting dose is 5 mg once daily. Depending on the patient's response, the dosage can, where applicable be decreased to 2.5 mg or increased to 10 mg daily. Alternatively, dosage can be initiated at 2.5 mg daily and titrated upward according to blood pressure response and patient tolerance. The usual maintenance dosage is 2.5-10 mg given once daily.
If necessary another antihypertensive agent may be added. The standard 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.
Stable angina pectoris: 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.
Felodipine can be used in combination with beta-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.
Elderly population: Initial treatment with lowest available dose should be considered. The usual initial dose is 2.5 mg daily.
Hepatic impairment: Patients with impaired hepatic function may have elevated plasma concentrations of felodipine and may respond to lower doses. US licensed product information recommends that an initial dose of 2.5 mg once daily should be used in patients with hepatic impairment.
Renal impairment: Dose adjustment is not needed in patients with impaired renal function. The pharmacokinetics are not significantly affected in patients with impaired renal function.
Pediatric population: There is limited clinical trial experience of the use of felodipine in hypertensive pediatric patients. Felodipine is not recommended in children.
Mode of administration: Felodipine is administered orally. The tablets should be taken in the morning and be swallowed with water.
In order to keep the prolonged release properties, Felodipine film-coated tablet must not be divided, chewed or crushed. The tablets can be administered without food or following a light meal not rich in fat or carbohydrate.

Symptoms: Overdosage may cause excessive peripheral vasodilatation with marked hypotension and sometimes bradycardia.
Management: Activated charcoal, induction of vomiting or gastric lavage. If appropriate or indicated. Severe hypotension should be treated symptomatically with the patient placed supine and the legs elevated. In case of accompanying Bradycardia, atropine 0.5-1 mg should be administered intravenously. 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 α1-adrenoceptor may be given e.g. metaraminol or phenylephrine if the previously-mentioned measures are insufficient.

Known hypersensitivity to felodipine or any other component of the product.
Unstable angina pectoris.
Pregnancy.
Other dihydropyridines because of the theoretical risk of cross-reactivity.
Patients with clinically significant aortic stenosis, haemodynamically significant cardiac valvular obstruction, dynamic cardiac outflow obstruction, uncompensated heart failure and during or within one month of an acute myocardial infarction.
As with other calcium channel blockers, felodipine should be discontinued in patients who develop cardiogenic shock.

Because of the slow onset of hypotensive effect with extended-release tablets containing felodipine, these dosage forms are not suitable for use as acute therapy in rapidly reducing blood pressure in patients with severe hypertension in whom reduction of blood pressure was considered urgent (i.e., hypertensive urgencies) nor in hypertensive emergencies.
Concomitant administration of drugs that strongly induce or inhibit CYP3A4 enzymes result in extensively decreased or increased plasma levels of felodipine, respectively. Therefore, such combinations should be avoided.
Felodipine may cause significant hypotension with subsequent tachycardia. This may lead to myocardial ischaemia in susceptible patients.
Propensity for tachycardia.
Secondary prevention of myocardial infarction.
Malignant hypertension.
Severe left ventricular dysfunction.
Mild gingival enlargement has been reported in patients with pronounced gingivitis/periodontitis. The enlargement can be avoided or reversed by careful dental hygiene.
Felodipine is cleared by the liver. Consequently higher therapeutic concentrations and response can be expected in patients with clearly reduced liver function.
Felodipine contains lactose and patients with hereditary galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take Felodipine.
Effect on ability to drive and use machine: Patients should know how they react to felodipine before they drive or use machines because occasionally dizziness or fatigue may occur.

Pregnancy: Felodipine should not be given during pregnancy.
Lactation: Felodipine has been detected in breast milk, and due to insufficient data on potential effect on the infant, treatment is not recommended during breast-feeding.

Very common: Peripheral oedema.
Common: Headache, Flush.
Uncommon: Dizziness, paraesthesia, tachycardia, palpitations, hypotension, nausea, abdominal pain, rash, pruritus, fatigue.
Rare: Syncope, vomiting, urticaria, arthralgia, myalgia, impotence/sexual dysfunction.
Very rare: Gingival hyperplasia, gingivitis, increased liver enzymes, photosensitivity reactions, leucocytoclastic vasculitis, pollakisuria, hypersensitivity reactions.

Felodipine is metabolised in the liver by cytochrome P450 3A4 (CYP3A4); hence, interactions may occur if concomitantly administrated with felodipine.
With other drugs sharing the same metabolic partway (e.g. quindine (felodipine plasma concentration increase), diltiazem (felodipine plasma concentration increase), tacrolimus (tacrolimus exposure increase)).
With enzyme inducers (phenytoin, carbamazepine, phenobarbital, rifampicin, barbiturates, efavirenz, nevirapine, St. John's wort). These interactions lead to decreased plasma concentration of felodipine.
With enzyme inhibitors (verapamil, cimetidine, erythromycin, itraconazole, ketoconazole, HIV protease inhibitors, non-nucleoside reverse transcriptase inhibitors, quinupristin, dalfopristin, ethanol, nefazodone, grapefruit juice). These interactions lead to increased plasma concentration of felodipine.
β-Adrenergic blocking agents (propranolol, timolol): The risk of severe hypotension, exacerbation of angina, congestive heart failure and arrhythmia may be increased.
Fentanyl: Severe hypotension has occurred during surgery in patients receiving felodipine, a β-Adrenergic blocking agent and fentanyl concomitantly.
Digoxin: The serum digoxin concentrations may increase.
Hypotensive agents: Concomitant administration of felodipine with hypotensive agents (e.g. methyldopa, hydralazine, captopril, doxazosin) may increase the incidence of severe hypotension.

Store in a well-closed container, in a dry place. Do not store above 30°C.

Calcium Antagonists

C08CA02 - felodipine ; Belongs to the class of dihydropyridine derivative selective calcium-channel blockers with mainly vascular effects. Used in the treatment of cardiovascular diseases.

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