Active ingredients: Felodipine
Prevex 5 mg prolonged-release tablets
Prevex 10 mg prolonged-release tablets
Indications Why is Prevex used? What is it for?
Dihydropyridine derivative with antihypertensive and antianginal activity.
Hypertension. Stable angina pectoris
Contraindications When Prevex should not be used
Pregnancy; known hypersensitivity to felodipine or to any of the excipients; uncompensated heart failure; acute myocardial infarction; unstable angina pectoris; hemodynamically significant cardiac valve obstruction; dynamic obstruction of cardiac outflow; cardiogenic shock.
Precautions for use What you need to know before taking Prevex
Felodipine can cause the onset of significant hypotension, resulting in tachycardia. This can cause myocardial ischaemia in predisposed patients.
Felodipine should be used with caution in patients who have a predisposition to develop tachycardia.
Felodipine is eliminated by the liver. Consequently, higher therapeutic concentrations and a superior response can be expected in patients with clearly reduced liver function (See also section DOSE, METHOD AND TIME OF ADMINISTRATION).
Mild gingival hyperplasia has been reported in patients with marked gingivitis / periodontitis. Such hyperplasia can be avoided or reversed by "careful dental hygiene
Interactions Which drugs or foods may change the effect of Prevex
Enzymatic interactions
Felodipine is metabolised in the liver by cytochrome P450 3A4 (CYP3A4). CYP3A4 inhibitors and inducers may affect felodipine plasma concentrations.
Interactions causing an increase in the plasma concentration of felodipine
Cytochrome P450 3A4 enzyme inhibitors, such as cimetidine, erythromycin, itraconazole, ketoconazole, anti-HIV drugs / protease inhibitors (e.g. ritonavir) and certain flavonoids present in grapefruit juice have been shown to cause increased plasma concentrations of felodipine.
Interactions causing decreased plasma concentration of felodipine Enzyme inducers of cytochrome P450 3A4 such as phenytoin, carbamazepine, rifampicin, barbiturates, efavirenz, nevirapine and Hypericum Perforatum (St. John's wort) may lead to decreased plasma concentrations of felodipine.
Other interactions
Ciclosporin: Felodipine does not produce changes in plasma concentrations of cyclosporine.
Tacrolimus: Felodipine may increase the concentration of tacrolimus. When taken together, the serum concentrations of tacrolimus should be controlled and the dosage of tacrolimus may need to be adjusted.
Warnings It is important to know that:
Prevex contains lactose so in case of ascertained intolerance to sugars contact your doctor before taking the medicine.
Fertility, pregnancy and lactation
Pregnancy: Prevex should not be used during pregnancy.
Breastfeeding: Felodipine is detected in breast milk. However, if the mother takes therapeutic doses while breastfeeding, this drug is unlikely to affect the infant.
Fertility: No data on patient fertility are available.
Effects on ability to drive and use machines
Patients should know how they react to felodipine treatment before driving or using machines, as dizziness or fatigue may occur sporadically.
Dosage and method of use How to use Prevex: Dosage
Hypertension
The dose should be adjusted on an individual basis.
Treatment can start with a dose of 5 mg once a day. When needed, the dose can be reduced to 2.5 mg or increased to 10 mg per day based on the patient's response. If necessary, another antihypertensive can be added.
The usual maintenance dose is 5 mg once a day.
Hepatic impairment
Patients with hepatic impairment may have elevated plasma concentrations of felodipine and may respond to treatment with lower doses (see section Precautions for use).
Angina pectoris
The dose should be adjusted on an individual basis.
Treatment should be started with a dose of 5 mg once daily, and should be increased to 10 mg once daily as needed.
Elderly population Treatment should begin with the lowest available dose.
Renal impairment
No dose adjustment is necessary in patients with impaired renal function.
Pediatric population
The experience gained from clinical trials on the use of felodipine in pediatric hypertensive patients is limited.
Administration
The tablet should be taken in the morning, swallowed whole with water and should not be broken, crushed or chewed in order to maintain the sustained release properties. The tablets can be taken on an empty stomach or after a light meal low in fat or carbohydrates.
Overdose What to do if you have taken too much Prevex
Symptoms: Overdose can cause excessive peripheral vasodilation, with marked hypotension and sometimes bradycardia.
Treatment: activated charcoal, if necessary, perform gastric lavage.
If severe hypotension occurs, symptomatic treatment should be instituted.
Place the patient supine with the lower limbs elevated.
In case of concomitant bradycardia, 0.5-1 mg of atropine should be administered intravenously.
If this is not enough, increase the volume by infusing physiological solutions (saline, glucose or dextran). If the measures described above are insufficient, sympathomimetic drugs with a predominant effect on α1-adrenergic receptors can be administered.
Side Effects What are the side effects of Prevex
Felodipine can cause flushing, headache, palpitations, dizziness, fatigue.
These reactions, which usually appear at the start of treatment or when the administered dose is increased, are generally transient and diminish in intensity over time.
Felodipine can also cause dose-dependent ankle edema, induced by precapillary vasodilation and unrelated to generalized fluid retention.
Based on the experience gained from clinical studies, 2% of patients discontinued treatment due to the onset of ankle edema.
Mild gingival hyperplasia has been observed in patients with pronounced gingivitis / periodontitis. This hyperplasia can be avoided or treated with "careful oral hygiene. Nausea, abdominal pain, rash, tachycardia, hypotension, dizziness, paraesthesia, pruritus, asthenia, peripheral edema have also been reported. Arthralgia and myalgia have been reported rarely. , urticaria, vomiting, syncope, cases of impotence and disorders of the sexual sphere .. Very rarely have been reported hypersensitivity reactions (eg angioedema and fever), increased liver enzymes, photosensitivity, leukocytoclastic vasculitis, frequent urge to urinate.
Compliance with the instructions contained in the package leaflet reduces the risk of undesirable effects.
It is important to inform the doctor or pharmacist of any undesirable effect, even if not described in the package leaflet.
Expiry and Retention
Expiry: see the expiry date printed on the package.
WARNING: do not use the medicine after the expiry date indicated on the package. This date refers to the intact, properly stored packaging.
Store below 30 ° C.
KEEP THE MEDICINAL PRODUCT OUT OF THE REACH AND SIGHT OF CHILDREN
Other Information
Composition
Prevex 5 mg prolonged-release tablets
One prolonged-release tablet contains:
active ingredient: felodipine 5 mg.
Prevex 5 mg tablet is pink, circular, biconvex, engraved with "A / Fm" on one side and "5" on the other side, 9 mm in diameter.
Excipients: 40 polyoxylated hydrogenated castor oil; hydroxypropylcellulose; propyl gallate; hypromellose; sodium aluminum silicate; microcrystalline cellulose; anhydrous lactose; sodium stearyl fumarate; polyethylene glycol 6000; titanium dioxide E171; iron oxide E172; carnauba wax; purified water.
Prevex 10 mg prolonged-release tablets
One prolonged-release tablet contains:
active ingredient: felodipine 10 mg.
Prevex 10 mg tablet is reddish brown, circular, biconvex, engraved with "A / FE" on one side and "10" on the other side, 9 mm in diameter.
Excipients: 40 polyoxylated hydrogenated castor oil; hydroxypropylcellulose; propyl gallate; hypromellose; sodium aluminum silicate; microcrystalline cellulose; anhydrous lactose; sodium stearyl fumarate; polyethylene glycol 6000; titanium dioxide E171; iron oxide E176; carnauba wax; purified water.
Pharmaceutical form and content
Prevex 5 mg prolonged-release tablets:
28 prolonged-release tablets of 5 mg.
Prevex 10 mg prolonged-release tablets:
14 prolonged-release tablets of 10 mg.
28 prolonged-release tablets of 10 mg - NON-MARKET PACKAGING.
Source Package Leaflet: AIFA (Italian Medicines Agency). Content published in January 2016. The information present may not be up-to-date.
To have access to the most up-to-date version, it is advisable to access the AIFA (Italian Medicines Agency) website. Disclaimer and useful information.
01.0 NAME OF THE MEDICINAL PRODUCT
PREVEX
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION
Prevex 5 mg prolonged-release tablets
Each tablet contains 5 mg of felodipine.
Excipients with known effects:
Each tablet contains 28 mg of lactose and 5 mg of macrogolglycerol hydroxystearate.
Prevex 10 mg prolonged-release tablets
Each tablet contains 10 mg of felodipine.
Excipients with known effects:
Each tablet contains 28 mg of lactose and 10 mg of macrogolglycerol hydroxystearate.
For the full list of excipients, see section 6.1
03.0 PHARMACEUTICAL FORM
Prevex 5 mg prolonged-release tablets
The tablet is pink, circular, biconvex, engraved with A / Fm on one side and 5 on the other side, with a diameter of 9 mm.
Prevex 10 mg prolonged-release tablets
The tablet is reddish brown, circular, biconvex, with A / FE engraved on one side and 10 on the other side, 9 mm in diameter.
04.0 CLINICAL INFORMATION
04.1 Therapeutic indications
Hypertension
Stable angina pectoris
04.2 Posology and method of administration
Dosage
Hypertension
The dose should be adjusted on an individual basis. Treatment can be started with a dose of 5 mg once daily. When needed, the dose can be reduced to 2.5 mg or increased to 10 mg per day based on the patient's response. If necessary, another antihypertensive can be added. The usual maintenance dose is 5 mg once a day.
Angina pectoris
The dose should be adjusted on an individual basis. Treatment should be started with a dose of 5 mg once daily and, if necessary, increased to 10 mg once daily.
Elderly population
Initial treatment with the lowest available dose should be considered
Renal impairment
No dose adjustment is necessary in patients with impaired renal function.
Hepatic impairment
Patients with hepatic impairment may have elevated plasma concentrations of felodipine and may respond to treatment with lower doses (see section 4.4).
Pediatric population
Experience from clinical trials on the use of felodipine in pediatric hypertensive patients is limited (see sections 5.1 and 5.2).
Method of administration
The tablets should be taken in the morning and swallowed with water. To maintain the prolonged release properties, the tablets should not be divided, crushed or chewed. The tablets can be taken without food or after a light meal low in fat or carbohydrates.
04.3 Contraindications
• Pregnancy
• Hypersensitivity to felodipine or to any of the excipients listed in section 6.1
• Uncompensated heart failure
• Acute myocardial infarction
• Unstable angina pectoris
• Hemodynamically significant cardiac valve obstruction
• Dynamic obstruction of cardiac outflow
04.4 Special warnings and appropriate precautions for use
The efficacy and safety of felodipine in the treatment of hypertensive emergencies have not been studied.
Felodipine can cause the onset of significant hypotension, resulting in tachycardia. This can cause myocardial ischaemia in susceptible patients.
Felodipine is eliminated by the liver. Consequently, higher therapeutic concentrations and a superior response can be expected in patients with clearly reduced liver function (see section 4.2).
Concomitant administration of medicinal products that significantly induce or inhibit CYP3A4 enzymes results in a marked decrease or increase in plasma felodipine levels, respectively. Concomitant administration should therefore be avoided (see section 4.5).
Prevex contains lactose. Patients with rare hereditary problems of galactose intolerance or glucose-galactose malabsorption should not take this medicine.
Prevex contains castor oil, which can cause stomach upset and diarrhea.
Mild gingival enlargement has been reported in patients with marked gingivitis / periodontitis. This enlargement can be avoided or reversed with "careful dental hygiene.
04.5 Interactions with other medicinal products and other forms of interaction
Felodipine is metabolised in the liver by cytochrome P450 3A4 (CYP3A4). Concomitant administration with substances that interfere with CYP3A4 enzymes may affect the plasma concentrations of felodipine.
Enzymatic interactions
Inhibitors and inducers of the cytochrome P450 isoenzyme 3A4 may affect the plasma concentrations of felodipine.
Interactions causing an increase in the plasma concentration of felodipine
Enzyme inhibitors of the CYP3A4 enzyme have been shown to cause increased plasma concentrations of felodipine.
Felodipine Cmax and AUC increased 8-fold and 6-fold, respectively, when felodipine was administered with the potent CYP3A4 inhibitor itraconazole. When felodipine and erythromycin were co-administered, felodipine Cmax and AUC increased. about 2.5 times. Cimetidine increased felodipine Cmax and AUC by approximately 55%. Combination with potent CYP3A4 inhibitors should be avoided.
In case of clinically significant adverse events due to elevated felodipine exposure when administered in combination with potent CYP3A4 inhibitors, adjustment of the felodipine dose and / or discontinuation of the CYP3A4 inhibitor should be considered.
Examples:
• Cimetidine
• Erythromycin
• Itraconazole
• Ketoconazole
• Anti HIV / prosthesis inhibitors (eg ritonavir)
• Certain flavonoids present in grapefruit juice
Felodipine tablets should not be taken with grapefruit juice.
Interactions causing a decrease in the plasma concentration of felodipine
Enzyme inducers of the cytochrome P4503A4 system have been shown to cause decreased plasma concentrations of felodipine.
When felodipine was co-administered with carbamazepine, phenytoin or phenobarbital, felodipine Cmax and AUC decreased by 82% and 96%, respectively. Association with potent CYP3A4 inducers should be avoided.
In case of lack of efficacy due to reduced exposure to felodipine, when administered with potent CYP3A4 inducers, adjustment of the felodipine dose and / or discontinuation of the CYP3A4 inducer should be considered.
Examples:
• Phenytoin
• Carbamazepine
• Rifampicin
• Barbiturates
• Efavirenz
• Nevirapine
• Hypericum perforatum (St. John's wort)
Other interactions
Tacrolimus: Felodipine may increase the concentration of tacrolimus. When taken together, tacrolimus serum concentrations should be monitored and the tacrolimus dosage may need to be adjusted.
Ciclosporin: Felodipine does not produce changes in plasma concentrations of cyclosporine.
04.6 Pregnancy and breastfeeding
Pregnancy
Felodipine should not be used during pregnancy. Effects on fetal development thought to be due to the pharmacological action of felodipine have been reported in preclinical reproductive toxicity studies.
Feeding time
Felodipine has been detected in breast milk, due to the lack of data on the potential effect on the newborn, treatment is not recommended during breastfeeding.
Fertility
There are no data on the effects of felodipine on patient fertility. In a preclinical study of reproductive toxicity in rats (see section 5.3), effects on fetal development but no effects on fertility were reported at doses close to therapeutic.
04.7 Effects on ability to drive and use machines
Felodipine has mild or moderate effects on the ability to drive or use machines. If patients taking felodipine suffer from headache, nausea, dizziness or fatigue, the ability to react may be impaired. Particular caution is recommended at the start of treatment.
04.8 Undesirable effects
Summary of the safety profile
Felodipine can cause flushing, 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 they occur, these reactions are usually transient and diminish over time.
Patients treated with felodipine may experience dose-dependent ankle edema. This is due to precapillary vasodilation and is not related to any generalized water retention.
Mild gingival enlargement has been reported in patients with marked gingivitis / periodontitis. This enlargement can be avoided or reversed with "careful dental hygiene.
Table of adverse reactions
The adverse reactions listed below have been identified during clinical trials and in the post-marketing phase.
The following frequency definitions are used:
Very common ≥1 / 10
Common ≥1 / 100,
Uncommon ≥1 / 1,000,
Rare ≥1 / 10,000,
Very rare
Reporting of suspected adverse reactions
Reporting of suspected adverse reactions occurring after authorization of the medicinal product is important as it allows continuous monitoring of the benefit / risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system. "address www.agenziafarmaco.gov.it/it/responsabili.
04.9 Overdose
Symptoms
Overdose can cause excessive peripheral vasodilation, with marked hypotension and sometimes bradycardia.
Treatment if justified: activated vegetable charcoal, gastric lavage if performed within one hour after ingestion.
If severe hypotension occurs, symptomatic treatment should be instituted.
The patient should be placed in the supine position with the legs raised. In case of concomitant bradycardia, 0.5-1 mg of atropine should be administered intravenously. If this is not enough, the blood volume should be increased by infusion e.g. glucose, saline or dextran).
If the measures described above are insufficient, can sympathomimetic drugs with a predominant effect on adrenergic receptors be administered? 1.
05.0 PHARMACOLOGICAL PROPERTIES
05.1 Pharmacodynamic properties
Pharmacotherapeutic group: calcium channel blockers, dihydropyridine derivatives
ATC code: C08CA02
Mechanism of action
Felodipine is a highly selective vascular calcium channel blocker, which reduces blood pressure by reducing systemic vascular resistance. Due to its high degree of selectivity on arteriolar smooth muscle, felodipine, at therapeutic doses, does not have a direct effect on cardiac contractility and conduction.
Since there is no effect on venous wall smooth muscle or vasomotor adrenergic control, felodipine is not associated with orthostatic hypotension.
Felodipine has a mild natriuretic / diuretic effect and does not cause water retention.
Pharmacodynamic effects
Felodipine is effective in all stages of hypertension. It can be used both alone and in combination with other antihypertensive drugs, for example with beta-blockers, diuretics or ACE inhibitors, in order to obtain a greater antihypertensive effect. Felodipine is effective in reducing both systolic blood pressure (PAS) and diastolic blood pressure (PAD) and can be used in the treatment of isolated systolic hypertension.
Felodipine has an antianginal and anti-ischemic effect due to the improvement of the oxygen supply / demand balance. The reduction in coronary vascular resistance and the increase in coronary flow and oxygen supply by felodipine are due to dilation of the epicardial arteries and arterioles.
The reduction in systemic blood pressure caused by felodipine leads to a decrease in left ventricular afterload and a decrease in myocardial oxygen demand.
Felodipine improves exercise tolerance and reduces angina attacks in patients with stable exertional angina pectoris. Felodipine can be used alone or in combination with a beta blocker in patients with stable angina pectoris.
Hemodynamic effects
The primary haemodynamic effect of felodipine is a reduction in total peripheral vascular resistance, resulting in a decrease in blood pressure. These effects are dose-dependent. Generally there is a decrease in blood pressure two hours after the first oral dose and this decrease persists. for at least 24 hours, with a valley / peak ratio greater than 50%.
Plasma concentrations of felodipine are directly related to the reduction of peripheral vascular resistance and blood pressure.
Cardiac effects
At therapeutic doses, felodipine has no effect on cardiac contractility, atrioventricular conduction or refractoriness.
Antihypertensive treatment with felodipine is associated with a significant regression of pre-existing left ventricular hypertrophy.
Kidney effects
Felodipine has a natriuretic and diuretic effect due to the reduction of tubular reabsorption of filtered sodium. Felodipine does not modify the daily excretion of potassium. Renal vascular resistance is reduced by felodipine.
Felodipine does not affect the urinary excretion of albumin.
In patients treated with cyclosporine, after kidney transplantation, felodipine reduces blood pressure, improves renal blood flow and glomerular filtration rate. Felodipine is also able to improve the function of the transplanted kidney early.
Clinical efficacy
In the HOT (Hypertension Optimal Treatment) clinical trial with felodipine as background therapy, the correlation between major cardiovascular events (e.g. acute myocardial infarction, stroke and death from cardiovascular causes) and three target diastolic blood pressure levels ≤90 was investigated. mmHg, ≤85 mmHg and ≤80 mmHg and the blood pressure achieved with felodipine.
A total of 18,790 hypertensive patients (PAD 100-115 mmHg) aged between 50 and 80 years were followed for a mean period of 3.8 years (range 3.3-4.9). Felodipine was given as monotherapy or in combination with a beta blocker, and / or ACE inhibitor and / or diuretic. The study demonstrated the benefit of reducing PAS and PAD to levels of 139 and 83 mmHg, respectively.
Based on the STOP-2 study (Swedish Trial in Old Patients with Hypertension-2 study) conducted in 6614 patients aged 70 to 84 years, the calcium antagonists of the dihydropyridine class (felodipine and isradipine) demonstrated the same preventive effect. on cardiovascular mortality and morbidity of other classes of commonly used antihypertensive drugs, such as ACE inhibitors, beta-blockers and diuretics.
Pediatric population
The clinical experience of the use of felodipine in hypertensive pediatric patients is limited. In a randomized, double-blind, parallel-group, three-week study in children aged 6 to 16 years with primary hypertension, the antihypertensive effect of felodipine 2.5 mg (n = 33), 5 mg (n = 33) and 10 mg (n = 31) administered once daily was compared with placebo (n = 35). The study failed to demonstrate the efficacy of felodipine in lowering blood pressure in children aged 6 and 16 years (see section 4.2).
The long-term effects of felodipine on growth, puberty and general development have not been studied. Furthermore, the efficacy of long-term antihypertensive therapy of felodipine as therapy in childhood for the reduction of cardiovascular morbidity and mortality in adulthood has not been established.
05.2 Pharmacokinetic properties
Absorption
Following oral administration of the prolonged-release tablets, felodipine is completely absorbed from the gastrointestinal tract. The systemic bioavailability of felodipine is approximately 15% and is dose independent over the therapeutic range.
Prolonged-release tablets result in a prolonged absorption phase of felodipine. This results in a uniform plasma concentration curve and therapeutic concentrations still present 24 hours after administration. Maximum plasma concentrations (tmax) with the prolonged-release form are reached after 3-5 hours. The rate but not the extent of felodipine absorption is increased with the intake of high fat food.
Distribution
Plasma protein binding is approximately 99%, predominantly with the albumin fraction. The volume of distribution at steady state is 10 L / kg.
Biotransformation
Felodipine is extensively metabolised in the liver by cytochrome P450 3A4 (CYP3A4) and all identified metabolites are inactive.
Felodipine is a high clearance medicinal product, the mean blood clearance is 1200 ml / min. No significant accumulation occurs during prolonged treatments.
Elderly patients and those with impaired liver function have on average higher plasma concentrations of felodipine than younger patients. The pharmacokinetics of felodipine do not change in patients with impaired renal function including subjects on hemodialysis.
Elimination
The mean elimination half-life of felodipine is approximately 25 hours and steady state is reached after 5 days. During prolonged treatment there is no risk of accumulation. About 70% of the administered dose is excreted in the form of metabolites in the urine, the remaining fraction is excreted in the faeces.
Less than 0.5% of the administered dose is found unchanged in the urine.
Linearity / Non-linearity
Plasma concentrations are directly proportional to dose within the therapeutic range 2.5-10 mg.
Pediatric population
In a single dose pharmacokinetic study (5 mg extended-release felodipine) with a limited number of children aged 6 to 16 years (n = 12) there was no apparent correlation between age and AUC, C felodipine.
05.3 Preclinical safety data
Reproductive toxicity
In a fertility and general reproductive performance study in felodipine-treated rats, prolongation of parturition time leading to difficulty in labor was observed in the medium-dose and high-dose groups. increased fetal deaths and early postnatal deaths. These effects were attributed to the inhibitory effect on uterine contractility of felodipine at high doses. No effect on fertility was observed when rats were administered doses in the therapeutic range.
Reproduction studies in rabbits have shown dose-related and reversible enlargement of the mammary glands in mothers and dose-related digital abnormalities in fetuses. These abnormalities were found when felodipine was administered during the early stages of fetal development (before day 15 of pregnancy). An abnormal position of the distal phalanx was observed in a monkey reproduction study.
There are no other preclinical findings of concern and the reproductive results are considered to be related to the pharmacological action of felodipine when administered to normotensive animals. The clinical relevance of these findings for patients receiving felodipine is unknown. However, based on the findings. Internal database information for patient safety No cases of phalanx abnormalities have been reported in fetuses / neonates exposed to felodipine in utero.
06.0 PHARMACEUTICAL INFORMATION
06.1 Excipients
Core of the tablet
Hydroxypropylcellulose
Hypromellose 50 mPa • s
Hypromellose 10,000 mPa • s
Anhydrous lactose
macrogolglycerol hydroxystearate
Microcrystalline cellulose
Propyl gallate
Sodium aluminum silicate
Sodium stearyl fumarate
Coating
Carnauba wax
Red-brown iron oxide (E 172)
Yellow iron oxide (E 172)
Hypromellose 6 mPa • s
Macrogol 6000
Titanium dioxide (E 171)
06.2 Incompatibility
Not relevant.
06.3 Period of validity
3 years
06.4 Special precautions for storage
Do not store above 30 ° C
06.5 Nature of the immediate packaging and contents of the package
PVC / PVDC or aluminum blisters
Prevex 5 mg prolonged-release tablets
Pack sizes: 1 blister of 28 tablets or 2 blisters of 14 tablets or 4 blisters of 7 tablets
Prevex 10 mg prolonged-release tablets
Pack sizes: 1 blister of 14 tablets or 1 blister of 28 tablets or 2 blisters of 14 tablets or 4 blisters of 7 tablets.
Not all pack sizes may be marketed.
06.6 Instructions for use and handling
Unused medicine and wastes derived from this medicine must be disposed of in accordance with local regulations.
07.0 MARKETING AUTHORIZATION HOLDER
Simesa S.p.A.
Ferraris Palace
Via Ludovico il Moro 6 / C - Basiglio (MI)
08.0 MARKETING AUTHORIZATION NUMBER
027372010 "5 MG EXTENDED RELEASE TABLETS" 28 TABLETS
027372022 "10 MG EXTENDED RELEASE TABLETS" 14 TABLETS
027372034 "10 MG EXTENDED RELEASE TABLETS" 28 TABLETS
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION
Date of first authorization: 17 December 1991
Date of most recent renewal: January 2, 2007
10.0 DATE OF REVISION OF THE TEXT
June 17, 2017
