Vasexten - Package Leaflet

Indications Contraindications Precautions for use Interactions Warnings Dosage and method of use Overdose Undesirable Effects Shelf life and Storage Composition and pharmaceutical form

Active ingredients: Barnidipine (Barnidipine hydrochloride)

Vasexten 10 mg modified release capsules
Vasexten 20 mg modified release capsules

Why is Vasexten used? What is it for?

The active substance in Vasexten belongs to a group of medicines called calcium channel blockers. Vasexten causes blood vessels to dilate resulting in lowering of blood pressure. Vasexten capsules are "extended release". This means that the active principle is absorbed by the body gradually and its effect is prolonged over time. For this reason, only one administration per day is sufficient.

Vasexten is used to treat high blood pressure.

Contraindications When Vasexten should not be used

Do not take Vasexten

  • if you are allergic to barnidipine or any of the other ingredients of this medicine (listed in section 6)
  • if you are allergic to dihydropyridines (substances found in medicines used to treat hypertension)
  • if you suffer from liver disease
  • if you have severe kidney disease
  • if you have any of the following heart diseases: untreated heart failure, certain forms of chest pain (due to unstable angina pectoris) or acute cardiac arrest
  • if you use any of the following medicines: protease inhibitors (medicines used to treat AIDS), ketoconazole or itraconazole (medicines used to treat fungal infections), erythromycin or clarithromycin (antibiotics).

Precautions for use What you need to know before taking Vasexten

Talk to your doctor or pharmacist before taking Vasexten

  • if you have kidney disease
  • if you suffer from heart disease

Children and adolescents

Vasexten should not be given to children or adolescents under the age of 18.

Interactions Which drugs or foods may change the effect of Vasexten

Other medicines and Vasexten

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines.

This is especially important if you are using any of the following medicines, as they must not be taken together with Vasexten:

  • protease inhibitors (drugs used to treat AIDS)
  • ketoconazole or itraconazole (medicines used to treat fungal infections)
  • erythromycin or clarithromycin (antibiotics)

Also tell your doctor if you are taking:

  • other medicines to treat hypertension, which can cause blood pressure to drop further
  • cimetidine (medicine used to treat stomach diseases) as it may increase the effect of Vasexten
  • phenytoin or carbamazepine (medicines used to treat epilepsy) or rifampicin (an antibiotic), as you may need a higher dose of Vasexten. If you stop taking one of these medicines, your doctor may reduce your dose of Vasexten.

Vasexten with food, drink and alcohol

Take special care when drinking alcohol or grapefruit juice, as these drinks can increase the effect of Vasexten.

Warnings It is important to know that:

Pregnancy and breastfeeding

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.

You should not use Vasexten if you are pregnant unless clearly necessary. Do not use Vasexten if you are breastfeeding. It can be excreted in breast milk.

Driving and using machines

There are no data suggesting that Vasexten may impair the ability to drive and use machines. However, Vasexten can cause dizziness, so you should be sure of the effect this medicine has on you before driving or using machines.

Vasexten capsules contain sucrose.

If you have been told by your doctor that you have "intolerance to some sugars, contact your doctor before taking this medicine.

Dosage and method of use How to use Vasexten: Dosage

Dosage

Always take this medicine exactly as your doctor has told you. If in doubt, consult your doctor or pharmacist.

The usual starting dose is 1 capsule of Vasexten 10 mg once a day. Your doctor may increase this dose to 1 capsule of Vasexten 20 mg once a day, or two 10 mg capsules once a day.

If you are elderly you can use the normal dosage. Your doctor is more likely to follow you more closely at the start of treatment.

Instructions for proper use

  • Take the capsule once a day, in the morning. It is preferable to combine taking the capsule with a daily action, such as brushing your teeth or having breakfast.
  • Swallow the capsules whole, preferably with a glass of water. You can take Vasexten before, during or after a meal, as you prefer.
  • Even if you do not have any signs or symptoms of hypertension, it is important that you continue to take Vasexten every day to get the full benefits of lowering blood pressure.

Overdose What to do if you have taken too much Vasexten

If you take more Vasexten than you should

If you have accidentally taken a large amount of capsules at one time, you should contact your doctor immediately or ask to be taken to a hospital emergency room. Symptoms that may arise following an overdose are weakness, decreased or increased heart rate, drowsiness, confusion, nausea, vomiting and convulsions.

If you forget to take Vasexten

If you forget to take Vasexten at the usual time of day, take the capsule as soon as possible on the same day. If you only remember the next day, do not take a double dose to make up for a forgotten capsule, but continue with your daily dose regularly.

If you have any further questions on the use of this medicine, ask your doctor or pharmacist

Side Effects What are the side effects of Vasexten

Like all medicines, this medicine can cause side effects, although not everybody gets them.

If you have a severe allergic reaction causing difficulty in breathing or dizziness, you should inform your doctor or nurse immediately.

Vasexten can cause:

Very common: affects more than 1 in 10 patients

  • headache
  • redness of the face
  • accumulation of fluid (edema) in the arms and legs

Common: affects up to 1 in 10 patients:

  • dizziness
  • palpitations

Not known: frequency cannot be estimated from the available data

  • rapid heartbeat
  • blood tests showing changes in liver function
  • rash

These side effects usually reduce or disappear during the course of treatment (within one month for fluid accumulation and within two weeks for facial flushing, headache and palpitations).

If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet.

Expiry and Retention

Keep this medicine out of the sight and reach of children.

Store Vasexten capsules below 25 ° C.

Do not use Vasexten after the expiry date which is stated on the carton after "EXP". The expiry date refers to the last day of that month.

Do not throw any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. This will help protect the environment.

Composition and pharmaceutical form

What Vasexten contains

  • Each capsule of Vasexten contains 10 mg or 20 mg of barnidipine hydrochloride, equivalent to 9.3 mg and 18.6 mg of barnidipine per capsule, respectively.
  • The other ingredients are: Capsule contents: carboxymethylethylcellulose, polysorbate 80, sucrose, ethylcellulose and talc. Capsule shell: titanium dioxide (E 171), yellow iron oxide (E 172) and gelatin. Printing ink: shellac, propylene glycol (E 1520), black iron oxide (E 172), ammonia.

What Vasexten looks like and contents of the pack

Yellow capsules.

Vasexten 10 mg capsules are marked with code 155 10

Vasexten 20 mg capsules are marked with code 155 20

Vasexten capsules are packaged in aluminum / aluminum blisters (with PVC and polyamide coating) contained in cartons of 10, 14, 20, 28, 30, 50, 56, 98 or 100 capsules. Not all pack sizes may be marketed.

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.

Further information on Vasexten can be found in the "Summary of Characteristics" tab. 01.0 NAME OF THE MEDICINAL PRODUCT 02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION 03.0 PHARMACEUTICAL FORM 04.0 CLINICAL PARTICULARS 04.1 Therapeutic indications 04.2 Posology and method of administration 04.3 Contraindications 04.4 Special warnings and appropriate precautions for use 04.5 Interactions with other medicinal products and other forms of interaction 04.6 Pregnancy and lactation 04.7 Effects on ability to drive and use machines 04.8 Undesirable effects 04.9 Overdose 05.0 PHARMACOLOGICAL PROPERTIES 05.1 Pharmacodynamic properties 05.2 Pharmacokinetic properties 05.3 Preclinical safety data 06.0 PHARMACEUTICAL PARTICULARS 06.1 Excipients 06.2 Incompatibilities 06.3 Shelf life 06.4 Special precautions for storage 06.5 Nature of the immediate packaging and contents of the package 06.6 Instructions for use and handling 07.0 MARKETING AUTHORIZATION HOLDER 08.0 MARKETING AUTHORIZATION NUMBER 09 .0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION 10.0 DATE OF REVISION OF THE TEXT 11.0 FOR RADIO DRUGS, COMPLETE DATA ON INTERNAL RADIATION DOSIMETRY 12.0 FOR RADIO DRUGS, FURTHER DETAILED INSTRUCTIONS AND QUALITY CONTROLS

01.0 NAME OF THE MEDICINAL PRODUCT

VASEXTEN 10 MG MODIFIED RELEASE CAPSULES.

02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION

Vasexten contains barnidipine hydrochloride.

Vasexten® 10 mg modified-release capsules, hard contain 10 mg barnidipine hydrochloride, equivalent to 9.3 mg barnidipine per capsule.

For the full list of excipients see section 6.1.

03.0 PHARMACEUTICAL FORM

Modified-release capsules, hard.

Vasexten 10 mg modified release capsules are yellow and marked 155 10.

04.0 CLINICAL INFORMATION

04.1 Therapeutic indications

Mild to moderate essential hypertension.


04.2 Posology and method of administration

Dosage

The recommended starting dose is 10 mg once a day in the morning, but it can be increased to 20 mg once a day if needed. The decision to increase the dose should only be made after complete stability of blood pressure values ​​is achieved with the starting dose, which usually takes at least 3-6 weeks.

Children

As no data are available in children (below 18 years), barnidipine should not be given to children.

Elderly patients

The dose does not need to be adjusted in elderly patients. It is advisable to pay more attention at the beginning of the treatment.

Patients with renal dysfunction

In patients with mild to moderate renal dysfunction, care should be taken when increasing the dose from 10 to 20 mg once daily. See "Contraindications" and "Special warnings and precautions for use" sections.

Patients with hepatic insufficiency

See the "Contraindications" section.

Method of administration

Take the capsules preferably with a glass of water. Vasexten can be taken before, during or after a meal.


04.3 Contraindications

Hypersensitivity to the active substance (or to other dihydropyridines) or to any of the excipients.

Hepatic insufficiency. Severe renal dysfunction (creatinine clearance unstable angina pectoris and acute myocardial infarction (in the first 4 weeks). Heart failure not being treated.

Blood levels of barnidipine may increase when used in combination with potent CYP3A4 inhibitors (as shown in in vitro interaction studies). Therefore, antiproteasics, ketoconazole, itraconazole, erythromycin and clarithromycin should not be combined.


04.4 Special warnings and appropriate precautions for use

Vasexten should be used with caution in patients with mild to moderate renal dysfunction (creatinine clearance between 10 and 80 ml / min) (see section 4.2 "Posology and method of administration").

The combination of a calcium channel blocker with a drug that exerts a negative inotropic effect may cause heart failure, hypotension or one (other) myocardial infarction in high-risk patients (eg patients with a history of myocardial infarction).

As with all dihydropyridine derivatives, Vasexten should be used with caution in patients with left ventricular dysfunction, in patients with left ventricular outflow channel obstruction and in patients with isolated right heart decompensation, e.g. pulmonary heart.

Barnidipine has not been studied in NYHA class III or IV patients.

Caution is also recommended when administering barnidipine to patients with sick sinus disease (in the absence of a pacemaker).

Education in vitro indicate that barnidipine is metabolised by cytochrome P450 3A4 (CYP3A4). No interaction studies have been performed in vivo on the effect of drugs that inhibit or induce the cytochrome P450 3A4 enzyme on the pharmacokinetics of barnidipine. Based on the results of interaction studies in vitro, caution should be exercised when barnidipine is prescribed concomitantly with weak inhibitors or inducers of the CYP3A4 enzyme (see section "Interactions with other medicinal products and other forms of interaction").

The product contains sucrose; therefore patients with rare hereditary problems of fructose intolerance, glucose / galactose malabsorption syndrome or sucrase-somaltase insufficiency should not take this medicinal product.


04.5 Interactions with other medicinal products and other forms of interaction

The concomitant administration of barnidipine and other antihypertensive agents may result in an additional antihypertensive effect.

Vasexten can be used concomitantly with beta blockers or ACE inhibitors.

The pharmacokinetic interaction profile of barnidipine has not been thoroughly investigated. Education in vitro show that barnidipine is metabolised by cytochrome P450 3A4 (CYP3A4).

No in-depth interaction studies have been performed in vivo the effect of drugs that inhibit or induce the CYP3A4 enzyme on the pharmacokinetics of barnidipine.

Data obtained from studies in vitro show that cyclosporine can inhibit the metabolism of barnidipine. Until information from studies is available in vivo, barnidipine should not be prescribed concomitantly with potent CYP3A4 inhibitors, such as antiproteases, ketoconazole, itraconazole, erythromycin and clarithromycin (see section 4.3 "Contraindications"). Caution is advised in concomitant use of weak CYP3A4 inhibitors or inducers. In case of concomitant use with CYP3A4 inhibitors it is not recommended to increase the dose of barnidipine to 20 mg.

Concomitant administration of cimetidine in a specific interaction study resulted in, on average, a doubling of the plasma levels of barnidipine. Caution is therefore advised in concomitant use of barnidipine and cimetidine.

A higher dose of barnidipine may be needed when barnidipine is administered concomitantly with enzyme-inducing drugs, such as phenytoin, carbamazepine and rifampicin. Should the patient stop using an enzyme inducing drug, consideration should be given to reducing the dose of barnidipine.

Based on the results of interaction studies in vitro with (among others) simvastatin, metoprolol, diazepam and terfenadine, it is considered unlikely that barnidipine will affect the pharmacokinetics of other drugs which are metabolised by cytochrome P450 isoenzymes.

An interaction study in vivo demonstrated that barnidipine does not affect the pharmacokinetics of digoxin.

In an interaction study, alcohol resulted in an increase in plasma levels of barnidipine (40%), which is not considered clinically relevant. As with all vasodilators and antihypertensives, caution should be exercised in concomitant alcohol intake as it it could enhance its effects.

Although the kinetics of barnidipine were not significantly changed by the administration of grapefruit juice, a modest effect was observed.


04.6 Pregnancy and breastfeeding

Pregnancy

There is no clinical experience with barnidipine in pregnancy or during lactation. Animal studies do not suggest direct harmful effects on pregnancy, embryo / fetus or postnatal development. Only indirect effects have been observed (see 5.3). The class of dihydropyridines has shown the potential to prolong labor and delivery, which have not been observed with barnidipine, therefore barnidipine should only be used in pregnancy if the benefit justifies the potential risk to the fetus.

Feeding time

Animal test results have shown that barnidipine (or its metabolites) is excreted in human milk. Therefore, breastfeeding is not recommended while using barnidipine.


04.7 Effects on ability to drive and use machines

There are no data available indicating a possible negative influence of Vasexten on the ability to drive and operate machines. However, caution is advised, as dizziness or vertigo may occur during antihypertensive treatment.


04.8 Undesirable effects

System and organ classification 10 mg 20 mg Nervous system disorders Headache Common (≥1 / 100, Very common (≥1 / 10) Dizziness / vertigo Common (≥1 / 100, Common (≥1 / 100, Cardiac pathologies Palpitations Common (≥1 / 100, Common (≥1 / 100, Vascular pathologies Hot flashes Common (≥1 / 100, Very common (≥1 / 10) General disorders and administration site conditions Peripheral edema Common (≥1 / 100, Very common (≥1 / 10)

Symptoms tend to diminish or disappear during treatment (peripheral edema within one month and hot flashes, headache and palpitations within two weeks).

Rashes and a (reversible) increase in alkaline phosphatase and serum transaminases are known adverse events of other dihydropyridines. Although transient and reversible elevations of liver enzymes have been reported on rare occasions with barnidipine, they were not considered clinically relevant.

Although it has never been observed, the following adverse event may be of interest, as occurs with the use of other dihydropyridines: gingival hyperplasia.

Some dihydropyridines may rarely cause precordial pain and angina pectoris. Very rarely, patients with pre-existing angina pectoris may experience increased frequency, duration and severity of such attacks. There may be isolated cases of myocardial infarction.


04.9 Overdose

No cases of overdose have been reported.

Symptoms of intoxication

In general, clinical symptoms after a calcium channel blocker overdose develop within 30 to 60 minutes after administration of a dose 5 to 10 times the therapeutic dose.

The following side effects can theoretically be predicted: hypotension, electrophysiological effects (sinus bradycardia, AV conduction prolongation, 2nd and 3rd degree AV block), central nervous system effects (lightheadedness, confusion and, rarely, convulsions), gastrointestinal symptoms ( nausea and vomiting) and metabolic effects (hyperglycemia).

Treatment of intoxication

Inpatient treatment is necessary in the "event of" intoxication. Symptomatic treatment and continuous ECG monitoring are indicated.

In the event of an overdose, gastric lavage should be performed as soon as possible.

An intravenous injection (at a dose of 0.2 ml / kg body weight) of calcium (preferably 10 ml of a 10% calcium chloride solution) should be given over 5 minutes, up to a total dose of 10 ml. Myocardial contractility, sinus rhythm and atrioventricular conduction will therefore be improved.

The treatment can be repeated every 15-20 minutes (up to a total of 4 doses) based on the patient's response. Calcium levels need to be monitored.

05.0 PHARMACOLOGICAL PROPERTIES

05.1 Pharmacodynamic properties

Pharmacotherapeutic group: Antihypertensives. ATC code C08CA12.

Mechanism of action:

Barnidipine (pure S-isomer, S-isomer) is a lipophilic 1,4-dihydropyridine calcium channel blocker that exhibits a "high affinity with the calcium channels of smooth muscle cells in the vessel wall. The kinetics of barnidipine receptors is characterized by the appearance of d "slow action and a strong and lasting bond. The reduction of peripheral resistance caused by barnidipine causes a lowering of blood pressure. When using Vasexten, the antihypertensive effect persists for the entire 24 hour period.

The use of Vasexten in chronic treatment does not lead to an increase in the basic heart rate.

The impact of barnidipine on cardiovascular morbidity and mortality has not been studied.

However, recently concluded controlled studies with other long-acting dihydropyridines have indicated beneficial effects on morbidity and mortality similar to those of other antihypertensive agents in the hypertension of the elderly.

Metabolic Effects:

Barnidipine has no negative effect on the lipemic profile, blood glucose or electrolytes of the blood.


05.2 "Pharmacokinetic properties

Absorption:

After repeated administration of Vasexten® 20 mg to healthy subjects, concomitant consumption of food had no statistically significant effect on AUC, Cmax, Tmax or t½.

Maximum plasma levels are achieved 5-6 hours after oral administration of Vasexten® 20 mg.

Vasexten has an absolute bioavailability of 1.1%.

Plasma concentrations of barnidipine may show considerable interindividual variability.

Distribution:

Education in vitro show that barnidipine binds 26-32% to human erythrocytes and, to a high extent (89-95%), to plasma proteins. The analysis in vitro of the protein components indicates that barnidipine binds primarily to serum albumin, followed by alpha1 acid glycoprotein and high density lipoprotein. Binding to gamma globulins occurs to a much lesser extent.

In studies in vitro no drug interactions based on elimination of plasma protein binding were observed.

Biotransformation:

Barnidipine is metabolised to a large extent to inactive metabolites. There is no chiral inversion in vivo of the pure isomer S, S. The main reactions are the Ndebenzilization of the side chain, the hydrolysis of the N-benzylpyrrolidine ester, the oxidation of the 1,4-dihydropyridine ring, the hydrolysis of the methyl ester and the reduction of the nitro group The metabolism of barnidipine appears to be mediated mainly by the CYP3A family of isoenzymes.

Excretion:

The median terminal elimination half-life from plasma of Vasexten was 20 hours after repeated administration according to a two-compartment analytical model.

Elimination occurs primarily by metabolism. Barnidipine and / or its metabolites are excreted in faeces (60%), urine (40%) and exhaled air (less than 1%). Barnidipine is not excreted in urine. metabolized.

Special patient groups:

After a single dose, plasma levels of barnidipine are 3 to 4 times higher in patients with mild to moderate hepatic dysfunction than in healthy volunteers. The variability of plasma levels is also increased.

Plasma levels of barnidipine are on average doubled in patients with renal dysfunction who do not need to undergo hemodialysis compared to healthy volunteers. The mean plasma level in patients undergoing hemodialysis is more than 3 times higher than in healthy volunteers, accompanied by "increased variability.


05.3 Preclinical safety data

Non-clinical data reveal no special hazard for humans based on conventional studies of safety pharmacology, repeated dose toxicity, genotoxicity, carcinogenic potential, reproductive toxicity.

06.0 PHARMACEUTICAL INFORMATION

06.1 Excipients

The other ingredients of Vasexten are as follows:

Capsule contents:

carboxymethylethylcellulose, polysorbate 80, sucrose, ethylcellulose, talc.

Capsule:

titanium dioxide (E171), yellow iron oxide (E172) and gelatin.

Printing ink:

shellac, denatured alcohol, propylene glycol (E1520), purified water, n-butanol, isopropyl alcohol, black iron oxide (E172).


06.2 Incompatibility

Not relevant.


06.3 Period of validity

2 years.


06.4 Special precautions for storage

Do not store above 25 ° C.


06.5 Nature of the immediate packaging and contents of the package

Vasexten modified release capsules are packaged in cartons containing 10,14,20,28,30,50,56,98 or 100 capsules in aluminum-aluminum blisters (with PVC and polyamide coating).

One blister contains 7, 10 or 14 capsules.

Not all pack sizes may be marketed.


06.6 Instructions for use and handling

Do not remove the granules from the capsules.

07.0 MARKETING AUTHORIZATION HOLDER

Italfarmaco S.p.A. - Viale Fulvio Testi, 330 - 20126 Milan

Under license from Astellas Pharma S.p.A.

08.0 MARKETING AUTHORIZATION NUMBER

Vasexten® 10 mg modified release capsules - 28 capsules is registered under number 035144029 / M

09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION

November 19, 2001 / Renewal April 17, 2009

10.0 DATE OF REVISION OF THE TEXT

May 2010

11.0 FOR RADIO DRUGS, COMPLETE DATA ON THE INTERNAL RADIATION DOSIMETRY

12.0 FOR RADIO DRUGS, FURTHER DETAILED INSTRUCTIONS ON EXEMPORARY PREPARATION AND QUALITY CONTROL

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