Procoralan drug 7.5mg Servier treat stable angina (4 blisters x 14 tablets)

Dosage form Box of 4 blisters x 14 tablets
Specifications Ivabradine

Ingredient

Composition information	Content
Ivabradine	7.5mg

Uses

indication

Procoralan drug 7.5mg is indicated in the following cases:

Treatment of Halfy chronic stability:

Ivabradin is indicated to treat chronic angina symptoms in adults with coronary artery disease with normal sinus rhythms and heart frequency> 70 beats/min.

or in combination with beta blockers in patients who have not been fully controlled with the optimal dose of beta blockers.

Chronic heart failure :

Ivabradin is indicated in the treatment of chronic heart failure from NYHA II to IV, with systolic dysfunction, in patients with sinus arrhythmia and heart frequency> 75 beats/minute in combination with standard treatment including beta blockers or when beta blockers are contraindicated or when the instrumental blockers are intolerable.

Mechanism of impact

Ivabradin is a special reduction of heart frequency, due to selective inhibition and specific IF of the heart rate center, this ion line controls spontaneous diastolic reducing in the sinus node and the heart frequency regulator.

The effect on the heart of the drug is specific to the sinus button without affecting the transmission time in the atrial, atrial - ventricular, clear as well as no effect on the re -loss or myocardial contraction.

Ivabradin can also interact with the LH line in the retina, which is very similar to the LF line in the heart. This LH line is involved in the temporary resolution of the visual system by reducing the retinal response with dazzling light pulse.

In stimulating cases (for example: rapid change of brightness), the Ivabradin inhibits a part of the LH line as the foundation for the dazzling phenomenon that can be encountered in patients.

Phosphenes is described as a temporary glare in a certain region of the market.

Pharmacological effects

IVABRADIN's main pharmacological properties in humans is a specific reduction of heart frequency depending on the dose.

Analysis of heart frequency reduction with doses of up to 20 mg at a time and drink twice a day, it is clear that the tendency to reach the effect of the plateau along with the risk of a serious slow heart rate below 40 beats/minute

With the usual recommendations, the heart frequency decreases by about 10 beats/minute at leave and during practice. This leads to reducing the burden on the heart and reducing oxygen needs for the heart muscle.

Ivabradin has no effect on the transmission in the heart, to the constraints of the heart (no effect inhibiting myocardial shrinking) or to the re -generation of the ventricle:

In clinical physiological studies, Ivabradin does not work on the atrial - ventricular or ventricular or editing time on the electrocardiogram.

For patients with left ventricular dysfunction (blood emulsion of the left ventricle between 30% and 45%), IVABRADIN has no harmful effects on blood ratio.

Dynamic pharmacology

absorption

Ivabradin absorbs quickly and is almost completely after drinking with peak plasma concentrations after about 1 hour, if taken for drugs when hungry.

The absolute use of film tablets is about 40%, due to the first metabolism in the intestine and the liver.

Recommendations to take medicine at a meal to help reduce the change in each individual concentration.

distribution

Ivabradin attaches about 70% to plasma proteins and integral distributed in a stable state of nearly 100 liters in patients.

Peak concentration in plasma after long -term taken for recommended doses (5 mg each time, 2 times a day) is 22 ng/ml (CV = 29%). The average concentration in plasma is 10 ng/ml in a stable state (CV = 38%).

transformation

Ivabradin is strongly metabolized through the liver and intestines, by oxidizing through only Cytochrome P450 3A4 (CYP3A4).

The main metabolites are active as the derivative N - reducing methyl (S 18982) with a concentration of about 40% of the original Ivabradin active ingredient.

The metabolism of this active metabolite also through CYP3A4.

Ivabradin has weak affinity for CYP 3A4, does not inhibit or cause a clear touch of CYP3A4. Therefore, it is less likely that Ivabradin has changed the metabolism or plasma concentrations of the substrates of CYP3A4.

In contrast, strong CYP3A4 inhibitors and strong CYP3A4 induction substances can have a significant impact on the concentration of Ivabradine in plasma.

Elimination

Ivabradin eliminates the main sale time of 2 hours (70 - 75% of the area under the curve) in plasma, while the effective selling time is 11 hours.

General purification is about 400ml/min and the purification through the kidney is about 70 ml/min.

Elimination of metabolites through feces and urine with similar amounts.

About 4% of oral doses are intact through urine.

Linear/non -linear: IVABRADIN's dynamics is linear with oral dose of 0.5 - 24 mg.

Special subjects

For the elderly: There is no difference in pharmacokinetics (area under the curve and peak concentration) when comparing the elderly patient (≥ ≥ 65 years) or very elderly (≥ 75 years old) and the common population.

Renal failure: The effect of renal failure (creatinine clearance from 15 - 60 ml/min) on IVABRADIN's dynamics is at least, in accordance with the purification of the glomerular participation (about 20%) to the allocation of the IVABRADIN and Main metabolites S 18982.

Hepatic failure: For patients with mild liver failure (Child - Pugh to 7) The area under the curve of Ivabradin and of the main metabolites is about 20% higher than the person with normal liver function. The data is not strong enough to conclude for medium liver failure. There is no data on patients with severe liver failure.

Pediatric: IVABRADIN pharmacokinetics on children with chronic heart failure from 6 months to under 18 years of age is similar to pharmacokinetics described in the elderly when applying the dose mode based on age and weight.

Related between pharmacokinetics/pharmacokinetics (PK/PD)

Analysis of pharmacokinetics/pharmacokinetic relevance shows.

The heart frequency decreases is almost linear when increasing the concentrations of Ivabradine and S18982 in plasma until the dose of 15 - 20 mg, twice a day. With higher doses, the reduction of heart frequency will no longer be proportional to Ivabradine concentration in plasma and tend to reach the plains.

IVABRADIN's high concentration may be encountered when combined with ivabradin with strong CYP3A4 inhibitors that can lead to excessive heart frequency reduction.

While that risk will decrease when combined with moderate inhibitors CYP3A4.

Ivabradin's pharmacokinetics/pharmacokinetics relationship on children with chronic heart failure from 6 months to under 18 years of age similar to the pharmacokinetic/pharmacokinetic relationship has been described in adults.

Before taking Procoralan drug 7.5mg Servier treat stable angina (4 blisters x 14 tablets)

How to use

Procoralan drug 7.5mg in the form of oral, bright and dark tablets at meals.

Dosage

conventional dose in treatment symptoms of angina chronic stability:

The recommended treatment or adjustment of the treatment dose takes place when conducting many heart frequency measurements as well as electrocardiogram control or 24 -hour outpatient monitoring. Next dose should be increased in patients with a dose of 2.5 mg twice daily or 5 mg twice daily.

The maintenance dose should not exceed 7.5 mg twice daily. The clinical decrease in the heart frequency at three months. Heart number.

The treatment is only started in stable heart failure patients. or decrease to 2.5 mg twice daily (half of 5 mg twice daily) if the heart frequency is continuously under 50 beats/minute or in the case of symptoms related to slow heart rate such as dizziness, fatigue or hypotension. The span/minute or patients with symptoms related to the slow heart rate, the dose should be reduced to a lower dose in patients who are taking 7.5 mg twice daily or 5 mg twice daily. The span/minute or symptoms of slow heart rate exist.

Patients with renal impairment: Do not require adjusting dose in patients with renal impairment and creatinine clearance above 15 ml/min.

There is no data in patients with creatinine clearance below 15 ml/min. Ivabradine therefore should be used cautiously in these patients.

Patients with hepatic failure: Do not require adjusting the dose in patients with mild liver failure.

Should be cautious when using iVABRADIN for patients with average liver failure. Contraindicated to use Ivabradin for patients with severe liver failure, due to not being studied on this patient object and data on a sharp increase in concentration.

Children: Ivabradin's efficiency and safety in the treatment of chronic heart failure in children under 18 have not been set up.

The existing data is described in the "Pharmacokinetics" and "pharmacokinetics" section, but there has not been any recommendations for the dosage regime.

Note: The above dose is for reference only. Specific dosage depends on the condition and level of progression of the disease. For a suitable dose, you need to consult a doctor or medical specialist.

What to do when overdose?

How to handle: Serious slow rhythms need symptomatic treatment in deep specialties. In the case of a slow -intolered hemodynamic rhino, it may be necessary to consider symptomatic treatment, including intravenous beta stimulants like isoprenaline. If necessary, can temporarily place a pacemaker.

What to do when you forget 1 dose? However, if close to the next dose, skip the forgotten dose and take the next dose at the time as planned. Note that it should not be used double the prescribed dose.

Side Effects

When using Procoralan drug 7.5mg , you may experience unwanted effects (ADR):

is very common, ADR> 1/10

Visual disorders: dazzling phenomenon (phosphene).

Common, 1/100

visual disorders : blurred vision.

Cardiovascular disorders: slow heart rate, atrial atrial block, degree 1, external ventricular, atrial fibrillation.

Nervous system disorders: headache , dizziness.

Vascular disorders: Unsatisfied blood pressure.

Uncommon, (1/1000

Blood and lymphatic disorders: leukemia.

Metabolic and nutrient disorders: hyperuricemia.

visual disorders: double vision, visual decline.

Disorders of ears and maze: loss of balance.

Cardiovascular disorders: Brushing chest drums, external ventricular ventricular.

Nervous system disorders: fainting may be related to heart rate.

Pleeing disorders: Hypotension may be related to slow heart rate.

Disorders of the digestive system: nausea, constipation , diarrhea, abdominal pain.

Skin and subcutaneous tissue disorders: Evaluation, rash.

musculoskeletal disorders and connective tissue: cramps.

general disorder: fatigue, weakness may be related to the slow rhythm.

Parameters: hypernestic blood, prolonged qt on the electrocardiogram.

is very rare, (1/10000

Cardiovascular disorders: Atrial atrial block level 2, atrial block level 3.

Skin and subcutaneous tissue disorders: erythema, dermatitis, rash urticaria .

The common disorder: Feeling of instability, may be related to the slow rhythm.

Instructions on how to handle ADR

Notify the doctor the unwanted effects when using the drug.

Warnings

Before using the drug you need to read the instructions carefully and refer to the information below.

contraindicated

Procoralan drug 7.7mg Contraindications for the following cases:

Sensitive to any ingredients of the drug.

Heart frequency at leave less than 70 beats/minute before treatment.

Cardiococci.

Acute myocardial infarction.

Too low blood pressure (less than 90/50 mmHg).

Severe liver failure

Sinus dysfunction

Atrial sinus block

Acute or unstable heart failure

Unstable angina.

Depends on the pacemaker.

atrial block of level 3.

in combination with drugs with strong inhibitors of Cytochrome P450 3A4 such as antifungal drugs Azole (Ketoconazol, Itraconazole), Macrolid antibiotics (Erythromycin oral, Clarithromycin, Josamycin, Telithromycin), HIV -HIVIR, NELFIN -inhibitors ritonavir), nefazodone.

in combination with Verapamil or Diltiazem are medium inhibitors CYP3A4 with characteristic reduction in heart rate.

Pregnant women, nursing and women are likely to be pregnant without using safe contraception.

Caution when using

Lack of clinical results in patients with stable angina symptoms. Ivabradin is only indicated in patients with chronic stable angina because this drug does not bring the benefits on the heart.

heart rate measurement:

Because the heart rate may fluctuate over time, it is necessary to consider conducting heart rate measurement, electrocardiogram control or 24 -hour outpatient monitoring when determining the heart frequency before treatment with Ivabradin, which can be used for treatment monitoring for patients with heart rate under 50 beats/minute after the dose reduction.

arrhythmia:

Ivabradin is not effective for treating or preventing arrhythmia and may also lose effect when there is tachycardia (for example, ventricular tachycardia or ventricular tachycardia). Therefore, it is not recommended to use Ivabradine for patients with atrial fibrillation or other arrhythmias that interact with the function of the sinus node.

Patients with atrial block - Ventricity 2:

Do not use Ivabradin.

Used for patients with a slow heart rate:

Do not start treatment with Ivabradin for patients with heart rate before treatment before treatment less than 70 beats/minute. Persistent heart rate slow.

Coordination of calcium channel blockers:

It is not recommended to coordinate Ivabradin with calcium blockers that reduce heart frequency such as verapamil or diltiazem. With Calcium blockers Dihydropyridine.

Chronic heart failure:

Heart failure must be adequately controlled before considering IVABRADIN. Due to the small number of research patients.

stroke:

It is not recommended to use Ivabradin right after the stroke, because there is not enough data for these cases.

visual function:

Ivabradin has affected the function of the retina. pigment.

Patients with hypotension:

Lack of data in patients with hypotension is mild and medium and therefore, Ivabradin should be used for these objects.

Atrial fibrillation - arrhythmia:

There is no evidence of the risk of slow heartbeat (excess) when returning to the sinus rhythm if the heart shake is started for patients to use Ivabradin.

Used in patients with congenital QT syndrome or treatment with drugs that extend the qt segment:

It is necessary to avoid use in patients with congenital QT syndrome or treatment with drugs that extend the qt segment.

Patients with hypertension need to change blood pressure treatment:

When changing treatment in patients with chronic heart failure with Ivabradin, blood pressure should be monitored for an appropriate time due to studies showing that patients using iVabradin have more hypertension than placebo, but these periods are mainly passing after changing blood pressure treatment and does not affect the effectiveness of IVABRADIN.

excipients:

Because the tablet contains lactose, it should not be used for patients with genetic problems (rare) such as galactose intolerance, or deficiency of Lapp Lactase or Glucose-Galactose.

The ability to drive and operate machinery

A study conducted on healthy volunteers to assess the influence of Ivabradin on driving ability shows no change. However, cases affecting the ability to drive due to visual effects have been reported during circulation.

Ivabradin can temporarily cause dazzling eye phenomenon. The ability to appear dazzling eyes should be noted in the case of driving and operating machinery whose light intensity changes suddenly, especially driving at night.

Ivabradin does not affect the ability to operate machines.

Pregnancy

Women who are likely to get pregnant: Need to use appropriate contraception during treatment.

Pregnant women: No data or data existing is limited in using Ivabradin in pregnant women.

Animal studies have shown toxicity on reproduction. These studies have shown the consequences of fetal poisoning and teratogenicity. These risks on people are not known. Therefore, Ivabradine is contraindicated during pregnancy.

The period of breastfeeding

Animal studies have shown ivabradin excreted through breast milk. Therefore, ivabradine is contraindicated during breastfeeding. Women who need to be treated with Ivabradin should stop breastfeeding. And choose other food methods for children.

Drug interaction

Pharmacological interaction

Simultaneous use is not recommended:

substances that extend the qt segment:

Cardiovascular drugs extend the QT segment (for example, Quinidine, Sotalol, Disopyramide, Bepridil, Ibutilide, Amiodarone).

Non -cardiovascular drugs extend the QT segment (for example: Pimozide, Ziprasidone, ServinDole, Mefloquine, Halofantrine, Pentamidine, Cisapride, Erythromycin Tellary).

Avoid combining cardiovascular and non -cardiovascular drugs that extend the QT segment along with Ivabradin because of the severe QT segment that may be more serious due to heart rate decrease.

If you need to coordinate, you must closely monitor the heart state.

Use Caution Causes:

Diuretics reduce potassium (thiazide diuretics and diuretics): Hypokalemia may increase the risk of arrhythmia.

pharmacokinetic interaction

Cytochrom P450 3A4 (CYP3A4):

Ivabradin is only metabolized through CYP3A4 and is a very weak inhibitor of this cytochrom.

Ivabradin shows no effect on metabolism and to plasma concentrations of other substrates of CYP3A4 (mild, medium and strong inhibitors).

CYP3A4 inhibitors and induction are capable of interacting with Ivabradin and has an impact on the metabolism and pharmacokinetics of Ivabradin at clinical significance.

Determined drug interaction research is CYP3A4 inhibitors that increase the concentration of Ivabradin in plasma, while induction substances reduce IVABRADIN levels.

Increased plasma concentrations of Ivabradin may be associated with excessive risk of heart rate.

Simultaneous use is contraindicated:

Combining Ivabradin with powerful CYP3A4 inhibitors such as Azole antifungal drugs (ketoconazole, iTraconazole), Macrolide antibiotic (Clarithromycin, Erythromycin oral, Josamycin, Telithromycin), HIV Protase Inhibitors (Nelfinavir, Ritonavir) and Nefazodone) (see the control section).

Strong CYP3A4 inhibitors such as ketoconazole (200 mg, once a day) or josamycin (1 g, 2 times a day) increase the level of ivabradine in plasma to 7 to 8 times.

Do not coordinate with Ivabradin with moderate inhibitors CYP3A4:

Researching specific interactions on volunteers and on patients shows that if you use Ivabradin along with Diltiazem or Verapamil (which reduces the heart rate) will increase the concentration of Ivabradin (increase the area below the curve to 2-3 times) and slow the heart rate of 5 beats per minute.

Simultaneous use is not recommended:

Grapefruit juice:

Ivabradine concentration increased 2 times when used with grapefruit juice.

Use Caution Causes:

Average inhibitors CYP3A4: simultaneous use of Ivabradin with other medium inhibitors CYP3A4 (eg fluconazole) can be considered at the starting dose of 2.5 mg twice daily and if the heart frequency at break is over 70 beats/minute, with heart frequency monitoring.

CYP3A4 induction substances:

CYP3A4 induction substances (e.g. Rifampicin, Barbiturates, Phenytoin, Hypericum Perforatum [St John’s Wort] can reduce the concentration and degree of activity of Ivabradin. 10 mg twice a day with St John’s Wort has shown that the area under the curve (AUC) of Ivabradin is half reduced.

Other coordinates:

The specific studies on drug-drug interactions have proved that there is no significant influence on the following drugs on pharmacokinetics and IVABRADin's pharmacokinetics:

Proton pump inhibitors (omeprazole, lansoprazole ), Sildenafil, HMG inhibitors HMG Reductase (Simvastatin), Calci channel blockers Dihydropyridine (Amlodipine, Lacidipine), Digoxin and Warfarin. There are significant clinical influences of Ivabradin on the pharmacokinetics of Simvastatin, Amlodipine , lacidipine, pharmacokinetics and pharmacokinetics of Digoxin, Warfarin and on Aspirin's pharmacies.

In the important clinical trial III, the following drugs have been regularly coordinated with Ivabradin without any doubts related to safety issues:

Angiotensin transfer inhibitors, Angiotensin II antagonistic drugs, beta -blockers, diuretics, aldosterone anti -drugs, fast and prolonged effects, HMG Coa Reductase elimination, fibrate drugs, anti -pump inhibitors, oral diabetes, Aspirin and other platelets.

Children: Research on drug interaction so far has only been conducted in adults.

Storage

Store drugs below 300C.

Other drugs

Disclaimer

Every effort has been made to ensure that the information provided by Drugslib.com is accurate, up-to-date, and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. Drugslib.com information has been compiled for use by healthcare practitioners and consumers in the United States and therefore Drugslib.com does not warrant that uses outside of the United States are appropriate, unless specifically indicated otherwise. Drugslib.com's drug information does not endorse drugs, diagnose patients or recommend therapy. Drugslib.com's drug information is an informational resource designed to assist licensed healthcare practitioners in caring for their patients and/or to serve consumers viewing this service as a supplement to, and not a substitute for, the expertise, skill, knowledge and judgment of healthcare practitioners.

The absence of a warning for a given drug or drug combination in no way should be construed to indicate that the drug or drug combination is safe, effective or appropriate for any given patient. Drugslib.com does not assume any responsibility for any aspect of healthcare administered with the aid of information Drugslib.com provides. The information contained herein is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. If you have questions about the drugs you are taking, check with your doctor, nurse or pharmacist.