Isoptin sr-e 240

Package leaflet: Information for the patient

Warning! Keep this leaflet! Information on the immediate packaging in a foreign language.
Isoptin SR-E 240 (Izoptin SR 240 mg)
240 mg, prolonged-release tablets
Verapamili hydrochloridum
Isoptin SR-E 240 and Izoptin SR 240 mg are different trade names of the same medicinal product
written in Polish and Bulgarian, respectively.
Please read this leaflet carefully before taking the medicine, as it contains
important information for the patient.

• Keep this leaflet so that you can read it again if necessary.
• If you have any questions, please consult your doctor or pharmacist.
• This medicine has been prescribed for a specific individual. Do not pass it on to others. It may harm other people, even if their symptoms are the same.
• If you experience any adverse reactions, including any not listed in this leaflet, inform your doctor or pharmacist. See section 4.

Table of contents of the leaflet:

1. What is Isoptin SR-E 240 and what it is used for
2. Important information before taking Isoptin SR-E 240
3. How to take Isoptin SR-E 240
4. Possible side effects
5. How to store Isoptin SR-E 240
6. Contents of the pack and other information

1. What is Isoptin SR-E 240 and what it is used for

Isoptin SR-E 240 is available as prolonged-release tablets containing 240 mg of the active substance – verapamil hydrochloride. Verapamil hydrochloride is a selective calcium antagonist acting directly on cardiac muscle.
The mechanism of action of the drug consists in inhibiting the influx of calcium ions through the cell membrane into the cells of the cardiac muscle and vascular smooth muscle cells.
The drug exerts antihypertensive and antiarrhythmic effects.
The antihypertensive effect results from a reduction in peripheral resistance without a concomitant increase in heart rate. In patients with normal blood pressure, the drug does not exert a significant hypotensive effect.
The antiarrhythmic effect, particularly in cases of supraventricular arrhythmias, is due to slowing of conduction through the atrioventricular node. As a result, depending on the type of arrhythmia, sinus rhythm is restored and/or ventricular rate is normalized. The drug does not alter normal heart rate or only slightly reduces it.
Isoptin SR-E 240 is indicated for use in adults for the treatment of:

• arterial hypertension
• coronary artery disease (conditions characterized by insufficient oxygen supply to the myocardium), including:
  • chronic stable angina pectoris
  • unstable angina pectoris (with increasing pain, pain at rest)
  • Prinzmetal's angina
  • post-infarction angina without heart failure, when β-blockers are not indicated
• cardiac arrhythmias such as:
  • paroxysmal supraventricular tachycardia, atrial fibrillation/flutter with rapid atrioventricular conduction (excluding Wolff-Parkinson-White [WPW] syndrome or Lown-Ganong-Levine [LGL] syndrome)

2. Important information before using the medicine Isoptin SR-E 240

When not to use the medicine Isoptin SR-E 240

• if the patient is allergic to verapamil hydrochloride or any of the other ingredients of this medicine (listed in section 6)
• in cardiogenic shock
• in second- or third-degree atrioventricular block (except in patients with a properly functioning pacemaker)
• in sick sinus syndrome (except in patients with a properly functioning pacemaker)
• in heart failure with reduced ejection fraction below 35% and/or pulmonary artery wedge pressure above 20 mmHg (unless secondary to a supraventricular tachycardia that responds to verapamil treatment)
• in atrial fibrillation/flutter with an accessory conduction pathway (e.g. Wolff-Parkinson-White syndrome [WPW], Lown-Ganong-Levine syndrome [LGL]). Administration of the drug in these patients carries a risk of ventricular tachyarrhythmias, including ventricular fibrillation
• if the patient is taking ivabradine.

Warnings and precautions
Before starting treatment with Isoptin SR-E 240, discuss this with your doctor.
Particular caution is required in patients:

• with acute myocardial infarction complicated by bradycardia, significant hypotension, or left ventricular dysfunction
• with heart block, first-degree atrioventricular block, bradycardia, or asystole
• taking antiarrhythmic drugs or β-blockers
• taking digoxin
• with heart failure and ejection fraction above 35%
• with hypotension
• taking statins
• with neuromuscular transmission disorders [myasthenia gravis, Lambert-Eaton syndrome, late stages of Duchenne muscular dystrophy]
• with renal impairment
• with severe hepatic insufficiency.

Isoptin SR-E 240 and other medicines
Tell your doctor about all medicines currently taken or recently used, including medicines the patient intends to take.
Verapamil may interact with the following medicines:

• α-adrenergic blockers (e.g. prazosin, terazosin)
• antiarrhythmic drugs (e.g. flecainide, quinidine)
• bronchodilators (e.g. theophylline)
• anticonvulsants and antiepileptic drugs (e.g. carbamazepine, phenytoin)
• antidepressants (e.g. imipramine)
• antidiabetic drugs (e.g. glyburide)
• drugs used in gout (e.g. colchicine)
• drugs used in infections (e.g. clarithromycin, erythromycin, rifampicin, telithromycin)
• anticancer drugs (e.g. doxorubicin)
• barbiturates (e.g. phenobarbital)
• benzodiazepines and other anxiolytics (e.g. buspirone, midazolam)
• β-adrenergic blockers (e.g. metoprolol, propranolol)
• cardiac glycosides (e.g. digitoxin, digoxin)
• H-receptor antagonists (e.g. cimetidine)
• immunomodulatory and immunosuppressive drugs (e.g. cyclosporine, everolimus, sirolimus, tacrolimus)
• lipid-lowering agents (e.g. atorvastatin, lovastatin, simvastatin)
• serotonin receptor agonists (e.g. almotriptan)
• drugs increasing urinary excretion of uric acid (e.g. sulfinpyrazone)
• dabigatran (an anticoagulant) and direct oral anticoagulants
• ivabradine (used in the treatment of heart disease), see section "When not to use the medicine Isoptin SR-E 240"
• metformin (used in the treatment of diabetes). Verapamil may reduce the glucose-lowering effect of metformin.

Isoptin SR-E 240 with food and drink
Interactions may also occur with grapefruit juice and products containing St. John's wort extract.
Additional information on some interactions is provided below.
Antiviral drugs for human immunodeficiency virus (HIV)
Ritonavir may increase verapamil plasma concentration, enhancing the drug's effect. Caution is required when these drugs are used concomitantly, and if necessary, the verapamil dose should be reduced.
Lithium
Increased sensitivity to lithium (neurotoxicity) has been reported during concomitant treatment with Isoptin SR-E 240 and lithium, with unchanged or increased serum lithium concentrations. However, adding Isoptin SR-E 240 has also led to decreased serum lithium concentrations in patients chronically receiving oral lithium. Patients receiving both drugs should be closely monitored.
Neuromuscular blocking agents
The drug may enhance the effect of neuromuscular blocking agents (curare-like and depolarizing agents). Dose reduction of Isoptin SR-E 240 and/or the neuromuscular blocking agent may be necessary when these drugs are used simultaneously.
Acetylsalicylic acid
Increased tendency to bleeding.
Ethanol
Increased plasma concentration of ethanol.
HMG-CoA reductase inhibitors (statins)
In patients taking Isoptin SR-E 240, treatment with HMG-CoA reductase inhibitors (e.g. simvastatin, atorvastatin, or lovastatin) should be initiated with the lowest possible dose, which is then gradually increased.
If treatment with Isoptin SR-E 240 is started in patients already taking an HMG-CoA reductase inhibitor (e.g. simvastatin, atorvastatin, or lovastatin), consider reducing the statin dose and then readjusting it based on serum cholesterol levels.
The likelihood of interaction with fluvastatin, pravastatin, or rosuvastatin is lower.
Antihypertensive, diuretic, and vasodilating drugs
Enhancement of the hypotensive effect.

Pregnancy and breastfeeding
If the patient is pregnant or breastfeeding, suspects she may be pregnant, or plans to have a child, she should consult her doctor before using this medicine.
There are no data on the use of this medicine in pregnant women, and therefore it should only be used during pregnancy if absolutely necessary.
The drug passes into breast milk in small amounts. Risk to newborns and infants cannot be excluded. However, due to the possibility of serious adverse effects in breastfed infants, the medicine should only be used during breastfeeding if essential for the mother's health.

Driving and operating machinery
In some patients, Isoptin SR-E 240 may affect reaction ability to such an extent that it impairs the ability to drive vehicles, operate mechanical equipment, or work under hazardous conditions. This is especially likely during the initial phase of treatment, during dose escalation, when switching from another medicine, and when alcohol is consumed simultaneously. The drug may increase blood alcohol concentration and delay its elimination. Therefore, the effect of alcohol may be intensified.

Isoptin SR-E 240 contains Quinoline Yellow (E 104)
Isoptin SR-E 240 contains Quinoline Yellow (E 104), which may cause allergic reactions in some patients.

Isoptin SR-E 240 contains sodium
Isoptin SR-E 240 contains 37.1 mg of sodium (the main component of table salt) in one tablet. This corresponds to 1.9% of the maximum recommended daily dietary sodium intake for adults.

3. How to use Isoptin SR-E 240

This medicine should always be taken exactly as prescribed by your doctor. If in doubt, consult your doctor or pharmacist.
The dosage should be individually adjusted depending on the severity of the disease. Long-term clinical experience confirms that in all indications, the usual daily dose ranges from 240 mg to 360 mg. During long-term treatment, the daily dose should not exceed 480 mg; however, higher doses may be used in short-term treatment. There is no limitation on the duration of treatment. After prolonged use, this medicine must not be discontinued abruptly. Gradual dose reduction is recommended.

Oral administration. The tablet should be swallowed whole (do not suck or chew), with an adequate amount of fluid, preferably during or immediately after a meal.

Adults and adolescents with body weight above 50 kg
Hypertension: 120 mg to 480 mg daily, given in one or two divided doses.
Coronary artery disease, paroxysmal supraventricular tachycardia, atrial fibrillation, and atrial flutter: 120 mg to 480 mg daily, given in one or two divided doses.
If a dose of 120 mg is required, the medicinal product Isoptin SR prolonged-release tablets 120 mg should be administered.
In patients who may respond adequately to lower doses (e.g., patients with hepatic impairment or elderly patients), use of the medicinal product Isoptin 40 coated tablets 40 mg or Isoptin 80 coated tablets 80 mg is recommended.

Special populations
Children and adolescents
Isoptin SR-E 240 should not be used in children. In children, medicines with unmodified release should be used.

Renal impairment
Caution should be exercised and patients should be closely monitored when administering this medicine to patients with renal function disorders.

Hepatic impairment
In patients with hepatic impairment, drug metabolism is impaired to varying degrees depending on the severity of liver dysfunction, resulting in stronger and prolonged drug effects. Therefore, particular caution is required when determining dosage in patients with hepatic impairment, and low doses should be administered during the initial treatment period (see section Warnings and precautions).

Use of a higher than recommended dose of Isoptin SR-E 240
Symptoms
Hypotension, bradycardia, slowed conduction velocity up to high-degree atrioventricular block and sinus node arrest, hyperglycemia, stupor, metabolic acidosis, acute respiratory failure syndrome. Fatalities have occurred following overdose.

Treatment
In case of overdose, supportive treatment individually tailored should be primarily administered. In cases of intentional oral overdose, β-adrenergic stimulation and/or intravenous calcium (calcium chloride) have been effectively used. In the event of clinically significant hypotension or high-degree atrioventricular block, vasopressor agents or cardiac pacing should be used as appropriate. In case of asystole, standard management should be applied, including β-adrenergic stimulation (e.g., isoproterenol hydrochloride), other vasopressor agents, or cardiopulmonary resuscitation.
In case of overdose with verapamil hydrochloride in a prolonged-release formulation, due to slower drug absorption, the patient should be hospitalized and observed for up to 48 hours. Verapamil hydrochloride cannot be removed from the body by hemodialysis.

Missed dose of Isoptin SR-E 240
Do not take a double dose to make up for a missed dose.

Discontinuation of Isoptin SR-E 240
After prolonged use, this medicine must not be discontinued abruptly. Gradual dose reduction is recommended.

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone will experience them.
The most commonly reported adverse effects were: headache, dizziness, gastrointestinal disorders:
nausea, constipation and abdominal pain, as well as bradycardia, palpitations, hot flushes,
arterial hypotension, peripheral oedema and fatigue.
Adverse effects listed below are classified by system organ classes:
Common (in 1 to 10 patients out of 100 patients):

• central dizziness, headache
• bradycardia
• flushing with sensation of warmth, arterial hypotension
• constipation, nausea
• peripheral oedema

Uncommon (in 1 to 10 patients out of 1000 patients):

• palpitations, tachycardia
• abdominal pain
• fatigue

Rare (in 1 to 10 patients out of 10,000 patients):

• paraesthesia, muscle tremors
• somnolence
• tinnitus
• vomiting
• excessive sweating

Adverse effects occurring with unknown frequency (frequency cannot be estimated from the
available data):

• hypersensitivity reactions
• extrapyramidal disorders, seizures
• hyperkalaemia
• peripheral dizziness
• atrioventricular block (I\°, II\°, III\°), heart failure, sinus node arrest, sinus bradycardia, asystole (cardiac arrest)
• bronchospasm, dyspnoea
• abdominal discomfort, gingival hyperplasia, intestinal obstruction
• angioedema, Stevens-Johnson syndrome, erythema multiforme, alopecia, pruritus, itching, purpura, maculopapular rash, urticaria
• joint pain, muscle weakness, muscle pain
• renal failure
• erectile dysfunction, galactorrhoea, gynaecomastia
• increased prolactin blood concentration, increased liver enzyme activity

Post-marketing reports have included one case of paralysis (tetraparesis) following concomitant use of verapamil and colchicine.
If any of the adverse effects worsens or if any adverse effects not listed in this leaflet occur, consult a doctor or pharmacist.
Reporting of adverse effects
If any adverse effects occur, including any adverse effects not listed in this leaflet, inform a doctor or pharmacist. Adverse effects can be reported directly to the Department of Monitoring Adverse Drug Reactions, Office for Registration of Medicinal Products, Medical Devices and Biocidal Products, Al. Jerozolimskie 181C, 02-222 Warsaw, tel.: + 48 22 49 21 301, fax: + 48 22 49 21 309, website: https://smz.ezdrowie.gov.pl.
Reporting adverse effects helps provide more information on the safety of the medicine.

5. How to store the medicine Isoptin SR-E 240

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the packaging. The expiry date refers to the last day of the stated month.
Store below 25°C.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Contents of the packaging and other information

What Isoptin SR-E 240 contains
The active substance is verapamil hydrochloride 240 mg.
Excipients: microcrystalline cellulose, sodium alginate, povidone K30, magnesium stearate, purified water, hypromellose 2910, polyethylene glycol 400, polyethylene glycol 6000, talc, titanium dioxide (E 171), quinoline yellow aluminium lake (E 104) and indigo carmine (E 132), Montan wax glycol.

What Isoptin SR-E 240 looks like and contents of the pack
A light green, elongated tablet.
Isoptin SR-E 240 is available in packs containing:
20 tablets (2 blisters of 10 tablets each)
40 tablets (4 blisters of 10 tablets each)
PVC/PVDC blisters in a cardboard box.

For more detailed information, please contact the marketing authorisation holder or the parallel importer.

Marketing Authorisation Holder in Bulgaria, country of export:
Mylan EOOD
Office building Serdika, 48
Sitnyakovo Blvd., 7th floor, 1505 Sofia, Bulgaria

Manufacturer:
FAMAR A.V.E. Anthoussa Plant
Anthoussa Avenue 7
Anthoussa Attiki
15349, Greece
Mylan Hungary Kft.
Mylan utca 1
Komárom 2900
Hungary

Parallel Importer:
InPharm Sp. z o.o.
ul. Strumykowa 28/11
03-138 Warszawa

Repackaged in:
InPharm Sp. z o.o. Services sp. k.
ul. Chełmżyńska 249
04-458 Warszawa

Marketing Authorisation Number in Bulgaria, country of export: 20030014
Parallel Import Authorisation Number: 23/26