Package leaflet: Information for the patient

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

Keep this leaflet, as you may need to read it again.
If you have any further questions, please consult your doctor, pharmacist, or nurse.
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 effects, including any not listed in this leaflet, tell your doctor, pharmacist, or nurse. See section 4.

Contents of the leaflet:

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

1. What Isoptin SR-E 240 is 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 involves inhibition of calcium ion influx through the cell membrane into cardiac muscle cells and vascular smooth muscle cells.
The drug has antihypertensive and antiarrhythmic effects.
The antihypertensive effect results from reduced peripheral resistance without a concomitant increase in heart rate. In individuals with normal blood pressure, the drug does not exert a significant hypotensive effect.
The antiarrhythmic effect, particularly in supraventricular rhythm disorders, is due to slowing of atrioventricular nodal conduction. 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 inadequate oxygen supply to the myocardium), including:
- chronic stable angina pectoris
- unstable angina pectoris (with increasing pain, pain at rest)
- Prinzmetal's angina
- post-myocardial infarction angina in the absence of heart failure, when β-adrenolytic agents 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)

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2. Important information before using Isoptin SR-E 240

When not to use 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 functioning pacemaker)
in sick sinus syndrome (except in patients with a functioning pacemaker)
in heart failure with reduced ejection fraction below 35% and/or pulmonary capillary wedge pressure above 20 mmHg (unless secondary to supraventricular tachycardia responsive to verapamil treatment)
in atrial fibrillation/flutter with an accessory conduction pathway present (e.g. Wolff-Parkinson-White syndrome [WPW], Lown-Ganong-Levine syndrome [LGL]). Administration of the drug in such 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, consult your doctor.
Particular caution is required in patients:

with acute myocardial infarction complicated by bradycardia, significant hypotension, or left ventricular dysfunction
with conduction disorders, 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

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

α-adrenolytic agents (e.g. prazosin, terazosin)
antiarrhythmic drugs (e.g. flecainide, quinidine)
bronchodilators (e.g. theophylline)
anticonvulsants and antiepileptics (e.g. carbamazepine, phenytoin)
antidepressants (e.g. imipramine)
antidiabetic agents (e.g. glibenclamide)
antigout agents (e.g. colchicine)
antimicrobial agents (e.g. clarithromycin, erythromycin, rifampicin, telithromycin)
antineoplastic agents (e.g. doxorubicin)
barbiturates (e.g. phenobarbital)
benzodiazepines and other anxiolytics (e.g. buspirone, midazolam)
β-adrenolytic agents (e.g. metoprolol, propranolol)
cardiac glycosides (e.g. digitoxin, digoxin)
H\textsubscript{2}-receptor antagonists (e.g. cimetidine)
immunomodulatory and immunosuppressive agents (e.g. cyclosporine, everolimus, sirolimus, tacrolimus)
lipid-lowering agents (e.g. atorvastatin, lovastatin, simvastatin)
serotonin receptor agonists (e.g. almotriptan)
uricosuric agents (e.g. sulfinpyrazone)
dabigatran (an anticoagulant) and direct oral anticoagulants
ivabradine (used in the treatment of heart disease), see section "When not to use Isoptin"
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, thereby enhancing its 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 levels. However, addition of Isoptin SR-E 240 has also led to decreased serum lithium levels in patients chronically receiving stable oral doses of lithium. Close monitoring of patients receiving both drugs is required.

Neuromuscular blocking agents
The drug may potentiate 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 concurrently.

Acetylsalicylic acid
Increased tendency to bleeding.

Ethanol
Increased ethanol plasma concentration.

HMG-CoA reductase inhibitors (statins)
In patients receiving Isoptin SR-E 240, treatment with HMG-CoA reductase inhibitors (e.g. simvastatin, atorvastatin, or lovastatin) should be initiated at the lowest possible dose, which may then be 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 subsequently re-adjusting it based on serum cholesterol levels.
The likelihood of interaction with fluvastatin, pravastatin, or rosuvastatin is lower.

Antihypertensive, diuretic, and vasodilating agents
Enhancement of hypotensive effect.

Pregnancy and breastfeeding
If the patient is pregnant or breastfeeding, suspects she may be pregnant, or is planning 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 be used during pregnancy only 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 drug should be used during breastfeeding only 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 treatment period, during dose escalation, when switching from another medicine, and when alcohol is consumed concurrently. 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) per tablet. This corresponds to 1.9% of the maximum recommended daily sodium intake in the adult diet.

3. How to use Isoptin SR-E 240

This medicine should always be taken exactly as prescribed by your doctor. In case of 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 limit to the duration of treatment. After prolonged use, the medicine must not be discontinued abruptly. Gradual reduction of the dose 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.
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Adults and adolescents weighing over 50 kg
Hypertension: 120 mg to 480 mg per day as a single dose or in two divided doses.
Coronary artery disease, paroxysmal supraventricular tachycardia, atrial fibrillation, and atrial flutter: 120 mg to 480 mg per day as a single dose or in two divided doses.
If a 120 mg dose is required, 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), Isoptin 40 coated tablets 40 mg or Isoptin 80 coated tablets 80 mg are recommended.
Special populations
Children and adolescents
Isoptin SR-E 240 should not be used in children. In children, formulations with unmodified release should be used.
Renal impairment
Caution should be exercised when administering the medicine to patients with renal impairment, and the patient's condition should be closely monitored.
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 should be exercised when determining the 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 distress syndrome. Fatal outcomes 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 reactions such as hypotension or high-degree atrioventricular block, appropriate vasopressor drugs or cardiac pacing should be used, respectively. In case of asystole, standard management should be applied, including β-adrenergic stimulation (e.g. isoprenaline hydrochloride), other vasopressor drugs, or cardiopulmonary resuscitation.
In case of overdose with verapamil hydrochloride in a prolonged-release formulation, due to the slower absorption of the drug, 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
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After prolonged use, the medicine should not be discontinued abruptly. Gradual dose reduction is recommended.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone will experience them.
The most commonly occurring adverse reactions were: headache, dizziness, gastrointestinal disorders:
nausea, constipation and abdominal pain, as well as bradycardia, tachycardia, palpitations,
arterial hypotension, skin flushing with sensation of warmth, peripheral oedema and feeling of fatigue.
Adverse reactions are listed below by system organ class:
Common (in 1 to 10 patients out of 100):

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

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

palpitations, tachycardia
abdominal pain
feeling of fatigue

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

paraesthesia, muscle tremors
somnolence
tinnitus
vomiting
excessive sweating

Adverse reactions occurring at 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
disorders of erection, 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.
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If any of the adverse reactions worsen or if any adverse reactions not listed in this leaflet occur, inform a doctor or pharmacist.
Reporting of adverse reactions
If any adverse reactions occur, including any adverse reactions not listed in this leaflet, inform your doctor, pharmacist or nurse. Adverse reactions can be reported directly to the Department of Monitoring Adverse Drug Reactions of the 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 reactions enables further collection of information on the safety of the medicine.

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

Keep this medicine out of 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.
Do not store above 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 the medicine Isoptin SR-E 240 contains
The active substance is: verapamil hydrochloride 240 mg.
Excipients: microcrystalline cellulose, sodium alginate, povidone, magnesium stearate,
hypromellose, polyethylene glycol 400, polyethylene glycol 6000, talc, titanium dioxide (E 171),
quinoline yellow lake (E 104) and indigo carmine lake (E 132), glycol wax Montana.
What Isoptin SR-E 240 looks like and contents of the packaging
A light green, elongated tablet.
Isoptin SR-E 240 is available in pack sizes containing:
20 tablets or 40 tablets.
Blister packs in a cardboard carton.
For more detailed information, please contact the Marketing Authorisation Holder or Parallel Importer.
Marketing Authorisation Holder in Greece, the country of export:
Viatris Healthcare Limited, Damastown Industrial Park, Mulhuddart, Dublin 15, Dublin, Ireland
Manufacturer:
VIANEX A.E., 15 km Athinon Marathonos Avenue, 153 44 Pallini Attica, Greece
Parallel Importer:
Delfarma Sp. z o.o., ul. Św. Teresy od Dzieciątka Jezus 111, 91-222 Łódź
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Repackaged in:
Delfarma Sp. z o.o., ul. Św. Teresy od Dzieciątka Jezus 111, 91-222 Łódź
Marketing Authorisation Number in Greece, the country of export: 8571/06-02-2007
Parallel Import Licence Number: 33/26
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