Isoptin sr-e 240

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 SR 240 mg)
240 mg, prolonged-release tablets
Verapamili hydrochloridum
Isoptin SR-E 240 and Isoptin SR 240 mg are different trade names for the same medicinal product.
Please read this leaflet carefully before using 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 further 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 someone else, 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.

Leaflet contents:

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 involves inhibition of calcium ion influx through the cell membrane into cardiac muscle cells 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 individuals with normal blood pressure, the drug does not produce a significant hypotensive effect.
The antiarrhythmic effect, particularly in supraventricular rhythm disorders, 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 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 (except Wolff-Parkinson-White [WPW] syndrome or Lown-Ganong-Levine [LGL] syndrome)

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 cardiac pacemaker)
• in sick sinus syndrome (except in patients with a functioning cardiac pacemaker)
• in heart failure with reduced ejection fraction below 35% and/or pulmonary capillary wedge pressure above 20 mmHg (unless secondary to a supraventricular tachycardia responsive 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, consult your doctor.
Special caution is required in patients:

• with acute myocardial infarction complicated by bradycardia, significant hypotension, or left ventricular dysfunction
• with cardiac conduction disorders, first-degree atrioventricular block, bradycardia, or asystole
• taking antiarrhythmic drugs or β-adrenolytic agents
• 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
Inform your doctor about all medicines currently used or recently taken, including those planned for future use.
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 antiepileptic drugs (e.g. carbamazepine, phenytoin)
• antidepressants (e.g. imipramine)
• antidiabetic agents (e.g. glyburide)
• antigout agents (e.g. colchicine)
• antimicrobial agents (e.g. clarithromycin, erythromycin, rifampicin, telithromycin)
• anticancer drugs (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)
• histamine H₂-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 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 certain interactions is provided below.

Antiviral agents for human immunodeficiency virus (HIV)
Ritonavir may increase verapamil plasma concentrations, thereby enhancing its effects. Caution is required when these drugs are used concomitantly, and if necessary, the dose of verapamil 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 stable oral doses of lithium. Close monitoring of patients receiving both drugs is essential.

Neuromuscular blocking agents
The drug may potentiate the effects 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 plasma concentration of ethanol.

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 initiating Isoptin SR-E 240 in patients already taking an HMG-CoA reductase inhibitor (e.g. simvastatin, atorvastatin, or lovastatin), consider reducing the statin dose and subsequently readjusting 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 plans to become pregnant, 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 medication, and when alcohol is consumed concurrently. The drug may increase blood alcohol concentration and delay its elimination. Therefore, the effects of alcohol may be intensified.

Isoptin SR-E 240 contains quinoline yellow
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 (a major component of table salt) per 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 used as directed by the physician. In case of doubt, consult your doctor or pharmacist.
The dosage should be individually adjusted according to the severity of the disease. Long-term clinical experience confirms that in all indications, the daily dose usually 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 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 dose of 120 mg is required, the medicinal product Isoptin SR prolonged-release tablets 120 mg should be administered.
In patients who may exhibit an adequate response to lower doses (e.g., patients with hepatic impairment or elderly patients), the use of 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 immediate (unmodified) release should be used.

Renal function impairment
Caution should be exercised when administering the medicine to patients with renal function impairment, and the patient's condition should be closely monitored.

Hepatic function impairment
In patients with hepatic impairment, the metabolism of the drug is impaired to varying degrees depending on the extent of liver dysfunction, resulting in stronger and prolonged effects of the drug. Therefore, particular caution should be exercised when determining dosage in patients with hepatic impairment, and low doses should be administered during the initial phase of treatment (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-grade atrioventricular block and sinus node arrest, hyperglycemia, stupor, metabolic acidosis, acute respiratory distress syndrome. Fatalities have occurred as a result of overdose.

Treatment
In case of overdose, primarily individualized supportive treatment should be administered. For 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-grade atrioventricular block, appropriate vasopressor drugs or cardiac pacing should be used, respectively. In case of asystole, standard management should be implemented, including β-adrenergic stimulation (e.g., isoprenaline hydrochloride), other vasopressor agents, or cardiopulmonary resuscitation. In case of overdose with verapamil hydrochloride in a prolonged-release formulation, due to slower absorption of the drug, hospitalization and observation of the patient for up to 48 hours are required. 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 long-term use, this medicine must 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 experiences them.
The most commonly reported adverse reactions were: headache, dizziness, gastrointestinal disorders:
nausea, constipation and abdominal pain, as well as bradycardia, palpitations, flushing with a sensation of warmth, hypotension, peripheral oedema and fatigue.
Adverse reactions listed below are classified by system organ class:
Common (in 1 to 10 patients out of 100 patients):

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

Uncommon (in 1 to 10 patients out of 1,000 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 reactions 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, sinoatrial 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

After marketing authorisation, one case of paralysis (tetraparesis) has been reported following concomitant use of verapamil and colchicine.
If any of the adverse reactions worsen, or if any adverse reactions not listed in this leaflet occur, inform your doctor or pharmacist.
Reporting of adverse reactions
If you experience any adverse reactions, including any not listed in this leaflet, tell your doctor or pharmacist. Adverse reactions can be reported directly to the Department of Monitoring Adverse Drug Reactions at 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 helps to provide more information on the safety of the medicine.

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

Keep the 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, in the original packaging.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer in use. 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 K 30, magnesium stearate, purified water; and tablet coating: hypromellose 2910/3, polyethylene glycol 400, polyethylene glycol 6000, talc, titanium dioxide (E 171), quinoline yellow aluminium lake (E 104) and indigo carmine (E 132),
Montana wax.

What Isoptin SR-E 240 looks like and contents of the pack
Light green, elongated, biconvex tablets with a dividing score line and "2" logo on one side, and a dividing score line on the other side.
Isoptin SR-E 240 is available in packs of: 20 tablets and 40 tablets.
Blister packs made of PVC/PVDC/Al foil in a cardboard box.

For more detailed information, please contact the Marketing Authorisation Holder or the Parallel Importer.

Marketing Authorisation Holder in the Czech Republic, country of export:
Viatris Healthcare Limited
Damastown Industrial Park
Mulhuddart, Dublin 15
Dublin, Ireland

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

Parallel Importer:
Medezin Sp. z o.o.
ul. Zbąszyńska 3
91-342 Łódź
Poland

Repackaged in:
Medezin Sp. z o.o.
ul. Zbąszyńska 3
91-342 Łódź
Poland

Marketing Authorisation Number in the Czech Republic, country of export: 58/157/87-C
Parallel Import Authorisation Number: 111/26