Isoptin Sr-e 240

Leaflet attached to the packaging: patient information

Warning! The leaflet should be kept. Information on the immediate packaging in a foreign language.

Isoptin SR-E 240 (Isoptin RR 240 mg)

240 mg, prolonged-release tablets
Verapamil hydrochloride
Isoptin SR-E 240 and Isoptin RR 240 mg are different trade names for the same medicine.

You should carefully read the contents of the leaflet before taking the medicine, as it contains important information for the patient.

• You should keep this leaflet, so that you can read it again if you need to.
• If you have any doubts, you should consult a doctor or pharmacist.
• This medicine has been prescribed specifically for you. Do not pass it on to others. The medicine may harm another person, even if their symptoms are the same.
• If the patient experiences any side effects, including any side effects not listed in the leaflet, they should tell their doctor, pharmacist, or nurse. See section 4.

Table of contents of the leaflet:

• 1. What is Isoptin SR-E 240 and what is it 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 packaging and other information

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

Isoptin SR-E 240 is available in the form of prolonged-release tablets containing 240 mg of the active substance - verapamil hydrochloride. Verapamil hydrochloride is a selective calcium antagonist that acts directly on the heart muscle.
The action of the medicine is based on the inhibition of calcium ion passage through the cell membrane into the heart muscle cells and vascular smooth muscle cells.
The medicine has antihypertensive and antiarrhythmic effects.
The antihypertensive effect of the medicine is the result of a decrease in peripheral resistance without a simultaneous increase in heart rate. In the case of normal blood pressure, the medicine does not have a significant hypotensive effect.
The antiarrhythmic effect, especially in the case of supraventricular rhythm disturbances, is based on the slowing of conduction in the atrioventricular node. As a result, there is a restoration of sinus rhythm and/or normalization of ventricular contractions, depending on the type of rhythm disturbance. The medicine does not change the normal heart rate or only slightly reduces it.
Isoptin SR-E 240 is indicated for use in adults for the treatment of:

• hypertension
• coronary heart disease (states characterized by insufficient oxygen supply to the heart muscle), including:
• chronic stable angina pectoris
• unstable angina pectoris (with increasing pain, pain at rest)
• Prinzmetal's angina

Page 1 of 8

• angina pectoris after myocardial infarction without heart failure, when beta-adrenergic blockers are not indicated
• arrhythmias such as:
• paroxysmal supraventricular tachycardia, atrial fibrillation/flutter with rapid atrioventricular conduction (except for Wolff-Parkinson-White syndrome [WPW] or Lown-Ganong-Levine syndrome [LGL])

2. Important information before taking Isoptin SR-E 240

When not to take Isoptin SR-E 240

• in cardiogenic shock
• in second- or third-degree atrioventricular block (except for patients with a functioning pacemaker)
• in sick sinus syndrome (except for patients with a functioning pacemaker)
• in heart failure with reduced ejection fraction below 35% and/or pulmonary capillary wedge pressure above 20 mmHg (if not secondary to supraventricular tachycardia responding to verapamil treatment)
• in atrial fibrillation/flutter with accessory conduction (e.g. Wolff-Parkinson-White syndrome [WPW], Lown-Ganong-Levine syndrome [LGL]). In these patients, there is a risk of ventricular tachyarrhythmia, including ventricular fibrillation

Warnings and precautions

Before starting treatment with Isoptin SR-E 240, the patient should discuss it with their doctor.
Particular caution should be exercised in patients:

• with acute myocardial infarction complicated by rhythm disturbances, significant hypotension, or left ventricular dysfunction
• with heart block, first-degree atrioventricular block, rhythm disturbances, or asystole
• taking antiarrhythmic drugs, beta-adrenergic blockers
• taking digoxin
• with heart failure with 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 liver impairment

Isoptin SR-E 240 and other medicines

The patient should tell their doctor about all medicines they are currently taking or have recently taken, including those they plan to take.
Interactions with verapamil are possible with the following medicines:

• alpha-adrenergic blockers (e.g. prazosin, terazosin)
• antiarrhythmic drugs (e.g. flecainide, quinidine)
• bronchodilators (e.g. theophylline)
• antiepileptic drugs (e.g. carbamazepine, phenytoin)
• antidepressants (e.g. imipramine)
• antidiabetic drugs (e.g. gliburyde)
• drugs for gout (e.g. colchicine)
• antibiotics (e.g. clarithromycin, erythromycin, rifampicin, telithromycin)

Page 2 of 8

• anticancer drugs (e.g. doxorubicin)
• barbiturates (e.g. phenobarbital)
• benzodiazepines and other anxiolytic drugs (e.g. buspirone, midazolam)
• beta-adrenergic blockers (e.g. metoprolol, propranolol)
• cardiac glycosides (e.g. digitoxin, digoxin)
• H receptor antagonists (e.g. cimetidine)
• immunomodulating and immunosuppressive drugs (e.g. cyclosporine, everolimus, sirolimus, tacrolimus)
• lipid-lowering drugs (e.g. atorvastatin, lovastatin, simvastatin)
• serotonin receptor agonists (e.g. almotriptan)
• drugs increasing uric acid excretion (e.g. sulfinpyrazone)
• dabigatran (anticoagulant) and direct oral anticoagulants
• ivabradine (used in the treatment of heart diseases), see section "When not to take 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 with grapefruit juice and products containing St. John's wort extract are also possible.
Additional information on some interactions is provided below.
Antiviral drugs against human immunodeficiency virus (HIV)
Ritonavir may increase verapamil plasma concentrations, enhancing its effect. Caution should be exercised when these drugs are used together, 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 without changes or with increased lithium serum concentrations.
However, the addition of Isoptin SR-E 240 also resulted in decreased lithium serum concentrations in patients chronically receiving oral fixed doses of lithium. Patients receiving both drugs should be closely monitored.
Drugs blocking neuromuscular transmission
The medicine may enhance the effect of drugs blocking neuromuscular transmission (curare-like and depolarizing drugs). It may be necessary to reduce the dose of Isoptin SR-E 240 and/or the dose of the drug blocking neuromuscular transmission when these drugs are used together.
Acetylsalicylic acid
Increased risk of bleeding.
Ethyl alcohol
Increased ethanol plasma concentrations.
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 started with the lowest possible dose, which can then be gradually increased.
If the patient is already taking an HMG-CoA reductase inhibitor (e.g. simvastatin, atorvastatin, or lovastatin), the dose of the statin should be reduced and then readjusted based on serum cholesterol levels.
The likelihood of an interaction with fluvastatin, pravastatin, or rosuvastatin is lower.
Hypotensive, diuretic, and vasodilating drugs
Enhanced hypotensive effect.

Pregnancy and breastfeeding

If the patient is pregnant or breastfeeding, thinks they may be pregnant, or plans to have a child, they should consult their doctor before taking this medicine.
There are no data on the use of the medicine in pregnant women, and therefore, the medicine can only be used during pregnancy if it is absolutely necessary.
The medicine is excreted into breast milk in small amounts. The risk to newborns and infants cannot be excluded. However, due to the potential for serious side effects in breastfed infants, the medicine can only be used during breastfeeding if it is essential for the mother's health.

Driving and using machines

In some patients, Isoptin SR-E 240 may affect their ability to react to such an extent that it impairs their ability to drive vehicles, operate machinery, or work in hazardous conditions. This is especially true during the initial treatment period, when increasing the dose, when switching from another medicine, and when consuming alcohol. The medicine may increase ethanol plasma concentrations and delay its elimination. Therefore, the effect of alcohol may be enhanced.

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 (the main component of common salt) per tablet.
This corresponds to 1.9% of the maximum recommended daily intake of sodium in the diet for adults.

3. How to take Isoptin SR-E 240

This medicine should always be taken exactly as prescribed by the doctor. In case of doubts, the patient should consult their doctor or pharmacist.
The dose of the medicine should be adjusted individually, depending on the severity of the disease. Long-term clinical experience confirms that in all indications, the daily dose is usually between 240 mg and 360 mg. During long-term treatment, the daily dose should not exceed 480 mg, while in short-term treatment, a higher dose may be used. The duration of treatment is unlimited. After long-term treatment, the medicine should not be stopped abruptly. A gradual dose reduction is recommended.
Oral administration. The tablet should be swallowed whole (not sucked or chewed), with a sufficient amount of liquid, preferably during or immediately after a meal.
Adults and adolescents over 50 kg of body weight
Hypertension: 120 mg to 480 mg per day in one or two divided doses.
Coronary heart disease, paroxysmal supraventricular tachycardia, atrial fibrillation, and atrial flutter: 120 mg to 480 mg per day in one or two divided doses.
Page 4 of 8
In case a dose of 120 mg is necessary, Isoptin SR 120 mg prolonged-release tablets should be used.
In patients who may respond satisfactorily to small doses (e.g. patients with liver failure or elderly patients), Isoptin 40 mg or Isoptin 80 mg film-coated tablets should be used.
Special populations
Children and adolescents
Isoptin SR-E 240 should not be used in children. In children, non-modified release medicines should be used.
Renal impairment
When using the medicine in patients with renal impairment, caution should be exercised, and the patient's condition should be closely monitored.
Hepatic impairment
In patients with liver failure, the metabolism of the medicine is impaired to a varying degree, depending on the degree of liver failure, which makes the medicine act stronger and longer. Therefore, particular caution should be exercised when determining the dose in patients with liver failure, and small doses should be administered in the initial treatment period (see section "Warnings and precautions").

Overdose of Isoptin SR-E 240

Symptoms
Hypotension, bradycardia, slowing of conduction up to high-degree atrioventricular block and sinus arrest, hyperglycemia, stupor, metabolic acidosis, acute respiratory failure. Overdose has led to death.
Treatment
In case of overdose, supportive treatment should be administered, individually tailored. In the treatment of intentional overdose, beta-adrenergic stimulation and/or parenteral calcium (calcium chloride) have been effectively used. In case of significant hypotension or high-degree atrioventricular block, vasopressor drugs or cardiac pacing should be used, respectively. In case of asystole, standard procedures should be used, including beta-adrenergic stimulation (e.g. isoproterenol hydrochloride), other vasopressor drugs, or cardiopulmonary resuscitation.
If there is an overdose of verapamil hydrochloride in a prolonged-release form, due to slower absorption of the medicine, the patient should be hospitalized and monitored for up to 48 hours. Verapamil hydrochloride cannot be removed from the body by hemodialysis.

Missing a dose of Isoptin SR-E 240

A double dose should not be taken to make up for a missed dose.

Stopping treatment with Isoptin SR-E 240

After long-term treatment, the medicine should not be stopped abruptly. A gradual dose reduction is recommended.

4. Possible side effects

Like all medicines, Isoptin SR-E 240 can cause side effects, although not everybody gets them.
The most common side effects were: headache, dizziness, gastrointestinal disturbances: nausea, constipation, and abdominal pain, as well as bradycardia, tachycardia, palpitations, hypotension, flushing, peripheral edema, and fatigue.
Side effects are listed below by system organ class:
Common(in 1 to 10 patients out of 100):

• central dizziness, headache
• bradycardia
• flushing, hypotension
• constipation, nausea
• peripheral edema

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

• palpitations, tachycardia
• abdominal pain
• fatigue

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

• paresthesia, muscle tremors
• drowsiness
• tinnitus
• vomiting
• excessive sweating

Side effects with unknownfrequency (frequency cannot be estimated from available data):

• hypersensitivity reactions
• extrapyramidal disorders, seizures
• hyperkalemia
• peripheral dizziness
• atrioventricular block (first-, second-, or third-degree), heart failure, sinus arrest, sinus bradycardia, asystole (cardiac arrest)
• bronchospasm, dyspnea
• abdominal discomfort, gingival hyperplasia, intestinal obstruction
• angioedema, Stevens-Johnson syndrome, erythema multiforme, alopecia, pruritus, urticaria, rash, erythema
• arthralgia, muscle weakness, myalgia
• renal failure
• erectile dysfunction, galactorrhea, gynecomastia
• increased prolactin levels, increased liver enzyme activity

After marketing, one case of paralysis (quadriparesis) has been reported after concomitant use of verapamil and colchicine.
If any side effect worsens or any side effect not listed in the leaflet occurs, the patient should inform their doctor or pharmacist.

Reporting side effects

If side effects occur, including any side effects not listed in this leaflet, the patient should tell their doctor, pharmacist, or nurse. Side effects can be reported directly to the Department of Monitoring of Adverse Reactions to Medicinal Products 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
By reporting side effects, more information can be collected on the safety of the medicine.
Page 6 of 8

5. How to store Isoptin SR-E 240

The medicine should be stored 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 month.
Store in a temperature below 25°C, in the original packaging.
Medicines should not be disposed of via wastewater or household waste. The patient should ask their pharmacist how to dispose of medicines that are no longer needed. This will help protect the environment.

6. Contents of the packaging and other information

What Isoptin SR-E 240 contains

The active substance of the medicine is verapamil hydrochloride 240 mg.
The excipients are: microcrystalline cellulose, sodium alginate, povidone K 30, magnesium stearate, and the tablet coating: hypromellose, macrogol 400, macrogol 6000, talc, titanium dioxide (E 171), quinoline yellow (E 104), indigo carmine (E 132), and Montana glyceride wax.

What Isoptin SR-E 240 looks like and contents of the packaging

The tablet is light green, prolonged-release.
Isoptin SR-E 240 is available in packages containing:
20 tablets (2 blisters of 10 tablets each)
40 tablets (4 blisters of 10 tablets each)
Blisters of PVC-PVDC/Al in a cardboard box.
For more detailed information, the patient should contact the marketing authorization holder or the parallel importer.

Marketing authorization holder in Romania, the country of export:

Viatris Healthcare Limited
Damastown Industrial Park, Mulhuddart, Dublin 15, Dublin, Ireland

Manufacturer:

Abbvie Deutschland GmbH & Co. KG
Knollstrasse, 67061 Ludwigshafen, Germany
Famar A.V.E. Anthoussa Plant
Anthoussa Avenue 7, Anthoussa Attiki, 15349, Greece

Parallel importer:

Delfarma Sp. z o.o.
ul. Św. Teresy od Dzieciątka Jezus 111, 91-222 Łódź

Repackaged by:

Delfarma Sp. z o.o.
ul. Św. Teresy od Dzieciątka Jezus 111, 91-222 Łódź
Romanian marketing authorization number: 9522/2016/01

Parallel import authorization number: 85/21

Date of leaflet approval:07.06.2023
Page 7 of 8
[Information about the trademark]
Page 8 of 8