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 (Isoptine L.P.)
240 mg, prolonged-release tablets
Verapamili hydrochloridum
Isoptin SR-E 240 and Isoptine L.P. are different trade names for the same medicine.
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 doubts, please consult your doctor, pharmacist, or nurse.
• This medicine has been prescribed for a specific individual. Do not pass it on to others. This medicine may harm others, 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.

Table of contents of the leaflet:

1. What Isoptin SR-E 240 is 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 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 consists of inhibiting the passage of calcium ions through the cell membrane into cardiac muscle cells and vascular smooth muscle cells.
The drug exerts antihypertensive and antiarrhythmic effects.
The antihypertensive effect of the drug results from reduced 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, consists of slowing 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

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• post-myocardial infarction angina in the absence of heart failure, when β-blockers are not indicated
• cardiac arrhythmias such as:
  • paroxysmal supraventricular tachycardia, atrial fibrillation/flutter with rapid atrioventricular conduction (except Wolff-Parkinson-White syndrome [WPW] or Lown-Ganong-Levine syndrome [LGL])

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 supraventricular tachycardia that responds 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]). In such patients, administration of the drug may lead to 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 cardiac conduction disorders, first-degree atrioventricular block, bradycardia, asystole
• taking antiarrhythmic drugs or β-blockers
• taking digoxin
• with heart failure and ejection fraction above 35%
• with arterial 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 or recently taken by the patient, including those the patient plans 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 for gout (e.g. colchicine)
• drugs used in infections (e.g. clarithromycin, erythromycin, rifampicin, telithromycin)

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• 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 drugs (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 Isoptin SR-E 240"
• metformin (used in diabetes treatment). 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 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 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 concomitantly.
Acetylsalicylic acid
Increased tendency to bleeding.
Ethyl alcohol
Increased ethanol plasma concentration.
HMG-CoA reductase inhibitors (statins)
In patients treated with 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.
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The likelihood of interaction with fluvastatin, pravastatin or rosuvastatin is lower.
Antihypertensive drugs, diuretics and vasodilators
Enhancement of the 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, therefore the drug 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 may 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 occurs especially during the initial phase of treatment, during dose escalation, when switching from another medication, and when alcohol is consumed simultaneously. The drug may increase blood alcohol concentration and delay its elimination. Therefore, the effect of alcohol may be enhanced.
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 used as directed by the physician. In case of doubt, consult a 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 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, the drug must not be abruptly discontinued. 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 in one or two divided doses.
Coronary artery disease, paroxysmal supraventricular tachycardia, atrial fibrillation, and atrial flutter: 120 mg to 480 mg per day in one or two divided doses.
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If a 120 mg dose is required, 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), treatment with 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, formulations with unmodified release should be used.

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

Hepatic function impairment
In patients with hepatic impairment, drug metabolism is impaired to varying degrees depending on the severity of liver dysfunction, resulting in increased and prolonged drug effect. Therefore, particular caution should be exercised when determining dosage in patients with hepatic impairment, and low doses should be administered during initial 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-degree atrioventricular block and sinus node arrest, hyperglycemia, stupor, metabolic acidosis, acute respiratory distress 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, 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 agents, or cardiopulmonary resuscitation.
In case of overdose with verapamil hydrochloride in a prolonged-release formulation, due to 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
After prolonged use, the drug must not be abruptly discontinued. Gradual dose reduction is recommended.

4. Possible adverse reactions

Like all medicines, this medicine may 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,
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palpitations, 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, 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 twitching
• somnolence
• tinnitus
• vomiting
• excessive sweating

Adverse reactions occurring with unknown frequency (frequency cannot be
determined from 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

Since marketing authorisation, one case of paralysis (quadriparesis) 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, 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 helps to provide more information on the safety of this medicine.
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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.
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 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.
The excipients are: microcrystalline cellulose, sodium alginate, povidone, magnesium stearate,
purified water; and tablet coating: hypromellose, polyethylene glycol 400, polyethylene glycol 6000, talc, titanium
dioxide (E171), quinoline yellow aluminium lake (E 104) and indigo carmine (E 132), glycol wax Montana.

What Isoptin SR-E 240 looks like and contents of the pack
Light green, elongated tablet.
Isoptin SR-E 240 is available in packs containing:
20 tablets or 40 tablets.
Blister packs in a cardboard box.
For further information, please contact the Marketing Authorisation Holder or the Parallel Importer.

Marketing Authorisation Holder in France, country of export:
Viatris Médical, 1 bis place de la Défense, Tour Trinity – F 92400 Courbevoie, France

Manufacturer:
Famar A.V.E. Anthoussa Plant, Anthoussa Attiki, 15349 – Greece
Mylan Hungary Kft., Mylan Utca 1, Komarom, 2900, Hungary

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

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

Marketing Authorisation numbers in France, country of export: 34009 328 674 1 7
34009 371 524 8 8
Parallel Import Licence Number: 99/26
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