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 (Isoptine L.P. 240 mg), 240 mg, prolonged-release tablets
Verapamili hydrochloridum
Isoptin SR-E 240 and Isoptine L.P. 240 mg are different brand names for the same medicinal product.
Please read this leaflet carefully before taking this medicine, as it contains important information for you.

• 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. This medicine 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.

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 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 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 arrhythmias, is due to slowing of conduction in 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-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)

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 (AV) block (except in patients with a fully functioning cardiac pacemaker)
• in sick sinus syndrome (except in patients with a fully 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 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 cardiac conduction disorders, first-degree AV 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 impairment

Isoptin SR-E 240 and other medicines
Inform your doctor about all medicines currently taken or recently used, 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 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)
• H-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 concentrations, thereby enhancing its effects. 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 been associated with decreased serum lithium concentrations in patients on chronic oral lithium therapy. 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 concomitantly.

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 initiated in patients already taking an HMG-CoA reductase inhibitor (e.g. simvastatin, atorvastatin, or lovastatin), consider reducing the statin dose and subsequently readjust it based on serum cholesterol levels.
The likelihood of interaction with fluvastatin, pravastatin, or rosuvastatin is lower.

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

Pregnancy and breastfeeding
If the patient is pregnant or breastfeeding, suspects she may be pregnant, or is planning 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; therefore, the drug 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 drug 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 driving, operating machinery, or working in hazardous conditions may be impaired. This is particularly likely during the initial phase of treatment, during dose escalation, when switching from another medication, or 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 (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 (a main component of table salt) per tablet. This corresponds to 1.9% of the maximum daily recommended sodium intake in the diet 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 for all indications, the usual daily dose ranges from 240 mg to 360 mg. During prolonged 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 long-term 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 liquid, preferably during or immediately after a meal.

Adults and adolescents with body weight over 50 kg

• Hypertension: 120 mg to 480 mg per day, given in one or two divided doses.
• Coronary artery disease, paroxysmal supraventricular tachycardia, atrial fibrillation, and atrial flutter: 120 mg to 480 mg per day, 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 products 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 impairment.

Hepatic impairment
In patients with hepatic impairment, drug metabolism is impaired to varying degrees depending on the severity of liver dysfunction, resulting in increased intensity and duration of drug effect. Therefore, particular caution should be exercised 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 distress syndrome. Fatal outcomes have occurred following overdose.

Treatment
In overdose, primarily individualized supportive treatment should be 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., 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.

Stopping treatment with Isoptin SR-E 240
After long-term 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 disturbances:
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 effects listed below are classified by system organ class:
Common (in 1 to 10 patients out of 100 patients):

• 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 patients):

• palpitations, tachycardia
• abdominal pain
• feeling of 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 determined from available data):

• hypersensitivity reactions
• extrapyramidal disorders, seizures
• hyperkalaemia
• peripheral dizziness
• atrioventricular block (1st, 2nd, 3rd degree), 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 blood prolactin concentration, increased liver enzyme activity

Following marketing authorisation, one case of paralysis (quadriparesis) has been reported following concomitant use of verapamil and colchicine.
If any of the adverse effects worsen or if any adverse effects not listed in this leaflet occur, inform your doctor or pharmacist.
Reporting of adverse effects
If you experience any adverse effects, including any not listed in this leaflet, tell your doctor or pharmacist. Adverse effects can be reported directly to the Department of Monitoring of Adverse Drug Reactions at the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products, Al. Jerozolimskie 181C, 02-222 Warsaw, phone: +48 22 49 21 301, fax: +48 22 49 21 309, website: https://smz.ezdrowie.gov.pl.
Reporting adverse effects helps to provide more information on the safety of this medicine.

5. How to store 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. Such measures help protect the environment.

6. Contents of the pack 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 the tablet coating: hypromellose, polyethylene glycol 400, polyethylene glycol 6000, talc, titanium
dioxide (E 171), quinoline yellow aluminium lake (E 104) and indigo carmine (E 132), glycol wax Montana
(Glycowax Hoechst E).

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/Aluminium blisters in a cardboard box.

For further detailed 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 Avenue 7, Anthoussa Attiki, 15349, Greece
Mylan Hungary kft., Mylan utca 1, Komarom, 2900, Hungary

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

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

Marketing Authorisation numbers in France, country of export: 34009 328 674 1 7
34009 371 524 8 8

Parallel Import Licence number: 351/24