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 RR 240 mg)
240 mg, prolonged-release tablets
Verapamili hydrochloridum
Isoptin SR-E 240 and Isoptin RR 240 mg are different brand names of the same medicinal product.
Please read the entire leaflet carefully before using this 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, consult your doctor or pharmacist.
• This medicine has been prescribed for a specific individual. Do not pass it on to others. The medicine may harm another person, 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.

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 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 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 arrhythmias, 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 insufficient 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-blockers 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 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 a 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 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.
Particular caution is required in patients:

• with acute myocardial infarction complicated by bradycardia, significant hypotension, or left ventricular dysfunction
• with heart block, 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 impairment

Isoptin SR-E 240 and other medicines
Inform your doctor about all medicines currently used or recently used, including those planned for future use.
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)
• antigout agents (e.g. colchicine)
• drugs used in infections (e.g. clarithromycin, erythromycin, rifampicin, telithromycin)
• antineoplastic 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 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 heart disease treatment), see section "When not to use Isoptin"
• 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 of these 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, even without changes or with increased serum lithium concentrations. However, addition of Isoptin SR-E 240 has also been associated with 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 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 plasma ethanol 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 as needed.
If initiating treatment 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 drugs
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, 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 reactions 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 in hazardous conditions. This is especially likely during the initial treatment period, during dose escalation, when switching from another medicine, and when alcohol is consumed simultaneously. 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 main 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 taken exactly as prescribed 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 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 limitation on the duration of treatment. After prolonged use, the drug 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 daily in one or two divided doses.
Coronary artery disease, paroxysmal supraventricular tachycardia, atrial fibrillation, and atrial flutter: 120 mg to 480 mg daily in one or two divided doses.
If a 120 mg dose 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), 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, medications with unmodified release should be used.

Renal function impairment
Caution should be exercised and patients should be closely monitored when administering the drug to patients with renal function impairment.

Hepatic function 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 is required 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 higher than recommended dose of Isoptin SR-E 240
Symptoms
Hypotension, bradycardia, slowed conduction up to high-degree atrioventricular block and sinus node arrest, hyperglycemia, stupor, metabolic acidosis, acute respiratory failure syndrome. Fatal outcomes have occurred due to overdose.

Treatment
In case of 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., hydrochloride isoproterenol), other vasopressor drugs, 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.

Discontinuation of Isoptin SR-E 240
After prolonged use, the drug 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 will experience them.
The most commonly reported adverse reactions were: headache, dizziness, gastrointestinal disorders:
nausea, constipation and abdominal pain, as well as bradycardia, tachycardia, palpitations,
hypotension, skin flushing with sensation of warmth, peripheral edema and feeling of fatigue.
Adverse reactions are listed below by system organ class:
Common (in 1 to 10 patients out of 100 patients):

• central dizziness, headache
• bradycardia
• skin flushing with sensation of warmth, hypotension
• constipation, nausea
• peripheral edema

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

• palpitations, tachycardia
• abdominal pain
• feeling of fatigue

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

• paresthesia, muscle twitching
• somnolence
• tinnitus
• vomiting
• excessive sweating

Adverse reactions occurring with unknown frequency (frequency cannot be estimated from the available data):

• hypersensitivity reactions
• extrapyramidal disorders, seizures
• hyperkalemia
• peripheral dizziness
• atrioventricular block (1st, 2nd, 3rd degree), heart failure, sinus node arrest, sinus bradycardia, asystole (cardiac arrest)
• bronchospasm, dyspnea
• 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, galactorrhea, gynecomastia
• increased prolactin blood concentration, increased liver enzyme activity

Post-marketing reports have included one case of paralysis (quadriparesis) 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 those not listed in this leaflet, inform your doctor or pharmacist. 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 allows the collection of additional information on the safety of the medicine.

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

Keep the 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.
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 required. This will 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 other components are: microcrystalline cellulose, sodium alginate, povidone K 30, magnesium stearate, and the tablet coating: hypromellose type 2910 3 mPa·s, polyethylene glycol 400, polyethylene glycol 6000, talc, titanium dioxide (E 171), quinoline yellow (E 104) and indigo carmine (E 132), montan wax glycolated.

What Isoptin SR-E 240 looks like and contents of the pack
Film-coated tablets, elongated, light green in colour, with a score line for dividing into equal doses on both sides and the company logo (two triangles) on one side.

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/Al blisters in a cardboard box.

For further information, please contact the marketing authorisation holder or the parallel importer.

Marketing authorisation holder in Romania, country of export:
Viatris Healthcare Limited
Damastown Industrial Park
Mulhuddart, Dublin 15, Dublin
Ireland

Manufacturer:
FAMAR A.V.E. ANTHOUSSA PLANT
Anthoussa Avenue 7
Anthoussa Attiki
15349, Greece

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

Repackaged by:
InPharm Sp. z o.o. Services sp. k.
ul. Chełmżyńska 249
04-458 Warsaw
Poland
Pharma Innovations Sp. z o.o.
ul. Jagiellońska 76
03-301 Warsaw
Poland

Marketing authorisation number in Romania, country of export: 9522/2016/01
Parallel import authorisation number: 375/19