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 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 questions, please 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:

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 package 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, 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
  • 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 (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 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 (e.g. Wolff-Parkinson-White syndrome [WPW], Lown-Ganong-Levine syndrome [LGL]). Administration of the drug in these patients may lead to the 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-adrenolytic agents
• 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 impairment

Isoptin SR-E 240 and other medicines
Inform your doctor about all medicines currently or recently taken, 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 drugs (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 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 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 concentrations. However, addition of 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 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 taking 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 re-adjusting 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 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 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 under hazardous conditions. This is particularly likely during the initial phase of treatment, during dose escalation, when switching from another medicine, and when alcohol is consumed concurrently. The drug may increase blood alcohol concentration and delay its elimination. Therefore, the effects 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 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 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 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.
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 the 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 function impairment
Caution should be exercised when administering this medicine 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 hepatic dysfunction, resulting in stronger and prolonged drug effects. 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 case of overdose, supportive treatment tailored to the individual patient should primarily 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 procedures 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.

Discontinuation of Isoptin SR-E 240
After prolonged use, this medicine must not be discontinued abruptly. 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,
palpitations, arterial 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 patients):

• 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 reactions occurring with unknown frequency (frequency cannot be estimated from the available data):
• hypersensitivity reactions
• extrapyramidal disorders, seizures
• hyperkalaemia
• peripheral vertigo
• 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
• disorders of erection, galactorrhoea, gynaecomastia
• increased prolactin blood concentration, increased liver enzyme activity
  Since 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 any adverse reactions occur, including any adverse reactions 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 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 sight and reach of children.
Do not use this medicine after the expiry date stated on the carton after: Expiry (EXP) and on the blister after: EXP. 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. Following this advice helps 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
Excipients: microcrystalline cellulose, sodium alginate, povidone K 30, magnesium stearate
and 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
glycol.

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 (2 blisters of 10 tablets each)
40 tablets (4 blisters of 10 tablets each)
Blister made of PVC-PVDC/Al in a cardboard box.

For more detailed information, please contact the Marketing Authorisation Holder or the parallel importer.

Marketing Authorisation Holder in Romania, country of export:
Mylan Healthcare GmbH
Lütticher Straße 5, 53842 Troisdorf, Germany

Manufacturer:
Famar A.V.E. Anthoussa Plant
Anthoussa Avenue 7, Anthoussa Attiki, 15349, Greece

Parallel Importer:
Aga Kommerz spol. s r.o.
Frydecka 2006
737 01 Český Těšín
Czech Republic

Repackaged in:
Pharma Innovations Sp. z o.o.
ul. Jagiellońska 76
03-301 Warsaw
CEFEA Sp. z o.o. Sp. komandytowa
ul. Działkowa 56
02-234 Warsaw
Wytwórnia Euceryny Laboratorium Farmaceutyczne COEL S.J. E.Z.M. KONSTANTY
ul. Wł. Żeleńskiego 45
31-353 Kraków
Medezin Sp. z o.o.
ul. Zbąszyńska 3
91-342 Łódź

Marketing Authorisation Number in Romania, country of export: 9522/2016/01
Parallel Import Authorisation Number: 29/22