Isoptin sr-e 240

PACKAGE LEAFLET: INFORMATION FOR THE PATIENT

Warning! Keep the leaflet. Information on the immediate packaging 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 taking this medicine, as it contains
important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any further questions, ask 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.

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 involves inhibition of calcium ion influx through the cell membrane into cardiac muscle cells and vascular smooth muscle cells.
The medicine 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 medicine has no significant hypotensive effect.
The antiarrhythmic effect, particularly in supraventricular rhythm disorders, is due to slowing of conduction through the atrioventricular node. As a result, depending on the type of arrhythmia, sinus rhythm may be restored and/or ventricular rate normalized. The medicine 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 left ventricular 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 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
• receiving antiarrhythmic drugs or β-blockers
• receiving digoxin
• with heart failure and ejection fraction above 35%
• with hypotension
• receiving 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 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-adrenergic blockers (e.g. metoprolol, propranolol)
• cardiac glycosides (e.g. digitoxin, digoxin)
• H\textsubscript{2}-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 agents 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, adding 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 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 concurrently.

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.
If initiation of Isoptin SR-E 240 occurs in patients already receiving 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 agents, 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 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 particularly likely during the initial phase of treatment, during dose escalation, when switching from another medication, 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 (E104), 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 intake of sodium for adults.

3. How to use Isoptin SR-E 240

This medicine should always be taken exactly as directed by your doctor. If in doubt, consult your doctor or pharmacist.

The dose should be individually adjusted depending on 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, 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 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 as a single dose or in two divided doses.
• Angina pectoris, paroxysmal supraventricular tachycardia, atrial fibrillation, and atrial flutter: 120 mg to 480 mg per day as a single dose or in 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), 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, immediate-release formulations should be used.

Renal impairment
Caution should be exercised and patients should be closely monitored when administering this medicine to patients with impaired renal function.

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 prolonged duration of action. Therefore, particular caution should be exercised when determining the dose in patients with hepatic impairment, and low doses should be administered during the initial phase of treatment (see section Warnings and precautions).

Overdose 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
Treatment of overdose should primarily consist of individually tailored supportive measures. 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 agents or cardiac pacing should be instituted, respectively. In cases of asystole, standard management should be implemented, including β-adrenergic stimulation (e.g., hydrochloride isoproterenol), other vasopressor agents, or cardiopulmonary resuscitation.

In cases of overdose with hydrochloride verapamil in a prolonged-release formulation, due to slower absorption, the patient should be hospitalized and observed for up to 48 hours. Hydrochloride verapamil 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 can cause adverse reactions, although not everyone experiences 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 classification:

Common (in 1 to 10 patients out of 100):

• 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):

• 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 estimated from the 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, 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.
If you experience any adverse reactions, including any not listed in this leaflet, tell your doctor or pharmacist. Adverse reactions can be reported directly to the Department for 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
Adverse reactions can also be reported to the Marketing Authorisation Holder.
Reporting adverse reactions 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 carton and blister pack. The expiry date refers to the last day of the specified 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. Such measures 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 other components are: 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), indigo carmine (E 132), and glycol wax Montana.

What Isoptin SR-E 240 looks like and contents of the pack
The tablet is light green, elongated in shape.
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)
Blisters made of PVC-PVDC/Aluminum foil, packed in a cardboard box.
For more detailed information, please contact the marketing authorization holder or the parallel importer.

Marketing Authorization 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
ABBVIE DEUTSCHLAND GmbH & Co. KG
Knollstrasse
67061 Ludwigshafen
Germany

Parallel importer:
Medezin Sp. z o.o.
ul. Zbąszyńska 3
91-342 Łódź
Poland

Repackaged in:
Medezin Sp. z o.o.
ul. Zbąszyńska 3
91-342 Łódź
Poland
CEFEA Sp. z o.o. Sp. komandytowa
ul. Działkowa 56
02-234 Warszawa
Poland
Pharma Innovations Sp. z o.o.
ul. Jagiellońska 76
03-301 Warszawa
Poland
Synoptis Industrial Sp. z o.o.
ul. Szosa Bydgoska 58
87-100 Toruń
Poland
CANPOLAND SPÓŁKA AKCYJNA
ul. Beskidzka 190
91-610 Łódź
Poland

Number of marketing authorization in Romania, country of export: 9522/2016/01
Number of parallel import authorization: 232/22