Isoptin sr

Package leaflet: Information for the patient

Isoptin SR, 120 mg, prolonged-release tablets
Verapamili hydrochloridum
Please read the entire leaflet carefully before using this medicine, as it contains
important information for the patient.

• Keep this leaflet, as you may need to read it again.
• If you have any further questions, please consult your doctor or pharmacist.
• This medicine has been prescribed for a specific individual. Do not share it with 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 immediately. See section 4.

Table of contents:

1. What Isoptin SR is and what it is used for
2. Important information before taking Isoptin SR
3. How to take Isoptin SR
4. Possible side effects
5. How to store Isoptin SR
6. Contents of the package and other information

1. What Isoptin SR is and what it is used for

Isoptin SR is available as prolonged-release tablets containing 120 mg of the active substance – verapamil hydrochloride. Verapamil hydrochloride is a selective calcium antagonist acting directly on cardiac muscle.
The drug works by inhibiting the influx of calcium ions 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 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 is indicated for use in adults for the treatment of:

• arterial hypertension
• coronary artery disease (conditions characterized by inadequate oxygen supply to the heart muscle), 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

When not to use Isoptin SR

• 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 functioning pacemaker)
• in sick sinus syndrome (except in patients with a functioning pacemaker)
• in heart failure with ejection fraction below 35% and/or pulmonary capillary wedge pressure above 20 mmHg (unless secondary to 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, 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 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 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)
• 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 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 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 advised when these drugs are used concomitantly, and if necessary, the dose of verapamil should be reduced.

Lithium
Increased sensitivity to the effects of lithium (neurotoxicity) has been reported during concomitant treatment with Isoptin SR and lithium, with either unchanged or increased serum lithium concentrations. However, adding Isoptin SR has also been associated with decreased serum lithium levels in patients chronically receiving stable oral doses of lithium. Patients receiving both drugs should be closely monitored.

Neuromuscular blocking agents
The drug may enhance the effect of neuromuscular blocking agents (curare-like and depolarizing agents). Dose reduction of Isoptin SR 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 treated with Isoptin SR, therapy with HMG-CoA reductase inhibitors (e.g. simvastatin, atorvastatin, or lovastatin) should be initiated with the lowest possible dose, which is then gradually increased as needed.
If initiating treatment with Isoptin SR 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 drugs, diuretics, and vasodilators
Enhancement of 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, 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 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 may affect reaction ability to such an extent that it impairs the ability to drive vehicles, operate machinery, or work in hazardous conditions. This is particularly likely at the beginning 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 intensified.

Isoptin SR contains sodium
Isoptin SR contains less than 1 mmol (23 mg) of sodium per tablet, meaning the medicine is considered "sodium-free".

3. How to use Isoptin SR

This medicine should always be used 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 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 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.
In all the above indications, unless otherwise directed by the physician, the usual dose is: 1 or 2 tablets of Isoptin SR once or twice daily.
For patients who may respond adequately 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 should not be used in children. In children, immediate-release formulations 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 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).

Overdose of Isoptin SR
Symptoms
Hypotension, bradycardia, slowed conduction 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 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 hypotension or high-degree atrioventricular block, appropriate vasopressor agents 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 agents, or cardiopulmonary resuscitation. Following overdose with verapamil hydrochloride in a sustained-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
Do not take a double dose to make up for a missed dose.

Discontinuation of Isoptin SR
After prolonged use, the drug should 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 class:
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
˗ angioneurotic oedema, 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
After 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 a doctor or pharmacist.
If any adverse reactions occur, including any not listed in this leaflet, inform your doctor or pharmacist. Adverse reactions can be reported directly to the Department of Monitoring Adverse Drug Reactions at 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 provide more information on the safety of the medicine.

5. How to store the medicine Isoptin SR

Keep this medicine out of the 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.
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 packaging and other information

What Isoptin SR contains
The active substance is: verapamil hydrochloride 120 mg.
The other components are: microcrystalline cellulose, sodium alginate, povidone, magnesium stearate, purified water.
Tablet coating: hypromellose, polyethylene glycol 400, polyethylene glycol 6000, talc, titanium dioxide (E171), glycol wax.

What Isoptin SR looks like and contents of the pack
White, round, biconvex tablet.
Isoptin SR is available in packs containing:
40 tablets
100 tablets
Blister pack made of PCW/PVDC/Al foil in a cardboard box.

Marketing Authorisation Holder
Viatris Healthcare Sp. z o.o.
ul. Postępu 21B
02-676 Warszawa
Poland

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

Importer
Mylan Hungary Kft.
Mylan utca 1.
Komárom, 2900
Hungary

For more detailed information, please contact the Marketing Authorisation Holder:
Viatris Healthcare Sp. z o.o.
ul. Postępu 21B
02-676 Warszawa
Poland
Tel: (22) 546 64 00