Isoptin 40

Package leaflet: Information for the patient

Warning! Keep this leaflet! The information on the immediate packaging is in a foreign language.
Isoptin 40 (Isoptin)
40 mg, coated tablets
Verapamili hydrochloridum
Isoptin 40 and Isoptin 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 may read it again if necessary.
• If you have any questions, 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 someone else, 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 is Isoptin 40 and what is it used for
2. Important information before taking Isoptin 40
3. How to take Isoptin 40
4. Possible side effects
5. How to store Isoptin 40
6. Contents of the pack and other information

1. What is Isoptin 40 and what is it used for

Isoptin 40 is available as coated tablets containing 40 mg of the active substance

• verapamil hydrochloride. Verapamil hydrochloride is a selective calcium antagonist acting directly on cardiac muscle.

The drug acts by inhibiting the passage of calcium ions through the cell membrane into
cardiac muscle cells and vascular smooth muscle cells.
The medicine has 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 exert a significant hypotensive effect.
The antiarrhythmic effect, particularly in cases of 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 40 is indicated for use in adults, children, and adolescents for the treatment of:

• arterial hypertension
• coronary artery disease (conditions characterized by insufficient oxygen supply to the heart muscle), including:
• chronic stable angina pectoris
• unstable angina pectoris (with increasing pain, pain at rest)
• Prinzmetal's angina
• angina following myocardial infarction without heart failure, when β-adrenolytic agents are not indicated
• cardiac arrhythmias, such as:
• paroxysmal supraventricular tachycardia, atrial fibrillation/flutter with rapid atrioventricular conduction (except Wolff-Parkinson-White syndrome [WPW] or Lown-Ganong-Levine syndrome [LGL]).

2. Important information before using Isoptin 40

When not to use Isoptin 40

• 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 therapy)
• 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 ventricular tachyarrhythmias, including ventricular fibrillation
• if the patient is taking ivabradine.

Warnings and precautions
Before starting treatment with Isoptin 40, consult your doctor.
Special 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, 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.

Interaction of Isoptin 40 with other medicines
Inform your doctor about all medicines currently used 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)
• anticonvulsant 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(_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 40"
• metformin (used in the treatment of diabetes). Verapamil may reduce the glucose-lowering effect of metformin.

Isoptin 40 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 dose of verapamil should be reduced.

Lithium
Increased sensitivity to lithium (neurotoxicity) has been reported during concomitant treatment with Isoptin 40 and lithium, without changes or with increased serum lithium concentrations. However, adding Isoptin 40 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). It may be necessary to reduce the dose of Isoptin 40 and/or the neuromuscular blocking agent when used concomitantly.

Acetylsalicylic acid
Increased tendency to bleeding.

Ethanol
Increased plasma ethanol concentration.

HMG-CoA reductase inhibitors (statins)
In patients receiving Isoptin 40, 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 40 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-titrating 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 adequate data on the use of this medicine in pregnant women, and therefore it should be used during pregnancy only if clearly necessary.
The drug passes into breast milk in small amounts. Risk to newborns and infants cannot be excluded. However, due to the potential for 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 40 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 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.

Sodium content of Isoptin 40
Isoptin 40 contains less than 1 mmol (23 mg) of sodium per tablet, meaning the medicine is considered "sodium-free".

3. How to use Isoptin 40

This medicine should always be used according to the doctor's instructions. If in doubt, consult your
doctor or pharmacist.
Available on the market are: Isoptin 40 (40 mg), Isoptin 80 (80 mg).
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 time limit for using this medicine. After prolonged use, the
drug must not be abruptly discontinued. Gradual dose reduction is recommended.
Isoptin 40 should be used in patients who are expected to respond adequately to low doses (e.g.
patients with hepatic impairment or elderly patients). In patients requiring higher doses (e.g. 240 mg to
480 mg of verapamil hydrochloride per day), Isoptin 80, Isoptin SR, or Isoptin SR-E 240 should be used.
Oral administration.
The tablet should be swallowed whole (do not suck or chew), with sufficient liquid, preferably during
or immediately after a meal.
Adults and adolescents weighing over 50 kg
Hypertension: 120 mg to 480 mg per day in three divided doses.
Coronary artery disease, paroxysmal supraventricular tachycardia, atrial fibrillation, and atrial
flutter: 120 mg to 480 mg per day in three or four divided doses.
Special populations
Children and adolescents (only in cardiac rhythm disorders)
Up to 6 years of age: 80 mg to 120 mg of verapamil hydrochloride per day in two or three divided
doses.
From 6 to 14 years of age: 80 mg to 360 mg of verapamil hydrochloride per day in two, three, or
four divided doses.
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 a stronger and prolonged effect of the drug. 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 40
Symptoms
Hypotension, bradycardia, slowed conduction velocity up to high-degree atrioventricular block and
sinus node arrest, hyperglycemia, stupor, metabolic acidosis, acute respiratory failure syndrome.
Deaths have occurred due to overdose.
Treatment
In case of overdose, supportive treatment individually tailored should be primarily 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
electrostimulation should be used, respectively. In case of asystole, standard procedures should be
applied, including β-adrenergic stimulation (e.g. hydrochloride isoproterenol), other vasopressor drugs,
or cardiopulmonary resuscitation. Verapamil hydrochloride cannot be removed from the body by
hemodialysis.
Missed dose of Isoptin 40
Do not take a double dose to make up for a missed dose.
Discontinuation of Isoptin 40
After prolonged use, the drug must not be abruptly discontinued. 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 observed adverse reactions were: headache, dizziness, gastrointestinal disorders:
nausea, constipation and abdominal pain, as well as bradycardia, tachycardia, palpitations, hypotension,
flushing with a sensation of warmth, peripheral edema and fatigue.
Adverse reactions are listed below by system organ classification:
Common (in 1 to 10 patients out of 100):

• central dizziness, headaches
• bradycardia
• flushing with a sensation of warmth, hypotension
• constipation, nausea
• peripheral edema

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

• palpitations, tachycardia
• abdominal pain
• fatigue

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

• paresthesia, 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
• hyperkalemia
• peripheral dizziness
• atrioventricular block (I˚, II˚, III˚), 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 blood prolactin levels, increased liver enzyme activity

Post-marketing reports have included one case of paralysis (tetraparesis) following concomitant use of verapamil and colchicine.
Reporting of adverse reactions
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 of 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 reactions helps to provide more information on the safety of the medicine.

5. How to store Isoptin 40

Keep the medicine out of the 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 30°C.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer in use. This will help protect the environment.

6. Contents of the pack and other information

What Isoptin 40 contains
The active substance is verapamil hydrochloride. Each coated tablet contains 40 mg of verapamil hydrochloride.
The excipients are: calcium hydrogen phosphate, microcrystalline cellulose, colloidal anhydrous silica, sodium croscarmellose, magnesium stearate and the tablet coating: hypromellose 2910, sodium lauryl sulfate, polyethylene glycol 6000, talc, titanium dioxide (E 171).

What Isoptin 40 looks like and contents of the pack
Isoptin 40 is available in packs containing: 40 tablets or 50 tablets.
Blister packs made of PVC/aluminum in a cardboard carton.

For more detailed information, please contact the Marketing Authorisation Holder or the Parallel Importer.

Marketing Authorisation Holder in Greece, country of export:
Viatris Healthcare Limited
Damastown Industrial Park
Mulhuddart
Dublin 15
Dublin
Ireland

Manufacturer:
Vianex S.A. – Plant B, 15 km Marathonos Avenue, Pallini Attiki, 15351, Greece

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

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

Marketing Authorisation Numbers in Greece, country of export: 8571/06-02-2007
16446/26-02-2013

Parallel Import Licence Number: 29/21